Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

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Xiao ZHAO

2012-01-01

Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

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Ming Li

Full Text Available To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC.A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS, progression-free survival (PFS, response rate (RR, and different types of toxicity. Hazard ratios (HRs, odds ratios (ORs and their 95% confidence intervals (CIs were pooled using RevMan software.Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC improved survival compared with other platinum-based regimens (PBR in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04, especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02. No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively. Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities.Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

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Abdel Kader Y

2013-07-01

in advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. No significant difference in toxicity was observed between both treatment arms, apart from bevacizumab/carboplatin/paclitaxel-related risks as DVT, hypertension, proteinuria, sensory/motor neuropathy, and alopecia.Keywords: bevacizumab, non-small cell lung cancer, NSCLC, pemetrexed

(99m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab.

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Ma, Qingjie; Min, Kaiyin; Wang, Ting; Chen, Bin; Wen, Qiang; Wang, Fan; Ji, Tiefeng; Gao, Shi

2015-07-01

Functional imaging can help clinicians assess the individual response of advanced nonsquamous non-small cell lung cancer (NSCLC) to chemoradiation therapy plus bevacizumab. Our purpose is to investigate the ability of (99m)Tc-3PRGD2 single photon emission computed tomography/computed tomography (SPECT/CT) in predicting the early response to treatment. Patients with advanced nonsquamous NSCLC diagnosed by histological or cytological examination were imaged with (99m)Tc-3PRGD2 SPECT/CT at 3 time points: 1-3 days before the start of treatment (SPECT1), 40 Gy radiotherapy with 2 cycles of chemotherapy plus bevacizumab (SPECT2) and 4 weeks after chemoradiotherapy plus bevacizumab (SPECT3). The images were evaluated semiquantitatively by measuring the tumor to non-tumor ratio (T/N) and calculating the percentage change in T/N ratio. Short-term outcome was assessed by the treatment response evaluation according to the Response Evaluation Criteria in Solid Tumors criteria as: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients were divided two groups: responders (CR and PR) and nonresponders (SD and PD). To determine a threshold for percent reduction in T/N ratios, receiver-operating characteristic (ROC) curve analysis was used. Patients were grouped again based on the threshold of P1 (the change percentage from SPECT1 to SPECT2) and P2 (the change percentage from SPECT1 to SPECT3): P1 responders and P1 nonresponders; P2 responders and P2 nonresponders. Patients were followed up starting 4 weeks after completion of therapy and then every 3 months for the first 2 years and every 6 months after 2 years. OS of P1 responders, P1 nonresponders, P2 responders and P2 nonresponders was estimated and graphically illustrated using the Kaplan-Meier method and the log-rank test was used to test the null hypotheses of equal OS in subgroups of patients. A total of 28 patients completed all imaging and treatment. All primary

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

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Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

2014-05-01

Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (SAiL study. No new safety signals were reported.

Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

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Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

2014-06-01

Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

The Relevance of External Quality Assessment for Molecular Testing for ALK Positive Non-Small Cell Lung Cancer : Results from Two Pilot Rounds Show Room for Optimization

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Tembuyser, Lien; Tack, Veronique; Zwaenepoel, Karen; Pauwels, Patrick; Miller, Keith; Bubendorf, Lukas; Kerr, Keith; Schuuring, Ed; Thunnissen, Erik; Dequeker, Elisabeth M. C.

2014-01-01

Background and Purpose: Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK

A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

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Taipale K

2017-08-01

Full Text Available Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS and overall survival (OS relative to gemcitabine + cisplatin (induction sequences or best supportive care (BSC (maintenance sequences. Modeled health-care benefits were expressed as life-years (LYs and quality-adjusted LYs (QALYs (estimated using French EuroQol five-dimension questionnaire tariffs. The study was conducted from the payer perspective (National Health Insurance. Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed

Clinical potential of necitumumab in non-small cell lung carcinoma

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Genova C

2016-08-01

Full Text Available Carlo Genova,1–3 Fred R Hirsch1 1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; 2Lung Cancer Unit, IRCCS AOU San Martino IST, 3Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy Abstract: Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial; by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial. On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. Keywords: necitumumab, EGFR, non-small cell lung cancer, monoclonal antibody, H-score

Current treatments for advanced stage non-small cell lung cancer.

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Stinchcombe, Thomas E; Socinski, Mark A

2009-04-15

Lung cancer remains the leading cause of cancer mortality in the United States, and the majority of patients will have non-small cell lung cancer (NSCLC) and will present with locally advanced or metastatic disease. In the United States, the most common histology is adenocarcinoma, followed by squamous cell, large cell, and not otherwise specified. For patients with a preserved performance status (PS), double agent platinum-based therapy extends survival, improves quality of life (Qol), and reduces disease-related symptoms. The addition of a third cytotoxic agent increases toxicity without any clinical benefit. However, the addition of a targeted agent (bevacizumab, an antiangioegenesis agent, or cetuximab, an antibody against the epidermal growth factor receptor [EGFR]) to platinum-based therapy has yielded an improvement in survival compared with platinum-based therapy alone. To receive bevacizumab, patients are required to have nonsquamous histology, a PS of 0 or 1, and no evidence of brain metastases, hemoptysis, uncontrolled hypertension, and no need for therapeutic anticoagulation. The benefits of chemotherapy for patients with a poor performance status are less well defined, and the current recommendations are for treatment with single-agent chemotherapy. Elderly patients (defined as age > or = 70 yr) derive a survival and Qol benefit from chemotherapy treatment, and for the majority of elderly patients single-agent chemotherapy is the standard. However, elderly patients with a good performance status and without co-morbidities can tolerate platinum-based therapy without excessive toxicity and appear to derive a survival benefit similar to that in younger patients. Recently, a separate population of patients defined by a light or never-smoking history has been identified. This patient population appears to have unique clinical and molecular characteristics, and may benefit from initial therapy with an EGFR tyrosine kinase inhibitor. Once patients have

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.

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Okamoto, Isamu; Schuette, Wolfgang H W; Stinchcombe, Thomas E; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J; Zinner, Ralph G

2017-05-01

This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. All patients received pemetrexed 500 mg/m 2 every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated

Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

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Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

2012-10-01

Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

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Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

2015-01-01

In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

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Chen JH

2016-04-01

Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

New targeted treatments for non-small-cell lung cancer – role of nivolumab

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Zago G

2016-08-01

Full Text Available Giulia Zago,1,2,* Mirte Muller,1,* Michel van den Heuvel,1 Paul Baas1 1Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AvL, Amsterdam, the Netherlands; 2Medical Oncology 2, Istituto Oncologico Veneto (IOV, Padova, Italy *These authors contributed equally to this work Abstract: Non-small-cell lung cancer (NSCLC is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017 and non-squamous NSCLC (CheckMate 057. In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively. Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. Keywords: nivolumab, advanced non-small-cell lung cancer, immunotherapy, anti-PD-1

New targeted treatments for non-small-cell lung cancer - role of nivolumab.

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Zago, Giulia; Muller, Mirte; van den Heuvel, Michel; Baas, Paul

2016-01-01

Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors.

Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).

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Horn, Leora; Spigel, David R; Vokes, Everett E; Holgado, Esther; Ready, Neal; Steins, Martin; Poddubskaya, Elena; Borghaei, Hossein; Felip, Enriqueta; Paz-Ares, Luis; Pluzanski, Adam; Reckamp, Karen L; Burgio, Marco A; Kohlhäeufl, Martin; Waterhouse, David; Barlesi, Fabrice; Antonia, Scott; Arrieta, Oscar; Fayette, Jérôme; Crinò, Lucio; Rizvi, Naiyer; Reck, Martin; Hellmann, Matthew D; Geese, William J; Li, Ang; Blackwood-Chirchir, Anne; Healey, Diane; Brahmer, Julie; Eberhardt, Wilfried E E

2017-12-10

Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m 2 every 3 weeks). Minimum follow-up for survival was 24.2 months. Results Two-year overall survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%) versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%) versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the risk of death with nivolumab versus docetaxel remained similar to those reported in the primary analyses. Durable responses were observed with nivolumab; 10 (37%) of 27 confirmed responders with squamous NSCLC and 19 (34%) of 56 with nonsquamous NSCLC had ongoing responses after 2 years' minimum follow-up. No patient in either docetaxel group had an ongoing response. In the pooled analysis, the relative reduction in the risk of death with nivolumab versus docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of treatment-related adverse events were lower with nivolumab than with docetaxel (any grade, 68% v 88%; grade 3 to 4, 10% v 55%). Conclusion Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC.

Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

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Petrović Marina

2009-01-01

Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

A single-arm phase II trial of pazopanib in patients with advanced non-small cell lung cancer with non-squamous histology with disease progression on bevacizumab containing therapy.

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Weiss, Jared M; Villaruz, Liza C; Socinski, Mark A; Ivanova, Anastasia; Grilley-Olson, Juneko; Dhruva, Nirav; Stinchcombe, Thomas E

2014-11-01

Platinum-based chemotherapy with bevacizumab is a standard therapy for patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with non-squamous (NS) histology. Mechanisms of resistance to bevacizumab include increased VEGF signaling or activation of VEGF receptors. Pazopanib is a multi-targeted VEGF receptor tyrosine kinase with single agent activity in NSCLC. Stage IIIB/IV patients with adequate organ function, who progressed on a bevacizumab containing therapy were eligible if it had been ≤8 weeks since the last bevacizumab treatment. The primary end-point was disease control rate (DCR), defined as partial or complete response, or stable disease for ≥12 weeks. Patients were assessed radiographically every 2 cycles (6 weeks). A Simon 2-stage design was used, and if in the first stage ≤4 of 17 patients experienced disease control the trial was to have been stopped for futility. An unplanned analysis was performed after 15 patients were evaluable secondary to slow accrual. Between December 2010 and November 2013, 15 patients were treated on trial. The median age was 61 years (range 39-74), and all patients had stage IV disease. Of the 15 patients, 4 discontinued therapy prior to cycle 2 evaluation due to adverse events (n=3) and medical illness (n=1), 5 patients had progressive disease, 4 patients had stable disease for <12 weeks, and 2 patients had stable disease for ≥12 weeks. No responses were observed. The DCR observed was 13% (2/15), and the trial did not meet the criteria to proceed to the second stage. Episodes of grade 3 treatment related toxicities observed included: increased ALT (n=2), increased AST (n=1), anorexia (n=3), fatigue (n=3), hypertension (n=1), infection (n=1), mucositis (n=2), nausea (n=3), pericardial effusion (n=1), and vomiting (n=1). Pazopanib has limited activity in NSCLC-NS in patients who have experienced disease progression on bevacizumab. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Non-squamous cell neoplasms of the larynx: radiologic-pathologic correlation.

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Becker, M; Moulin, G; Kurt, A M; Dulgerov, P; Vukanovic, S; Zbären, P; Marchal, F; Rüfenacht, D A; Terrier, F

1998-01-01

A variety of benign and malignant non-squamous cell neoplasms may affect the larynx. Most of these uncommon laryngeal neoplasms are located beneath an intact mucosa, making diagnosis difficult with endoscopy alone, and sampling errors may occur if only traditional superficial biopsies are performed. In some laryngeal neoplasms, radiologic evaluation allows the correct diagnosis. Hemangiomas have very high signal intensity at T2-weighted magnetic resonance (MR) imaging and strong enhancement at both computed tomography (CT) and MR imaging after administration of contrast material. Phleboliths, which are pathognomonic for hemangiomas, are easily identified at CT. Chondrogenic tumors typically manifest with coarse or stippled calcifications at CT. Because of their high water content, chondrogenic tumors have very high signal intensity on T2-weighted MR images, whereas only moderate enhancement is observed after administration of contrast material. Lipomas typically manifest at both CT and MR imaging as homogeneous nonenhancing lesions. They are isoattenuating to subcutaneous fat at CT and isointense relative to subcutaneous fat with all MR pulse sequences. Metastases from renal adenocarcinoma typically demonstrate strong contrast enhancement and flow voids at MR imaging, and metastases from melanotic melanoma usually have high signal intensity on T1-weighted MR images and low signal intensity on T2-weighted images owing to the paramagnetic properties of melanin. Although radiologic findings are nonspecific in most other non-squamous cell neoplasms of the larynx (eg, Kaposi sarcoma, hematopoietic tumors, tumors of the minor salivary glands, metastases from amelanotic melanoma), cross-sectional imaging can play an important role in the diagnostic work-up of these unusual tumors by delineating the extent of submucosal tumor spread and directing the endoscopist to the appropriate site for the deep, transmucosal biopsies needed to establish the diagnosis. In addition, CT

MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.

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Dansin, Eric; Cinieri, Saverio; Garrido, Pilar; Griesinger, Frank; Isla, Dolores; Koehler, Manfred; Kohlhaeufl, Martin

2012-06-01

The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients.

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Garassino, Marina Chiara; Gelibter, Alain Jonathan; Grossi, Francesco; Chiari, Rita; Soto Parra, Hector; Cascinu, Stefano; Cognetti, Francesco; Turci, Daniele; Blasi, Livio; Bengala, Carmelo; Mini, Enrico; Baldini, Editta; Quadrini, Silvia; Ceresoli, Giovanni Luca; Antonelli, Paola; Vasile, Enrico; Pinto, Carmine; Fasola, Gianpiero; Galetta, Domenico; Macerelli, Marianna; Giannarelli, Diana; Lo Russo, Giuseppe; de Marinis, Filippo

2018-05-03

Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians' request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation-positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and

Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

International Nuclear Information System (INIS)

Minami, Seigo; Tachibana, Isao; Komuta, Kiyoshi; Kawase, Ichiro; Kijima, Takashi; Takahashi, Ryo; Kida, Hiroshi; Nakatani, Takeshi; Hamaguchi, Masanari; Takeuchi, Yoshiko; Nagatomo, Izumi; Yamamoto, Suguru

2012-01-01

Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m 2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

Science.gov (United States)

Fassan, Matteo; Indraccolo, Stefano; Calabrese, Fiorella; Favaretto, Adolfo; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Lunardi, Francesca; Attili, Ilaria; Pavan, Alberto; Rugge, Massimo; Guarneri, Valentina; Conte, PierFranco; Pasello, Giulia

2017-01-01

Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified. PMID:28427238

Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

Science.gov (United States)

West, Howard

2017-09-01

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

Maintenance therapy in advanced non-small cell lung cancer: current status and future implications.

Science.gov (United States)

Stinchcombe, Thomas E; Socinski, Mark A

2011-01-01

Maintenance therapy for patients with advanced non-small cell lung cancer has been an area of intense investigation. Maintenance therapy has been divided into two broad categories: continuation maintenance when the chemotherapy or targeted agent was part of a defined number of cycles of combination therapy and in the absence of disease progression is continued as a single agent or switch maintenance when a third agent is initiated after four cycles of platinum-based double-agent chemotherapy in the absence of disease progression. Two monoclonal antibodies, cetuximab and bevacizumab, are used as continuation maintenance, but the incremental benefit of the maintenance therapy with these agents is undetermined. Phase III trials have not revealed an overall survival benefit for continuation maintenance chemotherapy, and this approach should be considered investigational. Phase III trials have demonstrated an improvement in overall survival with switch maintenance therapy with pemetrexed compared with placebo in patients with nonsquamous histology and erlotinib compared with placebo. Phase III trials have not revealed an improvement in quality of life with maintenance therapy. In the trials of maintenance therapy, 30 to 40% of patients enrolled in the observation or placebo arm did not receive second-line therapy, and among the patients who did receive second-line therapy, there was significant heterogeneity in the therapy. The development of maintenance therapy has raised issues about the role of treatment-free intervals in routine clinical care, trial design issues such as the optimal endpoint, the ethics of a placebo arm, and the implications of maintenance therapy for first-line trials.

The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics.

Science.gov (United States)

Fumagalli, Caterina; Vacirca, Davide; Rappa, Alessandra; Passaro, Antonio; Guarize, Juliana; Rafaniello Raviele, Paola; de Marinis, Filippo; Spaggiari, Lorenzo; Casadio, Chiara; Viale, Giuseppe; Barberis, Massimo; Guerini-Rocco, Elena

2018-03-13

Molecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously. To evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC. A single-institution cohort of 535 non-squamous NSCLC was profiled using a next-generation sequencing panel targeting 22 actionable and cancer-related genes. 441 non-squamous NSCLC (82.4%) harboured at least one gene alteration, including 340 cases (63.6%) with clinically relevant molecular aberrations. Mutations have been detected in all but one gene ( FGFR1 ) of the panel. Recurrent alterations were observed in KRAS , TP53 , EGFR , STK11 and MET genes, whereas the remaining genes were mutated in <5% of the cases. Concurrent mutations were detected in 183 tumours (34.2%), mostly impairing KRAS or EGFR in association with TP53 alterations. The study highlights the feasibility of targeted next-generation sequencing in clinical setting. The majority of NSCLC harboured mutations in clinically relevant genes, thus identifying patients who might benefit from different targeted therapies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pemetrexed safety and pharmacokinetics in patients with third-space fluid

DEFF Research Database (Denmark)

Dickgreber, Nicolas J; Sørensen, Jens Benn; Paz-Ares, Luis G

2010-01-01

Pemetrexed is established as first-line treatment with cisplatin for malignant pleural mesothelioma and advanced nonsquamous non-small-cell lung cancer (NSCLC) and as single-agent second-line treatment for nonsquamous NSCLC. Because the structure and pharmacokinetics of pemetrexed are similar...

Targeted therapy for localized non-small-cell lung cancer: a review

Directory of Open Access Journals (Sweden)

Paleiron N

2016-07-01

Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

Emerging role of nivolumab in the management of patients with non-small-cell lung cancer: current data and future perspectives

Directory of Open Access Journals (Sweden)

Feld E

2017-07-01

Full Text Available Emily Feld, Leora Horn Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Immune-checkpoint inhibitors have become valuable therapies in the treatment of patients with non-small-cell lung cancer (NSCLC. Recent clinical trials have shown promising results with regard to efficacy and toxicity profiles of these agents compared to cytotoxic chemotherapy. Nivolumab was one of the first immune-checkpoint inhibitors to demonstrate clinical activity in patients with NSCLC, and is currently approved in the US for treatment of patients with advanced squamous and nonsquamous NSCLC who have progressed on or after platinum-based chemotherapy. This review provides an update on nivolumab’s pharmacology, safety, and efficacy, as established by the CheckMate trials. We also discuss specific applications and strategies for the use of nivolumab in NSCLC patients, as well as predictive biomarkers and their role in treatment selection. Keywords: nivolumab, non-small-cell lung cancer, immune-checkpoint inhibitor, PD1 

Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

Directory of Open Access Journals (Sweden)

Chouaïd C

2014-12-01

Full Text Available Christos Chouaïd,1 Perinne Crequit,2 Isabelle Borget,3 Alain Vergnenegre4 1Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal Créteil et Université de Paris Est Créteil, Paris, France; 2Service de Pneumologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; 3Service de Biostatistique et d’Epidémiologie, Institut Gustave Roussy, Villejuif, France; 4Unité d’Oncologie Thoracique et Cutanée, Centre Hospitalier Universitaire Limoges, Limoges, France Abstract: During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC, with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs per life-year gained (LYG were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY. In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY

65Plus: open-label study of bevacizumab in combination with pemetrexed or pemetrexed/carboplatin as first-line treatment of patients with advanced or recurrent nonsquamous non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Schuette W

2017-11-01

Full Text Available Wolfgang Schuette,1 Claus-Peter Schneider,2,3 Walburga Engel-Riedel,4 Christian Schumann,5,6 Martin Kohlhaeufl,7 Monika Heidi Ursel Serke,8 Gert Hoeffken,9 Cornelius Kortsik,10 Martin Reck11 1Department of Internal Medicine II, Hospital Martha-Maria Halle-Doelau, Halle, 2Department of Pneumonology, Central Hospital, Bad Berka, 3Department of Internal Medicine, DRK Manniske Hospital, Bad Frankenhausen, 4Cologne Clinics, Merheim Lung Hospital, Cologne, 5Pneumonology, Department of Internal Medicine II, University Hospital Ulm, 6Clinic for Pneumology, Thoracic Oncology, Sleep, and Respiratory Critical Care, Kempten-Oberallgäu, 7Center of Pneumonology and Chest Surgery, Hospital Schillerhoehe, Gerlingen, 8Pneumonology, Lung Clinics, Hemer, 9Center of Pneumonology, Chest and Vascular Surgery, Specialty Hospital Coswig, Coswig, 10Department of Pneumonology, Catholic Hospital, Mainz, 11Department of Thoracic Oncology, Lung Clinic, Grosshansdorf, Germany Background: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem versus carboplatin/pemetrexed plus bevacizumab (BevCPem in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC.Materials and methods: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119 or BevCPem (n=134. The primary outcome measure was progression-free survival. Secondary end points were overall survival, tumor response, and safety outcomes. Evaluations were performed for the whole study population and stratified according to Eastern Cooperative Oncology Group (ECOG performance status (PS.Results: Noninferiority of BevPem in comparison to BevCPem could not be demonstrated for the overall population (P=0.7864. Significant superiority of the combined treatment BevCPem was seen in patients of ECOG PS 0–1 (median

The option value of innovative treatments for non-small cell lung cancer and renal cell carcinoma.

Science.gov (United States)

Thornton Snider, Julia; Batt, Katharine; Wu, Yanyu; Tebeka, Mahlet Gizaw; Seabury, Seth

2017-10-01

To develop a model of the option value a therapy provides by enabling patients to live to see subsequent innovations and to apply the model to the case of nivolumab in renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). A model of the option value of nivolumab in RCC and NSCLC was developed and estimated. Data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and published clinical trial results were used to estimate survival curves for metastatic cancer patients with RCC, squamous NSCLC, or nonsquamous NSCLC. To estimate the conventional value of nivolumab, survival with the pre-nivolumab standard of care was compared with survival with nivolumab assuming no future innovation. To estimate the option value of nivolumab, long-term survival trends in RCC and squamous and nonsquamous NSCLC were measured in SEER to forecast mortality improvements that nivolumab patients may live to see. Compared with the previous standard of care, nivolumab extended life expectancy by 6.3 months in RCC, 7.5 months in squamous NSCLC, and 4.5 months in nonsquamous NSCLC, according to conventional methods. Accounting for expected future mortality trends, nivolumab patients are likely to gain an additional 1.2 months in RCC, 0.4 months in squamous NSCLC, and 0.5 months in nonsquamous NSCLC. These option values correspond to 18%, 5%, and 10% of the conventional value of nivolumab, respectively. Option value is important when valuing therapies like nivolumab that extend life in a rapidly evolving area of care.

Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

Directory of Open Access Journals (Sweden)

Jonathan González García

2017-01-01

Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Jaime Jesús

2010-03-01

Full Text Available Abstract Background To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC, additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS and overall survival (OS after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. Methods/Design Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2 and cisplatin (75 mg/m2 on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle plus best supportive care (BSC or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from

Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer

International Nuclear Information System (INIS)

Paz-Ares, Luis G; Altug, Sedat; Vaury, Alexandra Thareau; Jaime, Jesús Corral; Russo, Francesca; Visseren-Grul, Carla

2010-01-01

To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m 2 ) and cisplatin (75 mg/m 2 ) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m 2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction

Treatment of Stage IV Non-small Cell Lung Cancer

Science.gov (United States)

Evans, Tracey; Gettinger, Scott; Hensing, Thomas A.; VanDam Sequist, Lecia; Ireland, Belinda; Stinchcombe, Thomas E.

2013-01-01

Background: Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. Methods: A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. Results: The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Conclusions: Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the

Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

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Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

2011-06-01

First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

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Abdulaziz eAl Farsi

2014-06-01

Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

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Lister J

2012-10-01

Full Text Available Johanna Lister,1 Sanja Stanisic,1 Klaus Kaier,2 Christian Hagist,2 Dmitry Gultyaev,1 Stefan Walzer31Analytica LA-SER International Inc, Lörrach, Germany; 2Research Centre for Generational Contracts, University of Freiburg, Freiburg, Germany; 3F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, SwitzerlandBackground: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain.Methods: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses.Results: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working full-time and the proportion of patients who were able to return to work.Conclusion: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.Keywords: non-small-cell lung cancer, bevacizumab, chemotherapy, economic model, France, Germany, Italy, Spain

Targeting the VEGF pathway: antiangiogenic strategies in the treatment of non-small cell lung cancer.

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Aita, Marianna; Fasola, Gianpiero; Defferrari, Carlotta; Brianti, Annalisa; Bello, Maria Giovanna Dal; Follador, Alessandro; Sinaccio, Graziella; Pronzato, Paolo; Grossi, Francesco

2008-12-01

The management of advanced non-small cell lung cancer (NSCLC) has evolved considerably in recent years, due to a progressive understanding of tumour biology and the identification of promising molecular targets. Several agents have been developed so far inhibiting vascular endothelial growth factor (VEGF) - a key protein in tumour neoangiogenesis, growth and dissemination - or its receptor signalling system. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab - a humanised anti-VEGF monoclonal antibody - over chemotherapy (CT) alone led the U.S. Food and Drug Administration (FDA) to approve the novel combination for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. In a randomised phase III trial presented at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival (PFS) compared to the standard arm. Based on these data, the European Medicines Agency (EMEA) has granted marketing authorisation for bevacizumab in addition to any platinum-based CT for first-line treatment of advanced NSCLC other than predominantly squamous histology. Aim of this report is to provide an overview on bevacizumab in NSCLC, with special emphasis on clinical results presented at ASCO last meeting. Multitargeted tyrosine kinase inhibitors (TKIs), sharing a focus on both the angiogenesis process and additional cell-surface receptors, and VEGF Trap, a novel fusion protein with markedly higher affinity for VEGF than bevacizumab, will be briefly discussed as well.

Feasibility Study of Adjuvant Chemotherapy Using Taxane Plus Carboplatin for High-Risk Patients With Uterine Cervical Non-Squamous Cell Carcinoma After Radical Hysterectomy.

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Sato, Seiya; Shimada, Muneaki; Ohta, Tsuyoshi; Kojimahara, Takanobu; Tokunaga, Hideki; Takano, Tadao; Yamaguchi, Satoshi; Tanabe, Hiroshi; Nishio, Shin; Kigawa, Junzo

2016-03-01

We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy. Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial invasion were defined as high-risk factors. The patients were treated with 6 cycles of paclitaxel (PTX, 175 mg/m(2)) or docetaxel (DTX, 60 mg/m(2)) followed by CBDCA (area under the curve, 6) every 3 weeks. The primary end point was 2-year progression-free survival (PFS) rate, and the secondary end point was the assessment of adverse events. Twenty-two patients received PTX/CBDCA (TC) chemotherapy, and the remaining 15 patients underwent DTX/CBDCA (DC) chemotherapy. The 2-year PFS rate was 62.1% (95% confidence interval, 44.6%-75.5%). Patients receiving DC chemotherapy showed a better 2-year PFS rate compared to those with TC chemotherapy, but the difference was not statistically significant (80.0% vs 50.0%, P = 0.1400). The most common grade 3/4 adverse events were hematologic toxicities, which were generally well tolerable. Nonhematologic toxicity was generally mild. Taxane and CBDCA combination chemotherapy, especially DC chemotherapy, may be one of the useful adjuvant treatments for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.

Clinico-pathological study on non-squamous cell carcinomas of the oral cavity and oropharynx

International Nuclear Information System (INIS)

Chijiwa, Hideki; Sakamoto, Kikuo; Umeno, Hirohito; Nakashima, Tadashi; Suzuki, Gen; Hayabuchi, Naohumi

2007-01-01

We reviewed 22 cases of non-squamous cell carcinoma (NSCC) of the oral cavity and oropharynx that were treated at the Kurume University Hospital between 1976 and 2005. Two percent of the oral carcinomas and 5% of the oropharyngeal carcinomas were NSCCs. The 5-year and 10-year survival rates of NSCC in the oropharynx were 90%. There was no statistically significant difference in survival rate between squamous cell carcinoma (SCC) and NSCC (p=0.06). The 5-year and 10-year survival rates of NSCC in the oral cavity were 75% and 37%, respectively. There was no statistically significant difference in the survival rate between SCC and NSCC. Survival results well correlated with clinical stages. A significant difference between Stage I, II and III versus Stage IV was found (p=0.04). In contrast, no significant relationship was found between survival and histologic type, or between survival and treatment. Patients with adenoid cystic carcinoma of Grade III, peri-neural invasion or vessel invasion, are recommended to receive adjuvant therapy. (author)

An Epidemiologic study of Oral and Pharyngeal Nonsquamous Cell Malignant Tumors in Kerman province, Iran

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MR. Zarei

2007-03-01

Full Text Available Objective: The aim of the present study was to estimate crude and age-standardized incidence rates for oral and pharyngeal nonsquamous cell malignant tumors in Kerman province over a period of 11 years.Materials and Methods: The data used in this retrospective population-based study were extracted from the records registered in all pathology centers of Kerman province from 1991 to 2001. All confirmed cases of oral and pharyngeal nonsquamous cell malignant tumors were included in the study. The crude and age-standardized incidence rates per 1 million populations were calculated based on the 1996 census data and the population growth rate.Results: The total number of new nonsquamous cell cancers was 61, representing 18.2% of all oral and pharyngeal cancers in Kerman province. The average annual ageadjusted incidence rate per 1,000,000 population was 3.45 for both oral and pharyngeal tumors. The temporal variations in the annual incidence of oral and pharyngeal nonsquamous cell cancers was statistically significant (p=0.015. The most common types of nonsquamous cell malignant tumors in the oral cavity and pharynx were minor salivary tumors and lymphomas, respectively. The age-adjusted incidence was 0.74 formalignant salivary gland tumors, 0.66 for malignant melanomas, 0.4 for different types of sarcomas, and 1.65 for lymphomas.Conclusion: It can be concluded that the incidence rate and other features of nonsquamous cell malignant tumors of the oral cavity and pharynx in residents of Kerman province are similar to those reported by other investigators.

Pemetrexed safety and pharmacokinetics in patients with third-space fluid

DEFF Research Database (Denmark)

Dickgreber, Nicolas J; Sorensen, Jens Benn; Paz-Ares, Luis G

2010-01-01

Pemetrexed is established as first-line treatment with cisplatin for malignant pleural mesothelioma and advanced nonsquamous non-small-cell lung cancer (NSCLC) and as single-agent second-line treatment for nonsquamous NSCLC. Because the structure and pharmacokinetics of pemetrexed are similar to ...... to those of methotrexate, and methotrexate is associated with severe toxicity in patients with third-space fluid (TSF), the safety of pemetrexed in patients with TSF was evaluated....

Comparative study of lymph node metastasis from squamous cell carcinoma and non-squamous cell carcinoma on neck CT

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Lee, Hyoung Nam; Han, Jong Kyu; Kim, Hyung Hwan; Shin, Hyeong Cheol; Kim, Il Yong; Jou, Sung Shik [Dept. of Radiology, Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

2015-04-15

To assess the differential imaging findings of metastatic lymph nodes in squamous cell carcinoma (SCC) and non-squamous cell carcinoma (non-SCC) on neck CT and to facilitate the identification of primary focus before performing a biopsy. We retrospectively analyzed 46 patients with SCC and 50 patients with non-SCC who underwent neck CT from January 2006 to January 2011. Patients were divided into two groups; SCC and non-SCC. The total number of lymph nodes was 204 in the SCC group and 530 in the non-SCC group. Two observers were asked to assess the characteristics of abnormal lymph nodes (number, margin types, enhancement patterns, size, bilaterality, calcification, fat infiltration, conglomeration, invasion of adjacent tissue, and nodal distribution). Nodal distribution was evaluated by imaging-based nodal classification on neck CT. Between the SCC group and the non-Succ group except for cases of thyroid cancer, the number of lymph nodes and the number of lymph nodes smaller than 3 cm in the non-Succ group except for cases of thyroid cancer were significantly greater than those in the Succ group (p < 0.05). The number of lymph nodes, the number of lymph nodes smaller than 3 cm, and nodal distribution are helpful in differential diagnosis between Succ and non-Succ before performing a biopsy.

Chemotherapy related toxicity in locally advanced non-small cell lung cancer

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Bahl Amit

2006-01-01

Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

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Shu-Hui Yao

2016-03-01

Full Text Available Objective: To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer. Methods: A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected. Results: Progressionfree survival and median overall survival (mOS of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05; 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05, and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05. Conclusions: Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression.

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Rafael Rosell

Full Text Available BACKGROUND: Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin. RAP80 and Abraxas are interacting proteins that form complexes with BRCA1 and could modulate the effect of BRCA1. In order to further examine the effect of EGFR mutations and BRCA1 mRNA levels on outcome in advanced NSCLC, we performed a prospective non-randomized phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. In an exploratory analysis, we also examined the effect of RAP80 and Abraxas mRNA levels. METHODOLOGY/PRINCIPAL FINDINGS: We treated 123 metastatic non-squamous cell lung carcinoma patients using a customized approach. RNA and DNA were isolated from microdissected specimens from paraffin-embedded tumor tissue. Patients with EGFR mutations received erlotinib, and those without EGFR mutations received chemotherapy with or without cisplatin based on their BRCA1 mRNA levels: low, cisplatin plus gemcitabine; intermediate, cisplatin plus docetaxel; high, docetaxel alone. An exploratory analysis examined RAP80 and Abraxas expression. Median survival exceeded 28 months for 12 patients with EGFR mutations, and was 11 months for 38 patients with low BRCA1, 9 months for 40 patients with intermediate BRCA1, and 11 months for 33 patients with high BRCA1. Two-year survival was 73.3%, 41.2%, 15.6% and 0%, respectively. Median survival was influenced by RAP80 expression in the three BRCA1 groups. For example, for patients with both low BRCA1 and low RAP80, median survival exceeded 26 months. RAP80 was a significant factor for survival in patients treated according to BRCA1

Pemetrexed With Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer.

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Stinchcombe, Thomas E; Borghaei, Hossein; Barker, Scott S; Treat, Joseph Anthony; Obasaju, Coleman

2016-01-01

Standard platinum-based chemotherapy combinations for advanced non-small-cell lung cancer (NSCLC) have reached a plateau in terms of the survival benefit they offer for patients. In addition, the emerging clinical trend of tailored treatment based on patient characteristics has led to the development of therapeutic strategies that target specific cancer-related molecular pathways, including epidermal growth factor receptor (EGFR), angiogenesis, and anaplastic lymphoma kinase inhibitors. Current research is focused on combining targeted therapy with platinum-based chemotherapy in an endeavor to achieve an additional benefit in specific patient populations. Currently, pemetrexed is indicated for use in the first-line, maintenance, and second-line settings for the treatment of nonsquamous NSCLC. The combination of pemetrexed and cisplatin is well tolerated and is the approved standard first-line therapy. Thus, the pemetrexed-platinum backbone provides an attractive option for combination with targeted therapies. This review aims to summarize the current knowledge and future prospects of the use of pemetrexed-platinum as a backbone for combination with targeted therapies for NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

Metastatic squamous cell non-small-cell lung cancer (NSCLC: disrupting the drug treatment paradigm with immunotherapies

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Sarah L Scarpace

2015-10-01

Full Text Available Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR and anaplastic lymphoma kinase (ALK mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. Immunotherapies directed at the programmed cell death-1 receptor (PD-1 or its ligand (PD-L1 (nivolumab and pembrolizumab have demonstrated efficacy in both nonsquamous and squamous cell NSCLC. Because of their similar mechanism of action against the PD-L1/PD-1 pathway, both drugs have similar toxicity profiles related to immune-mediated adverse reactions that can generally be monitored and managed with oral corticosteroids. This paper provides an overview of drug therapy options for squamous cell NSCLC with a focus on the evidence and clinical application of the anti-PD1 therapies. A comparison of the dosing, administration, indications, and differences in the measurement of PD-L1 expression in the clinical trials of nivolumab and pembrolizumab is also provided.

Advances in surgical techniques in non-small cell lung cancer.

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Kim, Anthony W; Detterbeck, Frank C

2013-12-01

Thoracic surgery is a dynamic field, and many scientific, technological, technical, and organizational changes are occurring. A prominent example is the use of less invasive approaches to major resection of non-small cell lung cancer (NSCLC), both thoracoscopic and robotic. Sophisticated technology corroborated by clinical data has led to these approaches becoming accepted additions to the armamentarium. Additionally, improvements in perioperative pain management have also contributed to dramatically changing the experience of patients who undergo modern thoracic surgery. Lung cancer is being detected more often at an early stage. At the same time, advances in techniques, patient care, clinical science, and multidisciplinary treatment support an increased role for aggressive resection in the face of larger locally advanced tumors or for those with limited metastatic disease. These advances, conducted in the setting of multidisciplinary decision making, have resulted in real and palpable advancements for patients with lung cancer. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

International Nuclear Information System (INIS)

Anagnostou, Valsamo K; Boffa, Daniel; Gettinger, Scott; Detterbeck, Frank; Homer, Robert J; Dougenis, Dimitrios; Rimm, David L; Syrigos, Konstantinos N; Lowery, Frank J; Zolota, Vassiliki; Tzelepi, Vassiliki; Gopinath, Arun; Liceaga, Camil; Panagopoulos, Nikolaos; Frangia, Konstantina; Tanoue, Lynn

2010-01-01

Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA ® , a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients

Potential role of immunotherapy in advanced non-small-cell lung cancer

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de Mello RA

2016-12-01

Full Text Available Ramon Andrade de Mello,1–3 Ana Flávia Veloso,4 Paulo Esrom Catarina,4 Sara Nadine,5 Georgios Antoniou6 1Department of Biomedical Sciences and Medicine, University of Algarve, Faro, 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Research Center, Cearense School of Oncology, Instituto do Câncer do Ceará, 4Oncology & Hematology League, School of Medicine, State University of Ceará (UECE, Fortaleza, Brazil; 5Instituto de Ciências Biomédicas Abel Salazar (ICBAS, University of Porto, Porto, Portugal; 6Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK Abstract: Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib. As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework. Keywords: immunotherapy, non-small-cell lung cancer, nivolumab, pembrolizumab, ipilimumab, clinical trials, PD1, PDL1, CTLA4

[Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].

Science.gov (United States)

Zhang, Guowei; Wang, Huijuan; Ma, Zhiyong

2017-04-20

At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors

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Guowei ZHANG

2017-04-01

Full Text Available At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

Effects of icotinib on advanced non-small cell lung cancer with different EGFR phenotypes.

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Pan, Huiyun; Liu, Rong; Li, Shengjie; Fang, Hui; Wang, Ziwei; Huang, Sheng; Zhou, Jianying

2014-09-01

Icotinib is the first oral epidermal growth factor receptor (EGFR) tyrosine kinase receptor inhibitor, which has been proven to exert significant inhibitory effects on non-small cell lung cancer in vitro. Clinical evidence has showed that the efficacy of Icotinib on retreating advanced non-small cell lung cancer is comparable to Gefitinib. However, different phenotypes of EGFR can affect the therapeutic outcomes of EGFR tyrosine kinase receptor inhibitor. Therefore, our study focused on efficacy and safety of Icotinib in patients with advanced non-small cell lung cancer of different EGPR phenotypes. Clinical data of patients with advanced non-small cell lung cancer who received Icotinib treatment from August, 2011 to May, 2013 were retrospectively analyzed. Kaplan-Meier analysis was used for survival analysis and comparison. 18 wild-type EGFR and 51 mutant type were found in a total of 69 patients. Objective response rate of patients with mutant type EGFR was 54.9 % and disease control rate was 86.3 %. Objective response rate of wild-type patients was 11.1 % (P = 0.0013 vs mutant type), disease control rate was 50.0 % (P = 0.0017). Median progression-free survival (PFS) of mutant type and wild-type patients were 9.7 and 2.6 months, respectively (P Icotinib included rash, diarrhea, itching skin with occurrence rates of 24.6 % (17/69), 13.0 % (9/69), and 11.6 % (8/69), respectively. Most adverse reactions were grade I-II. Icotinib has great efficacy in EGFR mutated patients, making it an optimal regimen to treat EGFR mutated patients. Furthermore, most of adverse reactions associated with Icotinib treatment were tolerable.

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

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Imbs, Diane-Charlotte; El Cheikh, Raouf; Boyer, Arnaud; Ciccolini, Joseph; Mascaux, Céline; Lacarelle, Bruno; Barlesi, Fabrice; Barbolosi, Dominique; Benzekry, Sébastien

2018-01-01

Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC-bearing mice. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizumab and chemotherapy. Combining this data with a mathematical model of tumor growth under therapy accounting for the normalization effect, we predicted an optimal delay of 2.8 days between bevacizumab and chemotherapy. This prediction was confirmed experimentally, with reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged survival (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a similar increase in efficacy, thus emphasizing the utility of modeling support to identify optimal scheduling. The model could also be a useful tool in the clinic to personally tailor regimen sequences. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

[Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride].

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Nong, Jingying; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Hui; Wu, Yuhua; Lv, Jialin; Zhang, Quan; Zhang, Shucai

2013-05-01

Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

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Gota, Vikram; Kavathiya, Krunal; Doshi, Kartik; Gurjar, Murari; Damodaran, Solai E; Noronha, Vanita; Joshi, Amit; Prabhash, Kumar

2014-01-01

Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC). While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Sixteen of 46 patients (35%) had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively). Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively). Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Higher exposure to pemetrexed is associated with grade ≥3 hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in Indian patients needs further investigation

An Evidence-Based Approach to the Use of Predictive Biomarkers in the Treatment of Non- Small Cell Lung Cancer (NSCLC)

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Quinton, Cindy; Ellis, Peter M.

2011-01-01

Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research

Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting.

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Amy P Abernethy

Full Text Available To establish a baseline for care and overall survival (OS based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC without common actionable mutations.Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015. Patients with documented epidermal growth factor receptor (EGFR or anaplastic lymphoma kinase (ALK translocation were excluded. Anti-cancer drug therapy and overall survival were described overall, and by histology.A total of 2,014 patients with stage IV NSCLC without known EGFR or ALK genomic tumor aberrations initiated systemic anticancer therapy, 22% with squamous and 78% with nonsquamous histology. Their mean (SD age was 67 (10 years, 55% were male, and 87% had a smoking history. In nonsquamous NSCLC, carboplatin plus pemetrexed either without (25.7% or with bevacizumab (16% were the most common regimens; 26.6% of nonsquamous patients receiving induction therapy also received continuation maintenance therapy. In squamous NSCLC, carboplatin plus paclitaxel (37.6% or nab-paclitaxel (21.1% were the most commonly used regimens. Overall median OS was 9.7 months (95% CI: 9.1, 10.3, 8.5 months (95% CI: 7.4, 10.0 for squamous, and 10.0 months (95% CI: 9.4, 10.8 for nonsquamous NSCLC.The results provide context for evaluating the effect of shifting treatment patterns of NSCLC treatments on patient outcomes, and for community oncology benchmarking initiatives.

Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer.

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Lopes, Gabriel Lima; Vattimo, Edoardo Filippo de Queiroz; Castro Junior, Gilberto de

2015-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer *

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Lopes, Gabriel Lima; Vattimo, Edoardo Filippo de Queiroz; de Castro, Gilberto

2015-01-01

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC. PMID:26398757

Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

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Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

2014-01-01

Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

[Prognostic factors of advanced stage non-small-cell lung cancer].

