Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer

DEFF Research Database (Denmark)

Pøhl, Mette; Olsen, Karen Ege; Holst, Rene

2016-01-01

proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7...... that stage II-IIIA (HR 2.3), 34βE12+/K7+ (HR 1.6), and 34βE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p overall survival (p ...: Keratin 34βE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival....

Treatment selection for stage IIIA Hodgkin's disease patients

International Nuclear Information System (INIS)

Prosnitz, L.R.; Cooper, D.; Cox, E.B.; Kapp, D.S.; Farber, L.R.

1985-01-01

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III 2 , received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach. Complications from the treatments are discussed

Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects.

Science.gov (United States)

Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

2016-09-20

To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

Socioeconomic position and surgery for early-stage non-small-cell lung cancer

DEFF Research Database (Denmark)

Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne

2013-01-01

Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall......AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...

Treatment and survival of patients with non-small cell lung cancer Stage IIIA diagnosed in 1989-1994: a study in the region of the Comprehensive Cancer Centre East, The Netherlands.

NARCIS (Netherlands)

Dijck, J.A.A.M. van; Festen, J.; Kleijn, E.M.H.A. de; Kramer, G.W.P.M.; Tjan-Heijnen, V.C.; Verbeek, A.L.M.

2001-01-01

The purpose of this study was to gain insight into the treatment policy and survival of patients with non-small cell lung cancer (NSCLC) clinical stage IIIA in daily practice. We selected 212 patients, who had been diagnosed between 1989 and 1994 and registered by the Cancer Registry, Comprehensive

Stereotactic body radiotherapy for centrally located stage I NSCLC. A multicenter analysis

Energy Technology Data Exchange (ETDEWEB)

Schanne, Daniel H.; Nestle, Ursula; Grosu, Anca L. [Universitaetsklinik Freiburg, Klinik fuer Strahlenheilkunde, Freiburg (Germany); Allgaeuer, Michael [Barmherzige Brueder, Klinik fuer Strahlentherapie, Regensburg (Germany); Andratschke, Nicolaus; Molls, Michael [TU Muenchen, Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Muenchen (Germany); Appold, Steffen [Universitaetsklinikum Dresden, Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Dresden (Germany); Dieckmann, Ute [Allgemeines Krankenhaus Wien, Univ. Klinik fuer Strahlentherapie, Wien (Austria); Ernst, Iris [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie, Muenster (Germany); Ganswindt, Ute [LMU Muenchen, Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Muenchen (Germany); Holy, Richard [Universitaetsklinikum Aachen, Klinik fuer Strahlentherapie, Aachen (Germany); Nevinny-Stickel, Meinhard [Medizinischen Universitaet Innsbruck, Univ. Klinik fuer Strahlentherapie und Radioonkologie, Innsbruck (Austria); Semrau, Sabine [Universitaetsklinikum Erlangen, Strahlenklinik Erlangen, Erlangen (Germany); Sterzing, Florian [Universitaetsklinikum Heidelberg, Klinik fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Wittig, Andrea [Philipps-Universitaet Marburg, Klinik fuer Strahlentherapie und Radioonkologie, Marburg (Germany); Guckenberger, Matthias [Universitaet Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany)

2014-08-27

The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity. A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database. Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a median BED{sub 10} of 72 Gy and 84 Gy, respectively (p < 0.001). Fractionation differed as well with medians of 5 (central) and 3 (peripheral) fractions (p < 0.001). In the Kaplan-Meier analysis, 3-year actuarial overall survival was 29 % (central) and 51 % (peripheral; p = 0.004) and freedom from local progression was 52 % (central) and 84 % (peripheral; p < 0.001). Toxicity after treatment of central tumors was low with no grade III/IV and one grade V event. Mortality rates were 0 and 1 % after 30 and 60 days, respectively. Local tumor control in patients treated with SBRT for centrally located, early-stage NSCLC was favorable, provided ablative radiation doses were prescribed. This was, however, not the case in the majority of patients, possibly due to concerns about treatment-related toxicity. Reported toxicity was low, but prospective trials are needed to resolve the existing uncertainties and to establish safe high-dose regimens for this cohort of patients. (orig.) [German] Ziel

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

Science.gov (United States)

Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

2016-01-01

Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

Health and Recovery Program in Increasing Physical Activity Level in Stage IA-IIIA Endometrial Cancer Survivors

Science.gov (United States)

2018-03-05

Cancer Survivor; Endometrial Carcinoma; Stage I Uterine Corpus Cancer AJCC v7; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7

Negative effect of cyclin D1 overexpression on recurrence-free survival in stage II-IIIA lung adenocarcinoma and its expression modulation by vorinostat in vitro.

Science.gov (United States)

Lee, Eunju; Jin, DongHao; Lee, Bo Bin; Kim, Yujin; Han, Joungho; Shim, Young Mog; Kim, Duk-Hwan

2015-12-17

This study was aimed at identifying prognostic biomarkers for stage II-IIIA non-small cell lung cancer (NSCLC) according to histology and at investigating the effect of vorinostat on the expression of these biomarkers. Expression levels of cyclin D1, cyclin A2, cyclin E, and p16 proteins that are involved in the G1-to-S phase progression of cell cycle were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 372 samples of stage II-IIIA NSCLC. The effect of vorinostat on the expression of these proteins, impacts on cell cycle, and histone modification was explored in lung cancer cells. Abnormal expression of cyclin A2, cyclin D1, cyclin E, and p16 was found in 66, 47, 34, and 51 % of 372 cases, respectively. Amongst the four proteins, only cyclin D1 overexpression was significantly associated with poor recurrence-free survival (adjusted hazard ratio = 1.87; 95 % confidence interval = 1.12 - 2.69, P = 0.02) in adenocarcinoma but not in squamous cell carcinoma (P = 0.44). Vorinostat inhibited cell cycle progression to the S-phase and induced down-regulation of cyclin D1 in vitro. The down-regulation of cyclin D1 by vorinostat was comparable to a siRNA-mediated knockdown of cyclin D1 in A549 cells, but vorinostat in the presence of benzo[a]pyrene showed a differential effect in different lung cancer cell lines. Cyclin D1 down-regulation by vorinostat was associated with the accumulation of dimethyl-H3K9 at the promoter of the gene. The present study suggests that cyclin D1 may be an independent prognostic factor for recurrence-free survival in stage II-IIIA adenocarcinoma of lung and its expression may be modulated by vorinostat.

Ablative dose proton beam therapy for stage I and recurrent non-small cell lung carcinomas. Ablative dose PBT for NSCLC

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Lee, Sung Uk; Cho, Kwan Ho; Kim, Joo Young; Kim, Dae Yong; Kim, Tae Hyun; Suh, Yang-Gun; Kim, Yeon-Joo [Research Institute and Hospital, National Cancer Center, Proton Therapy Center, Goyang (Korea, Republic of); Moon, Sung Ho [Research Institute and Hospital, National Cancer Center, Proton Therapy Center, Goyang (Korea, Republic of); Research Institute and Hospital, National Cancer Center, Center for Lung Cancer, Goyang (Korea, Republic of); Research Institute and Hospital, National Cancer Center, Proton Therapy Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769 (Korea, Republic of); Pyo, Hong Ryull [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiation Oncology, Seoul (Korea, Republic of)

2016-09-15

To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC). A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50-72 CGE (cobalt gray equivalent) in 5-12 fractions was delivered. The median follow-up duration was 29 months (range 4-95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan-Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4-95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5-14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis-free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for ≤3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3-37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis. Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC. (orig.) [German] Beurteilung von Wirksamkeit und Sicherheit hypofraktionierter Protonentherapie (PBT) mit ablativen Dosen fuer nichtkleinzellige Lungenkarzinome (NSCLC) im Stadium I und rekurrierende NSCLC. Retrospektiv wurden insgesamt 55 NSCLC-Patienten (Stadium I: n = 42; rekurrierender Tumor: n = 13), analysiert. Sie waren mit einer Gesamtdosis von 50-72 CGE (''cobalt gray equivalent'') in 5-12 Fraktionen behandelt worden. Der Median der Follow

Systematic mediastinal lymphadenectomy or mediastinal lymph node sampling in patients with pathological stage I NSCLC: a meta-analysis.

Science.gov (United States)

Dong, Siyuan; Du, Jiang; Li, Wenya; Zhang, Shuguang; Zhong, Xinwen; Zhang, Lin

2015-02-01

To evaluate the evidence comparing systematic mediastinal lymphadenectomy (SML) and mediastinal lymph node sampling (MLS) in the treatment of pathological stage I NSCLC using meta-analytical techniques. A literature search was undertaken until January 2014 to identify the comparative studies evaluating 1-, 3-, and 5-year survival rates. The pooled odds ratios (OR) and the 95 % confidence intervals (95 % CI) were calculated with either the fixed or random effect models. One RCT study and four retrospective studies were included in our meta-analysis. These studies included a total of 711 patients: 317 treated with SML, and 394 treated with MLS. The SML and the MLS did not demonstrate a significant difference in the 1-year survival rate. There were significant statistical differences between the 3-year (P = 0.03) and 5-year survival rates (P = 0.004), which favored SML. This meta-analysis suggests that in pathological stage I NSCLC, the MLS can get the similar outcome to the SML in terms of 1-year survival rate. However, the SML is superior to MLS in terms of 3- and 5-year survival rates.

Comparative analysis of the long-term results of treatment in patients with Stages I-IIa breast cancer in relation to major prognostic factors

Directory of Open Access Journals (Sweden)

Yu. V. Efimkina

2010-01-01

Full Text Available The analysis of the long-term results of treatment in patients with Stages I-IIa breast cancer in relation to major prognostic factors re- vealed poor morphological factors that greatly influenced the lifespan of female patients, such as tumor invasion along the neural fibers, tumor necrosis, cancer emboli in the lymph gaps and vessels, vascular tumor invasion.

Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease. A multi-institutional treatment recommendation

Energy Technology Data Exchange (ETDEWEB)

Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Ruysscher, Dirk de [MAASTRO Clinic, Department of Radiation Oncology, Maastricht (Netherlands); Gaspar, Laurie E. [University of Colorado School of Medicine, Department of Radiation Oncology, Aurora, CO (United States); Guckenberger, Matthias [University Hospital Zurich, Department of Radiation Oncology, Zurich (Switzerland); Mehta, Minesh P. [Miami Cancer Institute, Department of Radiation Oncology, Miami, FL (United States); Cheung, Patrick; Sahgal, Arjun [Sunnybrook Health Sciences Centre and University of Toronto, Department of Radiation Oncology, Toronto (Canada)

2017-07-15

Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC. A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions' treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed. Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60 Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred. The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this. (orig.) [German] Fuer fruehe und lokal fortgeschrittene Stadien des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) wurden Behandlungsleitlinien publiziert

Preoperative staging of lung cancer with combined PET-CT

DEFF Research Database (Denmark)

Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann

2009-01-01

BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

Prognostic value and molecular correlates of a CT image-based quantitative pleural contact index in early stage NSCLC

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Lee, Juheon; Cui, Yi; Li, Bailiang; Wu, Jia; Gensheimer, Michael F. [Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA (United States); Sun, Xiaoli [First Affiliated Hospital of Zhejiang University, Radiotherapy Department, Hangzhou, Zhejiang (China); Li, Dengwang [Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA (United States); Shandong Normal University, Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, Institute of Biomedical Sciences, School of Physics and Electronics, Jinan Shi (China); Loo, Billy W.; Li, Ruijiang [Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA (United States); Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA (United States); Diehn, Maximilian [Stanford University School of Medicine, Department of Radiation Oncology, Stanford, CA (United States); Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA (United States); Stanford University School of Medicine, Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA (United States)

2018-02-15

To evaluate the prognostic value and molecular basis of a CT-derived pleural contact index (PCI) in early stage non-small cell lung cancer (NSCLC). We retrospectively analysed seven NSCLC cohorts. A quantitative PCI was defined on CT as the length of tumour-pleura interface normalised by tumour diameter. We evaluated the prognostic value of PCI in a discovery cohort (n = 117) and tested in an external cohort (n = 88) of stage I NSCLC. Additionally, we identified the molecular correlates and built a gene expression-based surrogate of PCI using another cohort of 89 patients. To further evaluate the prognostic relevance, we used four datasets totalling 775 stage I patients with publically available gene expression data and linked survival information. At a cutoff of 0.8, PCI stratified patients for overall survival in both imaging cohorts (log-rank p = 0.0076, 0.0304). Extracellular matrix (ECM) remodelling was enriched among genes associated with PCI (p = 0.0003). The genomic surrogate of PCI remained an independent predictor of overall survival in the gene expression cohorts (hazard ratio: 1.46, p = 0.0007) adjusting for age, gender, and tumour stage. CT-derived pleural contact index is associated with ECM remodelling and may serve as a noninvasive prognostic marker in early stage NSCLC. (orig.)

Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

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Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States)

2014-06-01

Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

International Nuclear Information System (INIS)

Sher, David J.; Liptay, Michael J.; Fidler, Mary Jo

2014-01-01

Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

Long-term results of a randomized controlled trial evaluating preoperative chemotherapy in resectable non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Chen ZW

2013-06-01

Full Text Available Zhiwei Chen,* Qingquan Luo,* Hong Jian, Zhen Zhou, Baijun Cheng, Shun Lu, Meilin LiaoShanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equallyObjective: We aimed to evaluate whether preoperative chemotherapy provides benefits in the survival and prognosis of patients with non-small cell lung cancer (NSCLC in resectable stages I to IIIA, except T1N0. Methods: In this randomized, controlled trial, 356 patients with stage I (except for T1N0, II and IIIA NSCLC were assigned to either the preoperative chemotherapy plus surgery arm (179 patients or the primary surgery arm (177 patients. Both treatments were followed by adjuvant chemotherapy. The end point of this study included overall survival (OS, progression-free survival (PFS, and survival rate associated with clinical remission. Results: Statistical survival difference was found between the preoperative chemotherapy plus surgery arm and the surgery-alone arm. However, the median survival time (MST in the preoperative chemotherapy arm was lower than that of surgery-alone arm (MST, 45.42 months vs 57.59 months (P = 0.016. When comparing the effect of preoperative chemotherapy at each stage of NSCLC, a statistical survival difference was found in stage II NSCLC but not in stage I and IIIA (MST 40.86 months vs 80.81 months (P = 0.044. However, no statistically significant difference in PFS was noticed between the two arms, except for stage I NSCLC (hazard radio [HR] = 0.87; 95% CI, 0.561−1.629; P = 0.027. The survival rate was higher for patients who had clinical remission after preoperative chemotherapy, but the differences did not reach statistical significance (MST 42.10 months vs 35.33 months (P = 0.630. Conclusion: Preoperative chemotherapy did not show benefits in OS and PFS for stage I-IIIA NSCLC patients. Keywords: NSCLC, neoadjuvent, mitomycin, cisplatin, vindesine

Reirradiation of recurrent node-positive non-small cell lung cancer after previous stereotactic radiotherapy for stage I disease. A multi-institutional treatment recommendation

International Nuclear Information System (INIS)

Nieder, Carsten; Ruysscher, Dirk de; Gaspar, Laurie E.; Guckenberger, Matthias; Mehta, Minesh P.; Cheung, Patrick; Sahgal, Arjun

2017-01-01

Practice guidelines have been developed for early-stage and locally advanced non-small cell lung cancer (NSCLC). However, many common clinical scenarios still require individualized decision making. This is true for locoregional relapse after initial stereotactic radiotherapy (stereotactic body radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an increasingly utilized curative treatment option for stage I NSCLC. A consortium of expert radiation oncologists was established with the aim of providing treatment recommendations. In this scenario, a case was distributed to six radiation oncologists who provided their institutions' treatment recommendations. In this case, a patient developed local and mediastinal relapse after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion was developed. Three institutions recommended evaluation for surgery. If the patient was not a surgical candidate, and/or refused surgery, definitive chemoradiation was recommended, including retreating the primary to full dose. European participants were more in favor of a non-surgical approach. None of the participants were reluctant to prescribe reirradiation, but two institutions prescribed doses lower than 60 Gy. Platinum-based doublets together with intensity-modulated radiotherapy were preferred. The institutional recommendations reflect the questions and uncertainties discussed in current stage III guidelines. All institutions agreed that previous SABR is not a contraindication for salvage chemoradiation. In the absence of high-quality prospective trials for recurrent NSCLC, all treatment options recommended in current guidelines for stage III disease can be considered in clinical scenarios such as this. (orig.) [de

Postoperative low-pelvic irradiation for stage I-IIA cervical cancer patients with risk factors other than pelvic lymph node metastasis

International Nuclear Information System (INIS)

Hong, J.-H.; Tsai, C.-S.; Lai, C.-H.; Chang, T.-C.; Wang, C.-C.; Lee, Steve P.; Tseng, C.-J.; Hsueh, Swei

2002-01-01

Purpose: To retrospectively investigate whether postoperative low-pelvic radiotherapy (RT) is an appropriate treatment for node-negative, high-risk Stage I-IIA cervical cancer patients. Methods and Materials: A total of 228 Stage I-IIA cervical cancer patients treated by radical surgery and postoperative RT were included in this study. All patients had histopathologically negative pelvic node metastasis, but at least one of the following risk factors: parametrial involvement, positive or close resection margins, invasion depth two-thirds or greater cervical stromal thickness. Seventy-nine patients (35%) received 30-50 Gy (median 44) to whole pelvis and a boost dose to the low pelvis (whole-pelvic RT group); the other 149 patients (65%) received low-pelvic RT only (low-pelvic RT group). For both groups, the total external RT dose to the low pelvis ranged from 40 to 60 Gy (median 50). The potential factors associated with survival, small bowel (gastrointestinal) complications, and leg lymphedema were analyzed, and patients who had a relapse in the upper pelvis were identified. Results: The 5-year overall and disease-specific survival rate was 84% and 86%, respectively. After multivariate analysis, only bulky tumor (≥4 cm) and non-squamous cell carcinoma were significantly associated with survival. Parametrial involvement, lymph-vascular invasion, ≤50.4 Gy to the low pelvis, positive or close margins, and low-pelvic RT alone did not significantly affect survival. Grade I-V small bowel complications occurred in 33 patients (15%). Whole pelvic RT and >50.4 Gy to the low pelvis, but not old age and treatment technique (AP-PA vs. box), were significantly associated with gastrointestinal complications. Three patients (2%) in the low-pelvic RT group and 6 patients (8%) in the whole-pelvic RT group were found to have Grade III or higher small bowel complications (p=0.023). Thirty-one percent of patients developed lymphedema of the leg. A dose to the low pelvis >50.4 Gy

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.

Preoperative Pulmonary Function Tests (PFTs) and Outcomes from Resected Early Stage Non-small Cell Lung Cancer (NSCLC).

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Almquist, Daniel; Khanal, Nabin; Smith, Lynette; Ganti, Apar Kishor

2018-05-01

Preoperative pulmonary function tests (PFTs) predict operative morbidity and mortality after resection in lung cancer. However, the impact of preoperative PFTs on overall outcomes in surgically-resected stage I and II non-small cell lung cancer (NSCLC) has not been well studied. This is a retrospective study of 149 patients who underwent surgical resection as first-line treatment for stage I and II NSCLC at a single center between 2003 and 2014. PFTs [forced expiratory volume in 1 sec (FEV1), Diffusing Capacity (DLCO)], both absolute values and percent predicted values were categorized into quartiles. The Kaplan-Meier method and Cox regression analysis were used to determine whether PFTs predicted for overall survival (OS). Logistic regression was used to estimate the risk of postoperative complications and length of stay (LOS) greater than 10 days based on the results of PFTs. The median age of the cohort was 68 years. The cohort was predominantly males (98.6%), current or ex-smokers (98%), with stage I NSCLC (82.76%). The majority of patients underwent a lobectomy (n=121, 81.21%). The predominant tumor histology was adenocarcinoma (n=70, 47%) followed by squamous cell carcinoma (n=61, 41%). The median follow-up of surviving patients was 53.2 months. DLCO was found to be a significant predictor of OS (HR=0.93, 95% CI=0.87-0.99; p=0.03) on univariate analysis. Although PFTs did not predict for postoperative complications, worse PFTs were significant predictors of length of stay >10 days. Preoperative PFTs did not predict for survival from resected early-stage NSCLC, but did predict for prolonged hospital stay following surgery. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

CyberKnife with tumor tracking: An effective alternative to wedge resection for high-risk surgical patients with stage I non-small cell lung cancer (NSCLC

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Sean eCollins

2012-02-01

Full Text Available Published data suggests that wedge resection for stage I NSCLC results in improved overall survival compared to stereotactic body radiation therapy (SBRT. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV. Treatment plans were designed using hundreds of pencil beams. Doses delivered to the PTV ranged from 42-60 Gy in 3 fractions. The 30-Gy isodose contour extended at least 1cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3-month follow-up intervals. Forty patients (median age 76 with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm and a mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1 of 57% (range, 21 - 111% were treated. A mean dose of 50 Gy was delivered to the PTV over 3 to 13 days (median, 7 days. The 30-Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12 -72 months follow-up, the 3-year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91% and 75% , respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1 to 2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

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2018-04-06

Ductal Breast Carcinoma; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Medullary Breast Carcinoma; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Tubular Breast Carcinoma

Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell lung cancer (NSCLC)

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Zimmermann, Frank B.; Geinitz, Hans; Schill, Sabine; Thamm, Reinhard; Nieder, Carsten; Schratzenstaller, Ulrich; Molls, Michael [Technical Univ., Klinikum rechts der Isar, Munich (Germany). Dept. of Radiation Oncology

2006-09-15

Stereotactic Radiotherapy has the potential to produce high local control rates with low risk of severe lung toxicity. From December 2000 to January 2006, 68 inoperable patients (median age 76 years) with stage I NSCLC received definitive hSRT. A mean total dose of 37.5 Gy (24-40 Gy; 60%-isodose) in 3-5 fractions was applied. Immobilisation was carried out by means of a vacuum couch and low pressure foil (Medical Intelligence, Schwab Muenchen, Germany). Staging procedures were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all patients. Clinical target volume was the tumor as seen in lung windowing of CT and in FDG-PET. Organ movements (6-22 mm) and patient positioning in the couch (3-12 mm) were added as safety margin for the definition of the planning target volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88% and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight patients due to cancer (12%), two to local tumor progression alone. Cancer-specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died from comorbidities, making a 53% overall 3-year survival. Fifty five percent of the patients were affected by mild acute and subacute side effects, with only 3% experiencing pneumonitis III. Late effects were pneumonitis III in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients. Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and significantly reduced lung capacity. It leads to high local control rates and should be offered to patients not amenable for curative resection.