Science.gov (United States)

Kwas, H; Guermazi, E; Khattab, A; Hrizi, C; Zendah, I; Ghédira, H

2017-09-01

Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years. To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages. A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013. The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment. The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Meta-Analysis of Platinum Plus Gemcitabine or Vinorelbine for Advanced Non-small Cell Lung Cancer

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Guanghui GAO

2009-01-01

Full Text Available Background and objective Platinum plus the third-generation agent doublet chemotherapy is the standard regimens and first line chemotherapy for advanced non-small cell lung cancer (NSCLC. The aim of this study is to determine the benefits and harms of platinum plus gemcitabine or vinorelbine for advanced NSCLC. Methods Thedatabases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words "non small cell lung cancer" or "Carcinoma, Non Small Cell Lung" so as to search the studies about the randomized controlled clinical trials (RCT that had compared the gemcitabine plus platinum versus vinorelbine plus platinum for advanced NSCLC. A meta-analysis was conducted. Results Nine randomized controlled trials, with total 2 186 patients,were included. The overall response rate and one-year survival rate of the gemcitabine group were not significantly different from that of vinorelbine regimen (RR=0.91, 95%CI: 0.81-1.03, P =0.15; RR=1.06, 95%CI: 0.96-1.18, P =0.27, respectively. The incidence rate of grade 3-4 netropenia, constipation, phlebitis and grade 1-4 neuropathy were higher in vinorelbine group, just like higher incidence rate of grade 3-4 thrombocytopenia in the gemcitabine group. Conclusion The curative effects of the gemcitabine or vinorelbine plus platinum regimens are similar. The choice of gemcitabine or vinorelbine depends on the toxicity of the drugs and patients' tolerance.

Present trends in the treatment of advanced non-small-cell lung cancer

International Nuclear Information System (INIS)

Parvez, T.; Iskandrani, A.

2003-01-01

Lung cancer is the leading cause of cancer deaths all over the world. As most patients present with advanced disease, major efforts have been made in the treatment of such disease with systemic chemotherapy. Several new agents and new combinations of chemotherapy have been developed recently. This article reviews the randomized clinical trials investigating chemotherapy for advanced non-small cell lung cancer (NSCLC) in relapse or progressive disease while being treated and in elderly patients. Therapies that incorporate new biological agents to target specific defects in lung cancer are also discussed. Several clinical trials have demonstrated improvement in overall survival as well as quality of life with presently available chemotherapy treatment of advanced NSCLC. Better options are available for the elderly as well as those having relapse after first line chemotherapy. Despite all this progress the 5-year survival rate still remains at a dismal 14%. New therapies with good results are still desired. (author)

Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer

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Gabriel Lima Lopes

2015-08-01

Full Text Available AbstractLung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21, first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs. Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

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McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

2010-01-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

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Gu, Aiqin; Shi, Chunlei; Xiong, Liwen; Chu, Tianqing; Pei, Jun; Han, Baohui

2013-02-01

To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (Picotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

[Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer].

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Qiao, Tiankui; Zhou, Daoan; Chen, Wei; Wang, Xianglian

2004-12-20

To observe the effects of MVP chemotherapy combined with concurrent radiotherapy for stage IIIB-IV non-small cell lung cancer. Sixty-two patients with stage IIIB-IV non-small cell lung cancer were randomized into two groups, concurrent radiochemotherapy group and MVP che-motherapy group. All patients in two groups were treated with MVP regimen (mitomycin C 6 mg/m² on day 1, vindesine 2 mg/m² on days 1, 8, and cisplatin 80-100 mg/m²). Patients in concurrent radiochemotherapy group received concurrent radiotherapy (46-56 Gy in 5-6 weeks). All patients received 2-4 cycles of MVP chemotherapy. The response rate was 48.4% and 19.4% in concurrent radiochemotherapy group and MVP group respectively (P MVP group.. The results show that efficacy of MVP chemotherapy combined with concurrent radiotherapy is significantly higher than that of MVP chemotherapy alone for advanced non-small cell lung cancer.

Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride

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Jingying NONG

2013-05-01

Full Text Available Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC. Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR was 45.0% and the disease control rate (DCR was 80.0%. The median progression-free survival (PFS time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively. RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively. RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively . There was no statistical difference in RR and PFS between those age <65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020. EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively. The side effects were generally mild and consisted of rash and diarrhea. Conclusion Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

Erlotinib in previously treated non-small-cell lung cancer

International Nuclear Information System (INIS)

Smrdel, U.; Kovac, V.

2006-01-01

Background. Erlotinib is a novel biological anti-tumour agent in the treatment of advanced non small cell lung cancer. It represents the molecularly-targeted therapy which has been studied extensively. Case report. We present a case of a patient who suffered from advanced non-small-cell lung cancer. After the progress of disease following a prior chemotherapy he was treated with erlotinib with remarkable effect which was shown at chest x ray and symptoms were quite reduced. Conclusions. In selected patients with advanced non-small-cell lung cancer Erlotinib improves survival and symptom control as it results in presented case. (author)

Epidermal Growth Factor Receptor Mutation Is Associated With Longer Local Control After Definitive Chemoradiotherapy in Patients With Stage III Nonsquamous Non–Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Yagishita, Shigehiro; Horinouchi, Hidehito; Katsui Taniyama, Tomoko; Nakamichi, Shinji; Kitazono, Satoru; Mizugaki, Hidenori; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Sumi, Minako; Shiraishi, Kouya; Kohno, Takashi; Furuta, Koh; Tsuta, Koji; Tamura, Tomohide

2015-01-01

Purpose: To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non–small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT). Patients and Methods: Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated. Results: A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR. Conclusions: Our study is the first to show radiosensitive biology of EGFR-mutated tumors in definitive CRT with curative intent. This finding could serve as a credible baseline estimate of EGFR-mutated population in stage III nonsquamous NSCLC

Epidermal Growth Factor Receptor Mutation Is Associated With Longer Local Control After Definitive Chemoradiotherapy in Patients With Stage III Nonsquamous Non–Small-Cell Lung Cancer

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Yagishita, Shigehiro [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Horinouchi, Hidehito, E-mail: hhorinou@ncc.go.jp [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Katsui Taniyama, Tomoko; Nakamichi, Shinji; Kitazono, Satoru; Mizugaki, Hidenori; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Shiraishi, Kouya; Kohno, Takashi [Division of Genome Biology, National Cancer Center Research Institute, Tokyo (Japan); Furuta, Koh [Department of Clinical Laboratories, National Cancer Center Hospital, Tokyo (Japan); Tsuta, Koji [Department of Pathology, National Cancer Center Hospital, Tokyo (Japan); Tamura, Tomohide [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan)

2015-01-01

Purpose: To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non–small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT). Patients and Methods: Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated. Results: A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR. Conclusions: Our study is the first to show radiosensitive biology of EGFR-mutated tumors in definitive CRT with curative intent. This finding could serve as a credible baseline estimate of EGFR-mutated population in stage III nonsquamous NSCLC.

CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

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Diana Rosa Fernández Ruiz

2017-02-01

Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

Non-cross resistant sequential single agent chemotherapy in first-line advanced non-small cell lung cancer patients: Results of a phase II study

NARCIS (Netherlands)

V. Surmont; J.G.J.V. Aerts (Joachim); K.Y. Tan; F.M.N.H. Schramel (Franz); R. Vernhout (Rene); H.C. Hoogsteden (Henk); R.J. van Klaveren (Rob)

2009-01-01

textabstractBackground. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell

Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

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Liang JL

2014-05-01

Full Text Available Jun-Li Liang,1 Xiao-Cang Ren,2 Qiang Lin2 1Department of Radiation Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, People’s Republic of China; 2Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, Hebei Province, People’s Republic of China Abstract: Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. Keywords: targeted therapy, EGFR-TKI, NSCLC

Treatment of stage IV non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

Science.gov (United States)

Socinski, Mark A; Evans, Tracey; Gettinger, Scott; Hensing, Thomas A; VanDam Sequist, Lecia; Ireland, Belinda; Stinchcombe, Thomas E

2013-05-01

Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the presence of specific genetic mutations.

Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

Science.gov (United States)

Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

2010-11-01

Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. Copyright © 2010 Elsevier Ltd. All rights reserved.

The End of Nihilism: Systemic Therapy of Advanced Non-Small Cell Lung Cancer.

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Ernani, Vinicius; Steuer, Conor E; Jahanzeb, Mohammad

2017-01-14

Lung cancer is the leading cause of cancer death in the United States and many other parts of the world. Non-small cell lung cancer (NSCLC) comprises 85-90% of lung cancers. Historically, the expected survival of patients with advanced disease has been estimated in months. In recent years, however, lung cancer has come to be seen as a treatable disease with multiple therapeutic options. Enormous advances in the understanding of its pathways and mechanisms have enabled personalized therapy in NSCLC. The evolving approach to therapy focuses on genomic profiling of the tumors to find molecular targets and develop specific agents for individualized therapy. In addition, maintenance therapy has emerged as a valid approach, and the choice of chemotherapy now varies by histology. Most recently, immunotherapy with checkpoint inhibitors has shown promising results, with impressive durations of response and a tolerable toxicity profile. Together, these discoveries have improved overall survival substantially in patient populations that have access to these advancements. We review the clinical data surrounding these impressive improvements.

Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Kim, Myung Soo; Lee, Ji Hae; Ha, Bo Ram; Lee, Re Na

2011-01-01

Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ≥2 radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ≥2 radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), V20, V30, V40, MLDipsi, V20ipsi, V30ipsi, and V40ipsi were associated with grade ≥2 radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ≥2 radiation pneumonitis. Concurrent

Improving chemotherapy for patients with advanced non-small cell lung cancer

DEFF Research Database (Denmark)

von Plessen, Christian

2011-01-01

INTRODUCTION: Lung cancer is the third most common mortal disease in industrialised countries and the prognosis has been slow to improve. The largest subgroup has locally advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, these patients can usually not be cured and the main...... project. The description of the experiences can serve as an example for the improvement of microsystems in settings with similar problems. Finally, in the registry study of Norwegian patients with lung cancer, we found significant geographical and temporal variations of the utilisation of chemotherapy...... that were related to survival. Potential areas of improvement in the system of care for lung cancer are recruitment of patients in clinical studies, standardisation of the processes of care in outpatient clinics, definition of strategic aims of quality, development of balanced quality indicators, as well...

The Impact of Smoking Status on the Efficacy of Erlotinib in Patients with Advanced Non-small Cell Lung Cancer

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Yilong WU

2009-12-01

Full Text Available Background and objective Erlotinib is a targeted treatment for advanced non-small cell lung cancer. Smoking status may be one of influencing factors of the efficacy of erlotinib. The aim of this study is to explore the impact of smoking status on the efficacy of erlotinib in patients with advanced non-small cell lung cancer. Methods Patients with nonsmall cell lung cancer who had been previously treated with at least one course of platinum based chemotherapy received 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression-free survival, overall survival were analyzed in the different smoking status groups. Kaplan-Meier method was used to analyze the survival rate. Results Fortyeight patients were enrolled into the study from December 2005 to September 2006. We followed up these patients until 28th December, 2008. Median follow up time was 30 months. The compliance rate was 100%. The response rate was 32.1% in the smoking group and 35% in the never smoking group (P=0.836; The median progression-free survival was 3 months and 9 months, respectively (P=0.033. The median overall survival was 5 months and 17 months, respectively (P=0.162. Conclusion Erlotinib is an effective drug for advanced non-small cell lung cancer patients with different smoking status. Progressionfree survival is better in the never smoking patients than the smoking patients.

Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

International Nuclear Information System (INIS)

Cho, Kwan Ho

2004-01-01

Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

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Ma, X-H; Tian, T-D; Liu, H-M; Li, Q-J; Gao, Q-L; Li, L; Shi, B

2017-01-01

To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (picotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.

Vascular Endothelial Growth Factor in Plasma and Pleural Effusion Is a Biomarker for Outcome After Bevacizumab plus Carboplatin-Paclitaxel Treatment for Non-small Cell Lung Cancer with Malignant Pleural Effusion.

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Tamiya, Motohiro; Tamiya, Akihiro; Yasue, Tomomi; Nakao, Keiko; Omachi, Naoki; Shiroyama, Takayuki; Tani, Eriko; Hamaguchi, Masanari; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Okishio, Kyoichi; Kawaguchi, Tomoya; Atagi, Shinji; Hirashima, Tomonori

2016-06-01

Malignant effusion is associated with high serum and plasma levels of vascular endothelial growth factor (VEGF). There are no biomarkers of outcome for bevacizumab treatment in patients with malignant pleural effusion (MPE). We previously reported that carboplatin-paclitaxel plus bevacizumab was effective for patients with advanced non-squamous non-small cell lung cancer (NSCLC) and MPE, although we did not evaluate the relationship between treatment outcomes and plasma or pleural effusion levels of VEGF. Therefore, this study evaluated whether plasma or pleural effusion VEGF might predict bevacizumab treatment outcome. We enrolled 23 patients with NSCLC and MPE between September 2010 and June 2012. Plasma VEGF levels were measured in 19 patients and pleural VEGF levels were measured in 22 patients. Compared to patients with a low plasma VEGF level, patients with a high level exhibited significantly shorter overall survival (OS: 13.8 vs. 6.5 months, p=0.04), progression-free survival (PFS: 8.7 vs. 4.8 months, peffusion, patients with a high VEGF level exhibited significantly shorter OS (19.6 vs. 6.9 months, peffusion may predict the outcome of bevacizumab treatment in patients with NSCLC and MPE. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

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Noemí Reguart

2010-06-01

Full Text Available Noemí Reguart1, Andrés Felipe Cardona2, Rafael Rosell31Medical Oncology Service, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain; 2Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, D.C., Colombia; 3Medical Oncology Service, Catalan Institute of Oncology, ICO, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: Erlotinib hydrochloride (Tarceva® is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR, with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents.Keywords: erlotinib, tyrosine kinase inhibitors, first line, maintenance, non-small-cell lung cancer

Chemotherapy options for the elderly patient with advanced non-small cell lung cancer.

LENUS (Irish Health Repository)

Hennessy, B T

2012-02-03

Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer (NSCLC). The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health.

Concurrent versus Sequential Chemoradiotherapy with Cisplatin and Vinorelbine in Locally Advanced Non-Small Cell Lung Cancer: A Randomized Study

Czech Academy of Sciences Publication Activity Database

Zatloukal, P.; Petruželka, L.; Zemanová, M.; Havel, L.; Janků, F.; Judas, L.; Kubík, A.; Křepela, E.; Fiala, P.; Pecen, Ladislav

2004-01-01

Roč. 46, - (2004), s. 87-98 ISSN 0169-5002 Institutional research plan: CEZ:AV0Z1030915 Keywords : concurrent chemoradiotherapy * sequential chemoradiotherapy * locally advanced non-small cell lung cancer * cisplatin * vinorelbine Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.914, year: 2004

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

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Shu Yong-Qian

2010-09-01

Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

Gefitinib in advanced non-small cell lung cancer: does it deserve a second chance?

Science.gov (United States)

Stinchcombe, Thomas E; Socinski, Mark A

2008-09-01

There has been intense investigation into the epidermal growth factor receptor (EGFR) as a therapeutic target in the treatment of non-small cell lung cancer (NSCLC). Currently there are two EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, approved for the treatment of advanced NSCLC. In a phase III trial (BR.21), treatment with erlotinib resulted in a statistically significant improvement in overall survival in patients who had experienced progression after one or two previous chemotherapy treatments in comparison with best supportive care (BSC). In contrast, in the Iressa Survival Evaluation in Lung Cancer (ISEL) trial, treatment with gefitinib did not result in a statistically significant improvement in overall survival time in comparison with BSC in patients who had received one or two previous chemotherapy treatments and were refractory to or intolerant of the previous chemotherapy. After the results of the ISEL trial, the U.S. Food and Drug Administration restricted the use of gefitinib, and gefitinib was effectively removed from routine clinical practice within the U.S. However, gefitinib was approved in other countries and clinical trials investigating gefitinib continued. Recently the Iressa Non-small cell lung cancer Trial Evaluating REsponse and Survival against Taxotere (INTEREST) trial met the primary endpoint of demonstrating noninferiority in terms of overall survival for gefitinib (250 mg daily) in comparison with docetaxel (75 mg/m(2) every 3 weeks). Patients treated with gefitinib experienced a lower rate of treatment-related toxicity and higher rate of improvement in quality of life. Results of recent gefitinib trials have been provocative, and suggest a role for gefitinib in the treatment of advanced NSCLC.

Efficacy of Icotinib Hydrochloride in the Treatment of Advanced Non-small Cell Lung Cancer

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Xianglei Ma

2013-09-01

Full Text Available Objective: To observe and evaluate the efficacy and adverse responses of icotinib hydrochloride in the treatment of advanced non-small cell lung cancer (NSCLC, and analyze the relative factors impacting its efficacy and prognosis. Methods: The clinical data of 260 patients with advanced NSCLC treated with icotinib hydrochloride in Jiangsu Cancer Hospital was retrospectively analyzed. Results: Four weeks after initial administration, 256 patients were evaluable for efficacy except 4 who withdrew the drug due to intolerable adverse responses. Among the 256 patients, there were 0 complete response (CR, 96 partial response (PR, 37.5%, 97 stable disease (SD, 37.9% and 63 progression disease (PD, 24.6%, with the objective remission rate (ORR and disease control rate (DCR being 37.6% and 75.4% respectively. However, in all patients, the median progression-free survival (PFS was 7 (0.4 - 16.3 months, and were 11 (1 - 16.3, 6 (0.4 - 11.3 and 5 (1 - 13.5 months in those treated with first-line, second-line, and ≥third-line treatments, respectively. Conclusion: Icotinib hydrochloride has significant efficiency and better safety for treating advanced NSCLC.

Feasibility of Pencil Beam Scanned Intensity Modulated Proton Therapy in Breath-hold for Locally Advanced Non-Small Cell Lung Cancer

DEFF Research Database (Denmark)

Gorgisyan, Jenny; Munck Af Rosenschold, Per; Perrin, Rosalind

2017-01-01

PURPOSE: We evaluated the feasibility of treating patients with locally advanced non-small cell lung cancer (NSCLC) with pencil beam scanned intensity modulated proton therapy (IMPT) in breath-hold. METHODS AND MATERIALS: Fifteen NSCLC patients who had previously received 66 Gy in 33 fractions wi...

Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.

Science.gov (United States)

Shi, Yuankai; Zhang, Li; Liu, Xiaoqing; Zhou, Caicun; Zhang, Li; Zhang, Shucai; Wang, Dong; Li, Qiang; Qin, Shukui; Hu, Chunhong; Zhang, Yiping; Chen, Jianhua; Cheng, Ying; Feng, Jifeng; Zhang, Helong; Song, Yong; Wu, Yi-Long; Xu, Nong; Zhou, Jianying; Luo, Rongcheng; Bai, Chunxue; Jin, Yening; Liu, Wenchao; Wei, Zhaohui; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Dai, Hong; Jiao, Shunchang; Wang, Jie; Liang, Li; Zhang, Weimin; Sun, Yan

2013-09-01

Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug

The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

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Rusch, V.W.; Griffin, B.R.; Livingston, R.B. (Univ. of Washington, Seattle (USA))

1989-10-01

Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

Improved radiotherapy for locally advanced Non-Small Cell Lung Carcinoma (NSCLC) patients

DEFF Research Database (Denmark)

Ottosson, Wiviann

to comply with the DIBH technique. For DIBH, the patients are guided to hold their breath almost at their maximum inspiration level during imaging and treatment. This leads to reduction of the breathing motion which decreases the movement of the tumor and OARs. It also expands the lung tissue which...... be reduced by the DIBH method for the lung cancer patients. The overall aim of the clinical part of this thesis was to clarify the potential benefit of offering DIBH gating, compared to free-breathing (FB), for lung cancer patients. Particularly, the benefits for locally advanced non-small cell lung cancer...... (NSCLC) patients were explored. For the dosimetric part of the thesis, the dosimetric aspects of correct dose calculations in heterogeneous patient-like geometries were studied. The clinical aspects of DIBH were evaluated in three different studies, where planning and setup verification images acquired...

Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

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Boutsikou E

2013-03-01

Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy

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Sørensen, Steffen Filskov; Zhou, Wei; Dolled-Filhart, Marisa

2016-01-01

with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD......-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9...... by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy....

[Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified].

Science.gov (United States)

Li, Xi; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Xinyong; Lv, Jialin; Wu, Yuhua; Zhang, Hui; Nong, Jingying; Zhang, Quan; Zhang, Shucai

2015-12-01

Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation and wild-type. Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. The patients' overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6%) and diarrhea (16.1%). Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.


Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

Science.gov (United States)

Stinchcombe, Thomas E; Bogart, Jeffrey A

2012-01-01

Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.

Personalized medicine for non-small-cell lung cancer: implications of recent advances in tissue acquisition for molecular and histologic testing.

Science.gov (United States)

Moreira, Andre L; Thornton, Raymond H

2012-09-01

In light of recent advances in individualized therapy for non-small-cell lung cancer (NSCLC), molecular and histologic profiling is essential for guiding therapeutic decisions. Results of these analyses may have implications for both response (eg, molecular testing for EGFR [epidermal growth factor receptor] mutations) and safety (eg, contraindications for squamous histology) in NSCLC. Most patients with NSCLC present with unresectable advanced disease; therefore, greater emphasis is being placed on minimally invasive tissue acquisition techniques, such as small biopsy and cytology specimens. Due to the need for increasing histologic and molecular information and increasingly smaller tissue sample sizes, efforts must be focused on optimizing tissue acquisition and the development of more sensitive molecular assays. Recent advances in tissue acquisition techniques and specimen preservation may help to address this challenge and lead to enhanced personalized treatment in NSCLC. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of Amifostine on Response Rates in Locally Advanced Non-Small-Cell Lung Cancer Patients Treated on Randomized Controlled Trials: A Meta-Analysis

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Mell, Loren K.; Malik, Renuka; Komaki, Ritsuko; Movsas, Benjamin; Swann, R. Suzanne; Langer, Corey; Antonadou, Dosia; Koukourakis, Michael; Mundt, Arno J.

2007-01-01

Purpose: Amifostine can reduce the cytotoxic effects of chemotherapy and radiotherapy in patients with locally advanced non-small-cell lung cancer, but concerns remain regarding its possible tumor-protective effects. Studies with sufficient statistical power to address this question are lacking. Methods and Materials: We performed a meta-analysis of all published clinical trials involving locally advanced non-small-cell lung cancer patients treated with radiotherapy with or without chemotherapy, who had been randomized to treatment with amifostine vs. no amifostine or placebo. Random effects estimates of the relative risk of overall, partial, and complete response were obtained. Results: Seven randomized trials involving 601 patients were identified. Response rate data were available for six studies (552 patients). The pooled relative risk (RR) estimate was 1.07 (95% confidence interval, 0.97-1.18; p = 0.18), 1.21 (95% confidence interval, 0.83-1.78; p = 0.33), and 0.99 (95% confidence interval, 0.78-1.26; p = 0.95) for overall, complete, and partial response, respectively (a RR >1 indicates improvement in response with amifostine compared with the control arm). The results were similar after sensitivity analyses. No evidence was found of treatment effect heterogeneity across the studies. Conclusions: Amifostine has no effect on tumor response in patients with locally advanced non-small-cell lung cancer treated with radiotherapy with or without chemotherapy

Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified

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Xi LI

2015-12-01

Full Text Available Background and objective Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC patients with EGFR mutation and wild-type. Methods Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. Results The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type with advanced NSCLC were enrolled in this study. The patients’ overall objective response rate (ORR was 51.6 % and the disease control rate (DCR was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6% and diarrhea (16.1%. Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.

Combination of docetaxel and cisplatin in the interventional treatment of advanced non-small cell lung cancer

International Nuclear Information System (INIS)

He Zhijiang; Liu Yunjun; Li Ezhen

2004-01-01

Objective: To evaluate the efficacy and toxicity of the combination of docetaxel and cisplatin in the interventional treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods: Thirty patients with locally advanced (stage III) or metastatic (stage IV) NSCLC were enrolled into the study. The patients received docetaxel 75 mg/m 2 per day by bronchial artery and vein, and cisplatin 40 mg 2 on day 1-3 of a 21-day cycle. Each patient should complete two cycles. Results: An objective response rate was obtained in 46.7% of 30 patients (one complete and 13 partial response), whereas 10 patients had stable disease and 6 patients were progressive. The response rate was 60% (9/15) in the initial patients, and 33.3% (5/15) in the retreated patients. The main toxicities were leukopenia (26.7% in grade III + IV) and thrombocytopenia (10% in grade III + IV). Conclusion: The combination of docetaxel and cisplatin by interventional treatment is a feasible, well-tolerated and active scheme in the treatment of advanced NSCLC. (authors)

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

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Mellema, Wouter W.; Masen-Poos, Lucie; Smit, Egbert F.; Hendriks, Lizza E. L.; Aerts, Joachim G.; Termeer, Arien; Goosens, Martijn J.; Smit, Hans J. M.; van den Heuvel, Michel M.; Wekken, van der Anthonie J.; Herder, Gerarda J. M.; Krouwels, Frans H.; Stigt, Jos A.; van den Borne, Ben E. E. M.; Haitjema, Tjeerd J.; Staal-Van den Brekel, Agnes J.; van Heemst, Robbert C.; Pouw, Ellen; Dingemans, Anne-Marie C.

2015-01-01

Objectives: As suggested by in-vitro data, we hypothesize that subtypes of ICRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Methods: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinumbased chemotherapy, were retrieved

[Comparison of NP and MVP regimen in treatment of advanced non-small cell lung cancer].

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Qiang, E; Wang, Song-ping; Liu, Shu-juan; Yiao, Juan

2002-12-01

Chemotherapy is the major treatment for advanced non-small cell lung cancer (NSCLC). However, the efficacy is not satisfactory. From January 1996 to December 2000, two chemotherapy regimen [NP: vinorelbine(NVB) + cisplatin(DDP); MVP: mitomycin (MMC) + vindesine(VDS) + cisplatin] have been used to treat 110 advanced NSCLC patients. The response and major adverse reaction were analyzed and compared. Forty-eight cases of advanced NSCLC (stage III-IV) patients were treated with NP (NVB: 25 mg/m2, d1, 8; DDP: 35 mg/m2, d1-3). The other 62 cases were treated with MVP regimen (MMC: 6 mg/m2, d1; VDS: 3 mg/m2, d1, 8; DDP: 30 mg/m2 d1-3). In NP group, the overall response rate was 50% (CR + PR = 24); medium response time was 5.5 months; medium survival time was 11 months. In MVP group, the overall response rate was 51.6% (CR + PR = 32), medium response time and survival time were 6.5 and 14.5 months, respectively. The major toxicities were myelosuppression and phlebitis in NP group, nausea/vomiting, myelosuppression in MVP group, respectively. NP and MVP regimen for advanced NSCLC have similar response rate (P > 0.05). Deep vein injection and improved infusion can be used to prevent phlebitis in NP regimen.

Serum peptide expression and treatment responses in patients with advanced non-small-cell lung cancer

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An, Juan; Tang, Chuan-Hao; Wang, Na; Liu, Yi; Lv, Jin; Xu, Bin; Li, Xiao-Yan; Guo, Wan-Feng; Gao, Hong-Jun; He, Kun; Liu, Xiao-Qing

2018-01-01

Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. PMID:29844828

[Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

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Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

2017-06-20

With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

Annual review of advances in lung cancer clinical research: a report for the year 2009.

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Stinchcombe, Thomas E; Bogart, Jeffrey; Wigle, Dennis A; Govindan, Ramaswamy

2010-07-01

The use of positron emission tomography compared with conventional staging increases the detection of extrathoracic metastases and reduces the number futile thoracotomies in patients being evaluated for surgical resection. Long-term follow-up of one of the two adjuvant chemotherapy trials revealed a continued overall survival (OS) benefit to adjuvant chemotherapy. In locally advanced non-small cell lung cancer, a phase III trial of chemoradiotherapy alone and with surgical resection revealed no statistically significant difference in OS between the treatment arms. In advanced stage non-small cell lung cancer, a phase III trial compared gefitinib with carboplatin and paclitaxel in a clinically enriched patient population for epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations; among patients with an EGFR TK mutation, patients in gefitinib arm compared with carboplatin and paclitaxel arm experienced a statistically significant superior response rate and progression-free survival, and among patients without EGFR TK mutation patients in the gefitinib arm compared with carboplatin and paclitaxel experienced a statistically significant inferior response rate and progression-free survival. A phase III trial of platinum-based therapy with and without cetuximab in the first-line setting revealed improved OS in the cetuximab arm. A phase III trial of maintenance pemetrexed compared with placebo in patients who had not progressed after initial platinum-based therapy revealed an improvement in OS of patients in the pemetrexed arm with nonsquamous histology. In limited-stage small cell lung cancer, a phase III trial compared standard and high-dose prophylactic cranial irradiation and revealed no significant difference in the rate of brain metastases between the two treatment arms.

Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

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2012-12-13

Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

A comprehensive review of nongenetic prognostic and predictive factors influencing the heterogeneity of outcomes in advanced non-small-cell lung cancer

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Cuyún Carter G

2014-10-01

Full Text Available Gebra Cuyún Carter,1 Amy M Barrett,2 James A Kaye,3 Astra M Liepa,1 Katherine B Winfree,1 William J John1 1Eli Lilly and Company, Indianapolis, IN, USA; 2RTI Health Solutions, Research Triangle Park, NC, USA; 3RTI Health Solutions, Waltham, MA, USA Abstract: While there have been advances in treatment options for those with advanced non-small-cell lung cancer, unmet medical needs remain, partly due to the heterogeneity of treatment effect observed among patients. The goals of this literature review were to provide updated information to complement past reviews and to identify a comprehensive set of nongenetic prognostic and predictive baseline factors that may account for heterogeneity of outcomes in advanced non-small-cell lung cancer. A review of the literature between 2000 and 2010 was performed using PubMed, Embase, and Cochrane Library. All relevant studies that met the inclusion criteria were selected and data elements were abstracted. A classification system was developed to evaluate the level of evidence for each study. A total of 54 studies were selected for inclusion. Patient-related factors (eg, performance status, sex, and age were the most extensively researched nongenetic prognostic factors, followed by disease stage and histology. Moderately researched prognostic factors were weight-related variables and number or site of metastases, and the least studied were comorbidities, previous therapy, smoking status, hemoglobin level, and health-related quality of life/symptom severity. The prognostic factors with the most consistently demonstrated associations with outcomes were performance status, number or site of metastases, previous therapy, smoking status, and health-related quality of life. Of the small number of studies that assessed predictive factors, those that were found to be significantly predictive of outcomes were performance status, age, disease stage, previous therapy, race, smoking status, sex, and histology. These

Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy

NARCIS (Netherlands)

Wink, Krista C. J.; Belderbos, José S. A.; Dieleman, Edith M. T.; Rossi, Maddalena; Rasch, Coen R. N.; Damhuis, Ronald A. M.; Houben, Ruud M. A.; Troost, Esther G. C.

2016-01-01

The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients).

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

Science.gov (United States)

Li, Xi; Yang, Xin-jie; Sun, Yi-fen; Qin, Na; Lü, Jia-lin; Wu, Yu-hua; Zhang, Hui; Zhang, Quan; Zhang, Shu-cai

2012-08-01

To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

Insulin-like growth factor 1 receptor expression in advanced non-small-cell lung cancer and its impact on overall survival

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Humar Mojca

2017-05-01

Full Text Available The insulin-like growth factor 1 receptor (IGF1R expression has been addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC in various studies; however, the associations between IGF1R expression and prognosis of advanced NSCLC patients is still controversial. The aim of our observational, cohort study was to evaluate the expression of IGF1R in advanced NSCLC and its prognostic role. A subgroup analysis was performed to address the influence of pre-existing type 2 diabetes mellitus (T2DM status on IGF1R expression and overall survival (OS.

Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab.

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Stinchcombe, Thomas E

2007-09-01

Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting.

[Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].

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Wang, Xiao-Yun; Zhao, Yu-Liang

2010-12-21

To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.

FDG PET in monitoring response to neoadjuvant chemoradiotherapy in patients with locally advanced non-small lung carcinoma

International Nuclear Information System (INIS)

Berlangieri, S. U.; Lee, S. T.; Chan, A. M.; Mitchell, P. L.; Knight, S. R.; Feigen, M. M.; Scott, A. M.

2009-01-01

Full text:Aim: The aim of our study was to correlate 18F-FDG PET response to neoadjuvant chemoradiotherapy with histopathology in patients with locally advanced non-small cell lung carcinoma. Methods: All patients with stage III NSCLC planned for surgery following induction chemotherpay and/or radiotherapy who underwent pre- and post-treatment FDG-PET between 2004 and 2007 were retrospectively reviewed. The PET scans were performed according to standard protocol. The clinical FDG-PET TNM stage was correlated with the histopathology of the surgical specimens. Results: There were 9 patients (6 M :3 F ), median age 59.7 years (range 49 to 73 years). Post-treatment FDG-PET correctly predicted mediastinal pathological N stage in 8/9 patients, with one patient having microsopic disease in two nodes. The post-treatment FDG-PET correctly predicted pathological T stage in 7/9 patients, with 2 patients having small volume T4 disease not detected by PET. Post-treatment FDG-PET correctly downstaged 4 patients. Of the 5 patients, incorrectly staged on the post-treatment FDG-PET, one patient had microscopic pN 2 disease, 2 had pN 1 disease, and 2 had pT 4 disease. Conclusion: Post-treatment FDG-PET is predictive of pathological nodal stage within the mediastinum in patients with locally advanced NSCLC treated with neoadjuvant chemoradiotherapy. FDG-PET does not detect microscopic or small volume disease, nor is it able to define the boundaries of mediastinal tissue invasion.

Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407

Science.gov (United States)

Govindan, Ramaswamy; Bogart, Jeffrey; Stinchcombe, Thomas; Wang, Xiaofei; Hodgson, Lydia; Kratzke, Robert; Garst, Jennifer; Brotherton, Timothy; Vokes, Everett E.

2011-01-01

Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC. PMID:21747084

Advanced reactor development for non-electric applications

International Nuclear Information System (INIS)

Chang, M.H.; Kim, S.H.

1996-01-01

Advance in the nuclear reactor technology achieved through nuclear power programs carried out in the world has led nuclear communities to direct its attention to a better and peaceful utilization of nuclear energy in addition to that for power generation. The efforts for non-electric application of nuclear energy has been pursued in a limited number of countries in the world for their special needs. However, those needs and the associated efforts contributed largely to the development and practical realization of advanced reactors characterized by highly improved reactor safety and reliability by deploying the most up-to-date safety technologies. Due mainly to the special purpose of utilization, economic reasons and ease in implementation of new advanced technologies, small and medium reactors have become a major stream in the reactor developments for non-electric applications. The purpose of this paper is to provide, to the interested nuclear society, the overview of the development status and design characteristics of selected advanced nuclear reactors previously developed and/or currently under development specially for non-electric applications. Major design technologies employed in those reactors to enhance the reactor safety and reliability are reviewed to present the underlying principles of the design. Along with the overview, this paper also introduces a development program and major design characteristics of an advanced integral reactor (SMART) for co-generation purpose currently under conceptual development in Korea. (author)

Chemotherapy for advanced non-small cell lung cancer in the elderly population

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Fábio Nasser Santos

Full Text Available ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs. As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10, MEDLINE (1966 to 31 October 2014, EMBASE (1974 to 31 October 2014, and Latin American Caribbean Health Sciences Literature (LILACS (1982 to 31 October 2014. In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS, one-year survival rate (1yOS, progression-free survival (PFS, objective response rate (ORR, major adverse events, and quality of life (QoL. MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy

Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Parikh, Ravi B.; Cronin, Angel M.; Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M.; Lo, Peter C.; Baldini, Elizabeth H.; Johnson, Bruce E.; Chen, Aileen B.

2014-01-01

Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients

Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

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Parikh, Ravi B. [Harvard Medical School, Boston, Massachusetts (United States); Cronin, Angel M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Lo, Peter C. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Baldini, Elizabeth H.; Johnson, Bruce E. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Chen, Aileen B., E-mail: achen@lroc.harvard.edu [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States)

2014-07-15

Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer

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Uğur Selek

2014-12-01

Full Text Available Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC. Three-dimensional radiotherapy (3DCRT has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT. IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques, treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non-small cell lung cancer.

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Shiroyama, Takayuki; Suzuki, Hidekazu; Tamiya, Motohiro; Tamiya, Akihiro; Tanaka, Ayako; Okamoto, Norio; Nakahama, Kenji; Taniguchi, Yoshihiko; Isa, Shun-Ichi; Inoue, Takako; Imamura, Fumio; Atagi, Shinji; Hirashima, Tomonori

2018-01-01

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27-87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin ALI ALI ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

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2017-04-12

Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

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Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

2014-08-01

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

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Qinghua ZHOU

2011-02-01

Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

Combined modality therapy for locally advanced non-small cell lung carcinoma

International Nuclear Information System (INIS)

Recine, D.; Rowland, K.; Reddy, S.; Lee, M.S.; Bonomi, P.; Taylor, S.; Faber, L.P.; Warren, W.; Kittle, C.F.; Hendrickson, F.R.

1990-01-01

Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

Advanced Microelectronics Technologies for Future Small Satellite Systems

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Alkalai, Leon

1999-01-01

Future small satellite systems for both Earth observation as well as deep-space exploration are greatly enabled by the technological advances in deep sub-micron microelectronics technologies. Whereas these technological advances are being fueled by the commercial (non-space) industries, more recently there has been an exciting new synergism evolving between the two otherwise disjointed markets. In other words, both the commercial and space industries are enabled by advances in low-power, highly integrated, miniaturized (low-volume), lightweight, and reliable real-time embedded systems. Recent announcements by commercial semiconductor manufacturers to introduce Silicon On Insulator (SOI) technology into their commercial product lines is driven by the need for high-performance low-power integrated devices. Moreover, SOI has been the technology of choice for many space semiconductor manufacturers where radiation requirements are critical. This technology has inherent radiation latch-up immunity built into the process, which makes it very attractive to space applications. In this paper, we describe the advanced microelectronics and avionics technologies under development by NASA's Deep Space Systems Technology Program (also known as X2000). These technologies are of significant benefit to both the commercial satellite as well as the deep-space and Earth orbiting science missions. Such a synergistic technology roadmap may truly enable quick turn-around, low-cost, and highly capable small satellite systems for both Earth observation as well as deep-space missions.

Prevalence of EGFR mutations in newly diagnosed locally advanced or metastatic non-small cell lung cancer Spanish patients and its association with histological subtypes and clinical features: The Spanish REASON study.

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Esteban, E; Majem, M; Martinez Aguillo, M; Martinez Banaclocha, N; Dómine, M; Gómez Aldaravi, L; Juan, O; Cajal, R; Gonzalez Arenas, M C; Provencio, M

2015-06-01

The aim of the REASON study is to determine the frequency of EGFR mutation in advanced non-small cell lung cancer (aNSCLC) patients in Spain (all histologies), and to better understand the clinical factors (gender, smoking habits and histological subtypes) that may be associated with EGFR mutations, in an unselected sample of aNSCLC patients. All newly diagnosed aNSCLC patients from 40 selected centers in Spain were prospectively included for a 6-month period. Patient characteristics were obtained from clinical records. Mutation testing was performed on available tumor samples. Exploratory analyses were performed to characterize the clinico-pathological factors associated with presence of EGFR mutations. From March 2010 to March 2011, 1113 patients were included in the study, of which 1009 patients provided sample for EGFR mutation analysis (90.7%). Mutation analysis was not feasible in 146/1113 patients (13.1%) due to either sample unavailability (79/1113; 7.1%) or sample inadequacy (67/1113; 6.0%). Twenty-five out of 1113 patients (2.3%) were excluded due to unavailable information. Most patients (99.5%) were Caucasian, 74.5% were male, and predominantly were current (38.1%) or former smokers (44.0%). Median age was 66 years (range 25-90) and 70.7% of patients had non-squamous histology (57.8% adenocarcinoma, 1.8% bronchoalveolar, 11.1% large-cell carcinoma). Exon 19 deletions and the exon 21 L858R point mutation were analyzed in 942/1009 (93.4%) samples. Mutation rate was 11.6% (82.6% exon 19 dels and 17.4% L858R). To be never smoker (38.1%), female (25.4%), with bronchioloalveolar carcinoma (22.2%) or adenocarcinoma (15.4%) histology was associated with a higher prevalence of EGFR mutations. Exons 18, 20 and 21 (excluding L858R) were analyzed in 505/942 samples, and EGFR mutations were found in 22/505 samples (4.4%). The estimated prevalence of sensitizing EGFR mutations (exon 19 del, exon 21 L858R) in an unselected samples of newly diagnosed aNSCLC patients in

The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer

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Nygaard, Anneli Dowler; Garm Spindler, Karen-Lise; Pallisgaard, Niels

2013-01-01

BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cf......DNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible....... RESULTS: The study included 246 patients receiving a minimum of 1 treatment cycle, and all but four were evaluable for response according to RECIST. Forty-three patients (17.5%) presented with a KRAS mutation. OS was 8.9 months and PFS by intention to treat 5.4 months. Patients with a detectable plasma...

Efficacy of Icotinib for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified

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Yiping ZHANG

2013-03-01

Full Text Available Background and objective As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Methods Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. Results The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation with NSCLC were enrolled in the current study. The patients’ overall objective response rate (ORR was 58.3% and the disease control rate (DCR in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001. Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41. Median overall survival (OS in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II and reversible with no grade IV toxicity. Conclusion Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

[Efficacy of icotinib for advanced non-small cell lung cancer patients with EGFR status identified].

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Song, Zhengbo; Yu, Xinmin; Cai, Jufen; Shao, Lan; Lin, Baochai; He, Chunxiao; Zhang, Beibei; Zhang, Yiping

2013-03-01

As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (Picotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity. Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

Does advanced lung inflammation index (ALI) have prognostic significance in metastatic non-small cell lung cancer?

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Ozyurek, Berna Akinci; Ozdemirel, Tugce Sahin; Ozden, Sertac Buyukyaylaci; Erdoğan, Yurdanur; Ozmen, Ozlem; Kaplan, Bekir; Kaplan, Tugba

2018-01-22

Lung cancer is the most commonly diagnosed and death-related cancer type and is more frequent in males. Non-small-cell lung cancer (NSCLC) accounts for about 85% of all case. In this study, it was aimed to research the relationship between advanced lung inflammation index (ALI) and the primary mass maximum standardized uptake value (SUVmax) and C-reactive protein (CRP) at initial diagnosis and the prognostic value of ALI in determining the survival in metastatic NSCLC. A total of 112 patients diagnosed as stage 4 non-small-lung cancer in our hospital between January 2006 and December 2013 were included in this study. ALI was calculated as body mass index (BMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR). The patients were divided into two groups as ALI ALI ≥ 18 (low inflammation). The log-rank test and Cox proportional hazard model were used to identify predictors of mortality. Evaluation was made of 94 male and 18 female patients with a mean age of 59.7 ± 9.9 years. A statistically significant negative relationship was determined between ALI and CRP values (P ALI and SUVmax values (P = .436). The median survival time in patients with ALI ALI ≥ 18, it was 16 months (P = .095). ALI is an easily calculated indicator of inflammation in lung cancer patients. Values <18 can be considered to predict a poor prognosis. © 2018 John Wiley & Sons Ltd.

Palliative radiotherapy in asymptomatic patients with locally advanced, unresectable, non-small cell lung cancer

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Reinfuss, M.; Skolyszewski, J.; Kowalska, T.; Rzepecki, W.; Kociolek, D.