Feasibility of accelerated radiotherapy (AR) using a concomitant boost for the treatment of unresectable non-small cell lung cancer (NSCLC): a phase II study

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Kumar, Parvesh; Wan, Jim; Paig, Camilo U.; Kun, Larry E.; Niell, H. Barry

1996-01-01

Purpose/Objective: The feasibility of AR using a concomitant boost in the treatment of unresectable NSCLC was prospectively tested in a phase II study. Materials and Methods: Twenty patients were enrolled to the protocol between 11/90 and 5/93. Stage distribution was as follows: Medically inoperable stage I = 5 (T 1 = 1, T 2 = 4), stage IIIA = 1, and stage IIIA(N 2 ) = 14. Planned AR delivered a total dose of 65 Gy in 45 fractions over five weeks using a 'field within a field technique'. The large field (day 1, a.m.) encompassed the primary lesion and adjacent lymph nodes to 45 Gy at 1.8 Gy/fraction (fx). A CT planned small field (day 8, >6 hours apart in p.m.) included only the primary lesion and overt nodal disease to 20 Gy at 1.0 Gy/fx. Doses were not corrected for lung inhomogeneity. Results: Median age of the 20 male enrolled patients was 68 years (range = 42-80 years). Eighteen (90%) of 20 patients completed the planned AR without any interruptions in therapy. One patient experienced a 4 day interruption due to tumor related obstructive pneumonia while the other patient missed 2 days secondary to non-treatment related small bowel obstruction. No incidence of grade ≥3 esophagitis was observed. One patient experienced pneumonitis within the radiation portal 1 month post-RT which response d to corticosteroid therapy; otherwise, no late sequelae were observed. The median total delivered dose was 65 Gy (range 64.0-65.4). At a minimum follow-up interval of 30 months, the 2-year Kaplan-Meier and median survival are 15% and 13.4 months, respectively for all 20 patients. Conclusion: AR using a concomitant boost to 65 Gy in 5 weeks for unresectable NSCLC is feasible with minimal acute or long term toxicity. Median survival in our study was similar to the chemo radiation arms of CALGB 8433 and RTOG 8808 protocols. Protocols which combine AR with chemotherapy should be explored for unresectable NSCLC

The Effect of Consolidation Chemotherapy for LA-NSCLC Patients Receiving Concurrent Chemoradiotherapy

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Yelda Varol

2016-09-01

Full Text Available Aim: The efficacy and safety of consolidation chemotherapy (CCT following concurrent chemoradiotherapy are not adequately established for patients with locally advanced non-small-cell lung cancer (LA-NSCLC. In this context, the present study aims to evaluate the efficacy and toxicity of CCT.Material and Method: We retrospectively analyzed the overall survival (OS and progression-free survival (PFS of 83 LA-NSCLC patients treated with concurrent CRT as an initial treatment with (n:20 or without CCT (n:63. All patients were cytohistologically proven to have NSCLC and diagnosed with clinical Stage III (n:48 for IIIA and n:35 for IIIB according to the staging system published by the American Joint Committee on Cancer (AJCC in 2009. All patients received curative thoracic radiotherapy with concurrent platinum doublet chemotherapy. Results: The mean age of the lung cancer patients was 59 (±7.3; 89.2% were male (n:74,and there were only 9 female patients (10.8%.When we compared the outcome of LA-NSCLC patients treated with CCT (median 10.4 months to the patients treated without CCT (median 13.8 months, the log-rank analysis demonstrated a statistically significant difference for an inferior progression-free survival (p=0.046 in patients receiving CCT. However, no significant association was observed for overall survival (17.4, 21 months, respectively (p>0.05. Patients with CCT presented higher levels of hematological side effects compared with the patients without CCT (p

Cost-effective analysis of PET application in NSCLC

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Gu Aichun; Liu Jianjun; Sun Xiaoguang; Shi Yiping; Huang Gang

2006-01-01

Objective: To evaluate the cost-effectiveness of PET and CT application for diagnosis of non-small cell lung cancer (NSCLC) in China. Methods: Using decision analysis method the diagnostic efficiency of PET and CT for diagnosis of NSCLC in china was analysed. And also the value of cost for accurate diagnosis (CAD), cost for accurate staging (CAS) and cost for effective therapy (CAT) was calculated. Results: (1) For the accurate diagnosis, CT was much more cost-effective than PET. (2) For the accurate staging, CT was still more cost-effective than PET. (3) For the all over diagnostic and therapeutic cost, PET was more cost-effective than CT. (4) The priority of PET to CT was for the diagnosis of stage I NSCLC. Conclusion: For the management of NSCLC patient in China, CT is more cost-effective for screening, whereas PET for clinical staging and monitoring therapeutic effect. (authors)

Overexpression of matrix metalloproteinase-7 and -9 in NSCLC tumor and stromal cells: correlation with a favorable clinical outcome.

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Stenvold, Helge; Donnem, Tom; Andersen, Sigve; Al-Saad, Samer; Al-Shibli, Khalid; Busund, Lill-Tove; Bremnes, Roy M

2012-02-01

Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC). From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells. In univariate analyses, high tumor cell MMP-7 expression (P=0.029) and high stromal MMP-9 expression (P=0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08-2.32, P=0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25-2.96, P=0.003) were independent positive prognostic factors for disease-specific survival. High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

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Baum, R.P.; Schmuecking, M.; Bonnet, R.; Presselt, N.; Przetak, C.; Junker, K.; Schneider, C.P.; Hoeffken, K.; Wendt, T.G.

2002-01-01

Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m 2 ) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m 2 ) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

Correlation of FDG-PET measurements with morphometric tumor response after induction chemotherapy and adjuvant radiotherapy in stage III non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Baum, R.P.; Niesen, A.; Griesinger, F.

2002-01-01

Full text: Docetaxel (D) and carboplatin (C) combination chemotherapy (DC) has shown high response rates in advanced NSCLC. Histologic tumor response after chemotherapy or combined modality induction is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction chemotherapy with etoposide, ifosfamide and cisplatin (VIP) has been shown to be predictive of outcome in NSCLC. Finally, erythropoietin (EPO) may prevent the decrease in hemoglobin levels that was seen in a previous study of DC (median drop 2.7 g/dl) and thus may enhance treatment efficacy. The aim of the present study was to correlate FDG-PET studies with histomorphometric findings after DC induction chemotherapy plus Epo. 33 patients (pts) with NSCLC stage IIIA (7 pts) or IIIB (24 pts) were enrolled and received treatment with D 100 mg/m 2 dl and C AUC 7.5 d2 q21 days for 4 cycles. Epo was given at 10,000 IU s.c. three times a week. All pts received adjuvant radiotherapy. Of 33 enrolled patients, 22 were evaluable for response by CT imaging. 14/22 pts (64 %) achieved PR. Of the 22 responders, 20 were evaluable for repeated FDG-PET studies. 13/20 pts had a decrease of standardized uptake values (SUV) and of the metabolic tumor index (MTI) by >50 %, 9/20 had SUV <2.5 (CR). Seven of these 9 pts underwent tumor resection, and specimens were subjected to morphometric analysis. In 7/7 cases, no vital tumor cells were detected in the specimens. In contrast to our previous study, hemoglobin levels increased by a median of 0.3 g/dl. Morphometric tumor response after induction chemotherapy correlates strongly with metabolic remission by FDG-PET. FDG-PET appears to be a useful non-invasive diagnostic tool to predict pathologic response and potentially long-term outcome in stage III NSCLC. (author)

Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

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2017-11-15

Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

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Stinchcombe, Thomas E; Morris, David E; Lee, Carrie B; Moore, Dominic T; Hayes, D Neil; Halle, Jan S; Rivera, M Patricia; Rosenman, Julian G; Socinski, Mark A

2008-03-01

Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT). Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy. Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% > or =5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20 months), respectively. Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing.

Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

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2017-05-03

Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

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Marte Eilertsen

Full Text Available INTRODUCTION: Monocarboxylate transporters (MCTs 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS in both cancer and tumor stromal cells in NSCLC. METHODS: Tissue micro arrays (TMAs were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. RESULTS: In univariate analyses; ↓ MCT1 (P = 0.021 and ↑ MCT4 (P = 0.027 expression in cancer cells, and ↑ MCT1 (P = 0.003, ↓ MCT2 (P = 0.006, ↓ MCT3 (P = 0.020 expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001, ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001, ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031 and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016 were significant independent poor prognostic markers for DSS. CONCLUSIONS: We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis.

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Huang, Xiongfeng; Wang, Jianmin; Chen, Qiao; Jiang, Jielin

2014-01-01

This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients. A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration's Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI). We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups. Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II-IIIA remains to be determined.

Local Control and Survival Following Concomitant Chemoradiotherapy in Inoperable Stage I Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Campeau, Marie-Pierre; Herschtal, Alan; Wheeler, Greg; Mac Manus, Michael; Wirth, Andrew; Michael, Michael; Hogg, Annette; Drummond, Elizabeth; Ball, David

2009-01-01

Purpose: Concomitant chemoradiotherapy (CRT) increases survival rates compared with radical radiotherapy alone (RT) in Stage III non-small-cell lung cancer (NSCLC), as a result of improved local control. The effect of CRT on local control in Stage I NSCLC is less well documented. We retrospectively reviewed local control and survival following CRT or RT for inoperable Stage I NSCLC patients. Methods and materials: Eligible patients had histologically/cytologically proved inoperable Stage I NSCLC and had undergone complete staging investigations including an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Radiotherapy was planned as (1) 60 Gy in 30 fractions over 6 weeks with or without concomitant chemotherapy or (2) 50-55 Gy in 20 fractions without chemotherapy. Results: Between 2000 and 2005, 73 patients met the eligibility criteria and were treated as follows: CRT (60 Gy)-39; RT (60 Gy)-23; RT (50-55 Gy)-11. The median follow-up time for all patients was 18 months (range, 1-81 months). Survival analysis was based on intent to treat. Local progression-free survival (PFS) at 2 years was 66% with CRT and 55% with RT. The 2-year distant PFS was 60% following CRT and 63% after RT. The 2-year PFS rates were 57% and 50%, respectively. The 2-year survival rate for patients treated with CRT was 57% and 33% in patients receiving RT. Conclusions: Despite the use of CRT and routine staging with FDG-PET, both local and distant recurrences remain important causes of treatment failure in patients with inoperable stage I NSCLC.

Impact of lymph node micrometastasis for the UICC stage in non-small cell lung carcinoma

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Ouyang Weiwei; Lu Bing; He Chang; Long Yiguo; Wang Ping

2007-01-01

Objective: To detect cytokeratin in routine pathology negative regional lymph nodes postoperatively in non-small cell lung carcinoma (NSCLC). To investigate the relationship of lymph node micrometastasis in P-TNM stages NSCLC and survival rates. Methods: From Jan. 1996 to Dec. 2003, 107 paraffin-embedded specimens of T1-T4N0-N1M0 NSCLC patients were collected. Anti-cytokeratin(CK) antibody AE1/AE3 was applied to detect cytokeratin with Envision TM method in routine pathological negative region lymph nodes in NSCLC, and selected negative control, positive control and blank control. The pulmo- nary hilar lymph node micrometastasis was upward regulated with stage pCK-N1, mediastinal lymph node mi- crometastatsis was upward regulated with stage pCK-N2. The result applied to SPSS11.0 software to process. Results: The CK positive rate was 29.9% in all the patients. The CK positive rate was 27% (21/78), 30% (7/23), 67%(4/6)in stage p- I, p-II and p-III, respectively. All these data showed the tendency by which detectable rate increased and was accompanied by disease progress. Comparing the annual survival rate and median survival time of the non-micrometastasis group with the micrometastasis group in two groups, the survival rate difference was statistically significant. Comparing the armnal survival rate and median sur- vival time in pCK-III A stage with p- I -II stage, pCK-III A stage annual survival rate and median survival time was significantly different(P=0.020). Similarly, comparing the survival rate in pCK-II B stage with p- I B stage, pCK- II B stage survival rate was significantly different( P = 0. 059). Comparing the survival time of pCK-IIIA stage with p-III stage, pCK-II B stage, with p-II B stage, euther survival time difference was statistically significant (P=0.838, 0.518). Conclusions: The rate of positive cytokeratin increase is accompanied by the disease progress in NSCLC. Positive cytokeratin has disadvantageous prognosis. It is showed that pCK-N1 may

Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer : a pooled analysis of two randomised trials

NARCIS (Netherlands)

Chang, Joe Y.; Senan, Suresh; Paul, Marinus A.; Mehran, Reza J.; Louie, Alexander V.; Balter, Peter; Groen, Harry; McRae, Stephen E.; Widder, Joachim; Feng, Lei; van den Borne, Ben E. E. M.; Munsell, Mark F.; Hurkmans, Coen; Berry, Donald A.; van Werkhoven, Erik; Kresl, John J.; Dingemans, Anne-Marie; Dawood, Omar; Haasbeek, Cornelis J. A.; Carpenter, Larry S.; De Jaeger, Katrien; Komaki, Ritsuko; Slotman, Ben J.; Smit, Egbert F.; Roth, Jack A.

Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3

Systems Support Mapping in Guiding Self-Management in Stage I-III Colorectal Cancer Survivors

Science.gov (United States)

2018-04-26

Cancer Survivor; Stage I Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Stage IIA Colorectal Cancer AJCC v8; Stage IIB Colorectal Cancer AJCC v8; Stage IIC Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8

[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.

Lymphovascular space invasion and tumor differentiation are predictors for postoperative recurrence in patients with pathological stage I nonsmall cell lung cancer

Directory of Open Access Journals (Sweden)

Ying-Yi Chen

2014-08-01

Conclusion: Tumor differentiation and LVSI were predictors of postoperative relapse for patients with pathological stage I NSCLC. Risk factors of postoperative recurrence in patients with pathological Stage I NSCLC may enable us to optimize the patient selection for postoperative adjuvant therapies to prevent possibly occult micrometastases.

Secondary malignancies in patients with stage IA-IIIA Hodgkin's lymphoma after radiation (chemoradiation) therapy using accelerated dose fractionation

International Nuclear Information System (INIS)

Sinajko, V.V.; Minajlo, I.I.; Veyakin, I.V.

2010-01-01

The incidence of secondary malignancies was investigated in 367 patients with stage IA-IIIA Hodgkin's lymphoma after radiation therapy using accelerated fractionation. For 20 years of the observation 24 of them developed 27(7.4%) tumors, besides their frequency did not depend on the disease stage and method of treatment.

Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

Science.gov (United States)

2018-05-30

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Grade 1 Peripheral Motor Neuropathy, CTCAE; Grade 1 Peripheral Sensory Neuropathy, CTCAE; Grade 2 Peripheral Motor Neuropathy, CTCAE; Grade 2 Peripheral Sensory Neuropathy, CTCAE; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Study of percutaneous 125I seeds implantation guided by CT in elderly patients of stage I peripheral non-small cell lung cancer

International Nuclear Information System (INIS)

Ke Mingyao; Yong Yazhi; Luo Bingqing; Wu Xuemei; Chen Lingling; Xie Hongqi

2011-01-01

Objective: To evaluate the efficacy, feasibility and safety of CT guided percutaneous 125 I seeds implantation in elderly patients of stage I peripheral non-small cell lung cancer (NSCLC). Methods: Clinical data of 16 elderly peripheral stage I NSCLC patients (10 squamous carcinoma and 6 adenocarcinoma; 13 stage I A and 3 stage I B ) who received radioactive 125 I seeds implantation because of refusal or being unsuited to operation or external radiotherapy were retrospectively analyzed. Prescribed dose was 140 - 160 Gy. Under CT guidance, 125 I seeds were implanted percutaneously into tumors for interstitial radiotherapy according to treatment plan system. Results: Mean number of 125 I seeds each patient received was 21.1. 12 complete response (CR) and 4 partial response (PR) were achieved. Total response rate (CR + PR) was 100%. 100% patients completed 10 to 56 months of follow-up, 15, 13, 8 and 6 patients completed 1-, 2-, 3-and 4-years' follow-up, respectively. The median local progression free time was 14 months. The 1-, 2-, 3-and 4-year overall survival rate were 60%, 54%, 50% and 33%, respectively (median : 14 months). 7 cases died of non-tumor disease and 5 died of metastasis. No severe complications were observed. Conclusions: CT guided 125 I seeds implantation is a safe, reliable and effective radical treatment method for elderly stage I peripheral NSCLC patients, who refuse to or are unsuitable to operation or external radiotherapy. (authors)

Failure patterns by prognostic group as determined by recursive partitioning analysis (RPA) of 1547 on four radiation therapy oncology group studies in operable non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Komaki, Ritsuko; Scott, Charles B.; Byhardt, Roger W.; Emami, Bahman; Asbell, Sucha O.; Russell, Anthony H.; Roach, Mack; Urtasun, Raul C.; Gaspar, Laurie E.

1997-01-01

Purpose: To identify groups of patients who might benefit from more aggressive systemic or local treatment based on failure patterns when unresectable NSCLC was treated by radiation therapy alone. Methods: 1547 patients from 4 RTOG trials treated by RT alone were analyzed for the patterns of first failure by PRA class which was defined by prognostic factors, e.g., stage, KPS, weight loss, pleural effusion, age. All patients were AJCC stage II, IIIA or IIIB with KPS of at least 50 and n previous radiotherapy or chemotherapy for their NSCLC. Progressions in the primary (within irradiated fields), thorax (outside irradiated area), brain and distant metastasis other than brain were compared (two-sided) for each failure category by RPA. Results: The RPA classes are four distinct subgroups that had significantly different median survivals of 12.6, 8.3, 6.2 and 3.3 months for classes I, II, III and IV respectively (all groups p=0.0002). Pair comparison showed that RPA I vs IV p<0.0001, I vs III p=0.006, II vs IV p<0.0001, and III vs IV p=0.06. Conclusions: These results suggest the burden of disease and physiologic compromise in class IV patients are sufficient to cause death before specific sites of failure can be discerned. Site specific treatment strategies (intensive local therapy, combination chemotherapy, prophylactic cranial irradiation) may lead to improved outcome in class I and II, but are unlikely to alter outcome in class III and IV

Experimental data report for transient flow calibration facility tests IIIA101, IIIA102, IIIA201, and IIIA202

International Nuclear Information System (INIS)

Wambach, J.L.

1980-01-01

Thermal-hydraulic response data are presented for the transient performance tests of an ECC pitot tube rake (IIIA201, IIIA202) and both an ECC pitot tube rake and modular drag disc-turbine transducer (DTT) rake (IIIA101, IIIA102). The tests were conducted in a system which provided full scale simulation of the pressure vessel and intact loop cold leg piping of the Loss of Fluid Test Facility (LOFT). A load cell system was used to provide a reference mass flow rate measurement

Octogenarians with early stage NSCLC undergoing SBRT-same outcomes as younger patients?

DEFF Research Database (Denmark)

Jeppesen, Stefan Starup; Schytte, T.; Brink, C.

2015-01-01

Purpose/Objective: The increase in life expectancy leads to an increased number of elderly patients (pts) diagnosed with NSCLC. Octogenarians can be a treatment challenge due to frailty and comorbidity. Stereotactic Body Radiotherapy (SBRT) has become the standard treatment for medical inoperable...... pts with early stage NSCLC. However, it is unknown if all pts have same benefit of SBRT due to lack of randomized studies. This retrospective single-institution study reports survival and control rates for medical inoperable octogenarians vs. pts 80 and 80 and 137 were 80 and 0.05). No difference...... in comorbidity measured by Charlson Score Index was observed. SBRT was generally well tolerated. A log rank test showed a significant difference of OS between patients >80 and 80 and 80 and...

Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

Science.gov (United States)

2018-02-01

Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

International Nuclear Information System (INIS)

Hata, Masaharu; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

2007-01-01

Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade ≥3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC

Fully automated VMAT treatment planning for advanced-stage NSCLC patients

Energy Technology Data Exchange (ETDEWEB)

Della Gala, Giuseppe [Erasmus MC Cancer Institute, Department of Radiation Oncology, Rotterdam (Netherlands); Universita di Bologna, Scuola di Scienze, Alma Mater Studiorum, Bologna (Italy); Dirkx, Maarten L.P.; Hoekstra, Nienke; Fransen, Dennie; Pol, Marjan van de; Heijmen, Ben J.M. [Erasmus MC Cancer Institute, Department of Radiation Oncology, Rotterdam (Netherlands); Lanconelli, Nico [Universita di Bologna, Scuola di Scienze, Alma Mater Studiorum, Bologna (Italy); Petit, Steven F. [Erasmus MC Cancer Institute, Department of Radiation Oncology, Rotterdam (Netherlands); Massachusetts General Hospital - Harvard Medical School, Department of Radiation Oncology, Boston, MA (United States)

2017-05-15

To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored. Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V{sub 95%} increased by 1.1% ± 1.1%), higher dose conformity (R{sub 50} reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p < 0.001). To render the six remaining autoVMAT plans clinically acceptable, a dosimetrist needed less than 10 min hands-on time for fine-tuning. AutoVMAT plans were also considered equivalent or better than manually optimized VMAT plans. For 6/16 patients, autoVMAT allowed tumor dose escalation of 5-10 Gy. Clinically deliverable, high-quality autoVMAT plans can be generated fully automatically for the vast majority of advanced-stage NSCLC patients. For a subset of patients, autoVMAT allowed for tumor dose escalation. (orig.) [German] Entwicklung einer vollautomatisierten, auf multiplen Kriterien basierenden volumenmodulierten Arc-Therapie-(VMAT-)Behandlungsplanung (autoVMAT) fuer kurativ behandelte Patienten mit nicht-kleinzelligem Bronchialkarzinom (NSCLC) im Stadium III/IV. Nach Konfiguration unseres auto

Comparison between surgery and radiofrequency ablation for stage I non-small cell lung cancer

International Nuclear Information System (INIS)

Kim, So Ri; Han, Hyo Jin; Park, Seoung Ju; Min, Kyung Hoon; Lee, Min Hee; Chung, Chi Ryang; Kim, Min Ho; Jin, Gong Yong; Lee, Yong Chul

2012-01-01

Surgical resection remains as the treatment of choice for non-small cell lung cancer (NSCLC) and provides the best opportunity for cure and long-term survival. Minimally invasive percutaneous ablative therapies, such as radiofrequency ablation (RFA) for treating lung cancers, are currently being studied as treatment alternatives. But, to date, there is little information on comparison of therapeutic effects between surgery and RFA in patients with early stage lung malignancy. We aimed to investigate the clinical significance of RFA as an alternative curative modality for the early stage lung cancer through analyzing the long-term mortality of both treatment groups; surgery vs. RFA. Twenty-two patients of stage I NSCLC were included for this comparative analysis. To minimize confounding effects, we conducted a matching process. In which patients of RFA group (n = 8) were matched with patients of surgery group (n = 14) on the following variables; gender, age (±3 years), tumor node metastasis stage, and calendar year of surgery or RFA (±2 years). The mean survival duration of RFA group and surgery group were 33.18 ± 7.90 and 45.49 ± 7.21, respectively (months, p = 0.297). Log-rank analysis showed that there was no significant difference in overall survival (p = 0.054) between two groups. These results have shown that RFA can offer the survival comparable to that by surgery to stage I NSCLC patients, especially to the patients impossible for the surgery. This study provides an evidence for the use of RFA as a treatment alternative with low procedural morbidity for inoperable early-stage NSCLC patients.

Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for Stage IIIA and Stage IIIB non-small cell lung cancer: results of a Phase I-II study by the GOTHA group

Energy Technology Data Exchange (ETDEWEB)

Alberto, P.; Mermillod, B. [Hopital Cantonal Geneve, Geneva (Switzerland); Mirimanoff, R.O.; Leyvraz, S.; Nagy-Mignotte, H.; Bolla, M.; Wellmann, D.; Moro, D.; Brambilla, E. [Hopital Cantonal Universitaire, Lausanne (Switzerland)

1995-08-01

The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy. (author).

Fully automated VMAT treatment planning for advanced-stage NSCLC patients

International Nuclear Information System (INIS)

Della Gala, Giuseppe; Dirkx, Maarten L.P.; Hoekstra, Nienke; Fransen, Dennie; Pol, Marjan van de; Heijmen, Ben J.M.; Lanconelli, Nico; Petit, Steven F.

2017-01-01

To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored. Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V_9_5_% increased by 1.1% ± 1.1%), higher dose conformity (R_5_0 reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p [de

Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

International Nuclear Information System (INIS)

Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E; Ditzel, Henrik J

2013-01-01

The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC. Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis. GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations. Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial

Revisiting the prognostic value of preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in early-stage (I and II) non-small cell lung cancers (NSCLC)

International Nuclear Information System (INIS)

Agarwal, Mohit; Brahmanday, Govinda; Bajaj, Sunil K.; Wong, Ching-Yee Oliver; Ravikrishnan, K.P.

2010-01-01

The aims were to determine if the maximum standardized uptake value (SUV max ) of the primary tumor as determined by preoperative 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET) is an independent predictor of overall survival and to assess its prognostic value after stratification according to pathological staging. A retrospective clinicopathologic review of 363 patients who had a preoperative 18 F-FDG PET done before undergoing attempted curative resection for early-stage (I and II) non-small cell lung cancer (NSCLC) was performed. Patients who had received any adjuvant or neoadjuvant chemotherapy or radiation therapy were excluded. The primary outcome measure was duration of overall survival. Receiver-operating characteristic (ROC) curves were plotted to find out the optimal cutoff values of SUV max yielding the maximal sensitivity plus specificity for predicting the overall survival. Survival curves stratified by median SUV max and optimal cutoff SUV max were estimated by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUV max 's independency of other prognostic factors for the prediction of overall survival. The median duration of follow-up was 981 days (2.7 years). The median SUV max was 5.9 for all subjects, 4.5 for stage IA, 8.4 for stage IB, and 10.9 for stage IIB. The optimal cutoff SUV max was 8.2 for all subjects. No optimal cutoff could be established for specific stages. In univariate analyses, each doubling of SUV max [i.e., each log (base 2) unit increase in SUV max ] was associated with a 1.28-fold [95% confidence interval (CI): 1.03-1.59, p = 0.029] increase in hazard of death. Univariate analyses did not show any significant difference in survival by SUV max when data were stratified according to pathological stage (p = 0.119, p = 0.818, and p = 0.882 for stages IA, IB, and IIB, respectively

Treatment of patients with minimal stage IIIA Hodgkin's disease

International Nuclear Information System (INIS)

Powlis, W.D.; Mauch, P.; Goffman, T.; Goodman, R.L.