1993-01-01

Between 1983 and 1990, 332 patients with non-small cell lung cancer (NSCLC) were referred to short-time, split-course palliative thoracic radiotherapy. The group consisted of patients with locally advanced (III o ), unresectable cancer, not suitable for curative radiotherapy, asymptomatic or having only minimal symptoms related to intrathoracic tumor. The therapeutic plan involved two series of irradiation. Tumor dose delivered in each series was 20 Gy given in five daily fractions over five treatment days. There were four weeks interval between series. Of 332 patients initially qualified to thoracic radiotherapy only 170 patients received the treatment; the other 162 patients were not irradiated because of treatment refusal or logistic problems concerning therapy. They made the control group of the study, receiving the best possible symptomatic care. Twelve-month survivals in the radiotherapy and control groups were 32.4% and 9.3%, respectively; 24-month survivals 11.2% and 0%, respectively. Improvement of survival after palliative thoracic radiotherapy was observed only in patients with clinical stage IIIA and Karnofsky's performance status (KPS) ≥ 70. (orig.) [de

Supportive care in the era of immunotherapies for advanced non-small-cell lung cancer.

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Awada, Gil; Klastersky, Jean

2018-03-01

The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting. These immunotherapies are associated with a distinct toxicity profile based on autoimmune organ toxicity which is a new challenge for supportive care during treatment with these drugs. The differential diagnosis of events occurring during immune checkpoint inhibitor treatment is broad: they can be due to immune-related or nonimmune-related adverse events, atypical tumor responses (pseudoprogression or hyperprogression) or events related to comorbidities or other treatments. The management of these patients includes a thorough baseline clinical, biological and radiologic evaluation, patient education, correct follow-up and management by a multidisciplinary team with a central role for the medical oncologist. Immune-related toxicities should be managed according to available guidelines.

Survival benefit from chemotherapy with mitomycin-c vinblastine and cisplatin in advanced non-small cell lung cancer

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Joaquin, C.F.

1992-01-01

Between January 1989 and May 1991 a prospective trial was conducted among the patients in the Lung Center of the Philippines who were diagnosed to have unresectable and metastatic non-small cell lung cancer (NSCLC). There were two groups of patients: those who consented to chemotherapy with the mitomycin, vinblastine and cisplatin regimen (n=31) and those who refused any form of chemotherapy or radiation (n=15). These groups were followed up and compared as to patient characteristics and duration of survival. The results show no identifiable features in the responders and non-responders to chemotherapy which could predict tumor response. The median survival of the untreated group was 15 weeks and that of the treated group was 34 weeks. This was statistically significant. No significant difference in survival between the responders and the non-responders was observed. The objective tumor response rate to the MVP regimen was 25.8%. The most common toxic effects were emesis and hematologic abnormalities. The study recommends the option of chemotherapy with the MVP regimen rather than no treatment at all after considering the risks and benefits for the patient with advanced stage NSCLC. (auth.). 19 refs.; 2 figs.; 4 tabs

Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy

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Pan, Yi; Brink, Carsten; Knap, Marianne

2016-01-01

PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...... significantly associated with esophagitis. The two models using the relative esophagus volume irradiated above 40Gy (V40, OR=2.18/10% volume) or the length of esophagus irradiated above 40Gy (L40, OR=4.03/5cm) were optimal. The upper part of esophagus was more sensitive and females experienced more toxicity...... than men. CONCLUSION: V40 and L40 were most effective dosimetric predictors of grade ⩾2 esophagitis. The upper part of esophagus was more sensitive....

Treatment decision-making for advanced non-small cell lung cancer and differences among European countries: 1st AIOT-ETOP meeting.

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Gridelli, Cesare; Stahel, Rolf; Besse, Benjamin; Ciardiello, Fortunato; Felip, Enriqueta; Gasparini, Stefano; Graziano, Paolo; Rossi, Antonio; de Marinis, Filippo

2011-12-01

The Italian Association of Thoracic Oncology (AIOT) and the European Thoracic Oncology Platform (ETOP) realized the first conjunct educational meeting, open to European oncologists involved in the treatment of thoracic malignancies, entitled "Advanced non-small cell lung cancer: new perspectives in first-line setting". The educational meeting included 8 interactive talks, held by European key opinion leaders, and 5 related clinical cases in which the attendees, divided in working tables based on their country origin, were involved for interactive discussion. The aim of this course was to elucidate the differences or similarities among the European countries in the first-line treatment of patients affected by advanced non-small cell lung cancer (NSCLC). Twenty-two attendees of the following countries participated: Austria, France, Italy, Spain, Swiss, and UK. As expected, some discrepancies between the groups were identified concerning the approach to the diagnostic phase, the choice of first-line regimen, the duration of treatment and the use of maintenance therapy. These discrepancies were mainly due to familiarity with specific therapies and lack of access to certain therapies due to local regulatory issues. The European Medicine Agency grants marketing of drugs in all Europe, regulatory agency of each country can register the drug, but can also deny public reimbursement thus restricting the options of the oncologist. The European Oncology Associations should join to their effort to achieve a uniform access to the cancer therapy for all patients in Europe. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The role of radiation therapy for stage IIIB non-small cell lung cancer. Impact of clinical nodal stage on survival

International Nuclear Information System (INIS)

Hayakawa, Kazushige; Mitsuhashi, Norio; Furuta, Masaya; Saito, Yoshihiro; Nakayama, Yuko; Katano, Susumu; Ohno, Tatsuya; Niibe, Hideo

1996-01-01

From 1976 through 1989, 46 patients with stage IIIB non-small cell lung cancer (NSCLC) without malignant effusion were treated with definitive radiation therapy (RT) at Gunma University Hospital. All patients were treated with 10 MV x-rays using antero posterior parallel opposed fields. The total dose ranged from 60 Gy to 70 Gy (mean dose; 66 Gy) with once daily standard fractionation. The actuarial two and five-year survival rates of the entire group were 22% and 10% respectively with a median survival time (MST) of 10 months. The survival of 18 patients with stage N0-2 disease was significantly better than the 28 patients with stage N3 disease (MST 21 versus 9 months; p<0.05). There were no significant differences in survival based on age and sex. However, there was a borderline difference in survival rates between patients with a performance status of 0-1 and those with status of 2-3 (p=0.06). Three patients with squamous cell carcinoma were alive after 5 years and were without disease progression. No patients with non-squamous cell carcinoma were free of disease after 5 years. These results provide support for the use of definitive RT to manage those patients with limited stage IIIB squamous cell carcinoma not extending to N3 stage. (author)

Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer.

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Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

2016-01-01

Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2-11.8 months), and median overall survival was 21.0 months (95% CI: 20.1-21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

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Meina WU

2011-03-01

Full Text Available Background and objective As there is a sharp increase in the incidence of lung cancer in women in recent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and better prognosis. The aim of this study is to analyze the clinical data of women with advanced non-small cell lung cancer (NSCLC retrospectively to explore the prognostic factors. Methods Clinical data of 541 female patients with advanced NSCLC were collected and followed up till death. The primary endpoint is overall survival (OS. SPSS 11.0 statistical analysis software was used for univariate and multivariate analysis. Results The mean age is 59 years (20 years-86 years, adenocarcinoma account for 80.2% (434/541. The median OS was 15 months (95%CI: 13.87-16.13, and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respectively. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the first-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were significantly correlated with the OS and survival rate (P < 0.05. Combined with multivariate analysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to first-line chemotherapy were independent prognostic factor for survival (P < 0.05. Conclusion There is a higher percentage of adenocarcinoma in female NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to first-line chemotherapy may become independent prognostic factors for survival of female patients with advanced NSCLC.

Definitive Radiotherapy of Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lee, Jong Young; Park, Kyung Ran

1995-01-01

Purpose : The effect of dose escalation of up to 6500 cGy on local control and survival was investigated in locally advanced non-small cell lung cancer. Materials and Methods : Ninety eight patients with biopsy-proven unresectable non-small cell lung cancer without distant metastases or medically inoperable patients with lower-stage were treated with definitive radiotherapy alone. Group A were treated by thoracic irradiation, 6000 cGy or less in total tumor dose with daily fractions of 180 to 200 cGy: and group B was treated with 6500 cGy of same daily fractions. Results : The actuarial overall survival rate for the entire group was 54% at 1 year, 26.6% at 2 years and 16.4% at 3 years with a median survival time of 13 months. Statistically significant prognostic factors that affect survival rate were stage and N-stage. However, no improvement in local control and survival has been seen with higher dose radiotherapy(group B). Conclusion : Dose escalation of up to 6500 cGy was no effect on local control and survival rate. To increase the survival rate of non-small cell lung cancer hyperfractionated radiotherapy or concurrent chemoradiotherapy should be considered

Treatment Choice for Advanced Non-small Cell Lung Cancer Patients Who Had Gradual Progression After EGFR-TKIs: 32 Cases Report

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Lin LIN

2013-10-01

Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in the treatment of the advanced non-small cell lung cancer (NSCLC, especially in the adenocarcinoma patients with activating EGFR mutations. But there is no published overview of the following treatment. This report through observing the efficacy, toxicity and overall survival of different treatments to the advanced NSCLC patients who had gradual progression after EGFR-TKIs, evaluates the influence of the continued treatment and switching chemotherapy. Methods Retrospective review is conducted on 32 cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs. One group accepted the continued treatment and the other group accepted the switching chemotherapy. Results The median overall survival of the continued treatment group is 36.0 months. The respose rate of the switching chemotherapy group is 43.75%, and clinical benefit rate (complete and partial response and stable disease is 87.5%. The median overall survival is 15.5 months. The main toxicities are nausea, vomiting and hematological toxicities. Conclusion For the advanced NSCLC patients who had gradual progression after EGFR-TKIs, the continued treatment is one of the acceptable choices.

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

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Xu J

2017-10-01

Full Text Available Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR-mutant non-small cell lung cancer (NSCLC who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure.Patients and methods: This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally. Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal.Results: Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS was 5.33 months (95% CI, 3.63–7.03 months. Moreover, the objective response rate (ORR was 11.1%, and the disease control rate (DCR was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4% and fatigue (37.0%.Conclusion: Apatinib plus

Health Resource Utilization in Patients with Advanced Non-Small Cell Lung Cancer Receiving Chemotherapy in China.

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Shi, Jing; Zhu, Jun

2016-01-01

Chemotherapy is the preferred treatment regimen for advanced lung cancer patients. This study investigated the health resources utilized by and medical expenses of patients with non-small cell lung cancer (NSCLC) as well as the influence of various chemotherapy regimens on the final medical costs in China. The aim of this study was to provide physicians with a reference to use as the basis for their choice of treatment. Data were collected from the Shanghai Chest Hospital's medical charts and billing database. The collected patient information included the baseline characteristics, medical history, chemotherapy regimens, and medical costs, which were used to estimate the health resources utilized by patients and the cost of treatment. This study included 328 patients, and the average total medical cost was $US14,165. This cost included drugs, which accounted for as much as 78.91% of the total cost, and chemotherapy drugs, which accounted for 51.58% of total drug expenses. The most frequently utilized chemotherapy drug was carboplatin, and the most expensive chemotherapy drug was erlotinib. In drug combinations, gemcitabine was utilized most frequently, the combination of gemcitabine and paclitaxel was the most expensive, and cisplatin was the least expensive drug. Epidermal growth factor receptor-positive patients were treated with targeted drug therapy (icotinib, erlotinib, and gefitinib). The use of recombinant human endostatin was often combined with a vinorelbine plus cisplatin regimen. Traditional Chinese medicines were the most frequently utilized non-chemotherapy drugs, and these drugs were also the most expensive. The final cost significantly depended on the specific chemotherapy regimen; thus, the rationale and cost of the chemotherapy regimen and adjuvant chemotherapy should be considered in patients with advanced NSCLC.

Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH)

NARCIS (Netherlands)

Peters, S.; Gettinger, S.; Johnson, M.L.; Janne, P.A.; Garassino, M.C.; Christoph, D.; Toh, C.K.; Rizvi, N.A.; Chaft, J.E.; Costa, E.; Patel, J.D.; Chow, L.Q.M.; Koczywas, M.; Ho, C.; Fruh, M.; Heuvel, M. van den; Rothenstein, J.; Reck, M.; Paz-Ares, L.; Shepherd, F.A.; Kurata, T.; Li, Z.; Qiu, J.; Kowanetz, M.; Mocci, S.; Shankar, G.; Sandler, A.; Felip, E.

2017-01-01

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or

A willingness-to-pay study of oral epidermal growth factor tyrosine kinase inhibitors in advanced non-small cell lung cancer.

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Leighl, Natasha B; Tsao, W Stephen; Zawisza, Dianne L; Nematollahi, Mahsan; Shepherd, Frances A

2006-01-01

Oral epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are new agents in the treatment of advanced non-small cell lung cancer (NSCLC). Phase II studies demonstrate objective tumor responses and symptom improvement, combined with minimal toxicity and the convenience of an oral agent. We evaluated patient utility through willingness-to-pay (WTP) for these agents in the treatment of advanced NSCLC in Canada. Advanced NSCLC patients and healthy subjects participated in a structured interview and bidding exercise, reviewing current evidence supporting EGFR TKI therapy in advanced NSCLC and patient willingness-to-pay for treatment. Fifty-seven patients and 54 healthy subjects participated. The median amount both groups were willing to pay for a month of oral EGFR TKI therapy was $100 CAD (range $0-5000 per month). A minority of NSCLC patients received employment income, the majority relying on disability, pension income, and social assistance for financial support. Affordability of these agents was a key concern for both advanced NSCLC patients and healthy subjects. Univariate predictors of WTP included marital status, prior chemotherapy treatment, receiving pension income or financial social assistance. In multivariate analysis, only prior chemotherapy remained a significant predictor of WTP (p=0.049). Both advanced NSCLC patients and healthy subjects feel oral EGFR TKIs are worth paying for in the treatment of advanced NSCLC, but are willing to pay only a fraction of the market price. As many advanced NSCLC patients are financially disadvantaged, the potential for restricted access to newer therapies is of concern.

Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

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Bianco, A; Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Rodriguez, R; Cuevas, M A; Alvarez, L A

1990-02-28

Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

Targeted therapies for locally advanced or metastatic squamous cell carcinoma of the lung.

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Stinchcombe, Thomas E

2013-12-01

Most patients with squamous cell carcinoma (SCC) present with advanced or metastatic disease at the time of diagnosis. Given the low prevalence of oncogenic driver mutations in SCC, I do not routinely perform molecular testing. The times that I perform molecular testing in SCC are for patients with SCC and a light or never smoking history, adenosquamous histology, or when the histological diagnosis is not definitive. For patients with a good performance status and adequate organ function, a platinum doublet is the standard therapy, and I generally use carboplatin and gemcitabine or carboplatin and paclitaxel. In the second-line setting for patients who are chemotherapy candidates, I will use docetaxel on a weekly or every three week schedule. Erlotinib is a treatment option in the third-line setting. My preference is for patients to participate in clinical trials because the development of novel therapies for patients with SCC has been slow compared with nonsquamous non-small cell lung cancer. Ongoing investigations into the genomics of SCC will hopefully identify driver mutations or alterations in pathways essential for oncogenesis and tumor growth and will lead to the development of targeted therapies. The complexity of the genomics of SCC will make the development of targeted therapies challenging.

Study of efficacy and toxicity of hypofractionated thoracic radiotherapy 17 gray in 2 fractions for palliation in advanced non-small-cell lung cancer

International Nuclear Information System (INIS)

Arif, S.; Rasul, S.; Haider, N.; Mahmood, A.; Syed, A.S.; Nadeem, M.

2012-01-01

Objective: To determine the efficacy and toxicity of hypofractionated thoracic radiotherapy 17 Gray (Gy) in 2 fractions for palliation in advanced non-small-cell lung carcinoma. Study design: A quasi-experimental study. Place and duration of study: Oncology department, Combined Military Hospital, Rawalpindi, from 4th July 2008 to 4th Nov 2009. Material and Methods: Fifty four patients with histologically and/or cytologically confirmed unresectable stages III and IV non small cell lung cancer, with performance status 2 or 3 and expected survival > 2 months were treated with megavoltage radiation therapy 17 Gy in 2 fractions one week apart, with symptoms due to intrathoracic disease (cough, dyspnea and hemoptysis) and toxicity due to radiation therapy (dysphagia secondary to esophagitis) assessed as per common toxicity criteria adverse event version 3.0 on day 0 before treatment and day 30 after start of treatment. Results: Grades of cough, hemoptysis and dyspnea showed significant improvement after treatment (p<0.001). A total of 42.68% patients showed an improvement in grade of cough (23 out of 54 patients), 85.7% of patients showed improvement in grade of hemoptysis (36 out of 42 patients) and 55.65% patients showed improvement in grade of dyspnea (30 out of 54 patients). Twenty two point two percent patients (12 out of 54) showed increase in grade of dysphagia. Although, there was a statistically significant increase in grade of dysphagia after treatment but it was limited to grade 1 and 2 only. Considering that no patient had grade 3 or 4 dysphagia, this toxicity was acceptable. Conclusion: Based on our results hypofractionated thoracic radiotherapy, 17 Gy in 2 fractions, is effective with acceptable toxicity in palliation in advanced non small cell lung cancer and is recommended as it will result in shorter duration of hospital stay and low hospital stay charges. (author)

The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

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Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-05-10

Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (PGPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Wei, Zhigang, E-mail: weizhigang321321@163.com; Ye, Xin, E-mail: yexintaian@aliyun.com; Yang, Xia, E-mail: yangxjinan@163.com; Zheng, Aimin, E-mail: am-zheng@163.com; Huang, Guanghui, E-mail: hgh3612@163.com; Li, Wenhong, E-mail: wenghong-li@163.com; Ni, Xiang, E-mail: asuka2521@hotmail.com; Wang, Jiao; Han, Xiaoying, E-mail: mylittlecarol@sina.com [Shandong Provincial Hospital Affiliated to Shandong University, Department of Oncology (China)

2015-02-15

PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

Energy Technology Data Exchange (ETDEWEB)

Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2013-05-01

Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

Science.gov (United States)

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

2016-11-01

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Arrieta, Oscar; Blake, Mónika; Mata-Moya, María Dolores de la; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-01-01

Background: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings

Expression of CD147 in advanced non-small cell lung cancer correlated with cisplatin-based chemotherapy resistance.

Science.gov (United States)

Zeng, H Z; Qu, Y Q; Liang, A B; Deng, A M; Zhang, W J; Xiu, B; Wang, H; Wang, H

2011-01-01

CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.

Comparison of Glasgow prognostic score and prognostic index in patients with advanced non-small cell lung cancer.

Science.gov (United States)

Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-03-01

Previous studies have shown that Glasgow prognostic score (GPS) and prognostic index (PI) are also powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to compare the prognostic value between GPS and PI. We enrolled consecutive patients with advanced NSCLC in this prospective cohort. GPS and PI were calculated before the onset of chemotherapy. The prognosis outcomes included 1-, 3-, and 5-year progression-free survival and overall survival (OS). The performance of two scores in predicting prognosis was analyzed regarding discrimination and calibration. 138 patients were included in the study. The area under the receiver operating characteristic curve for GPS predicting 1-year DFS was 0.62 (95 % confidence interval (CI) 0.56-0.68, P statistic showed good fit of the predicted 1-year DFS to the actual 1-year DFS by GPS (χ(2) = 4.326, P = 0.462), while no fit was found between the predicted 1-year DFS and the actual 1-year DFS by PI (χ(2) = 15.234, P = 0.091). Similar results of calibration power were found for predicting 3-year DFS, 5-year DFS, 1-year OS, 3-year OS, and 5-year OS by GPS and PI. GPS is more accurate than PI in predicting prognosis for patients with advanced NSCLC. GPS can be used as a useful and simple tool for predicting prognosis in patients with NSCLC. However, GPS only can be used for preliminary assessment because of low predicting accuracy.

Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

International Nuclear Information System (INIS)

Jotte, Robert M; Spigel, David R

2015-01-01

Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance

Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

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Lai XX

2016-04-01

Full Text Available Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC. We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55, hypertension (RR =5.34, and hemorrhagic events (RR =2.61. No statistically significant differences were found for gastrointestinal perforation (P=0.60, arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively, or fatal events (P=0.29.Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

Targeted Therapies for Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival.

Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

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Guetz S

2017-02-01

Full Text Available Sylvia Guetz,1,* Amanda Tufman,2,* Joachim von Pawel,3 Achim Rittmeyer,4 Astrid Borgmeier,2 Pierre Ferré,5 Birgit Edlich,6 Rudolf Maria Huber2 1Ev. Diakonissenkrankenhaus Leipzig, Leipzig, 2University Hospital Munich and Thoracic Oncology Centre Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (DZL CPC-M, Munich, 3Asklepios Fachkliniken Muenchen-Gauting, Gauting, 4Lungenfachklinik Immenhausen, Immenhausen, Germany; 5Pierre Fabre Pharmaceuticals, Oncology Research and Development Center, Toulouse, France; 6Pierre Fabre Pharma GmbH, Freiburg, Germany *These authors contributed equally to this work Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo in advanced non-small-cell lung cancer (NSCLC. Patients and methods: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP, overall survival (OS and tolerability. Results: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs. Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21�

Non-Meckel Small Intestine Diverticulitis

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Shamim Ejaz

2017-08-01

Full Text Available Non-Meckel small intestine diverticulitis can have many manifestations and its management is not well-defined. We report 4 unselect cases of small intestine diverticulitis; all patients were seen by the same physician at the Emergency Center at The University of Texas MD Anderson Cancer Center between 1999 and 2014. The median age at diagnosis of these patients was 82 years (range, 76–87 years. All 4 patients presented with acute onset of abdominal pain, and computed tomography scans showed characteristics of small intestine diverticulitis unrelated to cancer. Most of the diverticula were found in the region of the duodenum and jejuno-ileal segments of the small intestine. The patients, even those with peripancreatic inflammation and localized perforation, were treated conservatively. Non-Meckel diverticulitis can be overlooked in the initial diagnosis because of the location of the diverticulosis, the age of the patient, and the rarity of the disease. Because patients with non-Meckel small intestine diverticulitis can present with acute abdominal pain, non-Meckel small intestine diverticulitis should be considered in the differential diagnosis of patients with acute abdominal pain, and computed tomography scans can help identify the condition. Because of the rarity of non-Meckel small intestine diverticulitis, few studies have been published, and the data are inconclusive about how best to approach these patients. Our experience with these 4 elderly patients indicates that non-Meckel small intestine diverticulitis can be treated conservatively, which avoids the potential morbidity and mortality of a surgical approach.

Survival data for postoperative adjuvant chemotherapy comprising cisplatin plus vinorelbine after complete resection of non-small cell lung cancer.

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Kenmotsu, Hirotsugu; Ohde, Yasuhisa; Wakuda, Kazushige; Nakashima, Kazuhisa; Omori, Shota; Ono, Akira; Naito, Tateaki; Murakami, Haruyasu; Kojima, Hideaki; Takahashi, Shoji; Isaka, Mitsuhiro; Endo, Masahiro; Takahashi, Toshiaki

2017-09-01

Despite the efficacy of postoperative adjuvant cisplatin (CDDP)-based chemotherapy for patients who have undergone surgical resection of non-small cell lung cancer (NSCLC), few reports have presented survival data for Asian patients treated with adjuvant chemotherapy involving a combination of CDDP and vinorelbine (VNR). This study was performed to evaluate the survival of patients with NSCLC who received postoperative adjuvant chemotherapy comprising CDDP + VNR. We retrospectively evaluated patients with NSCLC who received adjuvant chemotherapy comprising CDDP + VNR at the Shizuoka Cancer Center between February 2006 and October 2011. One hundred patients who underwent surgical resection of NSCLC were included in this study. The patients' characteristics were as follows: median age 63 years (range 36-74 years), female 34%, never-smokers 20%, and non-squamous NSCLC 73%. Pathological stages IIA, IIB, and IIIA were observed in 31, 22, and 47% of patients, respectively. The 5- and 2-year overall survival rates were 73 and 93%, respectively. The 5- and 2-year relapse-free survival rates were 53 and 62%, respectively. Univariate analysis of prognostic factors showed that patient characteristics (sex, histology, and pathological stage) and CDDP dose intensity were not significantly associated with survival. In 48 patients who developed NSCLC recurrence, the 5-year survival rate after recurrence was 29%, and the median survival time after recurrence was 37 months. Our results suggest that the prognosis after surgical resection of NSCLC and adjuvant chemotherapy comprising CDDP + VNR might be improving compared with previous survival data of adjuvant chemotherapy for NSCLC.

Assessing functional status and the survival benefit of chemotherapy for advanced non-small cell lung cancer using administrative claims data.

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Feliciano, Josephine; Gardner, Lisa; Hendrick, Franklin; Edelman, Martin J; Davidoff, Amy

2015-01-01

Borderline or poor performance status (PS) patients comprise a significant proportion of those diagnosed with advanced non-small cell lung cancer (AdvNSCLC), but are often excluded from clinical trials. It is difficult to draw conclusions about the benefit of therapy in borderline PS patients due to lack of reliable PS assessments, and small clinical trial samples. Retrospective population-based secondary analyses may allow investigators to study under-represented populations in clinical trials. We hypothesized that patients with poor functional status derive benefit from chemotherapy compared good functional status, but that the magnitude of the benefit is lower compared to patients with good functional status. By utilizing a "disability status" (DS) measure as a proxy for PS, we offer a reliable mechanism for patient stratification that can be implemented in administrative claims data. Medicare beneficiaries diagnosed with AdvNSCLC between 2001 and 2005 were selected from the Surveillance, Epidemiology and End Results database linked to Medicare claims. Disability status, a previously developed and validated claims-based proxy for baseline PS, was implemented. Patients were assigned to good versus poor DS. Cox proportional hazard models were used to examine the differential effects of chemotherapy for the two DS groups on all-cause mortality, controlling for tumor and patient characteristics. Most patients in the cohort (n=21,019) were ≥75 years of age (59%), and non-Hispanic white (85%); 91% were assigned to good DS; 38% received chemotherapy. Chemotherapy had a strong protective effect among good DS patients (hazard ratio, 0.43; CI 0.42-0.45; pChemotherapy improves survival for advanced NSCLC patients with poor DS but to a lower magnitude than for good DS patients. The DS measure opens the door to assess outcomes for cancer patients with poor functional status using insurance claims data. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Recent advances in the treatment of non-small cell and small cell lung cancer.

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Stinchcombe, Thomas E

2014-01-01

Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival.

Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

International Nuclear Information System (INIS)

Farina, Davide; Morassi, Mauro; Maroldi, Roberto; Roca, Elisa; Tassi, Gianfranco; Cavalleri, Giuseppe

2013-01-01

To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

Unmet needs in squamous cell carcinoma of the lung: potential role for immunotherapy.

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Stinchcombe, Thomas E

2014-05-01

Squamous cell carcinoma of the lung accounts for 20-30% of non-small cell lung cancers (NSCLC). Despite the differences in disease characteristics between squamous and non-squamous NSCLC, both have historically been treated similarly in the clinic. Recently approved drugs have revealed differences in activity and safety profiles across histologic subtypes and have applicability in treating non-squamous, but not typically squamous, NSCLC. Exploration of immune checkpoints--co-inhibitory molecules used to regulate immune responses--has resulted in novel immunotherapies designed to interrupt signaling through the cytotoxic T lymphocyte-associated antigen-4 or programmed cell death protein-1 pathways on lymphocytes. Modulation of these pathways can lead to restored antitumor immune responses, and preliminary evidence shows that agents targeting these pathways have activity in lung cancer, including squamous NSCLC.

Lung cancer - non-small cell

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Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

Effectiveness of palliative radiotherapy in patients with non-small cell lung cancer

International Nuclear Information System (INIS)

Chmielewska, E.; Jaskiewicz, P.

2001-01-01

Lung cancer is the most frequent malignant neoplasm in Poland. During the last 25 years it has become the first reason of death of men and the second of women in Poland. Patients with non-small cell lung cancer constitute 75% of all lung cancer patients. The therapy of choice for the advanced, non-small cell lung cancer is radiotherapy with palliative assumption. Many papers indicate that this therapy has no influence on long-term survival, hence it is aimed at reducing the symptoms. The therapy brings relief to 70-80% of patients. At present no other method with similar effectiveness is known. The aim of the is study was to assess the effectiveness of palliative radiotherapy as a treatment of the advanced, non-small cell lung cancel, applied as a remedy for the symptoms resulting from the growth of a lung tumour: Improvement of the quality of life and long-term survivals were assessed and prognostic factors were analysed. Between 1990 and 1995, 2330 patients with lung cancer attended the Outpatient Clinic of the Maria Sklodowska-Curie Memorial Cancer Center in Warsaw. There were 1948 patients with the non-small cell lung cancer. From this group 832 patients were qualified to palliative radiotherapy that included the primary tumour. The documentation was found for 803 patients and this group was analysed. The group constituted of 115 women (14.3%) and 688 men (85.7%), aged 28 to 91 (mean 61). In the majority of cases a significant advancement of the disease was found: stage III A in 388 patients (48.3%) and stage III B in 358 patients (44.6%). Retrospective analysis of the results of the treatment was carried out. The material contained information on 803 patients. The basis for the analysis was the survival time. It was measured from the starting date of the irradiation to the date of death or the date of the last available information that the patient lives. The survival probability was calculated with the Kaplan-Meier method. Multidimensional analysis of the

A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer.

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Ahn, Hee Kyung; Jung, Minkyu; Sym, Sun Jin; Shin, Dong Bok; Kang, Shin Myung; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Cho, Eun Kyung

2014-08-01

Genexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation of paclitaxel that allows higher-dose administration with less hypersensitivity. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients as a first-line treatment. This is a prospective, single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on day 1 and day 8 of a 3-week cycle. Six cycles of chemotherapy were planned unless there was disease progression. The primary endpoint was overall response rate. Forty-three patients received the study drugs with a median of 4 cycles per patient (range 1-6). The overall response rate was 46.5%. The median progression-free survival was 4.0 months (95% CI 2.0-6.0 months), and median overall survival was 14.8 months (95% CI 9.1-20.5 months). The most common toxicities were anemia (n = 29, 67%), asthenia (n = 17, 40%), myalgia (n = 16, 37%), peripheral neuropathy (n = 15, 35 %), and diarrhea (n = 12, 30%). The most common grade 3/4 adverse events were neutropenia (n = 7, 16%) and pneumonia (n = 5, 12%). Two patients died of pneumonia and dyspnea. CrEL-free paclitaxel in combination with gemcitabine demonstrated favorable antitumor activity with little emetogenicities in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities were observed, and safety should be evaluated thoroughly in future studies.

Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

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Bersanelli, Melissa, E-mail: melissa.bersanelli@alice.it; Buti, Sebastiano; Camisa, Roberta [Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy); Brighenti, Matteo; Lazzarelli, Silvia [Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona (Italy); Mazza, Giancarlo [Radiology Division, Spedali Civili di Brescia, P.le Spedali Civili,1, 25123 Brescia (Italy); Passalacqua, Rodolfo, E-mail: melissa.bersanelli@alice.it [1Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy)

2014-09-30

The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m{sup 2} (Million International Unit/m{sup 2})twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

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Melissa Bersanelli

2014-09-01

Full Text Available The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group. The other 31 also received subcutaneous IL-2 (GIL-2 group: 1 MIU/m2 (Million International Unit/m2twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%, asthenia/anorexia (6% and diarrhea (7%; patients treated with IL-2 showed grade 2–3 fever (46%, fatigue (21% and arthralgia (13%. In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response and 5.1% (only partial response; a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8 and 4.1 (CI 95% = 2.6–5.7 months; a median overall survival of 20.1 (CI 95% = 5.1–35.1 and 6.9 (CI 95% = 4.9–8.9 months (p = 0.002; and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54 and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60 were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer.

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Nestle, Ursula; De Ruysscher, Dirk; Ricardi, Umberto; Geets, Xavier; Belderbos, Jose; Pöttgen, Christoph; Dziadiuszko, Rafal; Peeters, Stephanie; Lievens, Yolande; Hurkmans, Coen; Slotman, Ben; Ramella, Sara; Faivre-Finn, Corinne; McDonald, Fiona; Manapov, Farkhad; Putora, Paul Martin; LePéchoux, Cécile; Van Houtte, Paul

2018-04-01

Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Exploring hope and healing in patients living with advanced non-small cell lung cancer.

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Eustache, Chloe; Jibb, Emily; Grossman, Mary

2014-09-01

To explore the experience and meaning of hope in relation to the healing process of patients living with stage IIIb or IV non-small cell lung cancer. Interpretative qualitative study design. Peter Brojde Lung Cancer Centre in the Jewish General Hospital in Montreal, Quebec, Canada. 12 English- and French-speaking patients, aged 36-78 years. One 60-90-minute semistructured interview per participant was conducted. An inductive approach to data analysis was taken, involving immersion in the data, coding, classifying, and creating linkages. Four main themes emerged: (a) the morass of shattered hope, (b) tentative steps toward a new hope paradigm, (c) reframing hope within the context of a life-threatening illness, and (d) strengthening the link between hope and wellness. Patients described a process where hope was diminished or lost entirely, regained, and reshaped as they learned to live and grow following their diagnosis. This study adds to the literature by describing the dynamic nature of hope as well as factors facilitating or hindering the hope process. It demonstrates how finding meaning, a structural component of healing, can be used to envision a new hopeful future. This study suggests hope and healing cannot exist in isolation, and highlights the importance of understanding the fluctuating nature of hope in patients with advanced lung cancer to foster it, therefore promoting healing.

Crizotinib for Advanced Non-Small Cell Lung Cancer

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A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

Kanglaite for Treating Advanced Non-small-cell Lung Cancer: A Systematic Review

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Lina ZHU

2009-03-01

Full Text Available Background and objective In the past years, many reports on Kanglaite were publicated in China, researchers across the country. The aim of this study is to review the effectiveness and safety of Kanglaite for treating advanced non-small-cell lung cancer. Methods Authors searched the Cochrane Library, Pubmed, Embase, Cancerlit,CBM, CNKI and VIP. Mannual and additional search were also conducted. All randomized controlled trials/quasi- RCT comparing Kanglaite with other lung cancer treatment were included. Two reviewers independently performed data extraction and appraised the publications using the Juni instrument, disagreements were resolved by consensus. Double data were entered and analyzed by RevMan 4.2 software are by Cochrane Collaboration. Results Sixteen reports wereincluded in the meta-analysis. The quality of 16 studies was low. Pooling data of 5 studies indicated that the effect of Kanglaite+NP (Vinorelbine+Cisplatin was better than NP with RR 1.46, 95% Confidence Interval 1.13 to 1.91. Pooling data of 3 studies of MVP (Mitomycin+Vindsine+ Cisplatin plus Kanglaite indicated that the effect was better with RR 1.84, 95%CI 1.22 to 2.76. Pooling data of 2 studies showed that the effect of GP (Gemcitabine+Cisplatin plus Kanglaite was better than GP with RR 1.63, 95%CI 1.09 to 2.43. Fourteen studies revealed that Kanglaite may reduce the side-effectinduced by regular treatment. Ten studies showed regular treatment plus Kanglaite can stabilite/improve quality of life. Conclusion Kanglaite can enhance clinical effect of regular treatment, reduce side-effect and stabilite/improve quality of life, but the effect of Kanglaite being used in clinical settings needs to be confirmed by further large and multicenter.

{sup 18}F-alfatide PET/CT may predict short-term outcome of concurrent chemoradiotherapy in patients with advanced non-small cell lung cancer

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Luan, Xiaohui [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China); University of Jinan-Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, Jinan (China); Huang, Yong; Sun, Xiaorong; Ma, Li; Teng, Xuepeng; Lu, Hong [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiology, Jinan, Shandong (China); Gao, Song [Jining Infectious Diseases Hospital, Department of Oncology, Jining, Shandong (China); Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China)

2016-12-15

The study aims to investigate the role of {sup 18}F-alfatide positron emission tomography/computed tomography (PET/CT) in predicting the short-term outcome of concurrent chemoradiotherapy (CCRT) in patients with advanced non-small cell lung cancer (NSCLC). Eighteen patients with advanced NSCLC had undergone {sup 18}F-alfatide PET/CT scans before CCRT and PET/CT parameters including maximum and mean standard uptake values (SUV{sub max}/SUV{sub mean}), peak standard uptake values (SUV{sub peak}) and tumor volume (TV{sub PET} and TV{sub CT}) were obtained. The SUV{sub max} of tumor and normal tissues (lung, blood pool and muscle) were measured, and their ratios were denoted as T/NT (T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle}). Statistical methods included the Two-example t test, Wilcoxon rank-sum test, Receiver-operating characteristic (ROC) curve analysis and logistic regression analyses. We found that SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were higher in non-responders than in responders (P = 0.0024, P = 0.016, P < 0.001, P = 0.003, P = 0.004). According to ROC curve analysis, the thresholds of SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were 5.65, 4.46, 7.11, 5.41, and 11.75, respectively. The five parameters had high sensitivity, specificity and accuracy in distinguishing non-responders and responders. Multivariate logistic regression analyses showed that T/NT{sub lung} was an independent predictor of the short-term outcome of CCRT in patients with advanced NSCLC (P = 0.032). {sup 18}F-alfatide PET/CT may be useful in predicting the short-term outcome of CCRT in patients with advanced NSCLC. (orig.)

Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation

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Xiaowen JIANG

2016-04-01

Full Text Available Background and objective Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC treatment. Epithelial growth factor receptor (EGFR tyrosine kinase inhibitor (TKI can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS≥6 months] and analysis of the related risk factors for prognosis. Methods From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. Results The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010, Prior chemotherapy (P=0.001, Eastern Cooperative Oncology Group (ECOG score (P=0.001 were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1% and diarrhea (27 cases, 11.7%. Conclusion Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line.

[Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation].

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Jiang, Xiaowen; Wang, Wenxian; Zhang, Yiping

2016-04-20

Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC) treatment. Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS)≥6 months] and analysis of the related risk factors for prognosis. From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010), Prior chemotherapy (P=0.001), Eastern Cooperative Oncology Group (ECOG) score (P=0.001) were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1%) and diarrhea (27 cases, 11.7%). Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line. 
.

Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

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Shen YW

2016-02-01

Full Text Available Yan-Wei Shen,* Xiao-Man Zhang,* Shu-Ting Li, Meng Lv, Jiao Yang, Fan Wang, Zhe-Ling Chen, Bi-Yuan Wang, Pan Li, Ling Chen, Jin Yang Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background and objective: Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation.Patients and methods: Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1.Results: Among the 35 patients, the tumor objective response rate (ORR and disease control rate were 62.9% (22/35 and 88.6% (31/35, respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months, and median overall survival was 21.0 months (95% CI: 20.1–21.9 months. The most common drug-related toxicities were rashes (eleven patients and diarrhea (nine patients, but these were generally manageable and reversible.Conclusion: Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. Keywords: lung neoplasms, icotinib hydrochloride, first-line treatment

ERCC1 protein as a guide for individualized therapy of late-stage advanced non-small cell lung cancer.

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Gao, Zhiqiang; Han, Baohui; Shen, Jie; Gu, Aiqin; Qi, Dajiang; Huang, Jinsu; Shi, Chunlei; Xiong, Liwen; Zhao, Yizhuo; Jiang, Liyan; Wang, Huimin; Chen, Yurong

2011-09-01

Excision repair cross-complementation group 1 (ERCC1) protein has been associated with cisplatin resistance. The objective of this study was to investigate the correlation between ERCC1 protein levels and the therapeutic effect of individualized therapy in advanced non-small cell lung cancer (NSCLC). A total of 190 advanced NSCLC patients were included in this study. Patients were randomized into either the individualized therapy group or the standard therapy group at a ratio of 2:1. Patients in the standard therapy group were treated with either gemcitabine plus cisplatin or vinorelbine plus cisplatin. The expression of ERCC1 protein in lung cancer tissues of patients from the individualized therapy group was detected with immunohistochemistry. Patients with low ERCC1 levels received either gemcitabine plus cisplatin or vinorelbine plus cisplatin, and patients with high levels received gemcitabine plus vinorelbine. The main outcome assessments were response rate (RR), overall survival (OS) and time to progression (TTP). Follow-up data were recorded until September 30, 2010. RR, 1-year survival rate and TTP were not statistically significant. The median survival time was 10.10 months in the standard therapy group (95% CI 8.48-11.92) and 13.59 months in the individualized therapy group (95% CI 11.86-14.74). The difference in median survival time was significantly different between these groups (P=0.036). The median survival time was longer in the individualized group compared to the standard therapy group. ERCC1 protein expression in advanced NSCLC patients, however, was not significantly correlated with RR, OS and TTP in the individualized therapy group. Therefore, this study suggests that ERCC1 protein levels should be assessed in combination with additional biomarkers to determine an optimal index for individualized therapy in advanced NSCLC patients.

A single-arm, multicenter, safety-monitoring, phase IV study of icotinib in treating advanced non-small cell lung cancer (NSCLC).

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Hu, Xingsheng; Han, Baohui; Gu, Aiqin; Zhang, Yiping; Jiao, Shun Chang; Wang, Chang-Li; He, Jintao; Jia, Xueke; Zhang, Li; Peng, Jiewen; Wu, Meina; Ying, Kejing; Wang, Junye; Ma, Kewei; Zhang, Shucai; You, Changxuan; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2014-11-01

The phase 3 ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients, and this led to the approval of icotinib for NSCLC by the China Food and Drug Administration. A phase 4 study was conducted to assess the safety and efficacy of icotinib in a broad range of patients with advanced NSCLC across China. This study retrospectively analyzed data from unresectable, recurrent, and/or advanced NSCLC patients who received oral icotinib 125 mg three times per day. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR) and disease control rate (DCR), which were investigated overall and in subgroups such as patients with an EGFR mutation and elderly patients. Between August, 2011 and August, 2012, a total of 6087 advanced NSCLC patients were registered in this study, of which 5549 were evaluable for safety and tumor response. The median age was 63 years (range 21-95 years), and 1571 (28.3%) patients were over the age of 70. The majority of patients were non-smokers, and had adenocarcinoma and stage IV disease. The overall incidence of adverse drug reactions (ADRs) of any grade was 31.5%. The most common ADRs included rash (17.4%) and diarrhea (8.5%), and three patients experienced interstitial lung disease (ILD). The ORR and DCR were 30.0% and 80.6%, respectively, for the overall population, and 33.4% and 81.2%, 30.3% and 80.3%, and 30.4% and 89.3%, for first-line, second-line, and third-line or multiple line subsets, respectively. In 665 EGFR-mutated patients who were evaluable for tumor response, the ORR and DCR were 49.2% (327/665) and 92.3% (614/665), respectively. The data from over 6000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated a favorable toxicity profile and efficacy in the routine clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

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Mattsson, Johanna S. M.; Brunnström, Hans; Jabs, Verena; Edlund, Karolina; Jirström, Karin; Mindus, Stephanie; Fleur, Linnéa la; Pontén, Fredrik; Karlsson, Mats G.; Karlsson, Christina; Koyi, Hirsh; Brandén, Eva; Botling, Johan; Helenius, Gisela; Micke, Patrick; Svensson, Maria A.