1987-01-01

Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT

Comparison of VATS and Robotic Approaches For Clinical Stage I and II NSCLC Using the STS Database

Science.gov (United States)

Louie, Brian E.; Wilson, Jennifer L.; Kim, Sunghee; Cerfolio, Robert J.; Park, Bernard J.; Farivar, Alexander S.; Vallières, Eric; Aye, Ralph W.; Burfeind, William R.; Block, Mark I.

2016-01-01

Background Data from selected centers show that robotic lobectomy (RL) is safe, effective and has comparable 30-day mortality to video assisted lobectomy (VATS). However, widespread adoption of RL is controversial. We used the STS-GTS-Database to evaluate quality metrics for these two minimally invasive lobectomy techniques. Methods A database query for primary clinical stage I or II NSCLC at high volume centers from 2009 to 2013 identified 1,220 RLs and 12,378 VATS. Quality metrics evaluated included operative morbidity, 30-day mortality and nodal upstaging (NU), defined as cN0 to pN1. Multivariable logistic regression was used to evaluate NU. Results RL patients were older, less active, less likely to be an ever smoker, and had higher BMI (all p<0.05). They were also more likely to have coronary heart disease or hypertension (all p<0.001) and to have had preoperative mediastinal staging (p<0.0001). RL operative times were longer (median 186 vs 173 min, p<0.001); all other operative parameters were similar. All postoperative outcomes were similar including complications and 30-day mortality (RL 0.6% vs VATS 0.8%, p=0.4). Median length of stay was 4 days for both, but a higher proportion of RLs stayed < 4 days: 48% vs 39%, p<0.001. NU overall was similar (p=0.6), but with trends favoring VATS in the cT1b group, and RL in the cT2a group. Conclusions RL patients had more co-morbidities and RL operative times were longer, but quality outcome measures including complications, hospital stay, 30-day mortality, and NU suggest RL and VATS are equivalent. PMID:27209613

Radiofrequency Ablation for Early-Stage Nonsmall Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Takao Hiraki

2014-01-01

Full Text Available This review examines studies of radiofrequency ablation (RFA of nonsmall cell lung cancer (NSCLC and discusses the role of RFA in treatment of early-stage NSCLC. RFA is usually performed under local anesthesia with computed tomography guidance. RFA-associated mortality, while being rare, can result from pulmonary events. RFA causes pneumothorax in up to 63% of cases, although pneumothorax requiring chest drainage occurs in less than 15% of procedures. Other severe complications are rare. After RFA of stage I NSCLC, 31–42% of patients show local progression. The 1-, 2-, 3-, and 5-year overall survival rates after RFA of stage I NSCLC were 78% to 100%, 53% to 86%, 36% to 88%, and 25% to 61%, respectively. The median survival time ranged from 29 to 67 months. The 1-, 2-, and 3-year cancer-specific survival rates after RFA of stage I NSCLC were 89% to 100%, 92% to 93%, and 59% to 88%, respectively. RFA has a higher local failure rate than sublobar resection and stereotactic body radiation therapy (SBRT. Therefore, RFA may currently be reserved for early-stage NSCLC patients who are unfit for sublobar resection or SBRT. Various technologies are being developed to improve clinical outcomes of RFA for early-stage NSCLC.

Actualización en el tratamiento del cáncer pulmonar de células no pequeñas en etapa IIIA con afectación N2 Update on treatment of stage IIIA non-small cell lung cancer with N2 disease

Directory of Open Access Journals (Sweden)

Miguel Emilio García Rodríguez

2012-09-01

Full Text Available Los pacientes afectados de cáncer de células no pequeñas del pulmón en etapa IIIA, con afectación ganglionar N2, son comunes y considerados por muchos médicos como un subgrupo heterogéneo, y su tratamiento es controversial. Con el objetivo de realizar una revisión bibliográfica actualizada del tema en cuestión y definir cuáles son las opciones de tratamiento de estos enfermos en esta etapa, se realizó una búsqueda de resúmenes y artículos completos en diferentes bases de datos (Medline, Cochrane, Pubmed, Ebsco, Hinari, y se utilizó para ello el buscador End Note, con las siguientes palabras en inglés y su traducción en español: lung cáncer, stage IIIA, radiotherapy, chemotherapy, adyuvant treatment, surgery, limphoadenectomy. El manejo óptimo de pacientes en etapa IIIA N2 permanece como una de las áreas más polémicas en el cuidado del paciente con cáncer pulmonar de células no pequeñas, probablemente por las amplias variaciones patológicas en esta etapa, por lo que se acepta el tratamiento quirúrgico de primera intención en aquellos pacientes con una enfermedad N2 mínima y en el otro extremo se realiza tratamiento con quimiorradioterapia definitivo o prequirúrgico de inducción en casos seleccionados.The patients suffering stage IIIA non-small cell lung cancer with N2 ganglionic diseases are common and considered as an heterogeneous group by many physicians. Their treatment arouses controversies. For the purpose of making an updated literature review on this topic and defining the treatment options for these patients on this stage III, a number of full articles and of abstracts was searched on several database (Medline, Cochrane, Pubmed, Ebsco, Hinari. To this end, the End Note locator was used with the following English words and their respective Spanish translations: lung cancer, stage IIIa, radiotherapy, chemotherapy, adjuvant treatment, surgery, lymphoadenectomy. The optimal management of patients classified

Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report

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Takita, H.; Pitoniak, R.F.

2000-01-01

Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage I A. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed

Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy

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Hayakawa, Kazushige; Mitsuhashi, Norio; Saito, Yoshihiro

1996-01-01

The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P=0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P=0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P=0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P=0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy. (author)

Development of new therapeutic methods of lung cancer through team approach study

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Park, Jong Ho; Zo, Jae Ill; Baek, Hee Jong; Jung, Jin Haeng; Lee, Jae Cheol; Ryoo, Baek Yeol; Kim, Mi Sook; Choi, Du Hwan; Park, Sun Young; Lee, Hae Young

2000-12-01

The aims of this study were to make the lung cancer clinics in Korea Cancer Center Hospital, and to establish new therapeutic methods of lung cancer for increasing the cure rate and survival rate of patients. Also another purpose of this study was to establish a common treatment method in our hospital. All patients who were operated in Korea Cancer Center Hospital from 1987 due to lung cancer were followed up and evaluated. And we have been studied the effect of postoperative adjuvant therapy in stage I, II, IIIA non-small cell lung cancer patients from 1989 with the phase three study form. Follow-up examinations were scheduled in these patients and interim analysis was made. Also we have been studied the effect of chemo-therapeutic agents in small cell lung cancer patients from 1997 with the phase two study form. We evaluated the results of this study. Some important results of this study were as follows. 1. The new therapeutic method (surgery + MVP chemotherapy) was superior to the standard therapeutic one in stage I Non-small cell lung cancer patients. So, we have to change the standard method of treatment in stage I NSCLC. 2. Also, this new therapeutic method made a good result in stage II NSCLC patients. And this result was reported in The Annals of Thoracic Surgery. 3. However, this new therapeutic method was not superior to the standard treatment method (surgery only) in stage IIIA NSCLC patients. So, we must develop new chemo-therapeutic agents in the future for advanced NSCLC patients. 4. In the results of the randomized phase II studies about small cell lung cancer, there was no difference in survival between Etoposide + Carboplatin + Ifosfamide + Cisplatin group and Etoposide + Carboplatin + Ifosfamide + Cisplatin + Tamoxifen group in both the limited and extended types of small cell lung cancer patients

High-dose, hyperfractionated, accelerated radiotherapy using a concurrent boost for the treatment of nonsmall cell lung cancer: unusual toxicity and promising early results

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King, Stephen C.; Acker, Jeffrey C.; Kussin, Peter S.; Marks, Lawrence B.; Weeks, Kenneth J.; Leopold, Kenneth A.

1996-01-01

Purpose: The treatment of nonsmall cell lung cancer (NSCLC) with conventional radiotherapy (RT) results in inadequate local tumor control and survival. We report results of a Phase II trial designed to treat patients with a significantly increased total dose administered in a reduced overall treatment time using a hyperfractionated, accelerated treatment schedule with a concurrent boost technique. Methods and Materials: A total of 49 patients with unresectable Stage IIIA/IIIB (38 patients) or medically inoperable Stage I/II (11 patients) NSCLC were prospectively enrolled in this protocol. Radiation therapy was administered twice daily, 5 days/week with > 6 h between each treatment. The primary tumor and adjacent enlarged lymph nodes were treated to a total dose of 73.6 Gy in 46 fractions of 1.6 Gy each. Using a concurrent boost technique, electively irradiated nodal regions were simultaneously treated with a dose of 1.25 Gy/fraction for the first 36 fractions to a total dose of 45 Gy. Results: Median survival for the entire group of 49 patients is 15.3 months. Actuarial survival at 2 years is 46%: 60% for 11 Stage I/II patients, 55% for 21 Stage IIIA patients, and 26% for 17 Stage IIIB patients. The actuarial rate of freedom from local progression at 2 years is 64% for the entire group of 49 patients: 62% for Stage I/II patients, 70% for Stage IIIA patients, and 55% for Stage IIIB patients. Patients who underwent serial bronchoscopic reevaluation (4 Stage I/II, 8 Stage IIIA, and 6 Stage IIIB) have an actuarial rate of local control of 71% at 2 years. The median total treatment time was 32 days. Nine of 49 patients (18%) experienced Grade III acute esophageal toxicity. The 2-year actuarial risk of Grade III or greater late toxicity is 30%. The 2-year actuarial rate of severe-late pulmonary and skin-subcutaneous toxicity is 20% and 15%, respectively. Conclusion: This treatment regimen administers a substantially higher biologically effective dose compared with

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.

Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study

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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.)

Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

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Tsukioka, Takuma; Nishiyama, Noritoshi; Izumi, Nobuhiro; Mizuguchi, Shinjiro; Komatsu, Hiroaki; Okada, Satoshi; Toda, Michihito; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko

2017-04-01

Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The dutch national clinical audit for lung cancer: A tool to improve clinical practice? An analysis of unforeseen ipsilateral mediastinal lymph node involvement in the Dutch Lung Surgery Audit (DLSA).

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Heineman, David Jonathan; Beck, Naomi; Wouters, Michael Wilhelmus; van Brakel, Thomas Jan; Daniels, Johannes Marlene; Schreurs, Wilhelmina Hendrika; Dickhoff, Chris

2018-06-01

Optimal treatment selection for patients with non-small cell lung cancer (NSCLC) depends on the clinical stage of the disease. Particularly patients with mediastinal lymph node involvement (stage IIIA-N2) should be identified since they generally do not benefit from upfront surgery. Although the standardized preoperative use of PET-CT, EUS/EBUS and/or mediastinoscopy identifies most patients with mediastinal lymph node metastasis, a proportion of these patients is only diagnosed after surgery. The objective of this study was to identify all patients with unforeseen N2 disease after surgical resection for NSCLC in a large nationwide database and to evaluate the preoperative clinical staging process. Data was derived from the Dutch Lung Surgery Audit. Patients with pathological stage IIIA NSCLC after an anatomical resection between 2013 and 2015 were evaluated. Clinical and pathological TNM-stage were compared and an analysis was performed on the diagnostic work-up of patients with unforeseen N2 disease. From 3585 patients undergoing surgery for NSCLC between 2013 and 2015, a total of 527 patients with pathological stage IIIA NSCLC were included. Of all 527 patients, 254 patients were upstaged from a clinical N0 (n = 186) or N1 (n = 68) disease to a pathological N2 disease (7.1% unforeseen N2). In these 254 patients, 18 endoscopic ultrasounds, 62 endobronchial ultrasounds and 67 mediastinoscopies were performed preoperatively. In real world clinical practice in The Netherlands, the percentage of unforeseen N2 disease in patients undergoing surgery for NSCLC is seven percent. To further reduce this percentage, optimization of the standardized preoperative workup is necessary. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

MVP Chemotherapy and Hyperfractionated Radiotherapy for Stage III Unresectable Non-Small Cell Lung Cancer - Randomized for maintenance Chemotherapy vs. Observation; Preliminary Report-

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Choi, Euk Kyung; Chang, Hye Sook; Suh, Cheol Won

1991-01-01

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991. Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGY following 3 cycles of induction MVP (Mitomycin C 6 mg/m 2 , vinblastine 6 mg/m 2 , Cisplatin 60 mg/m 2 ) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 16 were analyzed for this preliminary report. The response rate of induction chemotherapy was 62.5%; partial response, 50% and minimal response, 12.5%. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue

Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer

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Jeremic, Branislav; Shibamoto, Yuta; Acimovic, Ljubisa; Milisavljevic, Slobodan

1997-01-01

Purpose: Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy. Methods and Materials: Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given. Results: The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity. Conclusion: The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC

Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

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Cheruvu, Praveena; Metcalfe, Su K; Metcalfe, Justin; Chen, Yuhchyau; Okunieff, Paul; Milano, Michael T

2011-01-01

Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed

Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes.

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Wang, Tao; Liu, Yang; Zhou, Bin; Wang, Zhi; Liang, Naichao; Zhang, Yundong; Dong, Zhouhuan; Li, Jie

2016-01-01

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR-TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC. We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA-IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis. A total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2-4 weeks' assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable. Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings.

Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

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Guerrera, Francesco; Errico, Luca; Evangelista, Andrea; Filosso, Pier Luigi; Ruffini, Enrico; Lisi, Elena; Bora, Giulia; Asteggiano, Elena; Olivetti, Stefania; Lausi, Paolo; Ardissone, Francesco; Oliaro, Alberto

2015-06-01

Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Outcomes of Risk-Adapted Fractionated Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

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Lagerwaard, Frank J.; Haasbeek, Cornelis J.A.; Smit, Egbert F.; Slotman, Ben J.; Senan, S.

2008-01-01

Purpose: High local control rates can be achieved using stereotactic radiotherapy in Stage I non-small-cell lung cancer (NSCLC), but reports have suggested that toxicity may be of concern. We evaluated early clinical outcomes of 'risk-adapted' fractionation schemes in patients treated in a single institution. Methods and Materials: Of 206 patients with Stage I NSCLC, 81% were unfit to undergo surgery and the rest refused surgery. Pathologic confirmation of malignancy was obtained in 31% of patients. All other patients had new or growing 18F-fluorodeoxyglucose positron emission tomography positive lesions with radiologic characteristics of malignancy. Planning four-dimensional computed tomography scans were performed and fractionation schemes used (3 x 20 Gy, 5 x 12 Gy, and 8 x 7.5 Gy) were determined by T stage and risk of normal tissue toxicity. Results: Median overall survival was 34 months, with 1- and 2-year survivals of 81% and 64%, respectively. Disease-free survival (DFS) at 1 and 2 years was 83% and 68%, respectively, and DFS correlated with T stage (p = 0.002). Local failure was observed in 7 patients (3%). The crude regional failure rate was 9%; isolated regional recurrence was observed in 4%. The distant progression-free survival at 1 and 2 years was 85% and 77%, respectively. SRT was well tolerated and severe late toxicity was observed in less than 3% of patients. Conclusions: SRT is well tolerated in patients with extensive comorbidity with high local control rates and minimal toxicity. Early outcomes are not inferior to those reported for conventional radiotherapy. In view of patient convenience, such risk-adapted SRT schedules should be considered treatment of choice in patients presenting with medically inoperable Stage I NSCLC

Stereotactic Body Radiotherapy (SBRT) for Operable Stage I Non-Small-Cell Lung Cancer: Can SBRT Be Comparable to Surgery?

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Onishi, Hiroshi, E-mail: honishi@yamanashi.ac.jp [School of Medicine, Yamanashi University, Yamanashi (Japan); Shirato, Hiroki [School of Medicine, Hokkaido University, Sapporo (Japan); Nagata, Yasushi [School of Medicine, Hiroshima University, Hiroshima (Japan); Hiraoka, Masahiro [School of Medicine, Kyoto University, Kyoto (Japan); Fujino, Masaharu [School of Medicine, Hokkaido University, Sapporo (Japan); School of Medicine, Yamanashi University, Yamanashi (Japan); Gomi, Kotaro [Cancer Institute Suwa Red-Cross Hospital, Suwa (Japan); Karasawa, Katsuyuki [Tokyo Metropolitan Komagome Hospital, Tokyo (Japan); Hayakawa, Kazushige; Niibe, Yuzuru [Kitasato University, Kanagawa (Japan); Takai, Yoshihiro [School of Medicine, Hirosaki University, Hirosaki (Japan); Kimura, Tomoki [School of Medicine, Kagawa University, Hiroshima (Japan); Takeda, Atsuya [Ofuna Chuo Hospital, Kanagawa (Japan); Ouchi, Atsushi [Keijinkai Hospital, Sapporo (Japan); Hareyama, Masato [Sapporo Medical University, Sapporo (Japan); Kokubo, Masaki [Institute of Biomedical Research and Innovation, Kobe (Japan); Kozuka, Takuyo [School of Cancer Institute Ariake Hospital, Tokyo (Japan); Arimoto, Takuro [Kitami Red Cross Hospital, Kitami (Japan); Hara, Ryusuke [National Institute of Radiological Science, Chiba (Japan); Itami, Jun [National Cancer Center, Tokyo (Japan); Araki, Tsutomu [School of Medicine, Yamanashi University, Yamanashi (Japan)

2011-12-01

Purpose: To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non-small-cell lung cancer (NSCLC), using a Japanese multi-institutional database. Patients and Methods: Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n = 65; T2N0M0, n = 22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45-72.5 Gy at the isocenter, administered in 3-10 fractions. Median calculated biological effective dose was 116 Gy (range, 100-141 Gy). Data were collected and analyzed retrospectively. Results: During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery. Conclusion: Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage I NSCLC. The survival rate for SBRT is potentially comparable to that for surgery.

Stereotactic Body Radiotherapy (SBRT) for Operable Stage I Non–Small-Cell Lung Cancer: Can SBRT Be Comparable to Surgery?

International Nuclear Information System (INIS)

Onishi, Hiroshi; Shirato, Hiroki; Nagata, Yasushi; Hiraoka, Masahiro; Fujino, Masaharu; Gomi, Kotaro; Karasawa, Katsuyuki; Hayakawa, Kazushige; Niibe, Yuzuru; Takai, Yoshihiro; Kimura, Tomoki; Takeda, Atsuya; Ouchi, Atsushi; Hareyama, Masato; Kokubo, Masaki; Kozuka, Takuyo; Arimoto, Takuro; Hara, Ryusuke; Itami, Jun; Araki, Tsutomu

2011-01-01

Purpose: To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non–small-cell lung cancer (NSCLC), using a Japanese multi-institutional database. Patients and Methods: Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n = 65; T2N0M0, n = 22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45–72.5 Gy at the isocenter, administered in 3–10 fractions. Median calculated biological effective dose was 116 Gy (range, 100–141 Gy). Data were collected and analyzed retrospectively. Results: During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery. Conclusion: Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage I NSCLC. The survival rate for SBRT is potentially comparable to that for surgery.

Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

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Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

2015-01-01

OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

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Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil

1999-01-01

This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m 2 ) on day 1 and oral Etoposide (50 mg/m 2 /day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor

Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

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Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

1999-06-01

This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

Long-term follow-up of a phase I/II trial of dose escalating three-dimensional conformal thoracic radiation therapy with induction and concurrent carboplatin and paclitaxel in unresectable stage IIIA/B non-small cell lung cancer.

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Stinchcombe, Thomas E; Lee, Carrie B; Moore, Dominic T; Rivera, M Patricia; Halle, Jan; Limentani, Steven; Rosenman, Julian G; Socinski, Mark A

2008-11-01

We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer.

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.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Accuracy in the Staging of Non-Small Cell Lung Cancer: Review and Cost-Effectiveness

International Nuclear Information System (INIS)

Gómez León, Nieves; Escalona, Sofía; Bandrés, Beatriz; Belda, Cristobal; Callejo, Daniel; Blasco, Juan Antonio

2014-01-01

Aim of the performed clinical study was to compare the accuracy and cost-effectiveness of PET/CT in the staging of non-small cell lung cancer (NSCLC). Material and Methods. Cross-sectional and prospective study including 103 patients with histologically confirmed NSCLC. All patients were examined using PET/CT with intravenous contrast medium. Those with disease stage ≤IIB underwent surgery (n = 40). Disease stage was confirmed based on histology results, which were compared with those of PET/CT and positron emission tomography (PET) and computed tomography (CT) separately. 63 patients classified with ≥IIIA disease stage by PET/CT did not undergo surgery. The cost-effectiveness of PET/CT for disease classification was examined using a decision tree analysis. Results. Compared with histology, the accuracy of PET/CT for disease staging has a positive predictive value of 80%, a negative predictive value of 95%, a sensitivity of 94%, and a specificity of 82%. For PET alone, these values are 53%, 66%, 60%, and 50%, whereas for CT alone they are 68%, 86%, 76%, and 72%, respectively. Incremental cost-effectiveness of PET/CT over CT alone was €17,412 quality-adjusted life-year (QALY). Conclusion. In our clinical study, PET/CT using intravenous contrast medium was an accurate and cost-effective method for staging of patients with NSCLC

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Accuracy in the Staging of Non-Small Cell Lung Cancer: Review and Cost-Effectiveness

International Nuclear Information System (INIS)

Leon, N.G.; Bandrs, B.; Escalona, S.; Callejo, D.; Blasco, J.A.; Belda, C.; Blasco, J.A.

2014-01-01

Aim of the performed clinical study was to compare the accuracy and cost-effectiveness of PET/CT in the staging of non-small cell lung cancer (NSCLC). Material and Methods. Cross-sectional and prospective study including 103 patients with histologically confirmed NSCLC. All patients were examined using PET/CT with intravenous contrast medium. Those with disease stage ≤IIB underwent surgery (η=40). Disease stage was confirmed based on histology results, which were compared with those of PET/CT and positron emission tomography (PET) and computed tomography (CT) separately. 63 patients classified with ≥IIIA disease stage by PET/CT did not undergo surgery. The cost-effectiveness of PET/CT for disease classification was examined using a decision tree analysis. Results. Compared with histology, the accuracy of PET/CT for disease staging has a positive predictive value of 80%, a negative predictive value of 95%, a sensitivity of 94%, and a specificity of 82%. For PET alone, these values are 53%, 66%, 60%, and 50%, whereas for CT alone they are 68%, 86%, 76%, and 72%, respectively. Incremental cost-effectiveness of PET/CT over CT alone was €17,412 quality-adjusted life-year (QALY). Conclusion. In our clinical study, PET/CT using intravenous contrast medium was an accurate and cost-effective method for staging of patients with NSCLC

Treatment of patients with minimal stage IIIA Hodgkin's disease

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Powlis, W.D.; Mauch, P.; Goffman, T.; Goodman, R.L.

1987-10-01

Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT.