2016-01-01

Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data. ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients. ALK rearrangements were detected in 1.7 % in the complete cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %) tumors showed high ALK gene expression (≥ 6 AU) and of them only three were positive by either FISH or IHC. The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC. The online version of this article (doi:10.1186/s12885-016-2646-x) contains

Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

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Zhang, Wenxiong; Wei, Yiping; Yu, Dongliang; Xu, Jianjun; Peng, Jinhua

2018-04-01

The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed. Forty studies comprising 9376 participants were included. The results suggested that gefitinib and erlotinib are effective for advanced NSCLC with comparable PFS (95% confidence intervals [CI]: 0.98-1.11, P = .15), OS (95% CI: 0.93-1.19, P = .45), ORR (95% CI: 0.99-1.16, P = .07), and DCR (95% CI: 0.92-1.03, P = .35). For erlotinib, dose reduction was significantly more frequent (95% CI: 0.10-0.57, P = .001) as were grade 3 to 5 AEs (95% CI: 0.36-0.79, P = .002). In the subgroup analysis, the erlotinib group had a significant higher rate and severity of skin rash, nausea/vomiting, fatigue, and stomatitis. Gefitinib was proven to be the better choice for advanced NSCLC, with equal antitumor effectiveness and fewer AEs compared with erlotinib. Further large-scale, well-designed randomized controlled trials are warranted to confirm our validation.

Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

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Yan SUN

2015-06-01

Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

Molecular profiling in Italian patients with advanced non-small-cell lung cancer: An observational prospective study.

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Gobbini, Elisa; Galetta, Domenico; Tiseo, Marcello; Graziano, Paolo; Rossi, Antonio; Bria, Emilio; Di Maio, Massimo; Rossi, Giulio; Gregorc, Vanesa; Riccardi, Ferdinando; Scotti, Vieri; Ceribelli, Anna; Buffoni, Lucio; Delmonte, Angelo; Franchina, Tindara; Migliorino, Maria Rita; Cortinovis, Diego; Pisconti, Salvatore; Bordi, Paola; Catino, Annamaria; Maiello, Evaristo; Arizio, Francesca; Novello, Silvia

2017-09-01

Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015. Information regarding molecular profiling and treatment choices were collected. Description of patients' outcome included overall survival (OS), progression-free survival in first (PFS1) and second-line (PFS2). Among 1787 patients enrolled, 1388 (78%) performed at least one molecular analysis during the history of disease: 76% were tested for EGFR, 53% for ALK, 27% for KRAS, 16% for ROS1, 14% for BRAF, 5% for HER2, 4% for MET and 1% for FGFR. The remaining 399 patients (22.3%) did not receive any molecular test. Among patients receiving at least one molecular analysis, 583 (42%) presented a molecular alteration. Considering EGFR mutated and/or ALK rearranged patients (402), for which target agents were routinely reimbursed at time of study in Italy, the 86% received a personalized treatment as first and/or second line: the 90% (286) of EGFR mutants received an EGFR tyrosine kinase inhibitor, mostly gefitinib (41.1%) or afatinib (36.4%) while 74% (62) of ALK translocated patients received an ALK inhibitor, mostly crizotinib (64%). Median OS was 9.34 months (95% CI 8.62-10.0), median PFS1 was 4.61 months (95%CI 4.31-4.84) and median PFS2 was 2.76 months (95%CI 2.57-3.19). In the Italian clinical practice, routine molecular assessment was largely applied in NSCLC patients, according to national guidelines, but a low level of ALK test was reached. Most of EGFR mutants an ALK rearranged patients received a personalized treatment as first and/or second line. Copyright © 2017 Elsevier

Treatment adherence in concurrent chemoradiation in patients with locally advanced non-small cell lung carcinoma: Results of daily intravenous prehydration

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Uyterlinde, Wilma; Chen, Chun; Nijkamp, Jasper; Obbink, Marieke Groot; Sonke, Jan-Jakob; Belderbos, Jose; Heuvel, Michel van den

2014-01-01

Purpose: To test the hypothesis that daily intravenous pre-hydration decreases renal toxicity and improves chemotherapy adherence in patients receiving daily cisplatin to concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with locally advanced NSCLC were treated between 2008 and August 2012 with daily 6 mg/m 2 cisplatin as a bolus injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since January 2011, the administration of cisplatin was routinely preceded by intravenous pre-hydration with 1 L of natriumchloride 0.9%. Patients were divided in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and glomerular filtration rate (GFR) were assessed twice weekly during treatment. Retrospectively, baseline data, toxicity, treatment adherence and efficacy data were compared. Results: Of the 356 patients 232 NPH patients and 100 PH patients were eligible. Patient-and treatment characteristics compared equally. The median of the maximum decrease in GFR was 24% and 8% for NPH and PH (p < 0.01), respectively. Sixty-nine percent of the patients in the NPH group completed the 24 administrations of cisplatin, as compared to 83% of the PH group (p < 0.01). Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued cisplatin treatment because of renal toxicity. Surprisingly, the incidence of acute esophageal toxicity grade ⩾2 decreased following prehydration: 62% vs. 34% (p < 0.001) for the NPH and PH groups, respectively. The one-year survival was comparable between groups (75% for NPH and 71% for PH). Conclusion: Daily pre-hydration was associated with a reduced rate of both renal and acute esophageal toxicity and an increased chemotherapy adherence in patients receiving daily dose of cisplatin and concurrent radiotherapy for locally advanced NSCLC

Induction chemotherapy combined with three-dimensional conformal radiation therapy for locally advanced non-small cell lung cancer

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Zheng Aiqing; Yu Jinming; Zhao Xianguang; Wang Xuetao; Wei Guangsheng

2005-01-01

Objective: To evaluate the effect and complication of induction chemotherapy combined with three-dimensional conformal radiation therapy (3DCRT) for locally advanced non small cell lung cancer (NSCLC). Methods: Ninety-two such patients were randomized into radiation therapy alone group(RT-, 50 patients) and induction chemotherapy combined radiotherapy group (CMT-, 42 patients). The induction chemotherapy consisted of 2-4 cycles of platinum-based regimen. Results: The overall median survival time was 15 months with 12 months in the RT group and 18 months in the CMT group (P=0.014) respectively. The 1-year overall survival rates were 48.6% and 71.2% in RT and CMT group, respectively (P=0.004). The 2-year survival rates were 20.8% and 37.6% in RT and CMT group, respectively (P=0.041). Treatment was well tolerated and the toxicities were similar in either group. Conclusion: The addition of induction chemotherapy to 3DCRT takes a survival advantage over 3DCRT alone for Stage III NSCLC without increasing toxicities. (authors)

Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer.

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Liu, Hui; Zhang, Tiantuo; Ye, Jin; Li, Hongtao; Huang, Jing; Li, Xiaodong; Wu, Benquan; Huang, Xubing; Hou, Jinghui

2012-10-01

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

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Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

2015-01-01

BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient...

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

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Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

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Ou Guangfei; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Feng Qinfu; Zhou Zongmei; Lv Jima; Liang Jun; Wang Mei; Yin Weibo

2007-01-01

Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

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V. Surmont

2009-01-01

Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

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Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Tao, May Lin; Goodman, Karyn A.; Keating, Nancy L.

2009-01-01

Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

Current and future molecular diagnostics in non-small-cell lung cancer.

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Li, Chun Man; Chu, Wing Ying; Wong, Di Lun; Tsang, Hin Fung; Tsui, Nancy Bo Yin; Chan, Charles Ming Lok; Xue, Vivian Wei Wen; Siu, Parco Ming Fai; Yung, Benjamin Yat Ming; Chan, Lawrence Wing Chi; Wong, Sze Chuen Cesar

2015-01-01

The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

[Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

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Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

2014-04-01

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

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Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

2007-07-01

Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

Gemcitabine, cisplatin, and hyperfractionated accelerated radiotherapy for locally advanced non-small cell lung cancer.

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Zwitter, Matjaz; Kovac, Viljem; Smrdel, Uros; Strojan, Primoz

2006-09-01

Due to potent radiosensitization and potential serious or fatal toxicity, concurrent gemcitabine and irradiation should only be applied within clinical trials. We here present experience from a phase I-II clinical trial for patients with locally advanced non-small cell lung cancer (NSCLC) treated with hyperfractionated accelerated radiotherapy and concurrent low-dose gemcitabine. Eligible patients had locally advanced inoperable NSCLC without pleural effusion, Eastern Cooperative Oncology Group performance status 0-1, were chemotherapy naïve and had no previous radiotherapy to the chest, and had adequate hematopoietic, liver, and kidney function. Routine brain computed tomography was not performed, and positron emission tomography/computed tomography was not available. Treatment consisted of three parts: induction chemotherapy with gemcitabine and cisplatin in standard doses, local treatment with concurrent chemotherapy and radiotherapy, and consolidation chemotherapy. Patients were irradiated with opposed AP-PA and oblique fields, using 2.5-D treatment planning. Although corrections for inhomogeneous tissue were made, volume of total lung receiving > or =20 Gy (V20) could not be determined. The trial started as phase I, aimed to determine the dose-limiting toxicity and maximal tolerated dose (MTD) for concurrent hyperfractionated radiotherapy (1.4 Gy twice daily) and gemcitabine 55 mg/m twice weekly as a radiosensitizer. Phase II of the trial then continued at the level of MTD. Twenty-eight patients with NSCLC, nine patients with stage IIIA, 16 patients with IIIB, and three patients with an inoperable recurrence after previous surgery, entered the trial. The first 12 patients entered Phase I of the trial at the initial level of 42 Gy in 30 fractions in 3 weeks. Dose-limiting toxicity was acute esophagitis; 47.6 Gy in 34 fractions in 3.5 weeks was the MTD for this regimen of concurrent chemotherapy and radiotherapy. In phase II of the trial, this dose was applied

Analysis of Differentially Expressed Proteins in Self-Paired Sera of Advanced Non-small Cell Lung Cancer Patients Responsive to Gefin

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Ying HUANG

2009-07-01

Full Text Available Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR tyrosine kinase inhibitor (TKI targeted therapy in advanced non-small cell lung cancer. Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. All samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1 was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z, 3242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04 were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73 up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation.

Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.

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Pérez, Juan E; Machiavelli, Mario R; Romero, Alberto O; Romero Acuña, Luis A; Domínguez, María E; Fasce, Hebe; Flores Acosta, Luis; Marrone, Nora; Romero Acuña, Juan M; Langhi, Mario J; Amato, Sonia; Bologna, Fabrina; Ortiz, Eduardo H; Leone, Bernardo A; Lacava, Juan A; Vallejo, Carlos T

2002-08-01

A phase II trial was performed to evaluate the efficacy and toxicity of the novel combination of vinorelbine and paclitaxel as first-line chemotherapy in patients with stages IIIB and IV non-small-cell lung cancer. From January 1997 to September 1999, 34 patients (9 stage IIIB and 25 stage IV) received a regimen consisting of the following: vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and 8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after vinorelbine) on day 1. Cycles were repeated every 28 days until progression of disease or unacceptable toxicity development. The median age was 57 years (range 41-70 years); median performance status was 1. Histology was as follows: squamous cell in 24 (71%), large cell in 1 (3%), and adenocarcinoma in 9 (26%). All patients are evaluable for toxicity, whereas 30 are evaluable for response (4 patients refused treatment). Objective response was recorded in 4 of 30 patients (13%, 95% CI 1-25%). No complete response was observed. Partial response was recorded in 4 patients (13%), no change in 10 patients (34%), and progressive disease in 16 patients (53%). The median time to treatment failure was 4 months and median survival was 9 months. The limiting toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity developed in 14 patients (41%) (without G3 or G4 episodes), and constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients), diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7 patients. Vinorelbine-paclitaxel combination showed only modest activity against locoregionally advanced or metastatic NSCLC.

[Prospective randomized study of HMVP, MVP, and HVP regimens in treatment of advanced non-small cell lung cancer].

Science.gov (United States)

Gao, Jian-Fei; Li, Chang-Sheng; Zhang, Bi-Cheng; Du, Guang-Zu; Zhang, Xin-Hua; Wang, Jun; Zhu, Yu-Ze; Ou, Wu-Ling; Yang, Bo

2004-04-01

Non-small cell lung cancer (NSCLC) is hyposensitive to the normal first and second-line chemotherapy regimens. Camptothecin derivative is becoming a hot point in the treatment of advanced NSCLC. The objective of this article was to evaluate the response, toxicity, and survival time of HMVP, MVP, and HVP regimens (detail in below) in the treatment of advanced NSCLC. A total of 134 cases with advanced NSCLC was randomized into three groups: HMVP group [46 patients, hydroxycamptothecin (HCPT) 12 mg/m(2) from d1 to d5, mitomycin C (MMC) 6 mg/m(2) d1, vindesine (VDS) 2.5-3 mg/m(2) d1 and d8, cisplatin (DDP) 50 mg/m(2) d2 and d3], MVP group (44 patients, MMC, VDS and DDP were the same as HMVP group) and HVP group (44 patients, HCPT, VDS, DDP were the same as HMVP group). The response rates were 39.54% (17/43), 35.57% (15/42), and 26.19% (11/42) in HMVP, MVP, and HVP groups, respectively; no significant difference was detected among the three groups (P >0.05). No significant difference was detected in the median time of remission, median survival time, and 1-, 2-year survival rates among the three groups. Moreover, no significant difference was detected in grade III-IV leukopenia, grade III-IV thrombocytopenia, grade III-IV nausea and vomiting and grade III-IV constipation among the three groups. The response rate of MVP regimen is slightly lower than that of HMVP regimen, but HMVP regimen do not show obvious superiority. It may increase toxicities such as leukopenia, nausea/vomiting, and constipation. The response rate of HVP regimen is slightly lower than that of MVP regimen.

Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

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Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

2013-01-01

This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

Directory of Open Access Journals (Sweden)

Giroux Leprieur E

2016-06-01

Full Text Available Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy depends on the phenotype of the progression, the

Utility values associated with advanced or metastatic non-small cell lung cancer: data needs for economic modeling.

Science.gov (United States)

Brown, Jacqueline; Cook, Keziah; Adamski, Kelly; Lau, Jocelyn; Bargo, Danielle; Breen, Sarah; Chawla, Anita

2017-04-01

Cost-effectiveness analyses often inform healthcare reimbursement decisions. The preferred measure of effectiveness is the quality adjusted life year (QALY) gained, where the quality of life adjustment is measured in terms of utility. Areas covered: We assessed the availability and variation of utility values for health states associated with advanced or metastatic non-small cell lung cancer (NSCLC) to identify values appropriate for cost-effectiveness models assessing alternative treatments. Our systematic search of six electronic databases (January 2000 to August 2015) found the current literature to be sparse in terms of utility values associated with NSCLC, identifying 27 studies. Utility values were most frequently reported over time and by treatment type, and less frequently by disease response, stage of disease, adverse events or disease comorbidities. Expert commentary: In response to rising healthcare costs, payers increasingly consider the cost-effectiveness of novel treatments in reimbursement decisions, especially in oncology. As the number of therapies available to treat NSCLC increases, cost-effectiveness analyses will play a key role in reimbursement decisions in this area. Quantifying the relationship between health and quality of life for NSCLC patients via utility values is an important component of assessing the cost effectiveness of novel treatments.

Recent advances in developing small molecules targeting RNA.

Science.gov (United States)

Guan, Lirui; Disney, Matthew D

2012-01-20

RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

Science.gov (United States)

Chen, H; Wang, H P; Zhang, L; Si, X Y

2017-01-01

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

Science.gov (United States)

Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

2015-07-01

Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence

Advanced Small Modular Reactor Economics Status Report

Energy Technology Data Exchange (ETDEWEB)

Harrison, Thomas J [ORNL

2014-10-01

This report describes the data collection work performed for an advanced small modular reactor (AdvSMR) economics analysis activity at the Oak Ridge National Laboratory. The methodology development and analytical results are described in separate, stand-alone documents as listed in the references. The economics analysis effort for the AdvSMR program combines the technical and fuel cycle aspects of advanced (non-light water reactor [LWR]) reactors with the market and production aspects of SMRs. This requires the collection, analysis, and synthesis of multiple unrelated and potentially high-uncertainty data sets from a wide range of data sources. Further, the nature of both economic and nuclear technology analysis requires at least a minor attempt at prediction and prognostication, and the far-term horizon for deployment of advanced nuclear systems introduces more uncertainty. Energy market uncertainty, especially the electricity market, is the result of the integration of commodity prices, demand fluctuation, and generation competition, as easily seen in deregulated markets. Depending on current or projected values for any of these factors, the economic attractiveness of any power plant construction project can change yearly or quarterly. For long-lead construction projects such as nuclear power plants, this uncertainty generates an implied and inherent risk for potential nuclear power plant owners and operators. The uncertainty in nuclear reactor and fuel cycle costs is in some respects better understood and quantified than the energy market uncertainty. The LWR-based fuel cycle has a long commercial history to use as its basis for cost estimation, and the current activities in LWR construction provide a reliable baseline for estimates for similar efforts. However, for advanced systems, the estimates and their associated uncertainties are based on forward-looking assumptions for performance after the system has been built and has achieved commercial operation

Clinical decision-making and health-related quality of life during first-line and maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC): findings from a real-world setting.

Science.gov (United States)

Sztankay, Monika; Giesinger, Johannes Maria; Zabernigg, August; Krempler, Elisabeth; Pall, Georg; Hilbe, Wolfgang; Burghuber, Otto; Hochmair, Maximilian; Rumpold, Gerhard; Doering, Stephan; Holzner, Bernhard

2017-08-23

Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT. Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients' and physicians' reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models. Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p loss (p = 0.043), constipation (p = 0.017) and chest pain (p = 0.022), and a deterioration in emotional functioning (p = 0.023) and cognitive functioning (p = 0.044) during MT. Our results indicate that HRQOL and symptom burden improve between first-line treatment to MT in some respects, although some late toxicity persists. Discrepancies between patients' and physicians

Advances of Drug Resistance Marker of Gemcitabine for Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Baorui LIU

2011-05-01

Full Text Available With the development of pharmacogenomics and pharmacogenetics, personal therapy based on genes has become one of the most effective ways to enhance chemotherapeutic effect on non-small cell lung cancer (NSCLC patients. Much attention has been paid to validate the predictive biomarkers of chemotherapy in order to guide chemotherapy and enhance effect in general. Gemcitabine is one of the common agents treating NSCLC recently. This review is mainly about the recent reports on potential biomarkers of Gemcitabine in tailored therapy of NSCLC.

Preserving Functional Lung Using Perfusion Imaging and Intensity-Modulated Radiation Therapy for Advanced-Stage Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Shioyama, Yoshiyuki; Jang, Si Young; Liu, H. Helen; Guerrero, Thomas; Wang, Xuanmin; Gayed, Isis W.; Erwin, William D.; Liao, Zhongxing; Chang, Joe Y.; Jeter, Melenda; Yaremko, Brian P.; Borghero, Yerko O.; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

2007-01-01

Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients

Preliminary Study for Conceptual Design of Advanced Long Life Small Modular Fast Reactor

Energy Technology Data Exchange (ETDEWEB)

Tak, Taewoo; Choe, Jiwon; Jeong, Yongjin; Lee, Deokjung [Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of); Kim, T. K. [Argonne National Laboratory, Argonne (United States)

2015-05-15

As one of the non-water coolant Small-Modular Reactor (SMR) core concepts for use in the mid- to long-term, ANL has proposed a 100 MWe Advanced sodium-cooled Fast Reactor core concept (AFR-100) targeting a small grid, transportable from pre-licensed factories to the remote plant site for affordable supply. Various breed-and-burn core concepts have been proposed to extend the reactor cycle length, which includes CANDLE with a cigar-type depletion strategy, TerraPower reactors with fuel shuffling for effective breeding, et al. UNIST has also proposed an ultra-long cycle fast reactor (UCFR) core concept having the power rating of 1000 MWe. By adopting the breed-and-burn strategies, the UCFR core can maintain criticality for a targeting reactor lifetime of 60 years without refueling. The objective of this project is to develop an advanced long-life SMR core concept by adopting both the small modular design features of the AFR-100 and the long-life breed-and-burn concept of the UCFR. A conceptual design of long life small modular fast reactor is under development by adopting both the small modular design features of the AFR-100 and the long-life breed-and-burn concept of the UCFR. The feasibility of the long-life fast reactor concepts was reviewed to obtain the core design guidelines and the reactor design requirements of long life small modular fast reactor were proposed in this study.

Gender, histology, and time of diagnosis are important factors for prognosis: analysis of 1499 never-smokers with advanced non-small cell lung cancer in Japan.

Science.gov (United States)

Kawaguchi, Tomoya; Takada, Minoru; Kubo, Akihito; Matsumura, Akihide; Fukai, Shimao; Tamura, Atsuhisa; Saito, Ryusei; Kawahara, Masaaki; Maruyama, Yosihito

2010-07-01

There has been a growing interest in lung cancer in never-smokers. Utilizing a database from the National Hospital Study Group for Lung Cancer, information for never-smokers and ever-smokers with advanced non-small cell lung cancer was obtained from 1990 to 2005, including clinicopathologic characteristics, chemotherapy response, and survival data. Time of diagnosis was classified into two periods: 1990-1999 and 2000-2005. Multivariate analysis was performed using the Cox regression and logistic regression method, including gender, age, performance status, histology, stage, and period of diagnosis. There were 1499 never-smokers and 3455 ever-smokers with advanced stage IIIB and IV diseases who received cytotoxic chemotherapy. Never-smokers generally included more females, were younger, with better performance status and more adenocarcinoma diagnosed (p time of diagnosis are important factors for prognosis in these patients.

Consciousness in humans and non-human animals: recent advances and future directions.

Science.gov (United States)

Boly, Melanie; Seth, Anil K; Wilke, Melanie; Ingmundson, Paul; Baars, Bernard; Laureys, Steven; Edelman, David B; Tsuchiya, Naotsugu

2013-10-31

This joint article reflects the authors' personal views regarding noteworthy advances in the neuroscience of consciousness in the last 10 years, and suggests what we feel may be promising future directions. It is based on a small conference at the Samoset Resort in Rockport, Maine, USA, in July of 2012, organized by the Mind Science Foundation of San Antonio, Texas. Here, we summarize recent advances in our understanding of subjectivity in humans and other animals, including empirical, applied, technical, and conceptual insights. These include the evidence for the importance of fronto-parietal connectivity and of "top-down" processes, both of which enable information to travel across distant cortical areas effectively, as well as numerous dissociations between consciousness and cognitive functions, such as attention, in humans. In addition, we describe the development of mental imagery paradigms, which made it possible to identify covert awareness in non-responsive subjects. Non-human animal consciousness research has also witnessed substantial advances on the specific role of cortical areas and higher order thalamus for consciousness, thanks to important technological enhancements. In addition, much progress has been made in the understanding of non-vertebrate cognition relevant to possible conscious states. Finally, major advances have been made in theories of consciousness, and also in their comparison with the available evidence. Along with reviewing these findings, each author suggests future avenues for research in their field of investigation.

Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Su Zi; Oh, So Won; Kim, Jin Soo; Kim, Ki Hwan; Kim, Yu Kyeong [SMG-Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

2014-12-15

To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT.One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean > or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

International Nuclear Information System (INIS)

Manapov, Farkhad; Roengvoraphoj, Olarn; Li, Ming Lun; Eze, Chukwuka

2017-01-01

Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] ≤ 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/ CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 ≤ 1 L)

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

Energy Technology Data Exchange (ETDEWEB)

Manapov, Farkhad; Roengvoraphoj, Olarn; Li, Ming Lun; Eze, Chukwuka [Dept. of Radiation Oncology, Ludwig-Maximilian University of Munich, Munich (Germany)

2017-06-15

Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] ≤ 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/ CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 ≤ 1 L)

Non-small-bowel abnormalities identified during small bowel capsule endoscopy

NARCIS (Netherlands)

Hoedemakers, Reinier; Westerhof, Jessie; Weersma, Rinse K.; Koornstra, Jan J.

2014-01-01

AIM: To investigate the incidence of non-small-bowel abnormalities in patients referred for small bowel capsule endoscopy, this single center study was performed. METHODS: Small bowel capsule endoscopy is an accepted technique to investigate obscure gastrointestinal bleeding. This is defined as

Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer.

Science.gov (United States)

Liu, Dongyang; Zhang, Li; Wu, Yiwen; Jiang, Ji; Tan, Fenlai; Wang, Yingxiang; Liu, Yong; Hu, Pei

2015-09-01

To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients with advanced non-small-cell lung cancer (NSCLC). Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated. Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154 (17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by ∼30%. Mean t1/2β was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients. Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

Science.gov (United States)

Lee, Dae Ho; Isobe, Hiroshi; Wirtz, Hubert; Aleixo, Sabina Bandeira; Parente, Phillip; de Marinis, Filippo; Huang, Min; Arunachalam, Ashwini; Kothari, Smita; Cao, Xiting; Donnini, Nello; Woodgate, Ann-Marie; de Castro, Javier

2018-03-01

Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC. This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC. The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries

SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

Directory of Open Access Journals (Sweden)

Deyan N. Davidov

2013-04-01

Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

The emerging role of ALK inhibitors in the treatment of advanced non-small cell lung cancer.

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Galetta, Domenico; Rossi, Antonio; Pisconti, Salvatore; Colucci, Giuseppe

2012-04-01

Most NSCLC patients are diagnosed in the advanced stage of the disease. Recently, chemotherapeutic agents have reached a plateau of effectiveness. Increased understanding of cancer biology has revealed several potential therapeutic strategies that have led to marketing of new biologic agents. The echinoderm microtubule-associated protein like-4-anaplastic lymphoma kinase (EML4-ALK) fusion oncogene represents one of the newest molecular targets in NSCLC, identifying a subset of NSCLC patients characterized by distinct clinicopathological features. The available results concerning ALK inhibitors for the treatment of advanced NSCLC patients. An electronic search was used to retrieve the articles addressing this topic. In a pivotal Phase I clinical trial, crizotinib (PF-02341066), a small-molecule ALK inhibitor, demonstrated impressive antitumor activity in the majority of NSCLC patients with ALK fusions. Phase III randomized trials investigating crizotinib in this subgroup of patients are ongoing. If the results from these large international trials confirm the efficacy of crizotinib in the subset of patients, the next few years could see the treatment of advanced NSCLC patients with ALK fusions. Specific inhibitors would realize the so called personalized medicine in subsets of this disease.

Identification of risk groups in patients with completely resected N1 non-small cell lung carcinoma

International Nuclear Information System (INIS)

Sawyer, T.E.; Bonner, J.A.; Gould, P.J.; Foote, R.L.; Deschamps, C.; Trastek, V.F.; Pairolero, P.C.; Allen, M.S.; Lange, C. M.; Li, H.

1997-01-01

Purpose: Although the potential benefits of radiation therapy and chemotherapy in the management of completely resected AJCC N1 non-small cell lung cancer are unknown, the majority of studies have failed to demonstrate a survival benefit with any neoadjuvant or adjuvant therapy. While it is possible that radiation therapy and chemotherapy are ineffective adjunctive therapies in this disease, it is also possible that previous studies have been diluted by the inclusion of patients at low risk for local recurrence and/or distant metastasis and therefore, this study was undertaken to assess these risks. Methods: From 1987 through 1990, 107 patients underwent complete resection of AJCC N1 non-small cell lung carcinoma and received no other treatment. These patients were the subject of a retrospective review to separate patients into high-, medium-, and low-risk groups with respect to freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival (OS) utilizing a regression analysis of Cox and a regression tree analysis (Breiman LI et al, Wadsworth International Group, Belmont, CA 1984). Results: The 5-year rates of FFLR, FFDM, and OS were 62%, 53%, and 32% respectively. The following factors were assessed for potential relationships with FFLR, FFDM, and OS: status of the pre-operative bronchoscopy, type of surgery performed (segmentectomy/wedge resection vs. lobectomy vs. bilobectomy/pneumonectomy), number of involved N1 nodes, number of involved N1 stations, number of N1 nodes removed, number of N2 nodes removed, number of lung lobes involved, tumor grade, tumor histology (squamous vs non-squamous), AJCC T-stage, pathologic tumor size, and pathologic margin status. Regression analyses revealed that the factors independently associated with an improved outcome included a positive bronchoscopy (FFLR, p=.005), a greater number of N1 nodes dissected (FFDM, p=.02), and a lesser T-stage (OS, p=.01). Regression tree analyses were then

Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value.

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Srdic, Drazena; Plestina, Sanja; Sverko-Peternac, Ana; Nikolac, Nora; Simundic, Ana-Maria; Samarzija, Miroslav

2016-11-01

Cancer cachexia and sarcopenia are frequently observed in cancer patients and associated with poor survival. The majority of studies of cancer cachexia and sarcopenia have been done in patients with solid tumors of different origins, and there are currently no good predictors of the benefit of chemotherapy or factors that predict survival in advanced cancer. The purpose of our prospective study was to evaluate prevalence of cachexia and sarcopenia using international consensus definition and criteria for diagnosis in patients with diagnosed advanced non-small cell lung cancer (NSCLC) stage IIIB and IV and their relation to chemotherapy toxicity and survival prediction. A secondary aim was to compare several biochemical markers (CRP, IL-6, protein, and albumin) with time to tumor progression in order to assess prognostic value or to guide a treatment. Between December 2013 and April 2015, the prospective cohort study of 100 Caucasian patients with advanced NSCLC stage IIIB or IV, who were referred consecutively to Department for Respiratory Diseases "Jordanovac," was evaluated. Anthropometric measurements and biochemical data (CRP, albumin, protein, IL-6, haemoglobin) together with body composition measurements (total muscle cross-sectional area, lumbar skeletal muscle index) were obtained for each patient before starting with platinum-doublet therapy. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment and time-to-tumor progression was determined prospectively. One hundred patients with advanced lung cancer were recruited: 67 were male and median age was 64 years. The median time to disease progression was 187 days. The prevalence of cachexia and sarcopenia in study cohort was 69 and 47 %, respectively. CRP, IL-6, and albumin concentration in cachectic compared to non-cachectic patients

Efficacy and safety of iodine-125 radioactive seeds brachytherapy for advanced non-small cell lung cancer-A meta-analysis.

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Zhang, Wenchao; Li, Jiawei; Li, Ran; Zhang, Ying; Han, Mingyong; Ma, Wei

This meta-analysis was conducted to investigate the efficacy and safety of 125 I brachytherapy for locally advanced non-small cell lung cancer (NSCLC). Trials comparing 125 I brachytherapy with chemotherapy in NSCLC were identified. Meta-analysis was performed to obtain pooled risk ratios for an overall response rate (ORR), disease control rate (DCR) and complications, and pooled hazard ratio for overall survival (OS). Fifteen studies including 1188 cases were included. The pooled result indicated that there were significant differences in ORR, DCR, and OS between 125 I brachytherapy combined with chemotherapy and chemotherapy alone, but no statistic differences in gastrointestinal symptoms, leukopenia, myelosuppression, and hemoglobin reduction. Patients treated with 125 I brachytherapy combined with chemotherapy have a higher relative risk of pneumothorax, bloody sputum, and pneumorrhagia compared with chemotherapy alone. Seeds migration only occurred in the group treated with 125 I brachytherapy. There were significant differences in ORR, DCR, and myelosuppression between 125 I brachytherapy alone and chemotherapy. 125 I brachytherapy combined with chemotherapy can significantly enhance the clinical efficacy and improve the OS of patients with advanced NSCLC without increasing the incidence of complications of chemotherapy. 125 I brachytherapy alone can significantly enhance the clinical efficacy and reduce the incidence of myelosuppression compared with chemotherapy. However, 125 I brachytherapy may cause lung injury. Large sample and higher-quality randomized controlled trials are needed to confirm the pooled results of complications. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Randomized Study of Concurrent Carboplatin, Paclitaxel, and Radiotherapy with or Without Prior Induction Chemotherapy in Patients with Locally Advanced Non-Small Cell Lung Cancer

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Gouda, Y.S.; Eldeeb, N.A.; Omar, A.M.; Kohail, H.M.; El-Geneidy, M.M.; Elkerm, Y.M.

2006-01-01

Background: Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy. Materials and Methods: In this trial 50 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m 2 ) and carboplatin (AUC 6) on day I and 28 th followed by concomitant paclitaxel (45 mg/m 2 ) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation. Results: A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagi tis was significantly higher in group A and B than in group C (ρ=0.023). Hematological toxicities was also significantly higher in group A and B than in group C (ρ=0.003). The response rate was significantly higher in group A and B than in group C (75%,79%, and 40% respectively) (ρ =0.020). The time to in-field progresion was significantly

Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

NARCIS (Netherlands)

A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

1994-01-01

textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

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Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

2016-01-01

Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

Is Huachansu Beneficial in Treating Advanced Non-Small-Cell Lung Cancer? Evidence from a Meta-Analysis of Its Efficacy Combined with Chemotherapy

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Bingduo Zhou

2015-01-01

Full Text Available Background. Huachansu, the sterilized water extract of Bufo bufo gargarizans toad skin, is used in China to alleviate the side-effects and enhance the therapeutic effect of chemotherapy in advanced non-small-cell lung cancer (NSCLC. We conducted a meta-analysis to assess Huachansu’s efficacy. Methods. We extensively searched electronic databases (CENTRAL, EMBASE, MEDLINE, CBM, Cochrane Library, CNKI, CEBM, WFDP, CSCD, CSTD, and IPA for randomized controlled trials containing Huachansu plus chemotherapy as the test group and chemotherapy as the control group. Seventeen trials were selected based on the selection criteria. The pooled relative ratio (RR of indicators with 95% confidence interval (95% CI was calculated for efficacy evaluation. Results. The meta-analysis demonstrated a statistically significant improvement in objective tumor response, one-year survival, Karnofsky performance status, pain relief, and alleviation of severe side-effects (nausea and vomiting, leukocytopenia in the test group as compared to the control group, but no significant difference in thrombocytopenia. Conclusions. This study demonstrated the efficacy of Huachansu combined with chemotherapy in the treatment of advanced NSCLC. However, limitations exist and high-quality trials are needed for further verification.

Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop

DEFF Research Database (Denmark)

Pirker, Robert; Herth, Felix J F; Kerr, Keith M

2010-01-01

Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR tyros...

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

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Rothschild SI

2014-09-01

Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

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Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

2012-12-15

Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

Development of Advanced Small Hydrogen Engines

Energy Technology Data Exchange (ETDEWEB)

Sapru, Krishna; Tan, Zhaosheng; Chao, Ben

2010-09-30

The main objective of the project is to develop advanced, low cost conversions of small (< 25 hp) gasoline internal combustion engines (ICEs) to run on hydrogen fuel while maintaining the same performance and durability. This final technical report summarizes the results of i) the details of the conversion of several small gasoline ICEs to run on hydrogen, ii) the durability test of a converted hydrogen engine and iii) the demonstration of a prototype bundled canister solid hydrogen storage system. Peak power of the hydrogen engine achieves 60% of the power output of the gasoline counterpart. The efforts to boost the engine power with various options including installing the over-sized turbocharger, retrofit of custom-made pistons with high compression ratio, an advanced ignition system, and various types of fuel injection systems are not realized. A converted Honda GC160 engine with ACS system to run with hydrogen fuel is successful. Total accumulative runtime is 785 hours. A prototype bundled canister solid hydrogen storage system having nominal capacity of 1.2 kg is designed, constructed and demonstrated. It is capable of supporting a wide range of output load of a hydrogen generator.

125I brachytherapy of locally advanced non-small-cell lung cancer after one cycle of first-line chemotherapy：a comparison with best supportive care

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Song J

2017-03-01

Full Text Available Jingjing Song* Xiaoxi Fan* Zhongwei Zhao* Minjiang Chen* Weiqian Chen, Fazong Wu, Dengke Zhang, Li Chen, Jianfei Tu, Jiansong Ji Department of Interventional Radiology, Zhejiang University Lishui Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, People’s Republic of China *These authors have contributed equally to this work Objectives: The objective of this study was to assess the efficacy of computed tomography (CT-guided 125I brachytherapy alone in improving the survival and quality of life of patients with unresectable locally advanced non-small-cell lung cancer (NSCLC after one cycle of first-line chemotherapy.Patients and methods: Sixteen patients with locally advanced NSCLC were treated with CT-guided 125I brachytherapy after one cycle of first-line chemotherapy (group A. Sixteen patients who received only best supportive care (group B were matched up with the patients in group A. Primary end point included survival, and secondary end point included assessment of safety, effectiveness of CT-guided 125I brachytherapy, and improvement in the quality of life.Results: The two groups were well balanced in terms of age, disease histology, tumor stage, tumor location, and performance status (P>0.05. The median follow-up time was 16 months (range, 3–30. The total tumor response rate was 75.0% in group A, which was significantly higher than that in group B (0.0% (P<0.01. The median progression-free survival time was 4.80 months for patients in group A and 1.35 months for patients in group B (P<0.001. Kaplan–Meier survival analysis showed that the median survival time of group A was 9.4±0.3 months versus 8.4±0.1 months in group B (P=0.013. Tumor-related symptoms of patients were significantly relieved, and the quality of life was markedly improved in group A than in group B.Conclusion: CT-guided 125I brachytherapy improved the survival of patients with locally advanced

Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

DEFF Research Database (Denmark)

Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu

2014-01-01

BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

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Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

2015-05-15

Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy.

Science.gov (United States)

Shao, Lan; Zhang, Beibei; He, Chunxiao; Lin, Baochai; Song, Zhengbo; Lou, Guangyuan; Yu, Xinmin; Zhang, Yiping

2014-01-01

The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients. The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model. The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity. Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Exploration of small RNA-seq data for small non-coding RNAs in Human Colorectal Cancer.

Science.gov (United States)

Koduru, Srinivas V; Tiwari, Amit K; Hazard, Sprague W; Mahajan, Milind; Ravnic, Dino J

2017-01-01

Background: Improved healthcare and recent breakthroughs in technology have substantially reduced cancer mortality rates worldwide. Recent advancements in next-generation sequencing (NGS) have allowed genomic analysis of the human transcriptome. Now, using NGS we can further look into small non-coding regions of RNAs (sncRNAs) such as microRNAs (miRNAs), Piwi-interacting-RNAs (piRNAs), long non-coding RNAs (lncRNAs), and small nuclear/nucleolar RNAs (sn/snoRNAs) among others. Recent studies looking at sncRNAs indicate their role in important biological processes such as cancer progression and predict their role as biomarkers for disease diagnosis, prognosis, and therapy. Results: In the present study, we data mined publically available small RNA sequencing data from colorectal tissue samples of eight matched patients (benign, tumor, and metastasis) and remapped the data for various small RNA annotations. We identified aberrant expression of 13 miRNAs in tumor and metastasis specimens [tumor vs benign group (19 miRNAs) and metastasis vs benign group (38 miRNAs)] of which five were upregulated, and eight were downregulated, during disease progression. Pathway analysis of aberrantly expressed miRNAs showed that the majority of miRNAs involved in colon cancer were also involved in other cancers. Analysis of piRNAs revealed six to be over-expressed in the tumor vs benign cohort and 24 in the metastasis vs benign group. Only two piRNAs were shared between the two cohorts. Examining other types of small RNAs [sn/snoRNAs, mt_rRNA, miscRNA, nonsense mediated decay (NMD), and rRNAs] identified 15 sncRNAs in the tumor vs benign group and 104 in the metastasis vs benign group, with only four others being commonly expressed. Conclusion: In summary, our comprehensive analysis on publicly available small RNA-seq data identified multiple differentially expressed sncRNAs during colorectal cancer progression at different stages compared to normal colon tissue. We speculate that

Combination of bronchial artery infusion chemotherapy and radiation therapy for locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Li Shuping; Cai Yuecheng; Wang Xiangming; Luo Jianyun; Lian Yingni; Ouyang Mingxin

2004-01-01

Objective: To compare the efficacy between bronchial artery infusion (BAI) chemotherapy plus radiation therapy and systemic chemotherapy plus radiation for locally advanced non-small cell lung cancer (NSCLC). Methods: One hundred and twenty-one patients with stage III NSCLC were randomized into treatment group (58 cases) and control group (63 cases). In the treatment group, all patients were administered with BAI for 2-3 sessions, followed by irradiation 4-7 days after BAI. In the control group, altogether 4-6 cycles of standard systemic chemotherapy were given. Radiation was delivered alternately between the cycles of chemotherapy. Results: The short-term, long-term survival, median response duration and median survival time were similar between the two groups, except patients with stage IIIb who had a higher distant metastasis rate in the treatment group. The major side effects of chemotherapy and radiotherapy were hematological, gastrointestinal toxicities, pneumonitis, mediastinitis, and esophagitis, respectively. The side effects were milder, better tolerated and did not influence the regimen schedule in the treatment group, as compared with the control group. Seven patients withdrew from the control group, and in 28 patients, the scheduled chemotherapy and radiation was delayed or canceled. Conclusions: Bronchial artery infusion plus radiation is more advantageous over systemic chemotherapy plus radiation in less toxicities, better compliance, shorter treatment courses and more cost-effectiveness

Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature.

Science.gov (United States)

Singh, Navneet; Jindal, Aditya; Behera, Digambar

2014-12-10

Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.

The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

Directory of Open Access Journals (Sweden)

Xingsheng Hu

Full Text Available Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC previously treated with platinum-based chemotherapy.Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety.From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m and 5.4 months (95%CI 3.1-7.9 m, respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127, diarrhea (12.6%, 16/127 and elevation of transaminase (15.7%, 20/127.In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy.ClinicalTrials.gov NCT02486354.

The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

Science.gov (United States)

Hu, Xingsheng; Zhang, Li; Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2015-01-01

Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. ClinicalTrials.gov NCT02486354.

Validation of Interobserver Agreement in Lung Cancer Assessment: Hematoxylin-Eosin Diagnostic Reproducibility for Non–Small Cell Lung Cancer

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Grilley-Olson, Juneko E.; Hayes, D. Neil; Moore, Dominic T.; Leslie, Kevin O.; Wilkerson, Matthew D.; Qaqish, Bahjat F.; Hayward, Michele C.; Cabanski, Christopher R.; Yin, Xiaoying; Socinski, Mark A.; Stinchcombe, Thomas E.; Thorne, Leigh B.; Allen, Timothy Craig; Banks, Peter M.; Beasley, Mary B.; Borczuk, Alain C.; Cagle, Philip T.; Christensen, Rebecca; Colby, Thomas V.; Deblois, Georgean G.; Elmberger, Göran; Graziano, Paolo; Hart, Craig F.; Jones, Kirk D.; Maia, Diane M.; Miller, C. Ryan; Nance, Keith V.; Travis, William D.; Funkhouser, William K.

2018-01-01

Context Precise subtype diagnosis of non–small cell lung carcinoma is increasingly relevant, based on the availability of subtype-specific therapies, such as bevacizumab and pemetrexed, and based on the subtype-specific prevalence of activating epidermal growth factor receptor mutations. Objectives To establish a baseline measure of inter-observer reproducibility for non–small cell lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health Organization classification, to estimate interobserver reproducibility for the therapeutically relevant squamous/nonsquamous subsets, and to examine characteristics that improve interobserver reproducibility. Design Primary, resected lung cancer specimens were converted to digital (virtual) slides. Based on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a diagnosis using the 2004 World Health Organization classification. Kappa statistics were calculated for each pathologist-pair for each slide and were summarized by classification scheme, pulmonary pathology expertise, diagnostic confidence, and neoplastic grade. Results The 12 pulmonary pathology experts and the 12 community pathologists each independently diagnosed 48 to 96 single hematoxylin-eosin digital slides derived from 96 cases of non–small cell lung carcinoma resection. Overall agreement improved with simplification from the comprehensive 44 World Health Organization diagnoses (κ = 0.25) to their 10 major header subtypes (κ = 0.48) and improved again with simplification into the therapeutically relevant squamous/nonsquamous dichotomy (κ = 0.55). Multivariate analysis showed that higher diagnostic agreement was associated with better differentiation, better slide quality, higher diagnostic confidence, similar years of pathology experience, and pulmonary pathology expertise. Conclusions These data define the baseline diagnostic agreement for hematoxylin-eosin diagnosis of non–small cell lung carcinoma

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

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Treat Joseph

2011-02-01

Full Text Available Abstract Background This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week pemetrexed given concurrently with radiotherapy (XRT for locally advanced and oligometastatic non-small cell lung cancer (NSCLC. Methods Eligible patients had Stage III or IV (oligometastatic NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6 during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1 of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT in dose level 1, an amended dose level (level 1A continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6 and pemetrexed (500 mg/m2 q3 weeks × 2 -3 cycles. Results Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis. There was one DLT (grade 5 pneumonitis in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease, the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated in stage III patients. Conclusions Concurrent carboplatin with dose-dense (q2week pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC. Trial Registration ClinicalTrials.gov NCT00330044

THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

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Deyan Davidov

2014-12-01

Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

International Nuclear Information System (INIS)

Zhu, Jun; Li, Te; Wang, Xiaohui; Ye, Ming; Cai, Jian; Xu, Yuejuan; Wu, Bin

2013-01-01

Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated. After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option

Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

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Zhu Jun

2013-01-01

Full Text Available Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER at a willingness-to-pay (WTP threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP was evaluated. Results After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP. The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. Conclusions These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy

International Nuclear Information System (INIS)

Trinkaus, Mateya E.; Rischin, Danny; Blum, Rob

2013-01-01

For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ( 18 F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent 18 F-FAZA PET scans and 18 F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment 18 F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P=0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P=0.38). Eight patients with baseline hypoxia had post treatment 18 F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P=0.42). Intra-lesional hypoxia, as detected by 18 F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

Radiation-induced esophagitis in local advanced non-small cell lung cancer after three-dimensional conformal radiotherapy

International Nuclear Information System (INIS)

Tian Dandan; Wang Yuxiang; Qiu Rong; Zhu Shuchai; Tian Xiuming; Qiao Xueying

2014-01-01

Objective: To explore radiation-induced esophagitis and its related factors in the patients with local advanced non-small cell lung cancer (NSCLC) which were treated with three-dimensional conformal radiation therapy (3D-CRT). Methods: From January 2001 to December 2008, 203 patients who suffered from stage Ⅲ NSCLC were achieved, including 163 males and 40 females, with a median age of 63 years old, while 79 cases were in stage Ⅲ_a and 124 in stage Ⅲ_b. The equivalent median dose of tumor was 62 Gy(range of 50-78 Gy). Among them, 74 cases were administered with radiotherapy alone, 45 with sequential radiotherapy and chemotherapy, 87 cases with concurrent radiochemotherapy. Radiation esophagitis was evaluated with RTOG standard. The dosimetric parameters was estimated from dose volume histogrma (DVH). The clinical and dosimetric parameters of radiation esophagitis were evaluated by spearman correlatived univariate and Logistic multivariable analysis.Results After radiotherapy, out of 203 patients, 87 had acute radiation esophagitis(RE), 47 in grade 1, 37 in grade 2, and 3 in grade 3 RE. According to spearman correlatived analysis, the correlatived factors included ages, chemotherapy, GTV, PTV, the mean doses of PTV and lung, the max and mean dose of esophagus, V_4_0, V_4_5, V_5_0, V_5_5, V_6_0, length of esophagus (total circumference) treated with 45 Gy (LETT_4_5), and LETT_5_0 (r = -0.162-0.235, P 0.05). There were 21 factors, such as gender, age, smoking, clinical stage, site of tumor, chemotherapy, GTV, PTV, mean dose of PTV and lung, max and mean dose of esophagus, V_4_0-V_6_0 of esophagus, LETT_4_5_-_6_0, incorporated into multivariable analysis, only chemotherapy and V_4_5 of esophagus were independent predicted factors(Wald = 4.626, 9.882, P < 0.05). Conclusions: In local advanced NSCLC after 3D-CRT, chemotherapy(especially concurrent radiochemotherapy) could increase radiation-induced esophagitis. The parameter of DVH could also be used to predict

Oligometastatic non-small-cell lung cancer: current treatment strategies

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Richard PJ

2016-11-01

Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study

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Morrow, C. J.; Trapani, F.; Metcalf, R. L.; Bertolini, G.; Hodgkinson, C. L.; Khandelwal, G.; Kelly, P.; Galvin, M.; Carter, L.; Simpson, K. L.; Williamson, S.; Wirth, C.; Simms, N.; Frankliln, L.; Frese, K. K.

2016-01-01

Background Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, ?liquid biopsies? such as circulating tumour cells (CTCs) are minimally invasive...

The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

Science.gov (United States)

Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

2010-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

Regional hyperthermia combined with radiotherapy for locally advanced non-small cell lung cancers. A multi-institutional prospective randomized trial of the International Atomic Energy Agency

International Nuclear Information System (INIS)

Mitsumori, Michihide; Hiraoka, Masahiro; Zeng Zhifan; Oliynychenko, P.; Park, Jeong-Ho; Choi, Ihl-Bohng; Tatsuzaki, Hideo; Tanaka, Yoshiaki

2007-01-01

An International Atomic Energy Agency (IAEA)-sponsored, multi-institutional prospective randomized trial was conducted to clarify whether the combination of hyperthermia and radiotherapy improves the local response rate of locally advanced non-small cell lung cancer (NSCLC) compared with that obtained by radiotherapy alone. Between October 1998 and April 2002, 80 patients with locally advanced NSCLC were randomized to receive either standard radiation therapy alone (RT) or radiation therapy combined with hyperthermia (RT+HT). The primary endpoint was the local response rate. The secondary endpoints were local progression-free survival and overall survival. The median follow-up period was 204 days for all patients and 450 days for surviving patients. There were no significant differences between the two arms with regard to local response rate (P=0.49) or overall survival rate (P=0.868). However, local progression-free survival was significantly better in the RT+HT arm (P=0.036). Toxicity was generally mild and no grade 3 late toxicity was observed in either arm. Although improvement of local progression-free survival was observed in the RT+HT arm, this prospective randomized study failed to show any substantial benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced NSCLC. (author)

[Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

Science.gov (United States)

Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

2015-06-01

This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Hope for progress after 40 years of futility? Novel approaches in the treatment of advanced stage III and IV non-small-cell-lung cancer: Stereotactic body radiation therapy, mediastinal lymphadenectomy, and novel systemic therapy

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Simon Fung Kee Fung

2012-01-01

Full Text Available Non-small-cell lung cancer (NSCLC remains a leading cause of cancer mortality. The majority of patients present with advanced (stage III-IV disease. Such patients are treated with a variety of therapies including surgery, radiation, and chemotherapy. Despite decades of work, however, overall survival in this group has been resistant to any substantial improvement. This review briefly details the evolution to the current standard of care for advanced NSCLC, advances in systemic therapy, and novel techniques (stereotactic body radiation therapy [SBRT], and transcervical extended mediastinal lymphadenectomy [TEMLA] or video-assisted mediastinal lymphadenectomy [VAMLA] that have been used in localized NSCLC. The utility of these techniques in advanced stage therapy and potential methods of combining these novel techniques with systemic therapy to improve survival are discussed.

Efficacy and safety of COX-2 inhibitors for advanced non-small-cell lung cancer with chemotherapy: a meta-analysis

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Dai P

2018-02-01

Full Text Available Ping Dai, Jing Li, Xiao-Ping Ma, Jian Huang, Juan-Juan Meng, Ping Gong Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China Background: The study of cyclooxygenase-2 (COX-2 inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.Results: Six eligible trials (1,794 patients were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48. Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib and treatment line (first or second chemotherapy. The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin, GP (double fluorine cytidine + cisplatin or carboplatin, or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin. The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25 and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50. However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1

Candidates for Intensive Local Treatment in cIIIA-N2 Non-Small Cell Lung Cancer: Deciphering the Heterogeneity

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Horinouchi, Hidehito, E-mail: hhorinou@ncc.go.jp [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo (Japan); Goto, Yasushi; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Sumi, Minako [Department of Radiation Therapy, National Cancer Center Hospital, Tokyo (Japan); Tamura, Tomohide [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Ohe, Yuichiro [Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo (Japan); Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo (Japan)

2016-01-01

Purpose: The purpose of this study was to refine the heterogeneous clinical stage IIIA non-small cell lung cancer (NSCLC) with N2 nodes status (cIIIA-N2) by clinicopathological characteristics before treatment. Methods and Materials: We analyzed data of consecutive patients with cIIIA-N2 NSCLC diagnosed between 1997 and 2010 and treated by chemoradiation therapy (CRT). The appearance of the mediastinal lymph nodes (MLNs) was classified into discrete or infiltrative according to the criteria proposed by the American College of Chest Physicians. In addition, the extent of MLN involvement (MLNI) was classified as limited (close to the primary tumor) or extensive (including upper MLNI in the case of tumors in the lower lobes and vice versa). Results: A total of 148 patients with cIIIA-N2 NSCLC was treated by CRT. The patient characteristics were as follows: males: 118; females: 30; median age: 62 years; appearance of the involved MLNs: 85 discrete, 63 infiltrative; extent of MLNI: 82 limited, 66 extensive; histology: 36 squamous, 112 nonsquamous. The median progression-free survival (PFS) and median overall survival (OS) in the entire subject population were 9.9 and 34.7 months, respectively. A discrete appearance of the involved MLNs and a limited extent of MLNI contributed significantly to a better PFS and OS. The percentages of cases with relapses within the irradiated field classified according to the characteristics of the MLNs were as follows; appearance of the MLNs (24.6% discrete, 18.9% infiltrative); extent of MLNI (25.9 limited, 17.9% extensive). Conclusions: Those with a discrete appearance of the involved MLNs and a limited extent of MLNI at diagnosis could show relatively more favorable outcomes and could be candidates for multimodality therapy.

Status of advanced small pressurized water reactors

International Nuclear Information System (INIS)

Chen Peipei; Zhou Yun

2012-01-01

In order to expand the nuclear power in energy and desalination, increase competitiveness in global nuclear power market, many developed countries with strong nuclear energy technology have realized the importance of Small Modular Reactor (SMR) and initiated heavy R and D programs in SMR. The Advanced Small Pressurized Water Reactor (ASPWR) is characterized by great advantages in safety and economy and can be used in remote power grid and replace mid/small size fossil plant economically. This paper reviews the history and current status of SMR and ASPWR, and also discusses the design concept, safety features and other advantages of ASPWR. The purpose of this paper is to provide an overall review of ASPWR technology in western countries, and to promote the R and D in ASPWR in China. (authors)

Comparison of single-agent chemotherapy and targeted therapy to first-line treatment in patients aged 80 years and older with advanced non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Zhang QQ

2015-04-01

Full Text Available Qianqian Zhang,1 Zhehai Wang,2 Jun Guo,2 Liyan Liu,2 Xiao Han,2 Minmin Li,1 Shu Fang,1 Xiang Bi,1 Ning Tang,1 Yang Liu1 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, 2Department of Oncology, Shandong Cancer Hospital, Jinan, People’s Republic of China Purpose: The aim of this study was to compare single-agent chemotherapy with targeted therapy in initial treatment and to explore a better choice of treatment for patients aged 80 years and older with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A retrospective chart review was conducted for 136 patients aged 80 years and older who were cytopathologically diagnosed and staged as advanced (stage IIIB or IV NSCLC. The patient population was divided into two treatment groups: 78 patients were allocated to the chemotherapy group (group A, pemetrexed or gemcitabine or docetaxel as a single agent, and 60 patients were allocated to another group and received epidermal growth factor-receptor tyrosine-kinase inhibitors (group B, erlotinib or gefitinib as a single agent. The primary end points were overall survival (OS and progression-free survival (PFS, and the secondary end points were response rate, disease-control rate, safety, and quality of life.Results: In group A and group B, respectively, the median PFS was 2 versus 4 months (P=0.013, and the median OS was 8 versus 16 months (P=0.025. The 1- and 2-year survival rates of the two groups were 23.7% (group A, 18 of 76 versus 76.7% (group B, 46 of 60 and 13.2% (group A, ten of 76 versus 10% (group B, six of 60, respectively. The response rate and disease-control rate were 28.9% versus 36.7% (P=0.39 and 57.9% versus 76.7% (P=0.022 in group A and group B, respectively.Conclusion: Elders aged 80 years and over with advanced NSCLC in group B had longer PFS and OS compared with group A. It was well tolerated in group B because of the mild adverse effects. Targeted therapy can be

The role of maintenance pemetrexed in the treatment of non-small-cell lung cancer

OpenAIRE

Rafii, S

2010-01-01

Saeed Rafii, Michael H CullenDepartment of Medical Oncology, Queen Elizabeth Hospital, University Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, United KingdomAbstract: Until recently, the weight of evidence has supported the discontinuation of ­chemotherapy in advanced non-small-cell lung cancer (NSCLC) after 4–6 cycles of induction therapy. This allows patients with limited life expectancy a “treatment holiday.” A minority of cases then go on to r...

High-dose cisplatin with dipyridamole in advanced non-small cell lung cancer. A Grupo Oncológico Cooperativo del Sur study.

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Vallejo, C T; Rabinovich, M G; Perez, J E; Rodriguez, R; Machiavelli, M R; Leone, B A; Romero, A D; Lacava, J A; Cuevas, M A; Langhi, M J

1995-06-01

From March 1991 to October 1992, 41 patients with advanced non-small cell lung cancer (NSCLC) (20 stage IIIB and 21 stage IV) received a regimen consisting of cisplatin (CP) 100 mg/m2 i.v. days 1 and 8, and dipyridamole (DPD) 100 mg p.o. 75 minutes before CP, and then at hours 6, 12, and 18 as first-line chemotherapy. Cycles were repeated every 28 days for a total of 3. Median age was 56 years (range: 40-70). All patients had a performance status 0 to 1 and a weight loss < or = 10%. Squamous-cell carcinoma was diagnosed in 19 patients; adenocarcinoma in 16, and large-cell carcinoma in 6. A total of 37 patients were fully evaluable for response, whereas 39 were assessable for toxicity. No complete responses were observed: 5 patients (14%) achieved partial response; 23 patients (62%) showed no change, and progressive disease was observed in 9 (24%). The median time to treatment failure was 4 months, whereas median survival was 8 months. The average dose intensity received at the end of the third course of therapy was 46 mg/m2/week. There were no drug-related deaths. Toxicity was mild to moderate, with a high incidence of ototoxicity (54%) and emesis (67%). In conclusion, these results failed to demonstrate any significant advantage from a high-dose CP regimen modulated by DPD in patients with advanced NSCLC.

Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

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Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek

2010-01-01

To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

IMPACT STUDY: MK-0646 (DALOTUZUMAB, INSULIN GROWTH FACTOR 1 RECEPTOR (IGF-1R ANTIBODY COMBINED WITH PEMETREXED AND CISPLATIN IN STAGE IV METASTATIC NON-SQUAMOUS LUNG CANCER

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Chao H Huang

2016-01-01

Full Text Available Background: Insulin-like growth factor 1 receptor (IGF-1R regulates cell growth, proliferation and apoptosis. Adenocarcinoma and never-smokers have a higher expression of IGF-1R, which is associated with worse overall survival. Dalotuzumab-MK0646 (D is a humanized monoclonal antibody that targets IGF-1R. Pemetrexed (P has higher activity in non-squamous lung cancer (NSQL. We initiated a randomized phase II trial to test the combination of P and Cisplatin (C +/- D in NSQL.Methods: Eligibility criteria: untreated NSQL stage IIIB or IV, ECOG 0 or 1, measurable disease, adequate renal, hepatic and hematologic function, and no other intercurrent illness. P at 500mg/m2 and C at 75mg/m2 IV were given every 3 weeks. D was given at 10mg/kg IV weekly on days 1, 8 and 15 of every 3-week cycle in the experimental group. The patients had a radiographic assessment after every 2 cycles and were treated for a maximum of 6 cycles if there was a response or stable disease. The primary objective of the study was to compare the clinical response rates of PC vs PC+D. Results: From 1/2009 to 2/2011, the study accrued 26 subjects: 16 male and 10 female, with a median age of 59; 14 were treated with PC and 12 were treated with PC+D. We observed 2 partial responses (PR, 7 stable disease (SD, 3 progressive disease (PD, and 2 were not evaluable (NE in the PC arm. In comparison, for the PC+D arm there were: 3 PR, 4 SD, 4 PD and 1 NE. The hematologic toxicity was similar in both groups. There higher incidence of hyperglycemia the experimental group; 4 cases with grade 3 and 1 case with grade 4. Conclusion: PC+D had a similar response rate compared to PC, with a higher rate of hyperglycemia. Identification of responders using predictive markers would be key to continuing the study of D in NSQL.

A Dosimetric Comparison of Dose Escalation with Simultaneous Integrated Boost for Locally Advanced Non-Small-Cell Lung Cancer

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Wenjuan Yang

2017-01-01

Full Text Available Background. Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC. We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT with a simultaneous integrated boost (SIB in locally advanced NSCLC. Methods. We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV. In the three SIB groups, the prescribed dose was 69 Gy, 75 Gy, and 81 Gy in 30 fractions to the internal gross tumor volume (iGTV. Results. The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P < 0.05, without increased normal tissue exposure or prolonged overall treatment time. Significant differences were not observed in the dose to the normal lung in terms of the V5 and V20 among the four IMRT plans. The maximum dose (Dmax in the esophagus moderately increased along with the prescribed dose (P < 0.05. Conclusions. Our results indicated that escalating the dose by SIB-IMRT is dosimetrically feasible; however, systematic evaluations via clinical trials are still warranted. We have designed a further clinical study (which is registered with ClinicalTrials.gov, number NCT02841228.

Non-small cell lung cancer in never smokers: a clinical entity to be identified.

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Santoro, Ilka Lopes; Ramos, Roberta Pulcheri; Franceschini, Juliana; Jamnik, Sergio; Fernandes, Ana Luisa Godoy

2011-01-01

It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among never-smokers with non-small cell lung cancer. All consecutive non-small cell lung cancer patients diagnosed (n = 285) between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current) were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable), gender (female vs. male), smoking status (never- vs. ever-smoker), the Karnofsky Performance Status Scale (continuous variable), histological type (adenocarcinoma vs. non-adenocarcinoma), AJCC staging (early vs. advanced staging), and treatment (chemotherapy and/or radiotherapy vs. the best treatment support). Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32%) and have adenocarcinoma (70% vs. 51%). Overall median survival was 15.7 months (95% CI: 13.2 to 18.2). The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc

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Fogliata Antonella

2010-10-01

Full Text Available Abstract Background To report acute toxicity, initial outcome results and planning therapeutic parameters in radiation treatment of advanced lung cancer (stage III with volumetric modulated arcs using RapidArc (RA. Methods Twenty-four consecutive patients were treated with RA. All showed locally advanced non-small cell lung cancer with stage IIIA-IIIB and with large volumes (GTV:299 ± 175 cm3, PTV:818 ± 206 cm3. Dose prescription was 66Gy in 33 fractions to mean PTV. Delivery was performed with two partial arcs with a 6 MV photon beam. Results From a dosimetric point of view, RA allowed us to respect most planning objectives on target volumes and organs at risk. In particular: for GTV D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; contra-lateral lung mean dose resulted in 13.7 ± 3.9Gy, for spinal cord D1% = 39.5 ± 4.0Gy, for heart V45Gy = 9.0 ± 7.0Gy, for esophagus D1% = 67.4 ± 2.2Gy. Delivery time was 133 ± 7s. At three months partial remission > 50% was observed in 56% of patients. Acute toxicities at 3 months showed 91% with grade 1 and 9% with grade 2 esophageal toxicity; 18% presented grade 1 and 9% with grade 2 pneumonia; no grade 3 acute toxicity was observed. The short follow-up does not allow assessment of local control and progression free survival. Conclusions RA proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.

Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

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Mehmood, Qurrat; Sun, Alexander; Becker, Nathan; Higgins, Jane; Marshall, Andrea; Le, Lisa W; Vines, Douglass C; McCloskey, Paula; Ford, Victoria; Clarke, Katy; Yap, Mei; Bezjak, Andrea; Bissonnette, Jean-Pierre

2016-02-01

Treatment of locally advanced non-small cell lung cancer with chemoradiotherapy (CRT) is limited by development of toxicity in normal tissue, including radiation esophagitis (RE). Increasingly, (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is being used for adaptive planning. Our aim was to assess changes in esophageal FDG uptake during CRT and relate the changes to the onset and severity of RE. This prospective study in patients with stage II-III non-small cell lung cancer involved serial four-dimensional computed tomography and PET scans during CRT (60-74Gy). RE was recorded weekly using the Common Terminology Criteria for Adverse Events (v4.0), and imaging was performed at weeks 0, 2, 4, and 7. Changes in the esophagus's peak standard uptake value (SUVpeak) were analyzed for each time point and correlated with grade of RE using the Wilcoxon rank-sum test. The volume of esophagus receiving 50 Gy (V50) and volume of esophagus receiving 60 Gy (V60) were correlated with the development of RE, and the C-statistic (area under the curve [AUC]) was calculated to measure predictivity of grade 3 RE. RE developed in 20 of 27 patients (74%), with grade 3 reached in 6 (22%). A significant percentage increase in SUVpeak in the patients with RE was noted at week 4 (p = 0.01) and week 7 (p = 0.03). For grade 3 RE, a significant percentage increase in SUVpeak was noted at week 2 (p = 0.01) and week 7 (p = 0.03) compared with that for less than grade 3 RE. Median V50 (46.3%) and V60 (33.4%) were significantly higher in patients with RE (p = 0.04). The AUC measurements suggested that the percentage change in SUVpeak at week 2 (AUC = 0.69) and V50 (AUC = 0.67) and V60 (AUC = 0.66) were similarly predictive of grade 3 RE. Serial FDG-PET images during CRT show significant increases in SUVpeak for patients in whom RE develops. The changes at week 2 may predict those at risk for the development of grade 3 RE and may be informative for adaptive planning and

Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer

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Shuyang YAO

2015-06-01

Full Text Available Background and objective This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed in previously treated advanced non-small cell lung cancer (NSCLC. Methods Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS was evaluated by Kaplan-Meier method. Results Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR (28.1% vs 18.2%, P=0.341, disease control rate (DFS(43.8% vs 45.5%, P=0.890, and PFS (4.3 months vs 3.8 months, P=0.506. In the icotinib group, the ORR of epidermal growth factor receptor (EGFR mutant was significantly higher than that of EGFR unknown or wild type (P=0.017. In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001. Conclusion Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Maintenance treatment of advanced non-small-cell lung cancer: results of an international expert panel meeting of the Italian association of thoracic oncology.

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Gridelli, Cesare; de Marinis, Filippo; Di Maio, Massimo; Ardizzoni, Andrea; Belani, Chandra P; Cappuzzo, Federico; Ciardiello, Fortunato; Fidias, Panagiotis; Paz-Ares, Luis; Perrone, Francesco; Pirker, Robert; De Petris, Luigi; Stahel, Rolf

2012-06-01

Several randomized trials have recently investigated the role of maintenance treatment for patients with advanced non-small-cell lung cancer (NSCLC) with responding or stable disease after completion of first-line chemotherapy. Maintenance strategy has relevant implications in terms of potential toxicity, logistics and costs, and all of these aspects should be taken into account, together with the magnitude of benefit for the patient. In order to assess the strengths and limitations of available evidence, to help clinical practice, and to suggest priorities for future clinical research, the Italian Association of Thoracic Oncology (AIOT) organized an International Experts Panel Meeting on maintenance treatment of advanced NSCLC, which took place in Sperlonga (Italy) in May 2011. Based on the available evidence, panelists agreed that maintenance therapy represents a treatment option in advanced NSCLC. Maintenance should be discussed with patients not progressed after 4-6 cycles of first-line chemotherapy, who are fit (performance status 0-1) and without persistent chemotherapy-induced toxicity. Patients need to be well informed about potential advantages and disadvantages of accepting additional therapy without a "treatment-free period". Two different strategies, switch or continuation maintenance, are supported by available evidence. At the moment, there is no direct comparison between switch maintenance and continuation maintenance. For future trials, the panel recommends the use of overall survival as the primary endpoint, with pre-defined second-line treatment. Translational research is essential to identify predictive factors, and should be performed, whenever feasible, in order to achieve treatment optimization with proper patient selection. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Evolution of Therapies in Non-Small Cell Lung Cancer

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Boolell, Vishal, E-mail: vishal.boolell@monashhealth.org.au; Alamgeer, Muhammad [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Watkins, David N. [Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); UNSW Faculty of Medicine, St Vincent’s Clinical School, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Department of Thoracic Medicine, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Ganju, Vinod [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia)

2015-09-09

The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

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Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

2015-10-01

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

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Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

2015-05-01

The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies.

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Jing Zhao

Full Text Available Treatment related death (TRD is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC patients treated with concurrent chemoradiotherapy (CCRT, and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients were eligible. The pooled TRD rate (accounting for heterogeneity was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI of TRDs was 1.08 (0.70-1.66 (P = 0.71. Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09-2.07, P = 0.008. No significant difference was found in TRDs between high (≥ 66 Gy and low (< 66 Gy radiation dose during CCRT (P = 0.605. Neither consolidation (P = 0.476 nor induction chemotherapy (P = 0.175 had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study.

The cost-effectiveness and cost-utility of high-dose palliative radiotherapy for advanced non-small-cell lung cancer

International Nuclear Information System (INIS)

Coy, Peter; Schaafsma, Joseph; Schofield, John A.

2000-01-01

Purpose: To compute cost-effectiveness/cost-utility (CE/CU) ratios, from the treatment clinic and societal perspectives, for high-dose palliative radiotherapy treatment (RT) for advanced non-small-cell lung cancer (NSCLC) against best supportive care (BSC) as comparator, and thereby demonstrate a method for computing CE/CU ratios when randomized clinical trial (RCT) data cannot be generated. Methods and Materials: Unit cost estimates based on an earlier reported 1989-90 analysis of treatment costs at the Vancouver Island Cancer Centre, Victoria, British Columbia, Canada, are updated to 1997-1998 and then used to compute the incremental cost of an average dose of high-dose palliative RT. The incremental number of life days and quality-adjusted life days (QALDs) attributable to treatment are from earlier reported regression analyses of the survival and quality-of-life data from patients who enrolled prospectively in a lung cancer management cost-effectiveness study at the clinic over a 2-year period from 1990 to 1992. Results: The baseline CE and CU ratios are $9245 Cdn per life year (LY) and $12,836 per quality-adjusted life year (QALY), respectively, from the clinic perspective; and $12,253/LY and $17,012/QALY, respectively, from the societal perspective. Multivariate sensitivity analysis for the CE ratio produces a range of $5513-28,270/LY from the clinic perspective, and $7307-37,465/LY from the societal perspective. Similar calculations for the CU ratio produce a range of $7205-37,134/QALY from the clinic perspective, and $9550-49,213/QALY from the societal perspective. Conclusion: The cost effectiveness and cost utility of high-dose palliative RT for advanced NSCLC compares favorably with the cost effectiveness of other forms of treatment for NSCLC, of treatments of other forms of cancer, and of many other commonly used medical interventions; and lies within the US $50,000/QALY benchmark often cited for cost-effective care

Definitive Upfront Stereotactic Ablative Radiotherapy Combined with Image-Guided, Intensity Modulated Radiotherapy (IG-IMRT or IG-IMRT Alone for Locally Advanced Non-Small Cell Lung Cancer.

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Alexander Chi

Full Text Available Image-guided (IG intensity-modulated radiotherapy (IMRT enables maximal tumor margin reduction for the sparing of organs at risk (OARs when used to treat locally advanced non-small cell lung cancer (NSCLC with definitive chemo-radiation. It also allows for the incorporation of stereotactic ablative radiotherapy (SABR into the treatment regimen. Here, we describe our initial experience in combining definitive upfront SABR to the primary lesion with chemo-radiation delivered with conventionally fractionated IG-IMRT to the remaining regional disease; along with clinical outcome following chemo-radiation with conventionally fractionated IG-IMRT alone in the treatment of locally advanced NSCLC.The clinical outcome of 29 patients with locally advanced NSCLC who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both was retrospectively reviewed.After a median follow up of 23.7 months, the median overall survival (OS and progression-free survival (PFS were 19.8 and 11.3 months, respectively. The 2 year local, regional, and distant control was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT alone. SABR + IG-IMRT was well tolerated. No ≥ grade 3 radiation-related toxicity was observed.Definitive upfront SABR followed by IG-IMRT in selected patients with locally advanced NSCLC warrants further investigation in future clinical trials, while chemo-radiation with IG-IMRT alone was well tolerated.

Durvalumab: a potential maintenance therapy in surgery-ineligible non-small-cell lung cancer

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Shafique MR

2018-05-01

Full Text Available Michael R Shafique, Lary A Robinson, Scott Antonia Department of Thoracic Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Lung cancer is the most common cancer worldwide and the most common cause of cancer-related death. Non-small-cell lung cancer comprises ~87% of newly diagnosed cases of lung cancer, and nearly one-third of these patients have stage III disease. Despite improvements in the treatment of stage IV lung cancer, particularly with the introduction and dissemination of checkpoint inhibitors, very little progress has been made in the treatment of stage III lung cancer. In this article, we discuss the general staging criteria and treatment options for stage III lung cancer. We review how concurrent radiation and chemotherapy can have immunomodulatory effects, supporting the rationale for incorporating immunotherapy into existing treatment paradigms. Finally, we discuss the results of the PACIFIC trial and implications for the treatment of stage III lung cancer. In the PACIFIC trial, adding durvalumab as a maintenance therapy following the completion of chemoradiotherapy improved progression-free survival in patients with locally advanced unresectable stage III lung cancer. On the strength of these results, durvalumab has been approved by the US Food and Drug Administration for use in this setting, representing the first advance in the treatment of stage III lung cancer in nearly a decade. Keywords: non-small-cell lung cancer, maintenance therapy, staging, immunotherapy, chemoradiation, surgery-ineligible, durvalumab

Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

International Nuclear Information System (INIS)

Zhao, Jun; Zheng, Shuang; Zhou, Qiyin; Li, Heming; Liu, Yunpeng; Qu, Xiujuan; Zhao, Mingfang; Jin, Bo; Yu, Ping; Hu, Xuejun; Teng, Yuee; Zhang, Jingdong; Luo, Ying; Zhang, Lingyun

2012-01-01

Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. This study showed that the reduction in plasma fibrinogen levels

An advanced algorithm for deformation estimation in non-urban areas

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Goel, Kanika; Adam, Nico

2012-09-01

This paper presents an advanced differential SAR interferometry stacking algorithm for high resolution deformation monitoring in non-urban areas with a focus on distributed scatterers (DSs). Techniques such as the Small Baseline Subset Algorithm (SBAS) have been proposed for processing DSs. SBAS makes use of small baseline differential interferogram subsets. Singular value decomposition (SVD), i.e. L2 norm minimization is applied to link independent subsets separated by large baselines. However, the interferograms used in SBAS are multilooked using a rectangular window to reduce phase noise caused for instance by temporal decorrelation, resulting in a loss of resolution and the superposition of topography and deformation signals from different objects. Moreover, these have to be individually phase unwrapped and this can be especially difficult in natural terrains. An improved deformation estimation technique is presented here which exploits high resolution SAR data and is suitable for rural areas. The implemented method makes use of small baseline differential interferograms and incorporates an object adaptive spatial phase filtering and residual topography removal for an accurate phase and coherence estimation, while preserving the high resolution provided by modern satellites. This is followed by retrieval of deformation via the SBAS approach, wherein, the phase inversion is performed using an L1 norm minimization which is more robust to the typical phase unwrapping errors encountered in non-urban areas. Meter resolution TerraSAR-X data of an underground gas storage reservoir in Germany is used for demonstrating the effectiveness of this newly developed technique in rural areas.

Non-small cell lung cancer in never smokers: a clinical entity to be identified

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Ilka Lopes Santoro

2011-01-01

Full Text Available OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among neversmokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285 between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable, gender (female vs. male, smoking status (never- vs. ever-smoker, the Karnofsky Performance Status Scale (continuous variable, histological type (adenocarcinoma vs. non-adenocarcinoma, AJCC staging (early vs. advanced staging, and treatment (chemotherapy and/or radiotherapy vs. the best treatment support. RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32% and have adenocarcinoma (70% vs. 51%. Overall median survival was 15.7 months (95% CI: 13.2 to 18.2. The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

Assesment of prognostic factors in radical radiotherapy for patients with non-small cell lung cancer

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Chmielewska, E.

2000-01-01

Lung cancer is still the most severe problem of oncology throughout the word. In Poland there are some 20 000 new cases per annum, among them non-small cell lung cancer accounts for about 16 000 cases. The basic method of therapy of non-small cell lung cancers is surgery; however, in Polish conditions only about 15% of patients qualify for it. Therefore, there remains a large group of patients who are potential candidates for radiotherapy. Evaluation of a group of patients qualified for radical radiotherapy according to uniform rules, treated with the same protocol and assesed by the same group of physicians. The obtained results of therapy allow to evaluate the usefulness of radical radiotherapy in patients with non-operable non-small cell lung cancer and serve as a basis of search for more effective radiotherapy protocols. The aim of the study is to attempt to define the prognostic, therapeutical, clinical-and population-related factors for survival and local control in patients with non-operable, non-small cell lung cancer. Between January 1, 1990, and December 31, 1995, there were 2330 patients with non-small cell lung in the Ambulatory of the Cancer Centre in Warsaw. Basing on the results of clinical examination and additional examination, 260 patients qualified for radical radiotherapy. In this group there were 31 women (12%) and 229 men (88%). In a majority of cases the stage of the disease was advanced: stage IIIA was found in 114 patients (44%), and stage IIIB in 73 patients (28%). Retrospective analysis of the results of treatment was carried out. The material covered 260 patients. The survival time and the time to local progression were the basis for the analysis. The survival probability was calculated whit the Kaplan-Meier method. Multidimensional analysis of the prognostic factors (age, clinical advancement of the disease, performance status, loss of weight, LDH and haemoglobin level, tumour size, pulmonary function, prior exploratory thoracotomy

Erlotinib in the Second/Third Line Treatment of Patients with Advanced Non-small Cell Lung Cancer

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Yilong WU

2009-05-01

Full Text Available Background and objective Erlotinib is a targeted drug for non-small cell lung cancer (NSCLC. The aim of this study is to evaluate the efficacy, influencing factors and toxicity of erlotinib in patients with NSCLC. Methods Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapyreceived 150 mg oral doses of erlotinib once daily until disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier methods was used to analyze the survival rate. Cox regression was used to define the predictive factors. Results Forty-eight patients were enrolled into the study from Dec, 2005 to Sep, 2006. We followed up these patients until 08.Dec.2008. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 7 days. Partial response 33.4% (16/48, stable disease 22.9% (11/48, and progressive disease 43.7% (21/48. Response rate was 33.4% (16/48. Disease control rate was 56.3% (27/48. One and two-year progression-free survival rates and overall survival rates were 25％(events 36, 8.3％ (events 40 and 43.8％ (death 27, 20.8％ (death 38; three-year overall survival 5.6％. The median progression-free survival time and median overall survival time was 5 months and 8 months, respectively. Performance status was the only predictor for overall survival in the Cox model (P <0.001. Skin toxicity(grade 1 to 3 was found in 93.7% patients. One patient discontinued erlotinib because of perianal abscess. Conclusion Erlotinib is another effective drug for patients with previously chemotherapy advanced NSCLC and accepted toxicity profile.

A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

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Valente Nancy

2005-02-01

Full Text Available Abstract Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC-derived exosomes (DEX loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC. Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4 and IV (N = 9 NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8, flu like illness (N = 1, and peripheral arm pain (N = 1. The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors

Real-life experience of ceritinib in crizotinib-pretreated ALK+ advanced non-small cell lung cancer patients

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Jacques Cadranel

2018-02-01

Full Text Available Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK positive (ALK+ non-small cell lung cancer (NSCLC in a French temporary authorisation for use (TAU study. The French TAU study included crizotinib-pretreated patients with advanced ALK+ or ROS proto-oncogene 1 positive (ROS1+ tumours. Patients received oral ceritinib (750 mg·day−1 as a starting dose and best tumour response (as evaluated by the investigator and safety were reported every 3 months. A total of 242 TAUs were granted from March 12, 2013 to August 05, 2015. Of the 242 patients, 228 had ALK+ NSCLC and 13 had ROS1+ NSCLC. The median age of ALK+ patients (n=214 was 58.5 years, 51.9% were female, 70.8% had an Eastern Cooperative Oncology Group (ECOG performance status (PS of 0–1 and 50.0% had brain metastases. Of the 149 efficacy evaluable ALK+ NSCLC patients, 5.4% had a complete response (CR, 47.0% had a partial response (PR and 22.8% had stable disease (SD. At September 05, 2015, the median duration of ceritinib treatment (n=182 was 3.9 months but 5.5 months for patients (n=71 with a follow-up of ≥12 months. Higher objective response rate (ORR was observed for patients with ECOG PS 0 to 1 (55.0% versus 42.4% and those receiving prior crizotinib for >5 months (51.6% versus 36.1%. Treatment-related adverse events (AEs were reported in 118 of 208 patients (56.7%, the most common being diarrhoea (22.1% and hepatic toxicity (19.7%. Ceritinib (750 mg·day−1 demonstrated efficacy similar efficacy to ASCEND-1, ASCEND-2 and phase 3 ASCEND-5 trials with manageable safety in crizotinib-pretreated patients with ALK+ NSCLC.

Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

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Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

2011-01-01

Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

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Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

2016-01-01

Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

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Chunxiang Zhang

Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

Immune-based Therapies for Non-small Cell Lung Cancer.

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Rafei, Hind; El-Bahesh, Ehab; Finianos, Antoine; Nassereddine, Samah; Tabbara, Imad

2017-02-01

Lung cancer is the leading cause of cancer-related death worldwide. Treatment of non-small cell lung cancer has evolved tremendously over the past decade. Specifically, immune checkpoint inhibitors have become an increasingly interesting target of pharmacological blockade. These immune inhibitors have shown promising results in front-line therapy and after failure of multiple lines, as well as in monotherapy and combination with other therapies. Vaccination in non-small cell lung cancer is also an emerging field of research that holds promising results for the future of immunotherapy in non-small cell lung cancer. This review presents a concise update on the most recent data regarding the role of checkpoint inhibitors as well as vaccination in non-small cell lung cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung cancer.

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Lee, Jinsoo; Chae, Jean; Lee, Sookyung; Kim, Kyungsuk; Eo, Wankyu; Kim, Sehyun; Choi, Woncheol; Cheon, Seong Ha

2013-01-01

Chemotherapy improves the survival of patients with advanced non-small cell lung cancer (NSCLC), but tumor progression is often inevitable. Strategies are needed to improve the therapeutic efficacy of chemotherapy. Over recent years, there has been increasing interest in the role of maintenance therapy after first-line chemotherapy. We investigated the efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract (aRVS) as maintenance therapy in patients with non-progressive disease following first-line chemotherapy. We reviewed the medical records of 33 patients with advanced NSCLC, who started treatment with aRVS in a state of tumor regression or stable disease after completion of four or six cycles of induction chemotherapy at the Integrative Cancer Center, Kyung Hee University Hospital at Gangdong from June 2006 to April 2012. The primary objective of this study was progression-free survival (PFS) of aRVS as maintenance therapy. Secondary objectives included assessments of disease control rate (DCR), overall survival (OS), and the safety of aRVS treatment. The median PFS was 5.2 months with a 6- and 12-month PFS rate of 40.6% and 12.9%, respectively. The DCR was 93.9% and the median OS was 34.8 months. The overall survival rates at 12, 24, and 36 months were 84.2%, 76.7% and 49.9%, respectively. We observed no hematologic toxicity, nephrotoxicity, or hepatotoxicity during aRVS treatment. In conclusion, maintenance therapy with aRVS for patients with advanced NSCLC is well-tolerated and offers encouraging improved PFS and OS compared with historical controls. Our data provide further evidence that aRVS may be used beyond disease progression in this clinical setting.

Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

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Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

2016-12-01

Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

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Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-01-01

Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine.

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Han, Yanxi; Li, Jinming

2017-10-26

In this era of precision medicine, molecular biology is becoming increasingly significant for the diagnosis and therapeutic management of non-small cell lung cancer. The specimen as the primary element of the whole testing flow is particularly important for maintaining the accuracy of gene alteration testing. Presently, the main sample types applied in routine diagnosis are tissue and cytology biopsies. Liquid biopsies are considered as the most promising alternatives when tissue and cytology samples are not available. Each sample type possesses its own strengths and weaknesses, pertaining to the disparity of sampling, preparation and preservation procedures, the heterogeneity of inter- or intratumors, the tumor cellularity (percentage and number of tumor cells) of specimens, etc., and none of them can individually be a "one size to fit all". Therefore, in this review, we summarized the strengths and weaknesses of different sample types that are widely used in clinical practice, offered solutions to reduce the negative impact of the samples and proposed an optimized strategy for choice of samples during the entire diagnostic course. We hope to provide valuable information to laboratories for choosing optimal clinical specimens to achieve comprehensive functional genomic landscapes and formulate individually tailored treatment plans for NSCLC patients that are in advanced stages.

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

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Shen, Xinglei; DeNittis, Albert; Werner-Wasik, Maria; Axelrod, Rita; Gilman, Paul; Meyer, Thomas; Treat, Joseph; Curran, Walter J; Machtay, Mitchell

2011-01-01

This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m 2 . Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m 2 , but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m 2 ) q3 weeks × 2 -3 cycles. Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m 2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.

The Evolution of Therapies in Non-Small Cell Lung Cancer

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Vishal Boolell

2015-09-01

Full Text Available The landscape of advanced non-small lung cancer (NSCLC therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR mutations and anaplastic lymphoma kinase (ALK gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs. Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 receptor (PD-1, which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

[Strategy for molecular testing in pulmonary carcinoma].

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Penault-Llorca, Frédérique; Tixier, Lucie; Perrot, Loïc; Cayre, Anne

2016-01-01

Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening. Copyright © 2016. Published by Elsevier Masson SAS.

PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data.

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Aguiar, Pedro N; De Mello, Ramon Andrade; Hall, Peter; Tadokoro, Hakaru; Lima Lopes, Gilberto de

2017-05-01

The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.

Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer.

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Xinzhe Dong

Full Text Available To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC.From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT. Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH] and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity. SUVmax and metabolic tumor volume (MTV were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS, and overall survival (OS.Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively. Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1% and specificity (80.0%~83.6% than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively. The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034 and PFS (P = 0.007, P = 0.039. In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021 and OS (HR 0.519, P = 0.015.The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response

Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands.

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Pompen, Marjolein; Gok, Murat; Novák, Annoesjka; van Wuijtswinkel, Rob; Biesma, Bonne; Schramel, Franz; Stigt, Jos; Smit, Hans; Postmus, Pieter

2009-04-01

Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective and reports on 2005 costs. Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on

Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

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Alifrangis, Costi; Carter, Philip; Cereser, Biancastella; Chandrasinghe, Pramodh; Belluz, Lisa Del Bel; Lim, Eric; Moderau, Nina; Poyia, Fotini; Tabassum, Neha; Zhang, Hua; Krell, Jonathan; Stebbing, Justin

2018-02-27

In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not ( P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group ( P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

Icotinib, a selective EGF receptor tyrosine kinase inhibitor, for the treatment of non-small-cell lung cancer.