Proton Beam Therapy for Patients With Medically Inoperable Stage I Non-Small-Cell Lung Cancer at the University of Tsukuba

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Nakayama, Hidetsugu; Sugahara, Shinji; Tokita, Mari; Satoh, Hiroaki; Tsuboi, Koji; Ishikawa, Shigemi; Tokuuye, Koichi

2010-01-01

Purpose: To evaluate in a retrospective review the role of proton beam therapy for patients with medically inoperable Stage I non-small-cell lung cancer (NSCLC). Patients and Methods: From November 2001 to July 2008, 55 medically inoperable patients with Stage I NSCLC were treated with proton beam therapy. A total of 58 (T1/T2, 30/28) tumors were treated. The median age of study participants was 77 years (range, 52-86 years). A total dose of 66 GyE in 10 fractions was given to peripherally located tumors and 72.6 GyE in 22 fractions to centrally located tumors. Results: The rates (95% confidence interval) of overall and progression-free survival of all patients and of local control of all tumors at 2 years were 97.8% (93.6-102.0%), 88.7% (77.9-99.5%), and 97.0% (91.1-102.8%), respectively. There was no statistically significant difference in progression-free rate between T1 and T2 tumors (p = 0.87). Two patients (3.6%) had deterioration in pulmonary function, and 2 patients (3.6%) had Grade 3 pneumonitis. Conclusion: Proton beam therapy was effective and well tolerated in medically inoperable patients with Stage I NSCLC.

Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer

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Chang Joe Y

2012-09-01

Full Text Available Abstract Background Stereotactic ablative radiotherapy (SABR can achieve excellent local control rates in early-stage non-small cell lung cancer (NSCLC and has emerged as a standard treatment option for patients who cannot undergo surgery or those with isolated recurrences. However, factors that may predict toxicity or survival are largely unknown. We sought here to identify predictors of survival and pneumonitis after SABR for NSCLC in a relatively large single-institution series. Methods Subjects were 130 patients with stage I NSCLC treated with four-dimensional computed tomography (4D CT –planned, on-board volumetric image–guided SABR to 50 Gy in 4 fractions. Disease was staged by positron emission tomography/computed tomography (PET/CT and scans were obtained again at the second follow-up after SABR. Results At a median follow-up time of 26 months, the 2-year local control rate was 98.5%. The median overall survival (OS time was 60 months, and OS rates were 93.0% at 1 year, 78.2% at 2 years, and 65.3% at 3 years. No patient experienced grade 4–5 toxicity; 15 had radiation pneumonitis (12 [9.3%] grade 2 and 3 [2.3%] grade 3. Performance status, standardized uptake value (SUVmax on staging PET/CT, tumor histology, and disease operability were associated with OS on univariate analysis, but only staging SUVmax was independently predictive on multivariate analysis (P = 0.034. Dosimetric factors were associated with radiation pneumonitis on univariate analysis, but only mean ipsilateral lung dose ≥9.14 Gy was significant on multivariate analysis (P = 0.005. Conclusions OS and radiation pneumonitis after SABR for stage I NSCLC can be predicted by staging PET SUVmax and ipsilateral mean lung dose, respectively.

Planning benchmark study for SBRT of early stage NSCLC. Results of the DEGRO Working Group Stereotactic Radiotherapy

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Moustakis, Christos [University Muenster, Department of Radiation Oncology, Muenster (Germany); German CyberKnife Center, Soest (Germany); Blanck, Oliver [UKSH Universitaetsklinikum Schleswig Holstein, Department of Radiation Oncology, Kiel (Germany); Saphir Radiosurgery Center, Guestrow and Frankfurt, Frankfurt (Germany); Ebrahimi Tazehmahalleh, Fatemeh [University Muenster, Department of Radiation Oncology, Muenster (Germany); City Hospital Dessau, Dessau (Germany); Chan, Mark ka heng [UKSH Universitaetsklinikum Schleswig Holstein, Department of Radiation Oncology, Kiel (Germany); Ernst, Iris; Haverkamp, Uwe; Eich, Hans Theodor [University Muenster, Department of Radiation Oncology, Muenster (Germany); German CyberKnife Center, Soest (Germany); Krieger, Thomas [University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Duma, Marciana-Nona; Oechsner, Markus [Technical University of Munich, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Ganswindt, Ute; Heinz, Christian [Ludwig-Maximilians-University, Department of Radiation Oncology, Munich (Germany); Alheit, Horst; Blank, Hilbert [Radiationtherapy Distler, Bautzen (Germany); Nestle, Ursula; Wiehle, Rolf [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Kornhuber, Christine; Ostheimer, Christian [University Halle, Department of Radiation Oncology, Halle (Germany); Petersen, Cordula [University Hospital Hamburg-Eppendorf, Hamburg (Germany); Pollul, Gerhard [University Mainz, Department of Radiation Oncology, Mainz (Germany); Baus, Wolfgang; Altenstein, Georg [University Hospital of Cologne, Cologne (Germany); Beckers, Eric; Jurianz, Katrin [Gamma Knife Center Krefeld, Krefeld (Germany); Sterzing, Florian [University Hospital Heidelberg, Heidelberg (Germany); Kretschmer, Matthias [Radiologische Allianz Hamburg, Hamburg (Germany); Seegenschmiedt, Heinrich; Maass, Torsten [Radiationtherapy and Cyberknife Center Hamburg, Hamburg (Germany); Droege, Stefan [Lung Clinic Hemer, Hemer (Germany); Wolf, Ulrich [University Leipzig, Department of Radiation Oncology, Leipzig (Germany); Schoeffler, Juergen [Radiationtherapy Department Boeblingen, Boeblingen (Germany); Guckenberger, Matthias [University Zurich, Department of Radiation Oncology, Zurich (Switzerland)

2017-10-15

The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle. (orig.) [German] Ziel war die Untersuchung der Variabilitaet der Bestrahlungsplanung der stereotaktischen Strahlentherapie (SBRT) fuer das nicht-kleinzellige Bronchialkarzinom (NSCLC) im

Quality of life during 5 years after stereotactic radiotherapy in stage I non-small cell lung cancer

International Nuclear Information System (INIS)

Ubels, Rutger J; Mokhles, Sahar; Andrinopoulou, Eleni R; Braat, Cornelia; Voort van Zyp, Noëlle C van der; Aluwini, Shafak; Aerts, Joachim G J V; Nuyttens, Joost J

2015-01-01

To determine the long-term impact of stereotactic radiotherapy (SRT) on the quality of life (QoL) of inoperable patients with early-stage non-small cell lung cancer (NSCLC). From January 2006 to February 2008, 39 patients with pathologically confirmed T1-2N0M0 NSCLC were treated with SRT. QoL, overall survival and local tumor control were assessed. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and the lung cancer-specific questionnaire QLQ-LC13 were used to investigate changes in QoL. Assessments were done before treatment, at 3 weeks, every 2–3 months during the first two years, and then every 6 months until 5 years after the treatment or death or progressive disease. The median follow up was 38 months. During the 5 years after treatment with SRT for stage I NSCLC, the level of QoL was maintained: There was a slow decline (slope: −0.015) of the global health status over the 5 years (p < 0.0001). The physical functioning and the role functioning improved slowly (slope: 0.006 and 0.004, resp.) over the years and this was also significant (p < 0.0001). The emotional functioning (EF) improved significantly at 1 year compared to the baseline. Two years after the treatment dyspnea slowly increased (slope: 0.005, p = 0.006). The actuarial overall survival was 62% at 2 years and 31% at 5-years. QoL was maintained 5 years after SRT for stage I NSCLC and EF improved significantly. Dyspnea slowly increased 2 years after the treatment

Multidisciplinary management of non small cell lung cancer (NSCLC in stage III: clinical case description. Recommendations and state of the art

Directory of Open Access Journals (Sweden)

Simona Carnio

2013-03-01

Full Text Available Lung cancer is the leading cause of cancer death in industrialized countries with progressive increase of its mortality rate. Non Small Cell Lung Cancer (NSCLC is approximately 80-85% of all lung cancers, being adenocarcinoma and squamous cell carcinoma the most common histologies. The majority of the patients with stage III clinical stage, presents a mediastinal lymph node involvement described with computed tomography (TC and/or positron emission tomography (PET. The current approach to patients with NSCLC is multidisciplinary, especially for those staged as potentially operable, both for staging and for a correct definition of best treatment strategy. Updated international and national Guidelines and recommendations can provide valuable support to the clinician.The case described concerns the accidental detection of a tumour in the lung in a 58-year-old man with arterial hypertension controlled with ACE inhibitors. The treatments agreed after a multidisciplinary approach are cisplatin and docetaxel, the surgical resection, and the radiotherapy. After three months the patient has neither metastasis nor relapse.

Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

Science.gov (United States)

2017-06-14

Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

Science.gov (United States)

2017-08-07

Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Pleural lavage cytology as an independent prognostic factor in non-small-cell lung cancer patients with stage I disease and adenocarcinoma.

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Hokka, Daisuke; Uchino, Kazuya; Tane, Kenta; Ogawa, Hiroyuki; Tane, Sinya; Tanaka, Yugo; Tauchi, Shunsuke; Nishio, Wataru; Yoshimura, Masahiro; Maniwa, Yoshimasa

2015-01-01

We previously reported that cancer cells may be detected through pleural lavage cytology (PLC). In this study, we sought to re-examine the prognostic significance of the PLC status based on an extended dataset with an additional follow-up period. Pleural lavage following thoracotomy was cytologically examined in 1,317 consecutive patients who were diagnosed with NSCLC between 1987 and 2004 at the Thoracic Surgery Units of Kobe University Graduate School of Medicine and Hyogo Cancer Center. Among the investigated patients, 46 exhibited positive cytological findings. The prognosis of these patients was significantly worse compared to that of patients without positive PLC. Of the 844 pathological stage I patients, 18 had a positive PLC status and their prognosis was significantly worse compared to that of patients with stage I disease without positive PLC. In conclusion, positive PLC findings were associated with a poor prognosis and this finding was significant for patients with stage I disease. These results suggest the need for PLC status evaluation during staging and treatment planning in patients with NSCLC.

Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery

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Haiyan Fu

2016-01-01

Full Text Available The reversibility of neuropathic lysosomal storage diseases, including MPS IIIA, is a major goal in therapeutic development, due to typically late diagnoses and a large population of untreated patients. We used self-complementary adeno-associated virus (scAAV serotype 9 vector expressing human N-sulfoglucosamine sulfohydrolase (SGSH to test the efficacy of treatment at later stages of the disease. We treated MPS IIIA mice at 1, 2, 3, 6, and 9 months of age with an intravenous injection of scAAV9-U1a-hSGSH vector, leading to restoration of SGSH activity and reduction of glycosaminoglycans (GAG throughout the central nervous system (CNS and somatic tissues at a dose of 5E12 vg/kg. Treatment up to 3 months age improved learning ability in the Morris water maze at 7.5 months, and lifespan was normalized. In mice treated at 6 months age, behavioral performance was impaired at 7.5 months, but did not decline further when retested at 12 months, and lifespan was increased, but not normalized. Treatment at 9 months did not increase life-span, though the GAG storage pathology in the CNS was improved. The study suggests that there is potential for gene therapy intervention in MPS IIIA at intermediate stages of the disease, and extends the clinical relevance of our systemic scAAV9-hSGSH gene delivery approach.

Influence of conformal radiotherapy technique on survival after chemoradiotherapy for patients with stage III non-small cell lung cancer in the National Cancer Data Base.

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Sher, David J; Koshy, Matthew; Liptay, Michael J; Fidler, Mary Jo

2014-07-01

Definitive chemoradiotherapy is a core treatment modality for patients with stage III non-small cell lung cancer (NSCLC). Although radiotherapy (RT) technologies have advanced dramatically, to the authors' knowledge relatively little is known regarding the importance of irradiation technique on outcome, particularly given the competing risk of distant metastasis. The National Cancer Data Base was used to determine predictors of overall survival (OS) in patients with AJCC stage III NSCLC who were treated with chemoradiotherapy, focusing on the importance of conformal RT (CRT). Patients with stage III NSCLC who were treated with chemoradiotherapy between 2003 and 2005 in the National Cancer Data Base were included. RT technique was defined as conventional, 3-dimensional-conformal, or intensity-modulated RT (IMRT), the latter 2 combined as CRT. Cox proportional hazards regression was performed for univariable and multivariable analyses of OS. The median, 3-year, and 5-year survival outcomes for the 13,292 patients were 12.9 months, 19%, and 11%, respectively. The 3-year and 5-year survival probabilities of patients receiving CRT versus no CRT were 22% versus 19% and 14% versus 11%, respectively (P < .0001). On multivariable analysis, CRT was found to be significantly associated with improved OS (hazards ratio, 0.89). This effect was confirmed on sensitivity analyses, including restricting the cohort to minimum 6-month survivors, young patients with stage IIIA disease, and propensity score-matching. Institutional academic status and patient volume were not found to be associated with OS. CRT was found to be independently associated with a survival advantage. These results reflect the importance of optimal locoregional therapy in patients with stage III NSCLC and provide motivation for further study of advanced RT technologies in patients with NSCLC. © 2014 American Cancer Society.