Science.gov (United States)

Tan, Fenlai; Shi, Yuankai; Wang, Yinxiang; Ding, Lieming; Yuan, Xiaobin; Sun, Yan

2015-01-01

Advanced non-small-cell lung cancer (NSCLC) is the main cause for cancer-related mortality. Treatments for advanced NSCLC are largely palliative and a benefit plateau appears to have reached with the platinum-based chemotherapy regimens. EGF receptor (EGFR) tyrosine kinase inhibitors gefitinib, erlotinib and afatinib came up with prolonged progression-free survival and improved quality of life, especially in EGFR-mutated patients. Icotinib is an oral selective EGFR tyrosine kinase, which was approved by China Food and Drug administration in June 2011 for treating advanced NSCLC. Its approval was based on the registered Phase III trial (ICOGEN), which showed icotinib is noninferior to gefitinib. This review will discuss the role of icotinib in NSCLC, and its potential application and ongoing investigations.

An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients

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Hatim I. Alghamdi

2018-03-01

Full Text Available Lung cancer ranks as the top cancer worldwide in terms of incidence and constitutes a major health problem. About 90% of lung cancer cases are diagnosed at advance stage where treatment is not available. Despite evidence that lung cancer screening improves survival, guidelines for lung cancer screening are still a subject for debate. In Saudi Arabia, only 14% of lung cancers are diagnosed at early stage and researches on survival and its predictors are lacking. This overview analysis was conducted on predictors of lung cancer mortality according to the two major cancer types, small-cell lung cancers (SCLCs and non-small cell lung cancers (NSCLCs in Saudi Arabia. A secondary data analysis was performed on small-cell lung cancers (SCLCs and Non-small cell lung cancers (NSCLCs registered in the Saudi Cancer Registry (SCR for the period 2009–2013 to estimate predictors of mortality for both lung cancer types. A total of 404 cases (197 SCLC and 207 NSCLC were included in the analysis, all Saudi nationals. A total of 213 (52.75% deaths occurred among lung cancer patients, 108 (54.82% among SCLCs and 105 (50.72% among NCSLCs. Three quarter of patients are diagnosis with advance stage for both SCLC & NSCLC. Univariate analysis revealed higher mean age at diagnosis in dead patients compared to alive patients for SCLCs (p = 0.04; but not NSCLCs, a lower mortality for NSCLCs diagnosed in 2013 (p = 0.025 and a significant difference in stage of tumor (p = 0.006 and (p = 0.035 for both SCLC and NSCLC respectively. In multiple logistic regression, stage of tumor was a strong predictor of mortality, where distant metastasis increased morality by 6-fold (OR = 5.87, 95% CI: 2.01 – 17.19 in SCLC and by 3-fold (OR = 3.29, 95% CI: 1.22 – 8.85 in NSCLC, compared to localized tumors. Those with NSCLC who were diagnosed in 2013 were less likely to die by 64% compared to NSCLC diagnosed in 2009 (OR = 0.36, 95% CI: 0.14 – 0.93. Age, sex, topography

An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients.

Science.gov (United States)

Alghamdi, Hatim I; Alshehri, Ali F; Farhat, Ghada N

2018-03-01

Lung cancer ranks as the top cancer worldwide in terms of incidence and constitutes a major health problem. About 90% of lung cancer cases are diagnosed at advance stage where treatment is not available. Despite evidence that lung cancer screening improves survival, guidelines for lung cancer screening are still a subject for debate. In Saudi Arabia, only 14% of lung cancers are diagnosed at early stage and researches on survival and its predictors are lacking. This overview analysis was conducted on predictors of lung cancer mortality according to the two major cancer types, small-cell lung cancers (SCLCs) and non-small cell lung cancers (NSCLCs) in Saudi Arabia. A secondary data analysis was performed on small-cell lung cancers (SCLCs) and Non-small cell lung cancers (NSCLCs) registered in the Saudi Cancer Registry (SCR) for the period 2009-2013 to estimate predictors of mortality for both lung cancer types. A total of 404 cases (197 SCLC and 207 NSCLC) were included in the analysis, all Saudi nationals. A total of 213 (52.75%) deaths occurred among lung cancer patients, 108 (54.82%) among SCLCs and 105 (50.72%) among NCSLCs. Three quarter of patients are diagnosis with advance stage for both SCLC & NSCLC. Univariate analysis revealed higher mean age at diagnosis in dead patients compared to alive patients for SCLCs (p=0.04); but not NSCLCs, a lower mortality for NSCLCs diagnosed in 2013 (p=0.025) and a significant difference in stage of tumor (p=0.006) and (p=0.035) for both SCLC and NSCLC respectively. In multiple logistic regression, stage of tumor was a strong predictor of mortality, where distant metastasis increased morality by 6-fold (OR=5.87, 95% CI: 2.01 - 17.19) in SCLC and by 3-fold (OR=3.29, 95% CI: 1.22 - 8.85) in NSCLC, compared to localized tumors. Those with NSCLC who were diagnosed in 2013 were less likely to die by 64% compared to NSCLC diagnosed in 2009 (OR=0.36, 95% CI: 0.14 - 0.93). Age, sex, topography and laterality were not associated with

Reliability of using circulating tumor cells for detecting epidermal growth factor receptor mutation status in advanced non-small-cell lung cancer patients: a meta-analysis and systematic review

Directory of Open Access Journals (Sweden)

Hu F

2018-03-01

Full Text Available Fang Hu,* Xiaowei Mao,* Yujun Zhang, Xiaoxuan Zheng, Ping Gu, Huimin Wang, Xueyan ZhangDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this workPurpose: To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC patients.Methods: We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve.Results: Eight eligible publications with 255 advanced NSCLC patients were included in this meta-analysis. Taking tumor tissues as reference, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating tumor cells for detecting the epidermal growth factor receptor mutation status were found to be 0.82 (95% confidence interval [CI]: 0.50–0.95, 0.95 (95% CI: 0.24–1.00, 16.81 (95% CI: 0.33–848.62, 0.19 (95% CI: 0.06–0.64, and 86.81 (95% CI: 1.22–6,154.15, respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94. The subgroup analysis showed that the factors of blood volume, histological type, EGFR-tyrosine kinase inhibitor therapy, and circulating tumor cell and tissue test methods for EGFR accounted for the significant difference of the pooled specificity. No significant difference was found between the pooled sensitivity of the subgroup.Conclusion: Our meta-analysis confirmed that circulating tumor cells are a good surrogate for

[Role of PET/CT in primitive non-small cell bronchopulmonary cancer].

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Soumia, Fdil; Leila, Achachi; Mohamed, Raoufi; Laila, Herrak; Mustapha, Elftouh

2017-01-01

Bronchopulmonary cancer is a real public health problem. Morphological imaging plays a central role in its diagnosis, staging as well as post-therapeutic assessment but it has some limitations. Metabolic imaging is a more recent technique which allows to significantly improve the overall imagery performance. We conducted a retrospective, descriptive and analytical study at the Ibn Sina Hospital and at the Military Hospital of instruction Mohammed V in Rabat over a period of 18 months, between September 2014 and February 2016, in order to evaluate the role of Fluorodeoxyglucose-PET/CT in the staging and restaging of non-small cell bronchopulmonary cancer. Initial staging showed a vast majority of locally advanced and metastatic stages: stage IV (40%), Stage IIIB (36%), Stage IIIA (16%), Stage II (8%). PET-CT allowed to detect new sites which were not initially seen on CT scan in 24 cases: 15 new ganglion sites, 8 new adrenal sites and 6 sites of bone lesions. PET/CT allowed to modify initial tumor stage in 60% of cases: upstaging in 23 patients (46%) and downstaging in 7 patients(14%). The initial stage remained unchanged in 40% of patients. Our study confirms the data from the literature concerning the superiority of PET-CT in comparison with CT scan, but only in the optimization of the non-small cell bronchopulmonary cancer management, in particular in locoregional and distant staging.

Monitoring Response to Antiangiogenic Therapy in Non-Small Cell Lung Cancer Using Imaging Markers Derived from PET and Dynamic Contrast-Enhanced MRI

NARCIS (Netherlands)

de Langen, Adrianus J.; van den Boogaart, Vivian; Lubberink, Mark; Backes, Walter H.; Marcus, Johannes T.; van Tinteren, Harm; Pruim, Jan; Brans, Boudewijn; Leffers, Pieter; Dingemans, Anne-Marie C.; Smit, Egbert F.; Groen, Harry J. M.; Hoekstra, Otto S.

2011-01-01

With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell

Correlations between Ape1/Ref-1, ICAM-1 and IL-17A Levels in Serum and Radiation Pneumonitis for Local Advanced Non-small Cell Lung Cancer Patients

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Leiming GUO

2018-05-01

Full Text Available Background and objective The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1, intercellular adhesion molecules 1 (ICAM-1 and interleukin-17A (IL-17A before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC patients with concurrent chemoradiotherapy. Methods NSCLC patients (68 cases were treated with concurrent radiotherapy and chemotherapy, every patient’s normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. Results Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05. There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05. Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in

Editorial perspective--advances in B-cell non-Hodgkin's lymphoma

NARCIS (Netherlands)

Hagenbeek, A.; Bischof Delaloye, A.

2003-01-01

Radioimmunotherapy (RIT) represents an exciting new therapeutic option for the treatment of B-cell non-Hodgkin's lymphoma (NHL), emerging at a time when significant advances have been made in NHL classification, molecular genetics and treatment. Despite recent treatment advances, including the use

OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer

Science.gov (United States)

Zhang, Pengfei; Hutton, David; Li, Qiu

2018-01-01

Objectives Erlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although it has improved progression-free survival (PFS), overall survival (OS) was limited and erlotinib can be expensive. This cost-effectiveness analysis compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy. Setting First-line treatment of Asian patients with NSCLC with EGFR mutation. Methods A Markov model was created based on the results of the ENSURE (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and chemotherapy. The model simulates cancer progression and all causes of death. All medical costs were calculated from the perspective of the Chinese healthcare system. Main outcome measures The primary outcomes are costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results The combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy, respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16 months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most influential factors were the health utility of PFS, the cost of erlotinib and the health utility of progressed disease. Conclusion Erlotinib monotherapy may be acceptable as a cost-effective first-line treatment for NSCLC compared with gemcitabine-based chemotherapy. The results were robust to changes in assumptions. Trial registration number NCT01342965 and CTONG-0802. PMID:29654023

Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

Directory of Open Access Journals (Sweden)

Li-li ZHANG

2013-09-01

Full Text Available Objective　To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods　One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results　Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions　Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

Precise image-guided irradiation of small animals: a flexible non-profit platform

International Nuclear Information System (INIS)

Tillner, Falk; Thute, Prasad; Löck, Steffen; Dietrich, Antje; Fursov, Andriy; Haase, Robert; Lukas, Mathias; Krause, Mechthild; Baumann, Michael; Bütof, Rebecca; Enghardt, Wolfgang; Rimarzig, Bernd; Sobiella, Manfred

2016-01-01

Preclinical in vivo studies using small animals are essential to develop new therapeutic options in radiation oncology. Of particular interest are orthotopic tumour models, which better reflect the clinical situation in terms of growth patterns and microenvironmental parameters of the tumour as well as the interplay of tumours with the surrounding normal tissues. Such orthotopic models increase the technical demands and the complexity of preclinical studies as local irradiation with therapeutically relevant doses requires image-guided target localisation and accurate beam application. Moreover, advanced imaging techniques are needed for monitoring treatment outcome. We present a novel small animal image-guided radiation therapy (SAIGRT) system, which allows for precise and accurate, conformal irradiation and x-ray imaging of small animals. High accuracy is achieved by its robust construction, the precise movement of its components and a fast high-resolution flat-panel detector. Field forming and x-ray imaging is accomplished close to the animal resulting in a small penumbra and a high image quality. Feasibility for irradiating orthotopic models has been proven using lung tumour and glioblastoma models in mice. The SAIGRT system provides a flexible, non-profit academic research platform which can be adapted to specific experimental needs and therefore enables systematic preclinical trials in multicentre research networks. (paper)

Quality of life, symptom status and physical performance in patients with advanced non-small cell lung cancer undergoing chemotherapy: an exploratory analysis of secondary data.

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Shallwani, Shirin M; Simmonds, Maureen J; Kasymjanova, Goulnar; Spahija, Jadranka

2016-09-01

Our objectives were: (a) to identify predictors of change in health-related quality of life (HRQOL) in patients with advanced non-small cell lung cancer (NSCLC) undergoing chemotherapy; and (b) to characterize symptom status, nutritional status, physical performance and HRQOL in this population and to estimate the extent to which these variables change following two cycles of chemotherapy. A secondary analysis of a longitudinal observational study of 47 patients (24 men and 23 women) with newly diagnosed advanced NSCLC receiving two cycles of first-line chemotherapy was performed. Primary outcomes were changes in HRQOL (physical and mental component summaries (PCS and MCS) of the 36-item Short-Form Health Survey (SF-36)). Predictors in the models included pre-chemotherapy patient-reported symptoms (Schwartz Cancer Fatigue Scale (SCFS) and Lung Cancer Subscale), nutritional screening (Patient-Generated Subjective Global Assessment) and physical performance measures (6-min Walk Test (6MWT), one-minute chair rise test and grip strength). Mean SF-36 PCS score, 6MWT distance and grip strength declined following two cycles of chemotherapy (pmental component of HRQOL accounting for 13% and 9% of the variance, respectively. No significant predictors were found for change in the physical component of HRQOL. Pre-chemotherapy 6MWT distance and fatigue severity predicted change in the mental component of HRQOL in patients with advanced NSCLC undergoing chemotherapy, while physical performance declined during treatment. Clinical management of these factors may be useful for HRQOL optimization in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Radiotherapy of elderly patients with non-small-cell lung cancer

International Nuclear Information System (INIS)

Nakano, Kikuo; Hiramoto, Takehiko; Kumagai, Kazuhiko; Tukamoto, Yuji; Furonaka, Makoto; Hayakawa, Masanobu; Nakamura, Kenji

1996-01-01

Treatment results of patients aged 75 years or older (elderly group) with non-small-cell lung cancer were compared with those of patients aged 74 years or younger (younger group). In patients with stage III disease, radiotherapy alone resulted in a median survival of 11.5 months in the younger group and 5.5 months in the elderly group. There was a significant difference in survival rate between the two groups (P=0.0008). Moreover, the elderly group patients more frequently died of pneumonia and radiation pneumonitis than the younger group patients. However, results of radiotherapy were similar in the two groups of patients with stage I and II disease. Accordingly, these findings suggested that radiotherapy is an appropriate treatment modality for elderly lung cancer patients, but that individualized radiotherapy is needed for those with locally advanced stage. (author)

Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

Directory of Open Access Journals (Sweden)

Zhang D

2016-06-01

Full Text Available Dianbao Zhang,1,* Xianfen Zhang,2,* Chunling Zhao1 1Department of Medical Oncology, 2Department of Cardiac Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China *These authors contributed equally to this work Aims: To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs associated with antivascular endothelial growth factor (VEGF agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC patients. Methods: We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR, and 95% confidence intervals (CIs were pooled according to the heterogeneity of included trials. Results: A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048, but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82 compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively was observed in advanced NSCLC patients receiving anti-VEGF agents. Conclusion: The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. Keywords: anti-VEGF agents, toxicity, arterial thromboembolic events, venous thromboembolic events, meta-analysis

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

OpenAIRE

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who resp...

The correlation between clinical factors and radiation pneumonitis in advanced stage non-small-cell lung cancer treated with concurrent radiochemotherapy

International Nuclear Information System (INIS)

Han Lei; Lu Bing; Fu Heyi; Hu Yinxiang; Gan Jiaying; Li Huiqin

2011-01-01

Objective: To evaluate clinical factors as predictors of radiation pneumonitis (RP)in advanced stage non-small cell lung cancer (NSCLC) patients treated with concurrent radio chemotherapy when gross tumor volume is 70 Gy. Methods: Data of 84 patients with histologically proved NSCLC treated with 3DCRT or IMRT were collected. To evaluate the correlation between clinical parameters and radiation pneumonitis (RP). The clinical parameters were considered: pathological type, therapy agents, age,gender, stage, karnofsky performance status (KPS), smoking status, diabetes, chronic obstructive pulmonary disease (COPD). Results: The occurrence of grade 1, 2 RP was 63%, 33%, respectively. In univariate analysis, diabetes was significantly associated with RP of ≥ grade 1(χ 2 =4.03, P = 0.045)and ≥grade 2(χ 2 = 15.59, P =0.000). KPS was significantly associated with RP of ≥grade 1(χ 2 =3.98, P = 0.046)and ≥grade 2(χ 2 = 5.21, P = 0.023). In logistic multivariate analysis, diabetes was significantly associated with RP of ≥grade 1(χ 2 =5.50, P =0.019)and ≥grade 2(χ 2 = 12.92, P =0.000). KPS was significantly associated with RP of ≥ grade 1(χ 2 = 6.29, P = 0.012)and ≥ grade 2(χ 2 = 6.61, P =0.010). Conclusion: The definite statistical significant risk factors of RP are diabetes and KPS. (authors)

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer.

Science.gov (United States)

Mellema, Wouter W; Masen-Poos, Lucie; Smit, Egbert F; Hendriks, Lizza E L; Aerts, Joachim G; Termeer, Arien; Goosens, Martijn J; Smit, Hans J M; van den Heuvel, Michel M; van der Wekken, Anthonie J; Herder, Gerarda J M; Krouwels, Frans H; Stigt, Jos A; van den Borne, Ben E E M; Haitjema, Tjeerd J; Staal-Van den Brekel, Agnes J; van Heemst, Robbert C; Pouw, Ellen; Dingemans, Anne-Marie C

2015-11-01

As suggested by in-vitro data, we hypothesize that subtypes of KRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinum-based chemotherapy, were retrieved from hospital databases. to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%), G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes (n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; pchemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non-Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235.

Science.gov (United States)

Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A; Johnson, Douglas W; Bradley, Jeffrey D; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

2016-06-01

In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on (18)F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Patients with locally advanced NSCLC underwent (18)F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient's primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address overfitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan-Meier curves and log-rank testing were used to compare outcomes among patient groups. Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm(3), and the optimal SumMean cutpoint for tumors above 93.3 cm(3) was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy. Validation studies are warranted. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Design of the Advanced Virgo non-degenerate recycling cavities

International Nuclear Information System (INIS)

Granata, M; Barsuglia, M; Flaminio, R; Freise, A; Hild, S; Marque, J

2010-01-01

Advanced Virgo is the project to upgrade the interferometric gravitational wave detector Virgo, and it foresees the implementation of power and signal non-degenerate recycling cavities. Such cavities suppress the build-up of high order modes of the resonating sidebands, with some advantage for the commissioning of the detector and the build-up of the gravitational signal. Here we present the baseline design of the Advanced Virgo non-degenerate recycling cavities, giving some preliminary results of simulations about the tolerances of this design to astigmatism, mirror figure errors and thermal lensing.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Roman, Nicholas O., E-mail: nroman@mcvh-vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Shepherd, Wes [Department of Pulmonology, Virginia Commonwealth University, Richmond, VA (United States); Mukhopadhyay, Nitai [Department of Biostatistics, Virginia Commonwealth University, Richmond, VA (United States); Hugo, Geoffrey D.; Weiss, Elisabeth [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

2012-08-01

Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

International Nuclear Information System (INIS)

Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

2012-01-01

Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior–posterior), and z (superior–inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy–based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

Advanced non-destructive methods for an efficient service performance

International Nuclear Information System (INIS)

Rauschenbach, H.; Clossen-von Lanken Schulz, M.; Oberlin, R.

2015-01-01

Due to the power generation industry's desire to decrease outage time and extend inspection intervals for highly stressed turbine parts, advanced and reliable Non-destructive methods were developed by Siemens Non-destructive laboratory. Effective outage performance requires the optimized planning of all outage activities as well as modern Non-destructive examination methods, in order to examine the highly stressed components (turbine rotor, casings, valves, generator rotor) reliably and in short periods of access. This paper describes the experience of Siemens Energy with an ultrasonic Phased Array inspection technique for the inspection of radial entry pinned turbine blade roots. The developed inspection technique allows the ultrasonic inspection of steam turbine blades without blade removal. Furthermore advanced Non-destructive examination methods for joint bolts will be described, which offer a significant reduction of outage duration in comparison to conventional inspection techniques. (authors)

Quality of life assessment in advanced non-small-cell lung cancer patients undergoing an accelerated radiotherapy regimen: report of ECOG study 4593

International Nuclear Information System (INIS)

Auchter, Richard M.; Scholtens, Denise; Adak, Sudeshna; Wagner, Henry; Cella, David F.; Mehta, Minesh P.

2001-01-01

Purpose: To prospectively evaluate the quality of life (QOL) before, at completion, and after therapy for patients receiving an accelerated fractionation schedule of radiotherapy for advanced, unresectable non-small-cell lung cancer in a Phase II multi-institutional trial. Methods and Materials: The Functional Assessment of Cancer Therapy-Lung (FACT-L) patient questionnaire was used to score the QOL in patients enrolled in the Eastern Cooperative Oncology Group Phase II trial (ECOG 4593) of hyperfractionated accelerated radiotherapy in non-small-cell lung cancer. Radiotherapy (total dose 57.6 Gy in 36 fractions) was delivered during 15 days, with three radiation fractions given each treatment day. The protocol was activated in 1993, and 30 patients had accrued by November 1995. The FACT-L questionnaire was administered at study entry (baseline), on the last day of radiotherapy (assessment 2), and 4 weeks after therapy (assessment 3). The FACT-L includes scores for physical, functional, emotional, and social well-being (33 items), and a subscale of lung cancer symptoms (10 additional items). The summation of the physical, functional, and lung cancer symptom subscales (21 items) constitutes the Trial Outcome Index (TOI), considered the most clinically relevant outcome measure in lung cancer treatment trials. Results: The FACT-L completion rates at the designated study time points were as follows: baseline, 30 of 30 (100%); assessment 2, 29 (97%) of 30; and assessment 3, 24 (80%) of 30. At treatment completion, statistically significant declines in QOL scores were noted, compared with baseline for physical and functional well-being. Emotional well-being scores improved at both assessment 2 and assessment 3. The physical and functional scores returned approximately to baseline values at assessment 3. The change in TOI score was evaluated as a function of the clinical response to treatment, toxicity grade, and survival; no clear association was noted. A trend for the

The role of Gefitinib in patients with non-small-cell lung cancer in India

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Asmita Anilkumar Mehta

2013-01-01

Full Text Available Background: Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, represents a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC. We analyzed the data of patients who received Gefitinib for NSCLC in a tertiary care center in South India. Materials and Methods: Sixty-three patients with advanced NSCLC who had received Gefitinib either after failure of conventional chemotherapy or were previously not treated as they were unfit or unwilling for conventional treatment were included in the analysis. Results: The median follow-up for the cohort was 311 days (range 11-1544 days. Median time to progression was 161 (range 9-883 days. Complete and partial remission was seen in 1 (2% and 6 (9% patients, respectively, with overall response rate of 11%. Twenty-four (38% patients had stable disease. Gefitinib was well tolerated with no significant side effects. Conclusion: Gefitinib shows anti-tumor activity in pretreated or previously untreated patients with advanced NSCLC. It has a favorable toxicity profile and is well tolerated. Gefitinib should be considered as a viable therapy in patients with NSCLC.

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

International Nuclear Information System (INIS)

Berman, Abigail T.; James, Sara St.; Rengan, Ramesh

2015-01-01

Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning

Treatment paradigms for advanced stage non-small cell lung cancer in the era of multiple lines of therapy.

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Stinchcombe, Thomas E; Socinski, Mark A

2009-02-01

The duration of first-line and the timing of second-line therapy for advanced non-small cell lung cancer has been an area of recent investigation. Five trials have been performed that have investigated shorter (3-4 cycles) versus longer duration of platinum-based therapy; four trials revealed an equivalent overall survival with the shorter duration of therapy, and one trial revealed superior survival with the longer duration of therapy. The toxicity and quality of life data has either been equivalent or favored the shorter duration of therapy. Two trials have investigated the timing of a second-line therapy after completion of four cycles of platinum-based therapy versus the standard treatment paradigm of initiating second-line therapy upon disease progression. Both of these trials have revealed a statistically significant improvement in the progression-free survival, and a trend towards improved survival for the earlier use of second-line therapy. Only 50 to 60% of patients on the standard treatment arm initiated second-line therapy, and the promising results observed are most likely related to the fact that a higher percentage of patients received second-line therapy on the experimental arm. Several trials have investigated maintenance chemotherapy, and these trials have not revealed a survival benefit probably due to the fact that many patients experience disease progression or unacceptable toxicity during the initial or maintenance therapy. The addition of a targeted agent (bevacizumab or cetuximab) to the initial chemotherapy and the continuation of the targeted agent after completion of the chemotherapy have yielded superior overall survival in comparison to chemotherapy alone. The incremental benefit of the maintenance therapy with the targeted agent is unknown.

Cetuximab and biomarkers in non-small-cell lung carcinoma

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Patil N

2012-07-01

Full Text Available Nitin Patil, Mohammed Abba, Heike AllgayerDepartment of Experimental Surgery, Medical Faculty Mannheim, University of Heidelberg and Molecular Oncology of Solid Tumors Unit, German Cancer Research Center (DKFZ, Heidelberg, GermanyAbstract: Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC, as in several other cancer types, the epidermal growth factor receptor (EGFR and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.Keywords: NSCLC, cetuximab, biomarker, cancer progression

The treatment of metastatic non-small cell lung cancer in the elderly: an evidence-based approach

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David E Dawe

2014-07-01

Full Text Available An increasing proportion of patients with advanced NSCLC are over 70 years old, raising unique challenges for treatment decision-making. While these patients are underrepresented in clinical trials, there is an emerging body of evidence associated with this group. The lesson of comprehensive geriatric assessment is that chronological age does not always correlate with physiological age and a variety of important comorbidities and geriatric syndromes can go undetected in a typical history and physical. These comorbidities and expected physiologic changes due to aging complicate decision-making around appropriate treatment. This review discusses geriatric assessment in elderly cancer patients and evaluates the current evidence for chemotherapy and targeted therapy for patients with advanced non-small cell lung cancer aged ≥70 years.

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial

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Rizvi, Naiyer A; Mazières, Julien; Planchard, David; Stinchcombe, Thomas E; Dy, Grace K; Antonia, Scott J; Horn, Leora; Lena, Hervé; Minenza, Elisa; Mennecier, Bertrand; Otterson, Gregory A; Campos, Luis T; Gandara, David R; Levy, Benjamin P; Nair, Suresh G; Zalcman, Gérard; Wolf, Jürgen; Souquet, Pierre-Jean; Baldini, Editta; Cappuzzo, Federico; Chouaid, Christos; Dowlati, Afshin; Sanborn, Rachel; Lopez-Chavez, Ariel; Grohe, Christian; Huber, Rudolf M; Harbison, Christopher T; Baudelet, Christine; Lestini, Brian J; Ramalingam, Suresh S

2015-01-01

Summary Background Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. Methods We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Findings Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Interpretation Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in

Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

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Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

2016-10-01

Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Science.gov (United States)

Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

2013-01-01

Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907

Non-proliferation and advances in nuclear science

International Nuclear Information System (INIS)

Iyengar, P.K.

1995-01-01

So far, the non-proliferation treaty (NPT) has concentrated on safeguard regimes based on technologies relating to the production of uranium and plutonium in nuclear reactors, and on their potential diversion for use in nuclear weapons. As nuclear science advances, however, nuclear technology both peaceful and for weapons will change, and for the NPT to remain relevant, it must reflect these changes. At this juncture, when the NPT is coming up for review in a year's time, it is important for physicists to take a fresh look at recent advances in nuclear science, and inform the policy-makers and the public at large about their potential for impacting nuclear technology in the future. In this article a few such advances are highlighted and their implications for the NPT are considered. (author). 4 refs

Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study

International Nuclear Information System (INIS)

Catalano, G.; Jereczek-Fossa, B.A.; Pas, T. de; Leon, M.E.; Cattani, F.; Spaggiari, L.; Veronesi, G.; Braud, F. de; Orecchia, R.

2005-01-01

Purpose: to evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA-IIIB non-small cell lung cancer (NSCLC). Patients and methods: iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. Results: from February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). Conclusion: in this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC. (orig.)

Cost and effectiveness studies in non-small cell lung cancer

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Pinar Yalcin-Balcik

2015-02-01

Full Text Available Lung cancer disease diagnosis and treatment is costly. As the numbers of inflicted rise so does the economic burden assumed for this cancer type. When the treatment expenditures are considered for all types of cancer, the lung cancer is thought to occupy a 20% share. The disease examined in two basic groups as small-cell lung cancer and non-small cell lung cancer (NSCLC is the most frequently encountered type of its kind nationally and in the World. This study considers the cost, effectiveness and cost effectiveness of platinum based chemotherapy medications with active ingredients pemetrexed and gemcitabine used for NSCLC. A review of studies relevant to the advanced stage NSCLC where majority of patients are positioned is foreseen to be useful to the decision makers since policy makers, regulating authorities and physicians require more information due to increased overall finance and costs, as well as treatment cost effectiveness. Furthermore, due to the entry attempt of pemetrexed active ingredient to the list of reimbursed medications for the first stage lung cancer treatment, it is assumed that a review of studies containing pemetrexed and gemcitabine will draw the attention of decision makers at the Social Security Instutition. [TAF Prev Med Bull 2015; 14(1.000: 55-64

Comparison of Outcomes for Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer Treated With Induction Chemotherapy Followed By Concurrent Chemoradiation vs. Concurrent Chemoradiation Alone

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Huang, Eugene H.; Liao Zhongxing; Cox, James D.; Guerrero, Thomas M.; Chang, Joe Y.; Jeter, Melinda; Borghero, Yerko; Wei Xiong; Fossella, Frank; Herbst, Roy S.; Blumenschein, George R.; Moran, Cesar; Allen, Pamela K.; Komaki, Ritsuko

2007-01-01

Purpose: To retrospectively compare outcomes for patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) treated at our institution with concurrent chemoradiation with or without induction chemotherapy. Methods and Materials: We retrospectively analyzed 265 consecutive patients who received definitive treatment with three-dimensional conformal radiation and concurrent chemotherapy. Of these, 127 patients received induction chemotherapy before concurrent chemoradiation. Results: The two groups of patients (with induction vs. without induction chemotherapy) were similar in age, performance status, weight loss, histology, grade, and stage. Patients who received induction chemotherapy had better overall survival (median, 1.9 vs. 1.4 years; 5-year rate, 25% vs. 12%; p < 0.001) and distant metastasis-free survival (5-year rate, 42% vs. 23%; p = 0.021). Locoregional control was not significantly different between the two groups. Multivariate analysis showed that induction chemotherapy was the most significant factor affecting overall survival, with a hazard ratio of 0.55 (95% confidence interval 0.40-0.75; p < 0.001). A planned subgroup analysis showed that induction chemotherapy was associated with a significant overall survival benefit for patients with adenocarcinoma or large-cell carcinoma (5-year rate, 24% vs. 8%; p = 0.003) but not for those with squamous cell carcinoma. A multivariate analysis of patients with adenocarcinoma or large-cell carcinoma confirmed that induction chemotherapy was the most significant factor associated with better overall survival, with a hazard ratio of 0.47 (95% confidence interval, 0.28-0.78; p = 0.003). Conclusion: Our retrospective analysis suggests that in combination with concurrent chemoradiation, induction chemotherapy may provide a small but significant survival benefit for patients with unresectable locally advanced adenocarcinoma or large-cell carcinoma of the lung

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

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Abigail T. Berman

2015-07-01

Full Text Available Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT, through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC, as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Bodner, William R. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Halmos, Balazs; Cheng, Haiying; Perez-Soler, Roman [Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Keller, Steven M. [Department of Cardiothoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Garg, Madhur [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2017-02-01

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for

A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

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Bang Sun-Hwi

2012-06-01

Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

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Xiaohui Zeng

Full Text Available BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC after four chemotherapeutic cycles (21 days per cycle of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP threshold of $16,349 (3 × per-capita gross domestic product of China. The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib

Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

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Dan PU

2013-11-01

Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

Science.gov (United States)

Liang, Wenhua; Wu, Xuan; Fang, Wenfeng; Zhao, Yuanyuan; Yang, Yunpeng; Hu, Zhihuang; Xue, Cong; Zhang, Jing; Zhang, Jianwei; Ma, Yuxiang; Zhou, Ting; Yan, Yue; Hou, Xue; Qin, Tao; Dinglin, Xiaoxiao; Tian, Ying; Huang, Peiyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

2014-01-01

Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons. We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR), progression free survival (PFS), overall survival (OS) were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs) based on Bayesian network integrated the efficacy and specific toxicities of all included treatments. Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, Picotinib (19%, 29%, NA, NA), respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib. The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially better efficacy but significant higher toxicities compared with gefitinib and icotinib.

Hybridization-based reconstruction of small non-coding RNA transcripts from deep sequencing data.

Science.gov (United States)

Ragan, Chikako; Mowry, Bryan J; Bauer, Denis C

2012-09-01

Recent advances in RNA sequencing technology (RNA-Seq) enables comprehensive profiling of RNAs by producing millions of short sequence reads from size-fractionated RNA libraries. Although conventional tools for detecting and distinguishing non-coding RNAs (ncRNAs) from reference-genome data can be applied to sequence data, ncRNA detection can be improved by harnessing the full information content provided by this new technology. Here we present NorahDesk, the first unbiased and universally applicable method for small ncRNAs detection from RNA-Seq data. NorahDesk utilizes the coverage-distribution of small RNA sequence data as well as thermodynamic assessments of secondary structure to reliably predict and annotate ncRNA classes. Using publicly available mouse sequence data from brain, skeletal muscle, testis and ovary, we evaluated our method with an emphasis on the performance for microRNAs (miRNAs) and piwi-interacting small RNA (piRNA). We compared our method with Dario and mirDeep2 and found that NorahDesk produces longer transcripts with higher read coverage. This feature makes it the first method particularly suitable for the prediction of both known and novel piRNAs.

Are there any dosimetric advantages in using VMAT for treatment of locally advanced non-small cell lung cancer?

International Nuclear Information System (INIS)

Rousseau, D.; Krhili, S.; Yossi, S.; Cellier, P.; Paumier, A.; Autret, D.; Dupas, A.; Edouard, M.; Mahe, M.A.; Giraud, P.; Le Pechoux, C.; Denis, F.

2012-01-01

Purpose. - To analyse the dosimetric differences between the conventional conformal radiation therapy (CR) and the volumetric modulated arc therapy (VMAT) for non-small-cell locally advanced lung cancer (NSCLC). Patients and methods. - Two plans (CR and VMAT) were calculated for ten NSCLC patients. Dose to PTV, organs at risk and external contours (body), conformity index (PTV volume/volume of the 95% reference isodose) and homogeneity index ([maximal dose - minimal dose]/dose prescription) were compared. Results. - Doses delivered to PTV (homogeneity index, maximal, minimal and mean dose) are similar with both techniques but conformity index is improved by 60% with VMAT: from 0.55 ± 0.07 with CR to 0.89 ± 0.07 with VMAT (P = 0.002). Pulmonary protection is improved with VMAT: with CR and VMAT, respectively, the mean lung dose is 14.1 ± 5.2 Gy and 12.2 ± 4.5 Gy, the lung volume which receives at least 30 Gy (V30) is 20 ± 8% and 14 ± 5%, and the V20 is 24 ± 11% and 20 ± 10% (P = 0.002). The mean dose received by the body is also 9% lower (P = 0.004) and V5 is 13% higher (P = 0.004) with VMAT. V10 and V15 were similar with both modalities. From 20 Gy and higher, irradiated body volume is larger with CR than with VMAT. The relative difference increases with the dose: from 10% for 20 Gy (P = 0.014) up to 39% for 62.7 Gy (P = 0.002). Conclusion. - Compared to CR, VMAT greatly improves conformity and reduces mean dose and dose delivered from 20 Gy and higher to the lungs and the body. (authors)

Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

Science.gov (United States)

Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

2016-01-01

If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. The multimodality treatment was feasible, and triple

Non small-cell lung cancer and treatment options after tyrosine kinase inhibitors failure in the first line

International Nuclear Information System (INIS)

Chowaniecova, G.

2014-01-01

Introduction: Advanced non-small cell lung cancer with present epidermal growth factor receptor (EGFR) sensitising mutation is standardly treated with tyrosine kinase inhibitors (TKI). During treatment a resistance to TKI develops, disease progresses. We differ primary and secondary resistance. The most effective treatment after TKI failure is not definitively proven. Standard chemotherapy is usually introduced, eventually it is possible to use other TKI in the next lines. Case: The author presents a case of 60-year old patient with lung adenocarcinoma with EGFR sensitising mutation, where primary resistance to TKI was observed. Chemotherapy after progression was introduced. Planned therapy with afatnib was not carried out due to deterioration of patient´s condition. Conclusion: Presented case of EGFR mutation-positive patient represents an example of not very frequent primary resistance to TKI. Mechanisms of primary resistance are not well understood. Treatment after first line TKI failure in non-small cell lung cancer with EGFR mutation represents a challenge for medical research. (author)

SUCCESSFUL REGISTRATION OF DOMESTIC BIOANALOGUE OF BEVACIZUMAB – NEW OPPORTUNITIES FOR EFFECTIVE TREA TMENT OF PATIENTS WITH NON-SQUAMOUS CELL NON-SMALL CELL LUNG CANCER

Directory of Open Access Journals (Sweden)

S. V. Orlov

2015-01-01

Full Text Available Comparison of the efficacy and safety of drugs "Avegra®" and "Avastin®" used in combination with paclitaxel and carboplatin as first-line therapy in patients with locally inoperable or metastatic NSCLC. The study included 138 patients, male and female aged 18 to 75 years with newly diagnosed inoperable or widespread metastatic NSCLC (except squamous cell NSCLC, relevant eligibility criteria. After passing screening, patients were centrally randomized in one of the study groups in a 1:1 ratio. Treatment was carried out according to the following scheme: "Avegra®" or "Avastin®", 15 mg/kg intravenously over 90 minutes immediately after carboplatin on day 1 of each 3‑week cycle + paclitaxel 175 mg/m² intravenously over 3 hours on day 1 of each 3‑week cycle + carboplatin dose required to achieve AUC 6 mg/ml×min, intravenously over 15–30 minutes, immediately following paclitaxel, on the first day of each three-week cycle. The treatment lasted for six cycles of three weeks or until progression or until the development of intolerable toxic effects. Based on CT scan assessment performed by an independent specialist, the overall response rate (ORR, partial response rate + complete response rate defined as a primary endpoint was 42.59% (95% CI 30.33–55.83% in "Avegra®" arm and 39.29% (95% CI 27.58–52.27% in "Avastin®" arm, respectively. The difference in ORR between study drug and comparator was 3.30% with 95% CI –14.96–21.40% (р =0.874, the Pearson x² test with Yates correction. The lower limit of calculated 95% CI (-14.96% exceeds the specified non-inferiority margin and it is indicating the non-inferiority of "Avegra®" efficacy compared to "Avastin®". During the study period the incidence of adverse events, including severe adverse events (grade 3–4 according to CTCAE related with the investigational drugs, did not have statistically significant differences in both study arms.The drug "Avegra®" in direct comparison to

Development of hemipenes in the ball python snake Python regius.

Science.gov (United States)

Leal, Francisca; Cohn, Martin J

2015-01-01

Within amniotes, external copulatory organs have undergone extensive morphological diversification. One of the most extreme examples is squamate (lizards and snakes) hemipenes, which are paired copulatory organs that extend from the lateral margins of the cloaca. Here, we describe the development of hemipenes in a basal snake, the ball python (Python regius). Snake hemipenes arise as a pair of lateral swellings on either side of the caudal part of the cloaca, and these paired outgrowths persist to form the left and right hemipenes. In non-squamate amniotes, external genitalia form from paired swellings that arise on the anterior side of the cloaca, which then fuse medially to form a single genital tubercle, the anlagen of the penis or clitoris. Whereas in non-squamate amniotes, Sonic hedgehog (Shh)-expressing cells of the cloacal endoderm form the urethral or sulcus epithelium and are required for phallus outgrowth, the hemipenes of squamates lack an endodermal contribution, and the sulcus does not express Shh. Thus, snake hemipenes differ from the genital tubercles of non-squamate amniotes both in their embryonic origins and in at least part of patterning mechanisms, which raises the possibility that hemipenes may not be direct homologs of the unpaired amniote penis. Nonetheless, we find that some developmental genes show similar expression patterns in snake hemipenes buds and non-squamate genital tubercles, suggesting that homologous developmental mechanisms are involved in aspects of external genital development across amniotes, even when these structures may have different developmental origins and may have arisen independently during evolution.

Bevacizumab in the treatment of NSCLC: patient selection and perspectives

Directory of Open Access Journals (Sweden)

Russo AE

2017-12-01

Full Text Available Alessia E Russo,1 Domenico Priolo,1 Giovanna Antonelli,1 Massimo Libra,2 James A McCubrey,3 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina (Messina, Italy; 2Laboratory of Translational Oncology & Functional Genomics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; 3Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA Abstract: Non-small-cell lung cancer (NSCLC represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis. Bevacizumab (bev; Avastin® is a recombinant humanized monoclonal antibody that neutralizes VEGF’s biologic activity through a steric blocking of its binding with VEGF receptor. Currently, bev is the only antiangiogenic agent approved for the first-line treatment of advanced or recurrent nonsquamous NSCLC in “bev-eligible” patients. The ineligibility to receive bev is related to its toxicity. In the pivotal trials of bev in NSCLC, fatal bleeding events including pulmonary hemorrhage were observed with rates higher in the chemotherapy-plus-bev group. Therefore, in order to reduce the incidence of severe pulmonary hemorrhage, numerous exclusion criteria have been characteristically applied for bev such as central tumor localization or tumor cavitation, use of anticoagulant therapy, presence of brain metastases, age of patients (elderly. Subsequent studies designed to evaluate the safety of bev have demonstrated that this agent is safe and

Advance High Temperature Inspection Capabilities for Small Modular Reactors: Part 1 - Ultrasonics

Energy Technology Data Exchange (ETDEWEB)

Bond, Leonard J. [Iowa State Univ., Ames, IA (United States); Bowler, John R. [Iowa State Univ., Ames, IA (United States)

2017-08-30

The project objective was to investigate the development non-destructive evaluation techniques for advanced small modular reactors (aSMR), where the research sought to provide key enabling inspection technologies needed to support the design and maintenance of reactor component performance. The project tasks for the development of inspection techniques to be applied to small modular reactor are being addressed through two related activities. The first is focused on high temperature ultrasonic transducers development (this report Part 1) and the second is focused on an advanced eddy current inspection capability (Part 2). For both inspection techniques the primary aim is to develop in-service inspection techniques that can be carried out under standby condition in a fast reactor at a temperature of approximately 250°C in the presence of liquid sodium. The piezoelectric material and the bonding between layers have been recognized as key factors fundamental for development of robust ultrasonic transducers. Dielectric constant characterization of bismuth scantanate-lead titanate ((1-x)BiScO₃-xPbTiO₃) (BS-PT) has shown a high Curie temperature in excess of 450°C , suitable for hot stand-by inspection in liquid metal reactors. High temperature pulse-echo contact measurements have been performed with BS-PT bonded to 12.5 mm thick 1018-low carbon steel plate from 20C up to 260 C. High temperature air-backed immersion transducers have been developed with BS-PT, high temperature epoxy and quarter wavlength nickel plate, needed for wetting ability in liquid sodium. Ultrasonic immersion measurements have been performed in water up to 92C and in silicone oil up to 140C. Physics based models have been validated with room temperature experimental data with benchmark artifical defects.

Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

2012-08-01

Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer. A phase I study

Energy Technology Data Exchange (ETDEWEB)

Gagel, B.; Piroth, M.; Pinkawa, M.; Fischedik, K.; Asadpour, B.; Schmachtenberg, A.; Eble, M.J. [Dept. of Radiotherapy, RWTH Aachen (Germany); Reinartz, P.; Zimny, M.; Buell, U. [Dept. of Nuclear Medicine, RWTH Aachen (Germany); Stanzel, S. [Inst. for Medical Statistics, RWTH Aachen (Germany); Breuer, C.; Skobel, E. [Dept. of Internal Medicine I, RWTH Aachen (Germany)

2006-05-15

Purpose: to determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). Patients and methods: ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m{sup 2}) and vinorelbine (30 mg/m{sup 2}) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [{sup 18}F] fluorodeoxyglucose positron emission tomography-(FDG-PET-) based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m{sup 2}. The dose of gemcitabine was increased by 100 mg/m{sup 2} until the MTD was realized. Three patients were enrolled for each dose level. Results: dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m{sup 2}, due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. Conclusion: after induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m{sup 2} every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy. (orig.)

Advanced uses of radiation in non-destructive evaluation

International Nuclear Information System (INIS)

Baldev Raj; Viswanathan, B.; Venkataraman, B.

1998-01-01

The increasing demand for newer materials and stringency of specifications, have expanded the scope of advanced uses of radiation in non-destructive evaluation of materials and industrial components. This paper highlights the application of some of the advanced techniques of radiography and residual stress measurements, using x-ray diffraction, for materials characterisation and testing, based on the results obtained at the author's laboratory. The application of positron annihilation techniques based on the use of radioisotopes and high resolution gamma ray spectroscopy, is introduced as non-destructive tools for materials characterisation. Selective examples of significant results obtained using this technique, on the radiation damage and early stages of fatigue damage in technologically important steels are reviewed from recent works at the author's laboratory and elsewhere. The scope of application of charge particle based thin layer activation method is briefly outlined. (author)

Discovery of non-peptide small molecular CXCR4 antagonists as anti-HIV agents: Recent advances and future opportunities.

Science.gov (United States)

Zhang, Heng; Kang, Dongwei; Huang, Boshi; Liu, Na; Zhao, Fabao; Zhan, Peng; Liu, Xinyong

2016-05-23

CXCR4 plays vital roles in HIV-1 life cycle for it's essential in mediating the interaction of host and virus and completing the entry process in the lifecycle of HIV-1 infection. Compared with some traditional targets, CXCR4 provides a novel and less mutated drug target in the battle against AIDS. Its antagonists have no cross resistance with other antagonists. Great achievements have been made recent years and a number of small molecular CXCR4 antagonists with diversity scaffolds have been discovered. In this review, recent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists are described. Moreover, some classical medicinal chemistry strategies and novel methodologies are also introduced. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Correlation of pre-and post-induction chemotherapy 18-FDG PET findings with histopathology in patients with locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Chan, Andrea M.; Berlangieri, Sam; Ngai, Michael W.

2009-01-01

Full text: Objective: To correlate 18F-FDG PET metabolic response to therapy with histopathology and survival, in patients with locally advanced (stage IIl) non-small cell lung carcinoma (NSCLC) receiving induction chemotherapy. Methods: A retrospective review of all patients with stage III NSCLC planned for induction chemotherapy and surgical resection, in whom pre- and post-chemotherapy FDG-PET at Austin Health between 2004 and 2007 was performed. The staging and positive nodal stations as determined by PET was compared to histopathological findings after resection. The tumour response on serial FDG PET was also compared to overall outcome. Results: 9 patients were included. There was a 100 % correlation between pre- or post- chemotherapy nodal staging and final histopathological nodal stage. Ninety percent of all positive nodal stations (9/10) seen on histopathology were correctly localised by pre- or post-chemotherapy FDG PET. Only one patient with a metastatic lymph node at nodal station 9 R could not be localised by prior PET studies. Of the patients in whom a down-staging in tumour status was observed on the postchemotherapy FDG-PET, 83% (5/6) of patients were still alive (follow-up range of 8 to 40 months) as compared with 33% (1/3 ) (follow-up range of 9-13 months) for non-responders. Conclusion: There is good correlation between pre- and/or post- chemotherapy FDG PET and final histopathology for the nodal staging of stage III NSCLC. There is an overall trend for those patients in whom PET resulted in a down-staging of tumour to have a longer survival.

Mechanical characteristics of historic mortars from tests on small-sample non-standard on small-sample non-standard specimens

Czech Academy of Sciences Publication Activity Database

Drdácký, Miloš; Slížková, Zuzana

2008-01-01

Roč. 17, č. 1 (2008), s. 20-29 ISSN 1407-7353 R&D Projects: GA ČR(CZ) GA103/06/1609 Institutional research plan: CEZ:AV0Z20710524 Keywords : small-sample non-standard testing * lime * historic mortar Subject RIV: AL - Art, Architecture, Cultural Heritage

Gefitinib versus vinorelbine in chemotherapy-naive elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized, phase II study.

Science.gov (United States)

Crinò, Lucio; Cappuzzo, Federico; Zatloukal, Petr; Reck, Martin; Pesek, Milos; Thompson, Joyce C; Ford, Hugo E R; Hirsch, Fred R; Varella-Garcia, Marileila; Ghiorghiu, Serban; Duffield, Emma L; Armour, Alison A; Speake, Georgina; Cullen, Michael

2008-09-10

This phase II, open-label, parallel-group study compared gefitinib with vinorelbine in chemotherapy-naïve elderly patients with advanced non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients (age >or= 70 years) were randomly assigned to gefitinib (250 mg/d orally) or vinorelbine (30 mg/m(2) infusion on days 1 and 8 of a 21-day cycle). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and tolerability. Exploratory end points included epidermal growth factor receptor (EGFR) gene copy number by fluorescent in situ hybridization (FISH). Patients were randomly assigned to gefitinib (n = 97) or to vinorelbine (n = 99). Hazard ratios (HR; gefitinib v vinorelbine) were 1.19 (95% CI, 0.85 to 1.65) for PFS and 0.98 (95% CI, 0.66 to 1.47) for OS. ORR and disease control rates were 3.1% (95% CI, 0.6 to 8.8) and 43.3% (for gefitinib) and 5.1% (95% CI, 1.7 to 11.4) and 53.5% (for vinorelbine), respectively. Overall QOL improvement and PSI rates were 24.3% and 36.6% (for gefitinib) and 10.9% and 31.0% (for vinorelbine), respectively. In the 54 patients who were EGFR FISH-positive, HRs were 3.13 (95% CI, 1.45 to 6.76) for PFS and 2.88 (95% CI, 1.21 to 6.83) for OS. There were fewer treatment-related grade 3 to 5 adverse events with gefitinib (12.8%) than with vinorelbine (41.7%). There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy-naïve, unselected elderly patients with advanced NSCLC, but there was better tolerability with gefitinib. Individuals who were EGFR FISH-positive benefited more from vinorelbine than from gefitinib; this unexpected finding requires further study.

Consequences of Anatomic Changes and Respiratory Motion on Radiation Dose Distributions in Conformal Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Britton, Keith R.; Starkschall, George; Liu, Helen; Chang, Joe Y.; Bilton, Stephen; Ezhil, Muthuveni; John-Baptiste, Sandra C.; Kantor, Michael; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

2009-01-01

Purpose: To determine the effect of interfractional changes in anatomy on the target and normal tissue dose distributions during course of radiotherapy in non-small-cell lung cancer patients. Methods and Materials: Weekly respiration-correlated four-dimensional computed tomography scans were acquired for 10 patients. Original beam arrangements from conventional and inverse treatment plans were transferred into each of the weekly four-dimensional computed tomography data sets, and the dose distributions were recalculated. Dosimetric changes to the target volumes and relevant normal structures relative to the baseline treatment plans were analyzed by dose-volume histograms. Results: The overall difference in the mean ± standard deviation of the doses to 95% of the planning target volume and internal target volume between the initial and weekly treatment plans was -11.9% ± 12.1% and -2.5% ± 3.9%, respectively. The mean ± standard deviation change in the internal target volume receiving 95% of the prescribed dose was -2.3% ± 4.1%. The overall differences in the mean ± standard deviation between the initial and weekly treatment plans was 3.1% ± 6.8% for the total lung volume exceeding 20 Gy, 2.2% ± 4.8% for mean total lung dose, and 34.3% ± 43.0% for the spinal cord maximal dose. Conclusion: Serial four-dimensional computed tomography scans provided useful anatomic information and dosimetric changes during radiotherapy. Although the observed dosimetric variations were small, on average, the interfractional changes in tumor volume, mobility, and patient setup was sometimes associated with dramatic dosimetric consequences. Therefore, for locally advanced lung cancer patients, efforts to include image-guided treatment and to perform repeated imaging during the treatment course are recommended

Supervisory Control System Architecture for Advanced Small Modular Reactors

Energy Technology Data Exchange (ETDEWEB)

Cetiner, Sacit M [ORNL; Cole, Daniel L [University of Pittsburgh; Fugate, David L [ORNL; Kisner, Roger A [ORNL; Melin, Alexander M [ORNL; Muhlheim, Michael David [ORNL; Rao, Nageswara S [ORNL; Wood, Richard Thomas [ORNL

2013-08-01

This technical report was generated as a product of the Supervisory Control for Multi-Modular SMR Plants project within the Instrumentation, Control and Human-Machine Interface technology area under the Advanced Small Modular Reactor (SMR) Research and Development Program of the U.S. Department of Energy. The report documents the definition of strategies, functional elements, and the structural architecture of a supervisory control system for multi-modular advanced SMR (AdvSMR) plants. This research activity advances the state-of-the art by incorporating decision making into the supervisory control system architectural layers through the introduction of a tiered-plant system approach. The report provides a brief history of hierarchical functional architectures and the current state-of-the-art, describes a reference AdvSMR to show the dependencies between systems, presents a hierarchical structure for supervisory control, indicates the importance of understanding trip setpoints, applies a new theoretic approach for comparing architectures, identifies cyber security controls that should be addressed early in system design, and describes ongoing work to develop system requirements and hardware/software configurations.

Advances in endoscopic surgery for small animal reproduction.

Science.gov (United States)

Katic, N; Dupré, G

2016-09-01

Although endoscopic surgery entered its "golden era" in the mid-1980s, it is still advancing at a tremendous pace. Novel surgical techniques and devices are continuously developed and applied, and new indications (and/or contraindications) for the use of endoscopic surgery are routinely reported in the literature and subjected to systematic assessments. Although endoscopic surgery (laparoscopy in particular) has already become established as the gold standard in human medicine, it has yet to be proven as a viable alternative to open surgery in the field of veterinary medicine. The advantages of minimally invasive surgery include better intra-operative visualization, reduced postoperative pain, reduced scar formation and increased postoperative mobility. Therefore, it is reasonable to expect that the application of this will continue to expand. Small animal reproduction, a field within the broad discipline of veterinary medicine, has already recognized and begun to reap the benefits of endoscopic surgery. Herein, we retrospectively review the most recent successful novel applications of endoscopic surgery in the small animal reproduction system to provide small animal reproductive surgeons with important knowledge to help improve their own veterinarian medical practice. © 2016 Blackwell Verlag GmbH.

The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies and perspective.

Science.gov (United States)

Guirgis, Helmy M

2018-02-20

The impact of programmed death receptor-ligand1 (PD-L1) on costs and value of the immune check point inhibitors (ICPI) has received minimal attention. 1- Design a sliding scale to grade survival in 2nd-line non-small-cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo), Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). Previously reported median overall survival (OS) and prices posted by parent company were utilized. The OS gains over controls in days were graded (gr) from A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year. Adverse events treatment costs (AEsTC) were reported separately. The cost/life-year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days × 360 days. The relative value of the ICPI were expressed as $100,000/C/LYG. Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr ¾ > 20%, AEsTC $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr ¾ were  10%. Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to 162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g 57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1 enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and Pembro from 0.15 to 0.53. Simplified methodology to grade OS and weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC, value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and enhanced value at seemingly justifiable costs.

Curative radiotherapy in non-small cell carcinoma of the lung

International Nuclear Information System (INIS)

Talton, B.M.; Constable, W.C.; Kersh, C.R.

1990-01-01

Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques.Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk

Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

Science.gov (United States)

Vallejo, C; Romero, A; Perez, J; Cuevas, M; Lacava, J; Sabatini, C; Dominguez, M; Rodriguez, R; Barbieri, M; Romero Acuña, L; Romero Acuña, J; Langhi, M; Amato, S; Salvadori, M; Ortiz, E; Machiavelli, M; Leone, B

1996-12-01

We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

Non-small cell lung cancer: current status of chemoradiation for locally advanced disease and an update on susceptibility and prevention

International Nuclear Information System (INIS)

Byhardt, Roger W.

1996-01-01

Locally advanced, inoperable non-small cell lung cancer (NSCLC) afflicts 40,000 patients yearly. The traditional treatment has been radiation therapy (RT) alone with 5 year survival rates averaging around 5%. Recent reports of randomized clinical trials using combined radiochemotherapy suggest significant improvement in survival compared to RT alone. These trials are difficult to evaluate because of differences in dose, timing and sequencing of both the chemotherapy (CT) and the RT. Dr. Byhardt will give an overview of the significant chemoradiation trials, especially with respect to the factors associated with reduction of local failure and distant metastasis. Dr. Tishler will review the biologic rationale of these regimens and make some prognostications about the potential role of new chemotherapy agents, new developments in RT dose-time-fractionation, and new RT technology in future radiochemotherapy trials. While progress continues to be made using the more traditional cancer treatment modalities, investigations in NSCLC epidemiology and prevention are providing new insights regarding susceptibility, etiology, failure risk stratification, and potential avenues of therapeutic intervention. Dr. Spitz will discuss NSCLC as a paradigm of an environmentally induced disease in which host susceptibility may be determined by genetically determined modulation of environmental exposures. A mutagen sensitivity assay can determine individuals at high risk for developing NSCLC if exposed to carcinogens such as those in cigarette smoke. This susceptibility may have prognostic implications that could influence choice of therapy. Highly susceptible individuals can also be selected for special counseling, smoking cessation, with consideration given to chemoprevention. Dr. Gritz will review major work done in this area

Advanced technologies related to a high temperature superconductor for small laboratory experiments

International Nuclear Information System (INIS)

Ogawa, Yuichi; Mito, Toshiyuki; Yanagi, Nagato

2006-01-01

Advanced technologies related to a high temperature superconductor materials and small refrigerator are reviewed. Mini-RT/RT-1 is designed and constructed as a plasma examination device. The element technology of low temperature apparatus, the results of performance tests and application examples are explained. The superconductors such as Bi 2 Sr 2 CaCu 2 O 8 (Bi-2212) for the low temperature phase, Bi 2 Sr 2 Ca 2 Cu 3 O 10 (Bi-2223) for the high temperature phase, and YBa 2 Cu 3 O y (YBCO or Y123) are described. Advanced 4K-Giford-Mcmahon (GM) refrigerator on the market put superconductor coil made of low temperature superconductor metals to practical use and extends its application field. Small laboratory is able to experiment on the high temperature superconductor materials. (S.Y.)

Clinical (non-histological) diagnosis of advanced prostate cancer ...

African Journals Online (AJOL)

2014-08-03

Aug 3, 2014 ... the cost of prostate biopsy itself is an important consideration, especially in ... ZAR1 068 200 (US$1 = ZAR8) was saved by treating men with advanced. ACP on the ... avoid the issue of possible non-compliance. The costs of ...

[Advances in the Research of the Regulation of Chinese Traditional Medicine Monomer and Its Derivatives on Autophagy in Non-small Cell Lung Cancer].

Science.gov (United States)

Xiang, Meiyi; Li, Ruilei; Zhang, Zhiwei; Song, Xin

2017-03-20

The high morbidity and mortality of non-small cell lung cancer (NSCLC) did influence the quality of life of tumor patients world-wide. There is an urgent need to develop new therapies that have high anti-tumor activity and low toxicity side effects. It is widely accepted that autophagy can play diverse roles in carcinogenesis, such as induces pro-death of lung cancer cells or helps the escape from cell death, making it become a proper anticancer target. It's believed that various monomers of Chinese traditional medicine closely correlates to anti-NSCLC activities, and that even could affect the acquired multiple drug resistance (MDR). Furthermore, autophagy might be the underling mechanisms which could play a role as the candidate targets of natural active compounds. Recent studies of terpenoids, alkaloid, dietary polyphenols, saponins and other active ingredients that extracted from a large variety of herbs suggest that different monomer compounds could either regulate the activity of pro-death autophagy or influence the level of protective autophagy of NSCLC cells, thus changing their drug sensitivity and cell viability. This paper aims to give a systemic description of the latest advances about natural compounds and their derivatives that involved in tumorigenesis of NSCLC via inducing the autophagy.

Multidisciplinary team approach for the management of patients with locally advanced non-small cell lung cancer: Searching the evidence to guide the decision

Energy Technology Data Exchange (ETDEWEB)

Oh, In Jae; Ahn, Sung Ja [Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

2017-03-15

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article.

Multidisciplinary team approach for the management of patients with locally advanced non-small cell lung cancer: Searching the evidence to guide the decision

International Nuclear Information System (INIS)

Oh, In Jae; Ahn, Sung Ja

2017-01-01

Locally advanced non-small cell lung cancer (LA-NSCLC) is composed of heterogeneous subgroups that require a multidisciplinary team approach in order to ensure optimal therapy for each patient. Since 2010, the National Comprehensive Cancer Network has recommended chemoradiation therapy (CRT) for bulky mediastinal disease and surgical combination for those patients with single-station N2 involvement who respond to neoadjuvant therapy. According to lung cancer tumor boards, thoracic surgeons make a decision on the resectability of the tumor, if it is determined to be unresectable, concurrent CRT (CCRT) is considered the next choice. However, the survival benefit of CCRT over sequential CRT or radiotherapy alone carries the risk of additional toxicity. Considering severe adverse events that may lead to death, fit patients who are able to tolerate CCRT must be identified by multidisciplinary tumor board. Decelerated approaches, such as sequential CRT or high-dose radiation alone may be a valuable alternative for patients who are not eligible for CCRT. As a new treatment strategy, investigators are interested in the application of the innovative radiation techniques, trimodality therapy combining surgery after high-dose definitive CCRT, and the combination of radiation with targeted or immunotherapy agents. The updated results and on-going studies are thoroughly reviewed in this article

Parent-Child Communication and Adjustment Among Children With Advanced and Non-Advanced Cancer in the First Year Following Diagnosis or Relapse.

Science.gov (United States)

Keim, Madelaine C; Lehmann, Vicky; Shultz, Emily L; Winning, Adrien M; Rausch, Joseph R; Barrera, Maru; Gilmer, Mary Jo; Murphy, Lexa K; Vannatta, Kathryn A; Compas, Bruce E; Gerhardt, Cynthia A

2017-09-01

To examine parent-child communication (i.e., openness, problems) and child adjustment among youth with advanced or non-advanced cancer and comparison children. Families (n = 125) were recruited after a child's diagnosis/relapse and stratified by advanced (n = 55) or non-advanced (n = 70) disease. Comparison children (n = 60) were recruited from local schools. Children (ages 10-17) reported on communication (Parent-Adolescent Communication Scale) with both parents, while mothers reported on child adjustment (Child Behavior Checklist) at enrollment (T1) and one year (T2). Openness/problems in communication did not differ across groups at T1, but problems with fathers were higher among children with non-advanced cancer versus comparisons at T2. Openness declined for all fathers, while changes in problems varied by group for both parents. T1 communication predicted later adjustment only for children with advanced cancer. Communication plays an important role, particularly for children with advanced cancer. Additional research with families affected by life-limiting conditions is needed. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Enteroclysis of non-neoplastic disorders of the small intestine

International Nuclear Information System (INIS)

Nolan, D.J.

2000-01-01

Enteroclysis is now widely used for examining the jejunum and ileum. The technique is ideal for demonstrating the extent and severity of disorders that cause morphological changes to the small intestine. In this review many non-neoplastic small intestinal disorders as demonstrated by enteroclysis are described and illustrated. (orig.)

Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

Science.gov (United States)

Zhang, Yaxiong; Zhang, Zhonghan; Huang, Xiaodan; Kang, Shiyang; Chen, Gang; Wu, Manli; Miao, Siyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

2017-09-01

Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib). Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of a prognostic scoring system based on the systemic inflammatory and nutritional status of patients with locally advanced non-small-cell lung cancer treated with chemoradiotherapy

International Nuclear Information System (INIS)

Mitsuyoshi, Takamasa; Matsuo, Yukinori; Itou, Hitoshi; Shintani, Takashi; Iizuka, Yusuke; Kim, Young Hak; Mizowaki, Takashi

2018-01-01

Systemic inflammation and poor nutritional status have a negative effect on the outcomes of cancer. Here, we analyzed the effects of the pretreatment inflammatory and nutritional status on clinical outcomes of locally advanced non-small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. We retrospectively reviewed 89 patients with locally advanced NSCLC treated with chemoradiotherapy between July 2006 and June 2013. Serum C-reactive protein (CRP) was assessed as an inflammatory marker, and serum albumin, body mass index (BMI) and skeletal mass index were assessed as nutritional status markers. The relationships between these markers and overall survival (OS) were assessed. The median OS was 24.6 months [95% confidence interval (CI): 19.4–39.3 months]. During follow-up, 58 patients (65%) had disease recurrence and 52 patients (58%) died. In multivariate Cox hazard analysis, CRP levels and BMI approached but did not achieve a significant association with OS (P = 0.062 and 0.094, respectively). Recursive partitioning analysis identified three prognostic groups based on hazard similarity (CRP-BMI scores): 0 = CRP < 0.3 mg/dl, 1 = CRP ≥ 0.3 mg/dl and BMI ≥ 18.5 kg/m 2 , and 2 = CRP ≥ 0.3 mg/dl and BMI < 18.5 kg/m 2 . The CRP-BMI score was significantly associated with OS (P = 0.023). Patients with scores of 0, 1 and 2 had median OS of 39.3, 24.5 and 14.5 months, respectively, and the scores also predicted the probability of receiving salvage treatment after recurrence. The CRP-BMI score is thus a simple and useful prognostic marker of clinical outcome for patients with locally advanced NSCLC treated with chemoradiotherapy.

Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer

Science.gov (United States)

Liu, Guangbo; Pei, Fen; Yang, Fengqing; Li, Lingxiao; Amin, Amit Dipak; Liu, Songnian; Buchan, J. Ross; Cho, William C.

2017-01-01

Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics. PMID:28208579

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

Science.gov (United States)

Han, Jing; Wang, Dongjin; Di, Shouyin; Hu, Wei; Liu, Dong; Li, Xiaofei; Reiter, Russel J.; Yan, Xiaolong

2016-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC. PMID:27102150

Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

Science.gov (United States)

Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

2016-08-01

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Stereotactic radiotherapy for non-small cell lung cancer: From concept to clinical reality. 2011 update

International Nuclear Information System (INIS)

Girard, N.; Mornex, F.

2011-01-01

Only 60% of patients with early-stage non-small cell lung cancer (NSCLC), a priori bearing a favorable prognosis, undergo radical resection because of the very frequent co-morbidities occurring in smokers, precluding surgery to be safely performed. Stereotactic radiotherapy consists of the use of multiple radiation micro-beams, allowing high doses of radiation to be delivered to the tumour (ranging from 7.5 to 20 Gy per fraction) in a small number of fractions (one to eight on average). Several studies with long-term follow-up are now available, showing the effectiveness of stereotactic radiotherapy to control stage I/II non-small cell lung cancer in medically inoperable patients. Local control rates are consistently reported to be above 95% with a median survival of 34 to 45 months. Because of these excellent results, stereotactic radiation therapy is now being evaluated in operable patients in several randomized trials with a surgical arm. Ultimately, the efficacy of stereotactic radiotherapy in early-stage tumours leads to hypothesize that it may represent an opportunity for locally-advanced tumors. The specific toxicities of stereotactic radiotherapy mostly correspond to radiation-induced chest wall side effects, especially for peripheral tumours. The use of adapted fractionation schemes has made feasible the use of stereotactic radiotherapy to treat proximal tumours. Overall, from a technical concept to the availability of specific treatment devices and the publication of clinical results, stereotactic radiotherapy represents a model of implementation in thoracic oncology. (authors)

Crizotinib for Untreated Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Science.gov (United States)

Morgan, Philip; Woolacott, Nerys; Biswas, Mousumi; Mebrahtu, Teumzghi; Harden, Melissa; Hodgson, Robert

2017-09-01

As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund. As part of this new appraisal, the company included a price discount patient access scheme (PAS). The Centre for Reviews and Dissemination and Centre for Health Economics Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company's submission and the ERG's review and summarises the resulting NICE guidance issued in August 2016. The main clinical-effectiveness data were derived from a multicentre randomised controlled trial-PROFILE 1014-that compared crizotinib with pemetrexed chemotherapy in combination with carboplatin or cisplatin in patients with untreated non-squamous ALK-positive NSCLC. In the trial, crizotinib demonstrated improvements in progression-free survival (PFS) and overall survival (OS). The company's economic model was a three-state 'area under the curve' Markov model. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be greater than £50,000 per quality-adjusted life-year (QALY) gained (excluding the PAS discount). The ERG assessment of the evidence submitted by the company raised a number of concerns. In terms of the clinical evidence, the OS benefit was highly uncertain due to the cross-over permitted in the trial and the immaturity of the data; only 26% of events had occurred by the data cut-off point. In the economic modelling, the most significant concerns related to the analysis

Tracking the Evolution of Non-Small-Cell Lung Cancer

DEFF Research Database (Denmark)

Jamal-Hanjani, Mariam; Wilson, Gareth A.; McGranahan, Nicholas

2017-01-01

Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine...... as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .)....

Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer

DEFF Research Database (Denmark)

Borghaei, Hossein; Alpaugh, Katherine; Hedlund, Gunnar

2009-01-01

recognizing the tumor-associated antigen 5T4. PATIENTS AND METHODS: Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose...

Energy Multiplier Module (EM{sup 2}) - advanced small modular reactor for electricity generation

Energy Technology Data Exchange (ETDEWEB)

Bertch, T.; Schleicher, R.; Choi, H.; Rawls, J., E-mail: timothy.bertch@ga.com [General Atomics, San Diego, California (United States)

2013-07-01

In order to provide cost effective nuclear energy in other than large reactor, large grid applications, fission technology needs to make further advances. 'Convert and burn' fast reactors offer long life cores, improved fuel utilization, reduced waste and other benefits while achieving cost effective energy production in a smaller reactor. General Atomics' Energy Multiplier Module (EM{sup 2}), a helium-cooled compact fast reactor that augments its fissile fuel load with either depleted uranium (DU) or used nuclear fuel (UNF). The convert and burn in-situ provides 250 MWe with a 30 year core life. High temperature provides a simple, high efficiency direct cycle gas turbine which along with modular construction, fewer systems, road shipment and minimum on site construction support cost effectiveness. Additional advantages in fuel cycle, non-proliferation and siting flexibility and its ability to meet all safety requirements make for an attractive power source, especially in remote and small grid regions. (author)

Advancing Toxicology Research Using In Vivo High Throughput Toxicology with Small Fish Models

Science.gov (United States)

Planchart, Antonio; Mattingly, Carolyn J.; Allen, David; Ceger, Patricia; Casey, Warren; Hinton, David; Kanungo, Jyotshna; Kullman, Seth W.; Tal, Tamara; Bondesson, Maria; Burgess, Shawn M.; Sullivan, Con; Kim, Carol; Behl, Mamta; Padilla, Stephanie; Reif, David M.; Tanguay, Robert L.; Hamm, Jon

2017-01-01

Summary Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health. PMID:27328013

Treatment of Early Stage Non-Small Cell Lung Cancer: Surgery or Stereotactic Ablative Radiotherapy?

Directory of Open Access Journals (Sweden)

Esengül Koçak Uzel

2015-03-01

Full Text Available The management of early-stage Non-small Cell Lung Cancer (NSCLC has improved recently due to advances in surgical and radiation modalities. Minimally-invasive procedures like Video-assisted thoracoscopic surgery (VATS lobectomy decreases the morbidity of surgery, while the numerous methods of staging the mediastinum such as endobronchial and endoscopic ultrasound-guided biopsies are helping to achieve the objectives much more effectively. Stereotactic Ablative Radiotherapy (SABR has become the frontrunner as the standard of care in medically inoperable early stage NSCLC patients, and has also been branded as tolerable and highly effective. Ongoing researches using SABR are continuously validating the optimal dosing and fractionation schemes, while at the same time instituting its role for both inoperable and operable patients.

Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies

International Nuclear Information System (INIS)

Muggia, F.M.; Blum, R.H.; Foreman, J.D.

1984-01-01

Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages

Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies

Energy Technology Data Exchange (ETDEWEB)

Muggia, F.M. (NYU Medical Center, New York); Blum, R.H.; Foreman, J.D.

1984-01-01

Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages.

Cetuximab for treating non-small cell lung cancer.

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Mazzarella, Luca; Guida, Alessandro; Curigliano, Giuseppe

2018-04-01

Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.

Treatment of stage III non-small cell lung cancer and limited-disease small-cell lung cancer

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El Sharouni, S.Y.

2009-01-01

This thesis concerns the treatment of stage III non-small cell lung cancer (NSCLC) and limited disease small-cell lung cancer (SCLC). We described a systematic review on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCLC stage III with the aim to define the

Feasibility of stereotactic body radiotherapy for locally-advanced non-small cell lung cancer

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Katrina Woodford

2017-10-01

Full Text Available SBRT was feasible for approximately half of the locally-advanced NSCLC patients we assessed and for these patients has the potential to reduce a 30 fraction course to 12 fractions. Using SBRT in this setting requires compromises in techniques and further compromises may allow SBRT in a greater proportion of patients.

Prevalence of advanced adenomas in small and diminutive colon polyps using direct measurement of size.

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Tsai, Franklin C; Strum, Williamson B

2011-08-01

Most studies reporting polyp size use visual estimates. Determining the prevalence of advanced histology based on direct measurement of polyp size may help guide the management of polyps found at optical colonoscopy (OC) and CT colonography (CTC). We designed a large, prospective study to assess the prevalence of advanced adenomas based on direct measurement of polyp size by a certified pathologists' assistant as reported in the pathology report. Patients between 40 and 89 years of age who presented for screening colonoscopy were included in our study. Advanced adenomas were defined as ≥10 mm or ≥25% villous features, high grade dysplasia or cancer. Polyps were divided by size into three groups: diminutive (≤5 mm), small (6-9 mm) and large (≥10 mm). If more than one adenoma was present, the most advanced was used for analysis. We evaluated 6,905 consecutive patients referred for colonoscopy between January 2005 and December 2006. Of the 4,967 who met the inclusion criteria, the mean age was 58.8 and consisted of 59% women. Overall, 930 (18.7%) had an adenoma; 248 (5%) were advanced adenomas including 8 (0.16%) cancers. Of 89 polyps≥10 mm, 76 (85%) had advanced histology; of 247 polyps 6-9 mm, 67 (27%) were advanced; of 1,025 polyps ≤5 mm, 105 (10%) were advanced. Thus, 172 of 248 (69%) patients with advanced adenomas had small or diminutive adenomas. Our data indicate the majority (69%) of advanced adenomas are advanced adenomas (10%). These findings may help guide the management of sub-centimeter colon polyps found by OC or CTC.

Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

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Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

2017-02-07

Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

Micrometastasis in non-small-cell lung cancer: Detection and staging

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Gholamreza Mohajeri

2012-01-01

Full Text Available Background: The clinical relevance of bone marrow micrometastasis (BMM in non-small-cell lung cancer is undetermined, and the value of such analyses in advanced stage patients has not been clearly assessed previously. This study was conducted to estimate the accuracy of both polymerase chain reaction (PCR and immunohistochemistry (IHC in micrometastases detection and determine the best site for bone marrow biopsy in order to find micrometastasis. Methods: This prospective cross-sectional study was performed in the Department of Thoracic Surgery, Alzahra University Hospital from September 2008 to June 2009. To evaluate the bone marrow, a 3-cm rib segment and an aspirated specimen from the iliac bone prior to tumor resection were taken. PCR and IHC were performed for each specimen to find micrometastasis. Results: Of 41 patients, 14 (34% were positive for BMM by PCR compared with two positive IHC (4.8%. All BMMs were diagnosed in rib segments, and iliac specimens were all free from metastatic lesion. Our data showed no significant association between variables such as age, sex, histology, tumor location, side of tumor, involved lobe, smoking, or weight loss and presence of BMM. Conclusion: PCR could use as a promising method for BMM detection. BMM in a sanctuary site (rib is not associated with advanced stages of lung cancer. In addition, when predictor variables such as age, sex, histology, tumor location, smoking, or weight loss are analyzed, no correlation can be found between micrometastasis prevalence and any of those variables.

Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study.

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Niho, Seiji; Ohe, Yuichiro; Ohmatsu, Hironobu; Umemura, Shigeki; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

2017-06-01

We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC). Patients not showing disease progression after induction platinum-based chemotherapy received S-1 at the dose of 40mg/m 2 twice daily for 14 consecutive days, every three weeks, with or without bevacizumab (Bev) at the dose of 15mg/kg. In cases where the induction chemotherapy regimen contained Bev, Bev was used as continuation maintenance chemotherapy where appropriate. The efficacy/toxicity of switch maintenance chemotherapy with S-1 and S-1+Bev was evaluated separately. The primary end point of this study was the treatment success rate at three months after the start of S-1 treatment. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities. Copyright © 2017. Published by Elsevier B.V.

Small angle slot divertor concept for long pulse advanced tokamaks

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Guo, H. Y.; Sang, C. F.; Stangeby, P. C.; Lao, L. L.; Taylor, T. S.; Thomas, D. M.

2017-04-01

SOLPS-EIRENE edge code analysis shows that a gas-tight slot divertor geometry with a small-angle (glancing-incidence) target, named the small angle slot (SAS) divertor, can achieve cold, dissipative/detached divertor conditions at relatively low values of plasma density at the outside midplane separatrix. SAS exhibits the following key features: (1) strong enhancement of the buildup of neutral density in a localized region near the plasma strike point on the divertor target; (2) spreading of the cooling front across the divertor target with the slot gradually flaring out from the strike point, thus effectively reducing both heat flux and erosion on the entire divertor target surface. Such a divertor may potentially provide a power and particle handling solution for long pulse advanced tokamaks.

Critical appraisal of pemetrexed in the treatment of NSCLC and metastatic pulmonary nodules

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Li X

2014-06-01

Full Text Available Xin Li, Sen Wei, Jun ChenTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of ChinaAbstract: Pemetrexed, a new multitarget antifolate antineoplastic agent, has significantly improved the overall survival in nonsquamous non-small-cell lung cancer patients. Presently, pemetrexed is recommended for first line treatment in combination with platinum derivatives, for second line treatment as a single agent and, more recently, as maintenance treatment after first line chemotherapy. In this article we critically appraise the status of pemetrexed including pharmacodynamics, pharmacokinetics, toxicity, and the cost effectiveness of pemetrexed, as well as the predictive biomarkers for pemetrexed based chemotherapy.Keywords: chemotherapy, non-small-cell lung cancer, pemetrexed

Spotlight on necitumumab in the treatment of non-small-cell lung carcinoma

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Thakur MK

2017-02-01

Full Text Available Manish K Thakur, Antoinette J Wozniak, Department of Oncology, Karmanos Cancer Center, Detroit, MI, USA Abstract: The treatment options for metastatic non-small-cell lung cancer (NSCLC have expanded dramatically in the last 10 years with the discovery of newer drugs and targeted therapy. Epidermal growth factor receptor (EGFR, when aberrantly activated, promotes cell growth and contributes in various ways to the malignant process. EGFR has become an important therapeutic target in a variety of malignancies. Small-molecule tyrosine kinase inhibitors (TKIs of EGFR are being used to treat advanced NSCLC and are particularly effective in the presence of EGFR mutations. Monoclonal antibodies have also been developed that block the EGFR at the cell surface and work in conjunction with chemotherapy. Necitumumab is a second-generation fully human IgG1 monoclonal antibody that has shown promise in metastatic NSCLC. The benefit has mostly been restricted to squamous cell lung cancer in the frontline setting. Considering that the survival advantage for these patients was modest, there is a need to discover biomarkers that will predict which patients will likely have the best outcomes. This review focuses on the development and clinical trial experience with necitumumab in NSCLC. Keywords: lung cancer, squamous cell, necitumumab, EGFR

Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer.

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Imai, Hisao; Kuwako, Tomohito; Kaira, Kyoichi; Masuda, Tomomi; Miura, Yosuke; Seki, Kaori; Sakurai, Reiko; Utsugi, Mitsuyoshi; Shimizu, Kimihiro; Sunaga, Noriaki; Tomizawa, Yoshio; Ishihara, Shinichi; Ishizuka, Takao; Mogi, Akira; Hisada, Takeshi; Minato, Koichi; Takise, Atsushi; Saito, Ryusei; Yamada, Masanobu

2017-03-01

In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (<18.5 kg/m 2 ), normal (18.5-25 kg/m 2 ), and overweight (≥25 kg/m 2 ). The median BSA and BW were 1.48 m 2 and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2, and 24.2 months, respectively. There were no significant differences in clinical outcomes according to BSA, BW, or BMI alone. Subgroup analysis based on the mutation type and BSA revealed no significant differences in PFS between the groups; however, the median OS in those with exon 19 deletion combined with low BSA was significantly favorable compared with the other groups. Gefitinib efficacy in patients with NSCLC harboring sensitive EGFR mutations did not differ according to BSA, BW, and BMI. However, OS was superior in patients with both the exon 19 deletion and low BSA.

A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

Science.gov (United States)

2018-01-29

Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the Risk and Prognosis of Portuguese Patients with Non-Small Cell Lung Cancer

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de Mello, Ramon Andrade; Ferreira, Mónica; Soares-Pires, Filipa; Costa, Sandra; Cunha, João; Oliveira, Pedro; Hespanhol, Venceslau; Reis, Rui Manuel

2013-01-01

Introduction Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. Materials and Methods Blood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS). Results One hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF –460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029. Conclusions Our study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well. PMID:24039754

Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

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Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

2015-01-01

Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (pENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all pENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

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Rooney, Claire; Sethi, Tariq

2015-10-01

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

A phase III comparison of radiation therapy with or without recombinant β-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04)

International Nuclear Information System (INIS)

Bradley, Jeffrey D.; Scott, Charles B.; Paris, Kristie J.; Demas, William F.; Machtay, Mitchell; Komaki, Ritsuko; Movsas, Benjamin; Rubin, Philip; Sause, William T.

2002-01-01

acute toxicities were primarily related to lung (n=8) and esophagus (n=7). No Grade 4 or 5 late toxicities were seen for patients in the radiation-alone arm. However, three patients on the β-interferon arm experienced Grade 4 toxicity, and one patient died. The 1-year survival rate for the RT-alone arm was 44% with a median survival time of 9.5 months. The 1-year survival on the β-interferon arm was 42% with a median survival of 10.3 months. There was no statistical difference in survival times (p=0.66). Conclusions: This multicenter, controlled Phase III trial failed to confirm the efficacy of Betaseron in patients receiving definitive radiotherapy for locally advanced, nonmetastatic non-small-cell lung cancer. The use of β-interferon led to greater rates of both acute and late treatment-related toxicity. The RTOG continues to investigate other biologic modifiers that may provide a nontoxic alternative for this poor-risk population

Clinical efficacy of first-generation EGFR-TKIs in patients with advanced non-small-cell lung cancer harboring EGFR exon 20 mutations

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Chen D

2016-07-01

Full Text Available Dan Chen,1 Zhengbo Song,2 Guoping Cheng3 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Chemotherapy, 3Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Purpose: Subsets of non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR mutations carry uncommon subtypes. We evaluated the efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs; erlotinib, gefitinib, and icotinib in patients with non-small-cell lung cancer carrying insertions and T790M and S768I mutations in EGFR exon 20. Patients and methods: Patients carrying EGFR exon 20 insertion/T790M/S768I mutations and treated with EGFR-TKIs were evaluated from 2005 to 2014 in Zhejiang Cancer Hospital. The efficacy was evaluated using the Kaplan–Meier method and compared with the log-rank test. Results: Sixty-two patients with exon 20 insertion/T790M/S768I mutations were enrolled. Mutations including exon 20 insertions and T790M and S768I mutations were observed in 29, 23, and ten patients, respectively. In total, the response rate and median progression-free survival (PFS were 8.1% and 2.1 months, respectively. Patients with S768I mutation manifested the longest median PFS (2.7 months, followed by those with T790M (2.4 months and exon 20 insertions (1.9 months; P=0.022. Patients with complex mutations show a better PFS than those with single mutations (2.7 months vs 1.9 months; P=0.034. Conclusion: First-generation EGFR-TKIs are less effective in patients with exon 20 uncommon mutations than in those with common mutations. Patients with complex mutations benefited more from first-generation EGFR-TKIs than those with single mutations. Keywords: non-small cell lung cancer, epidermal growth factor receptor, EGFR mutations, exon 20, tyrosine kinase inhibitor

Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

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Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

2016-01-01

The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Research Progress of the Resistance Mechanism of Non-small Cell Lung Cancer 
to EGFR-TKIs

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Huihui LIU

2013-10-01

Full Text Available Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months, most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.

Progress of PD-1/PD-L1 Inhibitors in Non-small Cell Lung Cancer

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Zhansheng JIANG

2017-02-01

Full Text Available Pembrolizumab, an inhibitor target programmed death 1 (PD-1, was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC. It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1 inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS with single pembrolizumab in first line was nearly 1 year (10.3 months, the hazard ratio for death fell by 40%. Overall survival (OS was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1% in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

Smoothing identification of systems with small non-linearities

Czech Academy of Sciences Publication Activity Database

Kozánek, Jan; Piranda, J.

2003-01-01

Roč. 38, č. 1 (2003), s. 71-84 ISSN 0025-6455 R&D Projects: GA ČR GA101/00/1471 Institutional research plan: CEZ:AV0Z2076919 Keywords : identification * small non-linearities * smoothing methods Subject RIV: BI - Acoustics Impact factor: 0.237, year: 2003

ORNL R and D on advanced small and medium power reactors: selected topics

International Nuclear Information System (INIS)

White, J.D.; Trauger, D.B.

1989-01-01

From 1984-1985, ORNL studied several innovative small and medium power nuclear concepts with respect to viability. Criteria for assessment of market attractiveness were developed and are described here. Using these criteria and descriptions of selected advanced reactor concepts, an assessment of their projected market viability in the time period 2000-2010 was made. All of these selected concepts could be considered as having the potential for meeting the criteria but, in most cases, considerable R and D would be required to reduce uncertainties. This work and later studies of safety and licensing of advanced, passively safe reactor concepts by ORNL are described. The results of these studies are taken into account in most of the current (FY 1989) work at ORNL on advanced reactors. A brief outline of this current work is given. One of the current R and D efforts at ORNL which addresses the operability and safety of advanced reactors is the Advanced Controls Program. Selected topics from this Program are described

ORNL R and D on advanced small and medium power reactors: Selected topics

International Nuclear Information System (INIS)

White, J.D.; Trauger, D.B.

1988-01-01

From 1984-1985, ORNL studied several innovative small and medium power nuclear concepts with respect to viability. Criteria for assessment of market attractiveness were developed and are described here. Using these criteria and descriptions of selected advanced reactor concepts, and assessment of their projected market viability in the time period 2000-2010 was made. All of these selected concepts could be considered as having the potential for meeting the criteria but, in most cases, considerable RandD would be required to reduce uncertainties. This work and later studies of safety and licensing of advanced, passively safe reactor concepts by ORNL are described. The results of these studies are taken into account in most of the current (FY 1989) work at ORNL on advanced reactors. A brief outline of this current work is given. One of the current RandD efforts at ORNL which addresses the operability and safety of advanced reactors is the Advanced Controls Program. Selected topics from this Program are described. 13 refs., 1 fig

Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer

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Veldore VH

2018-01-01

Full Text Available Vidya H Veldore,1,* Anuradha Choughule,2,* Tejaswi Routhu,1 Nitin Mandloi,1 Vanita Noronha,2 Amit Joshi,2 Amit Dutt,3 Ravi Gupta,1 Ramprasad Vedam,1 Kumar Prabhash2 1MedGenome Labs Private Ltd,, Bangalore, India; 2Tata Memorial Centre, Parel, Mumbai, India; 3The Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai, Maharashtra, India *These authors contributed equally to this work Abstract: Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA, from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS for EGFR mutation testing in non-small cell lung cancer (NSCLC. A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking allele specific real time PCR as one of the standard methods for tissue-based EGFR mutation testing, the ctDNA NGS test was validated on all the plasma derived cell-free DNA samples. We observed a high concordance (96.96% between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the EGFR gene. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%, 95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset of mutations was also verified on droplet digital PCR. Sixteen percent EGFR mutation positivity was observed in patients where only liquid biopsy was available, thus creating options for targeted therapy. This is the first and largest study from India, demonstrating successful validation of circulating cell-free DNA as a clinically

Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanes.

Science.gov (United States)

Tsavaris, N; Kosmas, C; Kopterides, P; Vadiaka, M; Kosmas, N; Skopelitis, H; Karadima, D; Kolliokosta, G; Tzima, E; Loukeris, D; Pagouni, E; Batziou, E; Xyla, V; Koufos, C

2008-03-01

Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

Guidance for Developing Principal Design Criteria for Advanced (Non-Light Water) Reactors

Energy Technology Data Exchange (ETDEWEB)

Holbrook, Mark [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinsey, Jim [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-03-01

In July 2013, the US Department of Energy (DOE) and US Nuclear Regulatory Commission (NRC) established a joint initiative to address a key portion of the licensing framework essential to advanced (non-light water) reactor technologies. The initiative addressed the “General Design Criteria for Nuclear Power Plants,” Appendix A to10 Code of Federal Regulations (CFR) 50, which were developed primarily for light water reactors (LWRs), specific to the needs of advanced reactor design and licensing. The need for General Design Criteria (GDC) clarifications in non-LWR applications has been consistently identified as a concern by the industry and varied stakeholders and was acknowledged by the NRC staff in their 2012 Report to Congress1 as an area for enhancement. The initiative to adapt GDC requirements for non-light water advanced reactor applications is being accomplished in two phases. Phase 1, managed by DOE, consisted of reviews, analyses and evaluations resulting in recommendations and deliverables to NRC as input for NRC staff development of regulatory guidance. Idaho National Laboratory (INL) developed this technical report using technical and reactor technology stakeholder inputs coupled with analysis and evaluations provided by a team of knowledgeable DOE national laboratory personnel with input from individual industry licensing consultants. The DOE national laboratory team reviewed six different classes of emerging commercial reactor technologies against 10 CFR 50 Appendix A GDC requirements and proposed guidance for their adapted use in non-LWR applications. The results of the Phase 1 analysis are contained in this report. A set of draft Advanced Reactor Design Criteria (ARDC) has been proposed for consideration by the NRC in the establishment of guidance for use by non-LWR designers and NRC staff. The proposed criteria were developed to preserve the underlying safety bases expressed by the original GDC, and recognizing that advanced reactors may take

Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer

International Nuclear Information System (INIS)

Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose-Javier; Rodriguez, Ignacio; Gimenez-Capitan, Ana; Molina-Vila, Miquel Angel; Vergnenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

2016-01-01

BRCA1 is a main component of homologous recombination and induces resistance to platinum in preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model. We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non-small-cell lung cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as cut-off point. The median progression-free survival of all 71 patients was 7.2 months whereas the median overall survival of the study population was 10.7 months. Among patients with low BRCA1 expression, the median PFS was 7.4 months in the presence of low HERC2 levels and 5.9 months for patients expressing high HERC2 levels (p = 0.01). The median OS was 15.3 months for patients expressing low levels of both genes and 7.4 months for those with low BRCA1 but high HERC2 (p = 0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology Group performance status 0–1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of progression (p = 0.03) and of death (p = 0.004). These findings confirm the potentiality of integrated DNA repair components analysis in predicting the sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the way for further refinement of the BRCA1 predictive model. The online version of this article (doi:10.1186/s12885-016-2339-5) contains supplementary material, which is available to authorized users

Liquid fiducial marker performance during radiotherapy of locally advanced non small cell lung cancer

DEFF Research Database (Denmark)

Rydhög, Jonas Scherman; Mortensen, Steen Riisgaard; Larsen, Klaus Richter

2016-01-01

We analysed the positional and structural stability of a long-term biodegradable liquid fiducial marker (BioXmark) for radiotherapy in patients with locally advanced lung cancer. Markers were injected via endoscopic- or endobronchial ultrasound in lymph nodes and reachable primary tumours. Marker...

[Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

Science.gov (United States)

Du, Shuhui; Qin, Da; Pang, Ruiqi; Zhang, Yeqing; Zhao, Siqi; Hu, Mu; Zhi, Xiuyi

2017-10-20

Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (PRadiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.

Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

International Nuclear Information System (INIS)

Fernandes, Annemarie T.; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

2010-01-01

Background: Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. Methods: We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Results: Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Conclusions: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.

Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes.

Science.gov (United States)

Fernandes, Annemarie T; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

2010-05-01

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Overexpression of EMMPRIN is associated with lymph node metastasis and advanced stage of non-small cell lung cancer: a retrospective study

OpenAIRE

Liu, Bing; Wan, Zhaohui; Sheng, Baowei; Lin, Yong; Fu, Tian; Zeng, Qingdi; Qi, Congcong

2017-01-01

Background Previous studies show that overexpression of EMMPRIN involved in the malignant biological behavior of tumors. This investigation was to disclose the expression status of EMMPRIN in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis of NSCLC. Methods The expression of EMMPRIN was examined using immunohistochemistry and enzyme-linked immunosorbent assay. The clinical value of EMMPRIN was evaluated by drawing a receiver operating characteristic (ROC) curve. Re...

An Experimental Study of Advanced Receivers in a Practical Dense Small Cells Network

DEFF Research Database (Denmark)

Assefa, Dereje; Berardinelli, Gilberto; Tavares, Fernando Menezes Leitão

2016-01-01

leads to significant limitations on the network throughput in such deployments. In addition, network densification introduces difficulty in network deployment. This paper presents a study on the benefits of advanced receiver in a practical uncoordinated dense small cells deployment. Our aim is to show...

EGFR mutation testing in patients with advanced non-small cell lung cancer: a comprehensive evaluation of real-world practice in an East Asian tertiary hospital.

Science.gov (United States)

Choi, Yoon-La; Sun, Jong-Mu; Cho, Juhee; Rampal, Sanjay; Han, Joungho; Parasuraman, Bhash; Guallar, Eliseo; Lee, Genehee; Lee, Jeeyun; Shim, Young Mog

2013-01-01

Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (Pwomen, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.

Evaluation of the PRHRS Performance Degradation due to Non-Condensable Gas for the Small and Medium Reactor using MARS-KS code

International Nuclear Information System (INIS)

Kim, Sook Kwan; Sim, Suk Ku; Park, Ju Yeop; Seol, Kwang Won; Ryu, Yong Ho

2011-01-01

The effect of non-condensable gas on the performance of PRHRS (Passive Residual Heat Removal System) of the Small and Medium Reactor(SMR) was evaluated during a loss of flow event. Since the TMI accident in 1979, the passive systems have been considered in the advanced reactors as a feature of design improvement because the passive system simplifies the system and thus increases the reliability of the system. The Westinghouse received the design certification from the USNRC for the AP600 and AP1000 passive type pressurized water reactors. The APR+ under development by KEPCO considers the use of PAFS (Passive Auxiliary Feedwater System). And the PRHRS is adopted as a passive secondary heat removal system for the SMART (System-integrated Modular Advanced ReacTor)

Molecular biologic study about the non-small cell lung carcinoma (2) : p53 gene alteration in non-small cell lung carcinoma

International Nuclear Information System (INIS)

Park, Jong Ho; Zo, Jae Ill; Paik, Hee Jong; Kim, Mi Hee

1996-12-01

The main purpose of this research was to identify of the p53 and 3p gene alteration in non-small cell lung cancer patients residing in Korea. Furthermore, we analyzed the relationship between the p53 and 3p gene alterations and the clinicopathologic results of lung cancer patients. And we have investigated the role of PCR-LOH in analyzing tumor samples for LOH of defined chromosomal loci. We have used the 40 samples obtained from the lung cancer patients who were diagnosed and operated curatively at Korea Cancer Center Hospital. We have isolated the high molecular weight. DNA from the tumors and normal tissues. And we have amplified the DNA with PCR method and used the microsatellite assay method to detect the altered p53 and 3p gene. The conclusions were as follow: 1) The 3p gene alteration was observed in 9/39 (23.1%) and p53 gene alteration was observed in 15/40 (37.5%) of resected non-small cell lung cancer. 2) There was no correlations between the 3p or p53 gene alterations and prognosis of patients, but further study is necessary. 3) PCR-LOH is a very useful tool for analyzing small amount of tumor samples for loss of heterozygosity of defined chromosomal loci. (author). 10 refs

Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

Science.gov (United States)

Kesarwala, Aparna H; Ko, Christine J; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E; O'Meara, William P; Simone, Charles B; Rengan, Ramesh

2015-05-01

Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. Published by Elsevier Inc.

Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Necdet Uskent

2017-10-01

Full Text Available Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc. This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3rd, 6th, 9th, and 12th months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.

Superiority of conventional intensity-modulated radiotherapy over helical tomotherapy in locally advanced non-small cell lung cancer. A comparative plan analysis

Energy Technology Data Exchange (ETDEWEB)

Song, C. [National Cancer Center, Research Institute and Hospital, Goyang (Korea, Republic of). Proton Therapy Center; Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiation Oncology; Pyo, H.; Kim, J. [Sungkyunkwan Univ. School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Lim, Y.K.; Kim, D.W.; Cho, K.H. [National Cancer Center, Research Institute and Hospital, Goyang (Korea, Republic of). Proton Therapy Center; Kim, W.C. [Inha Univ. School of Medicine, Incheon (Korea, Republic of). Dept. of Radiation Oncology; Kim, H.J. [Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiation Oncology

2012-10-15

Purpose: To compare helical tomotherapy (HT) and conventional intensity-modulated radiotherapy (IMRT) using a variety of dosimetric and radiobiologic indexes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and methods: A total of 20 patients with LA-NSCLC were enrolled. IMRT plans with 4-6 coplanar beams and HT plans were generated for each patient. Dose distributions and dosimetric indexes for the tumors and critical structures were computed for both plans and compared. Results: Both modalities created highly conformal plans. They did not differ in the volumes of lung exposed to > 20 Gy of radiation. The average mean lung dose, volume receiving {>=} 30 Gy, and volume receiving {>=} 10 Gy in HT planning were 18.3 Gy, 18.5%, and 57.1%, respectively, compared to 19.4 Gy, 25.4%, and 48.9%, respectively, with IMRT (p = 0.004, p < 0.001, and p < 0.001). The differences between HT and IMRT in lung volume receiving {>=} 10-20 Gy increased significantly as the planning target volume (PTV) increased. For 6 patients who had PTV greater than 700 cm{sup 3}, IMRT was superior to HT for 5 patients in terms of lung volume receiving {>=} 5-20 Gy. The integral dose to the entire thorax in HT plans was significantly higher than in IMRT plans. Conclusion: HT gave significantly better control of mean lung dose and volume receiving {>=} 30-40 Gy, whereas IMRT provided better control of the lung volume receiving {>=} 5-15 Gy and the integral dose to entire thorax. In most patients with PTV greater than 700 cm{sup 3}, IMRT was superior to HT in terms of lung volume receiving {>=} 5-20 Gy. It is therefore advised that caution should be exercised when planning LA-NSCLC using HT. (orig.)

Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial.

Science.gov (United States)

Ridolfi, Laura; Bertetto, Oscar; Santo, Antonio; Naglieri, Emanuele; Lopez, Massimo; Recchia, Francesco; Lissoni, Paolo; Galliano, Marco; Testore, Franco; Porta, Camillo; Maglie, Monica; Dall'agata, Monia; Fumagalli, Luca; Ridolfi, Ruggero

2011-10-01

Non-small cell lung cancer (NSCLC) is associated with IL-2-dependent cell-mediated immunodeficiency. As IL-2 is the main lymphocyte growth factor, a phase III randomized multicenter trial was conducted to evaluate the impact of subcutaneous low-dose IL-2 added to standard chemotherapy (CT) on overall survival (OS) in advanced NSCLC patients. Patients (n=241) with histologically confirmed stage IIIb or IV non-operable NSCLC underwent stratified randomization on the basis of center, ECOG PS, stage of disease and percentage of weight loss. Patients received gemcitabine (1000 mg/m2) on days 1 and 8 + cisplatin (100 mg/m2) on day 2 every 21 days for a maximum of 6 cycles [chemotherapy (CT) arm]. In the CT+IL-2 arm, patients also received low-dose subcutaneous IL-2 3,000,000 IU/die on days 3-5, 9-11, 15-17. The study had 90% power to detect a 20% absolute increase in 1-year OS with 118 patients/arm. An overall response (OR) rate of 12.8% (14% in the CT+IL-2 arm and 11.4% in CT arm) was observed. Stable disease was 70 and 66.7%, and progressive disease 16 and 21.8% in the CT+IL-2 and CT arms, respectively. No differences in response were found in any subgroup analysis. At a median follow-up of 32 months, 1-year OS was 45% for the CT+IL-2 arm vs. 51% for the CT arm (p=0.456 log-rank). Median progression-free survival was 6.6 months in the CT+IL-2 arm vs. 6.9 months in the CT arm (p=0.573, log-rank). A higher number of grade 4 toxicities were reported with CT+IL-2. The most common grade ≥3 adverse events were gastrointestinal toxicity (mainly nausea and diarrhea) and myelosuppression. No relevant differences in clinical outcome were observed from the addition of IL-2 to CT. Future studies investigating the role of T-regulators in chemoimmunotherapeutic regimens could be performed.

The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

Science.gov (United States)

Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

2018-01-01

The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Survival outcomes for oligometastasis in resected non-small cell lung cancer.

Science.gov (United States)

Shimada, Yoshihisa; Saji, Hisashi; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2015-10-01

We investigated the factors associated with post-recurrence survival and the treatment for non-small-cell lung cancer patients with postoperative distant recurrence, especially oligometastasis. We reviewed the data of 272 patients with distant recurrence who underwent resection of non-small-cell lung cancer from January 2000 through December 2011. The type of distant recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n = 196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy (surgery 5, radiotherapy 9, sequential local and systemic therapy 28, chemoradiotherapy 5). Multivariate analysis revealed older age, non-adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver metastases, bone metastases, and polymetastasis had significant associations with unfavorable post-recurrence survival. Subgroup analysis of patients with oligometastasis showed histology and disease-free interval had a great impact on survival. Smoking history and histology were associated with survival in patients with lung oligometastasis, whereas systemic treatment and longer disease-free interval were related to increased post-recurrence survival in those with brain oligometastasis. This study showed that an oligometastatic state per se was a significant favorable factor. Optimization of personalized systemic treatment and adding local treatment are important in the management of patients with non-small-cell lung cancer and oligometastasis. © The Author(s) 2015.

Proton beam therapy in non-small cell lung cancer: state of the art

Directory of Open Access Journals (Sweden)

Harada H

2017-08-01

Full Text Available Hideyuki Harada, Shigeyuki Murayama Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Nagaizumi, Shizuoka, Japan Abstract: This review summarizes the past and present status of proton beam therapy (PBT for lung cancer. PBT has a unique characteristic called the Bragg peak that enables a reduction in the dose of normal tissue around the tumor, but is sensitive to the uncertainties of density changes. The heterogeneity in electron density for thoracic lesions, such as those in the lung and mediastinum, and tumor movement according to respiration necessitates respiratory management for PBT to be applied in lung cancer patients. There are two types of PBT – a passively scattered approach and a scanning approach. Typically, a passively scattered approach is more robust for respiratory movement and a scanning approach could result in a more conformal dose distribution even when the tumor shape is complex. Large tumors of centrally located lung cancer may be more suitably irradiated than with intensity-modulated radiotherapy (IMRT or stereotactic body radiotherapy (SBRT. For a locally advanced lung cancer, PBT can spare the lung and heart more than photon IMRT. However, no randomized controlled trial has reported differences between PBT and IMRT or SBRT for early-stage and locally advanced lung cancers. Therefore, a well-designed controlled trial is warranted. Keywords: proton beam therapy, non-small cell lung cancer, survival, SBRT, IMRT

Insulin-like Growth Factor Receptor 1 mRNA Expression as a Prognostic Marker in Advanced Non-small Cell Lung Cancer

DEFF Research Database (Denmark)

Vilmar, Adam; Santoni-Rugiu, Eric; Cillas, Jesus Garcia-Fon

2014-01-01

BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be established as a biomarker in non-small cell lung cancer (NSCLC) but could prove useful in customized chemotherapy. We explored its prognostic value using both quantitative real-time reverse transcriptase polymerase chain......-points. RESULTS: Surgical tissue samples were available from 33 patients deemed inoperable. IGF1R status varied according to histopathology. Patients with tumors positive for IGF1R mRNA expression had a shorter progression-free and overall survival when compared to the negative sub-group (6.1 vs. 7.4 months, p=0...

Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

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Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Mehta, Par [Department of Radiation Oncology at Rush Copley Medical Center, Aurora, IL (United States); Khan, Atif [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Cancer Institute of New Jersey, New Brunswick, NJ (United States); Marsh, James C.; Zusag, Thomas W. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Warren, William H. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Bonomi, Philip [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Liptay, Michael; Faber, L. Penfield [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States)

2011-11-15

Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

Concurrent chemoradiotherapy for locally advanced lung carcinoma: present results and future prospects

International Nuclear Information System (INIS)

Reboul, F.; Vincent, P.; Brewer, Y.; Taulelle, M.

1997-01-01

The prognosis of locally advanced lung cancer is reportedly poor in all histologic types. In non-small cell lung cancer, radiation therapy alone results in disappointing long-term survival. Three recent randomized trials, however, have shown a limited but significant improvement of survival with induction chemotherapy, though local control remained poor in these studies as well as in small-cell lung cancer treated with chemotherapy and late radiotherapy. Tow randomized trials focusing on small-cell lung cancer have recently shown significant benefit due to the combination of early concurrent mediastinal irradiation and chemotherapy, with major improvement in local control and a more than 40% 2-year survival rate. The concept of concurrent chemoradiotherapy has also been studied in non-small cell carcinoma with several pilot studies leading to both encouraging results and improved survival rate (up to 40% at 2 years). Ongoing phase III trials are comparing sequential versus concurrent chemoradiotherapy and will define the role of radical surgery after chemoradiotherapy in locally advanced non-small cell lung cancer. (authors)

Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC).

Science.gov (United States)

Gu, Yuanlong; Lv, Huimin; Zhao, Juan; Li, Qi; Mu, Guannan; Li, Jiade; Wuyang, Jiazi; Lou, Ge; Wang, Ruitao; Zhang, Yanqiao; Huang, Xiaoyi

2017-09-01

Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACTcells in patients who received ≥4cycles of ACT was higher than that in patients treated with cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC. Copyright © 2017. Published by Elsevier B.V.

Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer.

Directory of Open Access Journals (Sweden)

Kyle R Cron

Full Text Available Despite optimal radiation therapy (RT, chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80-90% decrease in homologous recombination (HR, a 50% decrease in expression of NF-κB-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. IκBα RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-κB-mediated expression of Fanconi Anemia/HR DNA repair genes.

Small angle neutron scattering (SANS) under non-equilibrium conditions

International Nuclear Information System (INIS)

Oberthur, R.C.

1984-01-01

The use of small angle neutron scattering (SANS) for the study of systems under non-equilibrium conditions is illustrated by three types of experiments in the field of polymer research: - the relaxation of a system from an initial non-equilibrium state towards equilibrium, - the cyclic or repetitive installation of a series of non-equilibrium states in a system, - the steady non-equilibrium state maintained by a constant dissipation of energy within the system. Characteristic times obtained in these experiments with SANS are compared with the times obtained from quasi-elastic neutron and light scattering, which yield information about the equilibrium dynamics of the system. The limits of SANS applied to non-equilibrium systems for the measurement of relaxation times at different length scales are shown and compared to the limits of quasielastic neutron and light scattering

Adaptive/Nonadaptive Proton Radiation Planning and Outcomes in a Phase II Trial for Locally Advanced Non-small Cell Lung Cancer

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Koay, Eugene J.; Lege, David [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Cox, James D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2012-12-01

Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall

Advanced Small Modular Reactor Economics Model Development

Energy Technology Data Exchange (ETDEWEB)

Harrison, Thomas J [ORNL

2014-10-01

The US Department of Energy Office of Nuclear Energy’s Advanced Small Modular Reactor (SMR) research and development activities focus on four key areas: Developing assessment methods for evaluating advanced SMR technologies and characteristics; and Developing and testing of materials, fuels and fabrication techniques; and Resolving key regulatory issues identified by US Nuclear Regulatory Commission and industry; and Developing advanced instrumentation and controls and human-machine interfaces. This report focuses on development of assessment methods to evaluate advanced SMR technologies and characteristics. Specifically, this report describes the expansion and application of the economic modeling effort at Oak Ridge National Laboratory. Analysis of the current modeling methods shows that one of the primary concerns for the modeling effort is the handling of uncertainty in cost estimates. Monte Carlo–based methods are commonly used to handle uncertainty, especially when implemented by a stand-alone script within a program such as Python or MATLAB. However, a script-based model requires each potential user to have access to a compiler and an executable capable of handling the script. Making the model accessible to multiple independent analysts is best accomplished by implementing the model in a common computing tool such as Microsoft Excel. Excel is readily available and accessible to most system analysts, but it is not designed for straightforward implementation of a Monte Carlo–based method. Using a Monte Carlo algorithm requires in-spreadsheet scripting and statistical analyses or the use of add-ons such as Crystal Ball. An alternative method uses propagation of error calculations in the existing Excel-based system to estimate system cost uncertainty. This method has the advantage of using Microsoft Excel as is, but it requires the use of simplifying assumptions. These assumptions do not necessarily bring into question the analytical results. In fact, the

A competing risk model of first failure site after definitive (chemo) radiation therapy for locally advanced non-small cell lung cancer

DEFF Research Database (Denmark)

Nygård, Lotte; Vogelius, Ivan R; Fischer, Barbara M

2018-01-01

INTRODUCTION: The aim of the study was to build a model of first failure site and lesion specific failure probability after definitive chemo-radiotherapy for inoperable non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 251 patients receiving definitive chemo......-regional failure, multivariable logistic regression was applied to assess risk of each lesion being first site of failure. The two models were used in combination to predict lesion failure probability accounting for competing events. RESULTS: Adenocarcinoma had a lower hazard ratio (HR) of loco-regional (LR...

Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH).

Science.gov (United States)

Peters, Solange; Gettinger, Scott; Johnson, Melissa L; Jänne, Pasi A; Garassino, Marina C; Christoph, Daniel; Toh, Chee Keong; Rizvi, Naiyer A; Chaft, Jamie E; Carcereny Costa, Enric; Patel, Jyoti D; Chow, Laura Q M; Koczywas, Marianna; Ho, Cheryl; Früh, Martin; van den Heuvel, Michel; Rothenstein, Jeffrey; Reck, Martin; Paz-Ares, Luis; Shepherd, Frances A; Kurata, Takayasu; Li, Zhengrong; Qiu, Jiaheng; Kowanetz, Marcin; Mocci, Simonetta; Shankar, Geetha; Sandler, Alan; Felip, Enriqueta

2017-08-20

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good

Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients.

Directory of Open Access Journals (Sweden)

Xueying Zhao

Full Text Available TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS, overall survival (OS, and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10(-4. It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023. In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002. The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.

Value of low-dose 2 X 2 Gy palliative radiotherapy in advanced low-grade non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Ng, M.; Wirth, A.; Ryan, G.; MacManus, M.

2006-01-01

Low-dose radiotherapy over the last decade has been reported to provide effective palliation for patients with low-grade non-Hodgkin's lymphoma. In this retrospective case series of 10 patients, we report our early experience using low-dose radiotherapy (usually 2 x2 Gy) for patients with advanced-stage follicular, mucosal associated lymphoid tissue, mantle cell and small lymphocytic lymphomas. Median follow up was 27 weeks. Response rates were high (complete response, 70%; partial response, 20%), the response durable and the toxicity was minimal (no toxicity greater than grade 1). Low-dose irradiation is an effective treatment option for patients with low-grade lymphomas with local symptoms Copyright (2006) Blackwell Publishing Asia Pty Ltd

The small length scale effect for a non-local cantilever beam: a paradox solved.

Science.gov (United States)

Challamel, N; Wang, C M

2008-08-27

Non-local continuum mechanics allows one to account for the small length scale effect that becomes significant when dealing with microstructures or nanostructures. This paper presents some simplified non-local elastic beam models, for the bending analyses of small scale rods. Integral-type or gradient non-local models abandon the classical assumption of locality, and admit that stress depends not only on the strain value at that point but also on the strain values of all points on the body. There is a paradox still unresolved at this stage: some bending solutions of integral-based non-local elastic beams have been found to be identical to the classical (local) solution, i.e. the small scale effect is not present at all. One example is the Euler-Bernoulli cantilever nanobeam model with a point load which has application in microelectromechanical systems and nanoelectromechanical systems as an actuator. In this paper, it will be shown that this paradox may be overcome with a gradient elastic model as well as an integral non-local elastic model that is based on combining the local and the non-local curvatures in the constitutive elastic relation. The latter model comprises the classical gradient model and Eringen's integral model, and its application produces small length scale terms in the non-local elastic cantilever beam solution.

Multi-unit Operations in Non-Nuclear Systems: Lessons Learned for Small Modular Reactors

Energy Technology Data Exchange (ETDEWEB)

OHara J. M.; Higgins, J.; DAgostino, A.

2012-01-17

The nuclear-power community has reached the stage of proposing advanced reactor designs to support power generation for decades to come. Small modular reactors (SMRs) are one approach to meet these energy needs. While the power output of individual reactor modules is relatively small, they can be grouped to produce reactor sites with different outputs. Also, they can be designed to generate hydrogen, or to process heat. Many characteristics of SMRs are quite different from those of current plants and may be operated quite differently. One difference is that multiple units may be operated by a single crew (or a single operator) from one control room. The U.S. Nuclear Regulatory Commission (NRC) is examining the human factors engineering (HFE) aspects of SMRs to support licensing reviews. While we reviewed information on SMR designs to obtain information, the designs are not completed and all of the design and operational information is not yet available. Nor is there information on multi-unit operations as envisioned for SMRs available in operating experience. Thus, to gain a better understanding of multi-unit operations we sought the lesson learned from non-nuclear systems that have experience in multi-unit operations, specifically refineries, unmanned aerial vehicles and tele-intensive care units. In this paper we report the lessons learned from these systems and the implications for SMRs.

Erlotinib plus parenteral nutrition: an opportunity to get through the hardest days of advanced non-small cell lung cancer with cancer anorexia-cachexia syndrome.

Science.gov (United States)

Zang, Yuan-Sheng; Fang, Zheng; Li, Bing

2013-03-01

This case study details the poor performance status of a patient with non-small cell lung cancer and cancer anorexia-cachexia syndrome got through the hardest days of high tumor burden and malnutrition, by using a combined therapy of lung cancer-targeted therapy drug and parenteral nutrition. The related literatures were reviewed.

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

Science.gov (United States)

Gulley, James L; Rajan, Arun; Spigel, David R; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J L; Leach, Joseph; Edenfield, W Jeff; Wang, Ding; Grote, Hans Juergen; Heydebreck, Anja von; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

2017-05-01

Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing. Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2-11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and

Advancing Cardiovascular, Neurovascular and Renal Magnetic Resonance Imaging in Small Rodents Using Cryogenic Radiofrequency Coil Technology

Directory of Open Access Journals (Sweden)

Thoralf eNiendorf

2015-11-01

Full Text Available Research in pathologies of the brain, heart and kidney have gained immensely from the plethora of studies that have helped shape new methods in magnetic resonance (MR for characterizing preclinical disease models. Methodical probing into preclinical animal models by MR is invaluable since it allows a careful interpretation and extrapolation of data derived from these models to human disease. In this review we will focus on the applications of cryogenic radiofrequency (RF coils in small animal MR as a means of boosting image quality (e.g. by supporting MR microscopy and making data acquisition more efficient (e.g. by reducing measuring time; both being important constituents for thorough investigational studies on animal models of disease. This review attempts to make the (biomedical imaging, molecular medicine and pharmaceutical communities aware of this productive ferment and its outstanding significance for anatomical and functional MR in small rodents. The goal is to inspire a more intense interdisciplinary collaboration across the fields to further advance and progress non-invasive MR methods that ultimately support thorough (pathophysiological characterization of animal disease models. In this review, current and potential future applications for the RF coil technology in cardiovascular, neurovascular and renal disease will be discussed.

Aerodynamic shape optimization of non-straight small wind turbine blades

International Nuclear Information System (INIS)

Shen, Xin; Yang, Hong; Chen, Jinge; Zhu, Xiaocheng; Du, Zhaohui

2016-01-01

Graphical abstract: Small wind turbine blades with 3D stacking lines (sweep and bend) have been considered and analyzed with an optimization code based on the lifting surface method. The results indicated that the power capture and the rotor thrust can be improved with these more complex geometries. The starting behavior of the small wind turbines can be improved by the optimization of the blade chord and twist angle distribution. - Highlights: • The small wind turbine blade was optimized with non-straight shape. • Lifting surface method with free wake was used for aerodyanmic performace evaluation. • The non-straight shape can be used to increase energy production and decrease the thrust. • The energy production should be sacrificed in order to increase the starting behavior. - Abstract: Small wind turbines usually operate in sub-optimal wind conditions in order to satisfy the demand where it is needed. The aerodynamic performance of small horizontal axis wind turbines highly depends on the geometry. In the present study, the geometry of wind turbine blades are optimized not only in terms of the distribution of the chord and twist angle but also with 3-dimensional stacking line. As the blade with 3-dimensional stacking line is given sweep in the plan of rotation and dihedral in the plan containing the blade and rotor axis, the common used blade element momentum method can no longer provide accurate aerodynamic performance solution. A lifting surface method with free wake model is used as the aerodynamic model in the present work. The annual energy production and the starting performance are selected as optimization objective. The starting performance is evaluated based on blade element method. The optimization of the geometry of the non-straight wind turbine blades is carried out by using a micro-genetic algorithm. Results show that the wind turbine blades with properly designed 3-dimensional stacking line can increase the annual energy production and have

Phase 1 Study of CK-301 as a Single Agent in Subjects With Advanced Cancers

Science.gov (United States)

2018-01-02

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Malignant Mesothelioma, Advanced; Head and Neck Cancer; Melanoma; Merkel Cell Carcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Classical Hodgkin Lymphoma

Advances in Diagnosis of Respiratory Diseases of Small Ruminants

Directory of Open Access Journals (Sweden)

Sandip Chakraborty

2014-01-01

Full Text Available Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR, parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses.

Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

Science.gov (United States)

Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

2012-10-01

This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

Patient Experience of Symptoms and Side Effects when Treated with Osimertinib for Advanced Non-Small-Cell Lung Cancer: A Qualitative Interview Substudy.

Science.gov (United States)

Rydén, Anna; Blackhall, Fiona; Kim, Hye Ryun; Pillai, Rathi N; Braam, Lauren; Martin, Mona L; Walding, Andrew

2017-10-01

Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations. During the first interview (23 patients), the most commonly reported symptoms/side effects were coughing, itching, tiredness (each reported by 56.5% of patients), and rash (43.5%). During the second interview (21 patients), compared with the first interview, shortness of breath and diarrhea were reported by more patients (57.1 and 38.1%, respectively; both increased from 34.8%); tiredness remained predominant (42.9%); and itching (38.1%), coughing (38.1%), and rash (14.3%) were reported by fewer patients. At both interviews, the most frequently reported symptoms/side effects were also those most often rated by patients for bothersomeness and severity, and generally received mean scores in the low-to-moderate range. However, several rarely expressed symptoms/side effects (e.g., abdominal pain, frequent day time urination) received high bothersomeness ratings. At the second interview, patients were highly satisfied with osimertinib and had a low level of difficulty in coping with side effects during treatment. These data enhance our understanding of patients' experiences of symptoms/side effects, which could increase the accuracy of the osimertinib benefit-risk assessment, guide management of adverse events, and improve the information given to patients

Phase I/II Trial of Sequential Chemoradiotherapy Using a Novel Hypoxic Cell Radiosensitizer, Doranidazole (PR-350), in Patients With Locally Advanced Non-Small-Cell Lung Cancer (WJTOG-0002)

International Nuclear Information System (INIS)

Nishimura, Yasumasa; Nakagawa, Kazuhiko; Takeda, Koji; Tanaka, Masahiro; Segawa, Yoshihiko; Tsujino, Kayoko; Negoro, Shunichi; Fuwa, Nobukazu; Hida, Toyoaki; Kawahara, Masaaki; Katakami, Nobuyuki; Hirokawa, Keiko; Yamamoto, Nobuyuki; Fukuoka, Masahiro; Ariyoshi, Yutaka

2007-01-01

Purpose: This Phase I/II trial was conducted to assess the efficacy and safety of PR-350, a novel hypoxic cell radiosensitizer, when administered with thoracic radiation therapy (RT) after induction chemotherapy (CT) for locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Two cycles of cisplatin (80 mg/m 2 ) and paclitaxel (180 mg/m 2 ), or carboplatin (AUC = 6) and paclitaxel (200 mg/m 2 ) were given before RT of 60 Gy in 30 fractions. In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m 2 ) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses. Results: In total, 37 patients were enrolled. In Phase I (n = 20), PR-350 could be administered 30 times with concurrent thoracic RT. Thus, in Phase II (n = 17), PR-350 was administered 30 times. The major toxicity was radiation pneumonitis, with Grade 3 or more pneumonitis noted in 6 patients (16%) including 2 with treatment-related deaths. However, no Grade 3 or more esophageal toxicity was noted, and only Grade 1 peripheral neuropathy was noted in 9 patients (24%). For all 37 patients, the median survival time (MST) and the 2-year survival rate were 15.9 months and 24%, respectively. For 18 patients receiving 21 to 30 doses of PR-350, the MST and 2-year survival rate were 20.9 months and 33%, respectively. Conclusions: Thoracic RT combined with 30 daily administrations of PR-350 after induction CT was well tolerated and promising for locally advanced NSCLC

Capsule endoscopy: Beyond small bowel

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Samuel N Adler

2012-01-01

Full Text Available In this article the brief and dramatic history of capsule endoscopy of the digestive tract is reviewed. Capsule endoscopy offers a non invasive method to diagnose diseases that affect the esophagus, small bowel and colon. Technological improvements relating to optics, software, data recorders with two way communication have revolutionized this field. These advancements have produced better diagnostic performance.

Genomic Characterization of Non–Small-Cell Lung Cancer in African Americans by Targeted Massively Parallel Sequencing

Science.gov (United States)

Araujo, Luiz H.; Timmers, Cynthia; Bell, Erica Hlavin; Shilo, Konstantin; Lammers, Philip E.; Zhao, Weiqiang; Natarajan, Thanemozhi G.; Miller, Clinton J.; Zhang, Jianying; Yilmaz, Ayse S.; Liu, Tom; Coombes, Kevin; Amann, Joseph; Carbone, David P.

2015-01-01

Purpose Technologic advances have enabled the comprehensive analysis of genetic perturbations in non–small-cell lung cancer (NSCLC); however, African Americans have often been underrepresented in these studies. This ethnic group has higher lung cancer incidence and mortality rates, and some studies have suggested a lower incidence of epidermal growth factor receptor mutations. Herein, we report the most in-depth molecular profile of NSCLC in African Americans to date. Methods A custom panel was designed to cover the coding regions of 81 NSCLC-related genes and 40 ancestry-informative markers. Clinical samples were sequenced on a massively parallel sequencing instrument, and anaplastic lymphoma kinase translocation was evaluated by fluorescent in situ hybridization. Results The study cohort included 99 patients (61% males, 94% smokers) comprising 31 squamous and 68 nonsquamous cell carcinomas. We detected 227 nonsilent variants in the coding sequence, including 24 samples with nonoverlapping, classic driver alterations. The frequency of driver mutations was not significantly different from that of whites, and no association was found between genetic ancestry and the presence of somatic mutations. Copy number alteration analysis disclosed distinguishable amplifications in the 3q chromosome arm in squamous cell carcinomas and pointed toward a handful of targetable alterations. We also found frequent SMARCA4 mutations and protein loss, mostly in driver-negative tumors. Conclusion Our data suggest that African American ancestry may not be significantly different from European/white background for the presence of somatic driver mutations in NSCLC. Furthermore, we demonstrated that using a comprehensive genotyping approach could identify numerous targetable alterations, with potential impact on therapeutic decisions. PMID:25918285

Quality-of-care indicators for non-small cell lung cancer.

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Tanvetyanon, Tawee

2009-10-01

Quality-of-care indicators are measurable elements of practice performance that can be used to assess the quality or change in quality of the care provided. To date, the literature on quality-of-care indicators for non-small cell lung cancer (NSCLC) has not been reviewed. A search was performed to identify articles reporting on quality-of-care indicators specific for NSCLC published from January 2003 to May 2009 (using MEDLINE and American Society of Clinical Oncology abstract databases). Web sites of major quality care organizations were also searched. The identified indicators were then classified by their aspect of care provision (structure-of-care, process-of-care, or outcome-of-care indicator). For structure-of-care quality indicators, the most cited indicators were related to the quality of lung surgery. These included being National Cancer Institute-designated cancer centers or high-volume hospitals. For process-of-care quality indicators, the most common indicators were the receipt of surgery for early-stage NSCLC and the administration of chemotherapy for advanced-stage NSCLC. For outcome-of-care quality indicators, the most cited indicators were related to postoperative morbidity or mortality after lung surgery. Several quality-of-care indicators for NSCLC are available. Process-of-care indicators are the most studied. The use of these indicators to measure practice performance holds the promise of improving outcomes of patients with NSCLC.

Non-emergency small bowel obstruction: assessment of CT findings that predict need for surgery

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Deshmukh, Swati D.; Shin, David S.; Willmann, Juergen K.; Rosenberg, Jarrett; Shin, Lewis; Jeffrey, R.B. [Stanford University, School of Medicine, Department of Radiology, Stanford, CA (United States)

2011-05-15

To identify CT findings predictive of surgical management in non-emergency small bowel obstruction (SBO). Contrast-enhanced abdominal CT of 129 patients with non-emergency SBO were evaluated for small bowel luminal diameter, wall thickness, presence of the small bowel faeces sign (intraluminal particulate matter in a dilated small bowel) and length, transition point, submucosal oedema, mesenteric stranding, ascites and degree of obstruction (low grade partial, high grade partial and complete obstruction). Medical records were reviewed for age, gender, management and history of abdominal surgery, abdominal malignancy, or SBO. Statistical analyses were performed with Stata Release 9.2. Degree of obstruction was the only predictor of need for surgery. Whereas 18.0% of patients with low-grade partial obstruction (n = 50) underwent surgery, 32.5% of patients with high-grade partial obstruction (n = 77) and 100% of patients with complete obstruction (n = 2) required surgery (P = 0.004). The small bowel faeces sign was inversely predictive of surgery (P = 0.018). In non-emergency SBO patients with contrast-enhanced CT imaging, grade of obstruction predicts surgery, while the small bowel faeces sign inversely predicts need for surgery. (orig.)

Risk factors and survival outcome for non-elective referral in non-small cell lung cancer patients--analysis based on the National Lung Cancer Audit.

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Beckett, P; Tata, L J; Hubbard, R B

2014-03-01

Survival after diagnosis of lung cancer is poor and seemingly lower in the UK than other Western countries, due in large part to late presentation with advanced disease precluding curative treatment. Recent research suggests that around one-third of lung cancer patients reach specialist care after emergency presentation and have a worse survival outcome. Confirmation of these data and understanding which patients are affected may allow a targeted approach to improving outcomes. We used data from the UK National Lung Cancer Audit in a multivariate logistic regression model to quantify the association of non-elective referral in non-small cell lung cancer patients with covariates including age, sex, stage, performance status, co-morbidity and socioeconomic status and used the Kaplan-Meier method and Cox proportional hazards model to quantify survival by source of referral. In an analysis of 133,530 cases of NSCLC who presented 2006-2011, 19% of patients were referred non-electively (following an emergency admission to hospital or following an emergency presentation to A&E). This route of referral was strongly associated with more advanced disease stage (e.g. in Stage IV - OR: 2.34, 95% CI: 2.14-2.57, p<0.001) and worse performance status (e.g. in PS 4 - OR: 7.28, 95% CI: 6.75-7.86, p<0.001), but was also independently associated with worse socioeconomic status, and extremes of age. These patients were more likely to have died within 1 year of diagnosis (hazard ratio of 1.51 (95% CI: 1.49-1.54) after adjustment for key clinical variables. Our data confirm and quantify poorer survival in lung cancer patients who are referred non-electively to specialist care, which is more common in patients with poorer performance status, higher disease stage and less advantaged socioeconomic status. Work to tackle this late presentation should be urgently accelerated, since its realisation holds the promise of improved outcomes and better healthcare resource utilisation. Copyright �

Effects of advancing gestation and non-Caucasian race on ductus arteriosus gene expression

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Waleh, Nahid; Barrette, Anne Marie; Dagle, John M.; Momany, Allison; Jin, Chengshi; Hills, Nancy K.; Shelton, Elaine L.; Reese, Jeff; Clyman, Ronald I.

2015-01-01

Objective To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). Study design We collected three sets of DA tissue (n=93, n=89, n=91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "Non-Caucasian" DA. We used RT-PCR to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "Non-Caucasian" race, and gene expression. Results Mature gestation and Non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (e.g., calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all three tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "Non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "Non-Caucasian" DA. Conclusions Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "Non-Caucasian" PDA, making it more likely to close when inhibited by indomethacin. PMID:26265282

Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

Directory of Open Access Journals (Sweden)

Babu KG

2014-06-01

Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

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Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

2017-09-01

This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.