Surgery or stereotactic body radiotherapy for elderly stage I lung cancer? A propensity score matching analysis.

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Miyazaki, Takuro; Yamazaki, Takuya; Nakamura, Daisuke; Sato, Shuntaro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Kamohara, Ryotaro; Hatachi, Go; Nagayasu, Takeshi

2017-12-01

The aim of this study was to compare the outcomes of surgery and stereotactic body radiotherapy (SBRT) for elderly clinical stage I non-small cell lung cancer (NSCLC) patients. Patients ≥80 years of age with clinical stage I NSCLC between August 2008 and December 2014 were treated either surgery or SBRT. Propensity score matching was performed to reduce bias in various clinicopathological factors. Surgery was performed in 57 cases and SBRT in 41 cases. In the surgery group, the operations included 34 lobectomies and 23 sublobar resections. In the SBRT group, 27 cases were given 48 Gy in 4 fractions, and 14 were given 60 Gy in 10 fractions. Similar characteristics were identified in age (82 years), gender (male:female ratio 2:1), tumor size (2.2 cm), carcinoembryonic antigen (3.6 ng/ml), Charlson comorbidity index (1), Glasgow prognostic scale (0), and forced expiratory volume in 1 s (1.7 L) after matching. Before matching, the 5-year overall survival (OS) in surgery (68.3%) was significantly better than that in SBRT (47.4%, p = 0.02), and the 5-year disease-specific survival (DSS) (94.1%, 78.2%, p = 0.17) was not significantly different between the groups. The difference in the 5-year OS became non-significant between the matched pairs (57.0%, 49.1%, p = 0.56). The outcomes of surgery and SBRT for elderly patients with the early stage NSCLC were roughly the same.

Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent.

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Zhu, Jianwei; Li, Rui; Tiselius, Eva; Roudi, Raheleh; Teghararian, Olivia; Suo, Chen; Song, Huan

2017-12-16

Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For patients with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. While several new agents have now entered phase III clinical trials, we felt a systematic review was needed to address the question of the effectiveness and safety of immunotherapy in patients with stages I to III NSCLC. To evaluate the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) in patients with localised NSCLC (stages I to III) who received surgery or radiotherapy with curative intent. We searched the following databases (from inception to 20 January 2017): CENTRAL, MEDLINE, Embase, and CINAHL, and five trial registers. We also manually checked abstracts or reports from relevant conference proceedings and the reference lists of included trials. We searched for randomised controlled trials (RCTs) in adults (≥ 18 years) with histologically-confirmed early-stage (stages I to III) NSCLC after surgical resection, and those with unresectable locally advanced stage III NSCLC who had received radiotherapy with curative intent. For patients who had received primary surgical treatment, postoperative radiotherapy or chemoradiotherapy was allowed if it was used for both experimental and control groups. Two review authors independently selected eligible trials, assessed risk of bias, and extracted data. We used survival analysis to pool time-to-event data, expressing the intervention effect as a hazard ratio (HR). We calculated risk ratios (RR) for dichotomous data, and mean differences for continuous data, with 95% confidence intervals (CI). Due to clinical heterogeneity (immunotherapeutic agents with different underlying mechanisms), we used random-effects models for our meta-analyses. We

Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection.

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Wu, Yu-Chung; Wei, Nien-Chih; Hung, Jung-Jyh; Yeh, Yi-Chen; Su, Li-Jen; Hsu, Wen-Hu; Chou, Teh-Ying

2017-10-03

Lung cancer mortality remains high even after successful resection. Adjuvant treatment benefits stage II and III patients, but not stage I patients, and most studies fail to predict recurrence in stage I patients. Our study included 211 lung adenocarcinoma patients (stages I-IIIA; 81% stage I) who received curative resections at Taipei Veterans General Hospital between January 2001 and December 2012. We generated a prediction model using 153 samples, with validation using an additional 58 clinical outcome-blinded samples. Gene expression profiles were generated using formalin-fixed, paraffin-embedded tissue samples and microarrays. Data analysis was performed using a supervised clustering method. The prediction model generated from mixed stage samples successfully separated patients at high vs. low risk for recurrence. The validation tests hazard ratio (HR = 4.38) was similar to that of the training tests (HR = 4.53), indicating a robust training process. Our prediction model successfully distinguished high- from low-risk stage IA and IB patients, with a difference in 5-year disease-free survival between high- and low-risk patients of 42% for stage IA and 45% for stage IB ( p model for identifying lung adenocarcinoma patients at high risk for recurrence who may benefit from adjuvant therapy. Our prediction performance of the difference in disease free survival between high risk and low risk groups demonstrates more than two fold improvement over earlier published results.

Treatment Outcomes in Stage I Lung Cancer: A Comparison of Surgery and Stereotactic Body Radiation Therapy (SBRT)

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Puri, Varun; Crabtree, Traves D.; Bell, Jennifer M.; Broderick, Stephen R; Morgensztern, Daniel; Colditz, Graham A.; Kreisel, Daniel; Krupnick, A. Sasha; Patterson, G. Alexander; Meyers, Bryan F.; Patel, Aalok; Robinson, Clifford G.

2015-01-01

Introduction The relative roles of surgery and stereotactic body radiation therapy in stage I non-small cell lung cancer (NSCLC) are evolving particularly for marginally operable patients. Since there is limited prospective comparative data for these treatment modalities, we evaluated their relative use and outcomes at the population level using a national database. Methods Patient variables and treatment-related outcomes were abstracted for patients with clinical stage I NSCLC from the National Cancer Database. Patients receiving surgery were compared to those undergoing SBRT in exploratory unmatched and subsequent propensity matched analyses. Results Between 1998 and 2010, 117618 patients underwent surgery or SBRT for clinical stage I NSCLC. Of these, 111731 (95%) received surgery while 5887 (5%) underwent SBRT. Patients in the surgery group were younger, more likely to be males, and had higher Charlson comorbidity scores. SBRT patients were more likely to have T1 (vs.T2) tumors and receive treatment at academic centers. Thirty-day surgical mortality was 2596/109485 (2.4%). Median overall survival favored the surgery group in both unmatched (68.4 months vs. 33.3 months, p<.001) and matched analysis based on patient characteristics (62.3 months vs. 33.1months, p<.001). Disease specific survival was unavailable from the dataset. Conclusion In a propensity matched comparison, patients selected for surgery have improved survival compared with SBRT. In the absence of information on cause of death and with limited variables to characterize comorbidity, it is not possible to assess the relative contribution of patient selection or better cancer control towards the improved survival. Rigorous prospective studies are needed to optimize patient selection for SBRT in the high-risk surgical population. PMID:26334753

WE-FG-206-08: Pulmonary Functional Imaging Biomarkers of NSCLC to Guide and Optimize Functional Lung Avoidance Radiotherapy

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Sheikh, Khadija; Capaldi, Dante PI; Parraga, Grace [Robarts Research Institute (Canada); Hoover, Douglas A; Palma, David A [Department of Medical Biophysics, Department of Oncology, The University of Western Ontario, London (Canada); Yaremko, Brian P [Department of Oncology, The University of Western Ontario, London (Canada)

2016-06-15

Purpose: Functional lung avoidance radiotherapy promises optimized therapy planning by minimizing dose to well-functioning lung and maximizing dose to the rest of the lung. Patients with NSCLC commonly present with co-morbid COPD and heterogeneously distributed ventilation abnormalities stemming from emphysema, airways disease, and tumour burden. We hypothesized that pulmonary functional imaging methods may be used to optimize radiotherapy plans to avoid regions of well-functioning lung and significantly improve outcomes like quality-of-life and survival. To ascertain the utility of functional lung avoidance therapy in clinical practice, we measured COPD phenotypes in NSCLC patients enrolled in a randomized-controlled-clinical-trial prior to curative intent therapy. Methods: Thirty stage IIIA/IIIB NSCLC patients provided written informed consent to a randomized-controlled-clinical-trial ( http://clinicaltrials.gov/ct2/show/NCT02002052 ) comparing outcomes in patients randomized to standard or image-guided radiotherapy. Hyperpolarized noble gas MRI ventilation-defect-percent (VDP) (Kirby et al, Acad Radiol, 2012) as well as CT-emphysema measurements were determined. Patients were stratified based on quantitative imaging evidence of ventilation-defects and emphysema into two subgroups: 1) tumour-specific ventilation defects only (TSD), and, 2) tumour-specific and other ventilation defects with and without emphysema (TSD{sub VE}). Receiver-operating-characteristic (ROC) curves were used to characterize the performance of clinical measures as predictors of the presence of non-tumour specific ventilation defects. Results: Twenty-one out of thirty subjects (70%) had non-tumour specific ventilation defects (TSD{sub VE}) and nine subjects had ONLY tumour-specific defects (TSD). Subjects in the TSD{sub VE} group had significantly greater smoking-history (p=.006) and airflow obstruction (FEV{sub 1}/FVC) (p=.001). ROC analysis demonstrated an 87% classification rate for

Comorbidity and KPS are independent prognostic factors in stage I non-small-cell lung cancer

International Nuclear Information System (INIS)

Firat, Selim; Bousamra, Michael; Gore, Elizabeth; Byhardt, Roger W.

2002-01-01

Purpose: To determine the prognostic role of comorbidity in Stage I non-small-cell lung cancer (NSCLC) treated with surgery or radiotherapy (RT). Methods and Materials: One hundred sixty-three patients with clinical Stage I NSCLC were analyzed for overall survival (OS) and comorbidity. One hundred thirteen patients underwent surgery (surgical group) and 50 patients received definitive radiotherapy (RT group). Ninety-six percent of the surgical group had lobectomy or pneumonectomy, and negative margins were achieved in 96% of the patients. The median dose to the tumor for the RT group was 61.2 Gy (range 30.8-77.4). The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and the Charlson scale were used to rate comorbidity. Karnofsky performance scores (KPS) were available in 42 patients; the rest of the scores were determined retrospectively by two physicians independently, with 97% agreement. Results: The OS was 44% for the surgical group and 5% for the RT group at 5 years. Noncancer-related mortality was observed in 31% and 62% of the surgical and RT patients, respectively. On univariate analysis, performed on all patients (n=163), squamous cell histologic type (p 4 cm (p=0.065), >40 pack-year tobacco use (p 2 (p 2 (p=0.004), KPS 40 pack-year tobacco use, KPS <70, and presence of CIRS-G(4) were independently associated with an inferior OS. Treatment modality, T stage, and age did not have any statistically significant effect on OS. Statistically significant differences were found between the surgical and RT groups in Charlson score (p=0.001), CIRS-G total score (p=0.004), severity index (p=0.006), CIRS-G4(+) (p<0.001), KPS (p<0.001), amount of tobacco use (p=0.002), clinical tumor size (p<0.001), clinical T stage (p=0.01), forced expiratory volume in 1 s (p=0.001), and age (p=0.008), in favor of the surgical group. Conclusion: The presence of significant comorbidity and KPS of <70 are both important prognostic factors, but were found to be independent of each

A patient perspective on shared decision making in stage I non-small cell lung cancer: a mixed methods study.

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Hopmans, Wendy; Damman, Olga C; Senan, Suresh; Hartemink, Koen J; Smit, Egbert F; Timmermans, Danielle R M

2015-12-16

Surgery and stereotactic ablative radiotherapy (SABR) are both curative treatment options for patients with a stage I non-small cell lung cancer (NSCLC). Consequently, there is growing interest in studying the role of patients in treatment decision making. We studied how patients with stage I NSCLC perceived shared decision making (SDM) in general, and how they viewed different aspects of SDM. A sequential mixed methods design was used, consisting of qualitative interviews (N=11), as well as a survey study (N=76) focusing on different SDM-related aspects. Participants were interviewed to understand their own experience with treatment decision making. In the survey study, patients rated the importance of 20 aspects of shared decision making that were identified during interviews. Descriptive analysis and explorative factor analysis were performed. We assessed six qualitative themes covering SDM aspects that were determined by patients to be important. The survey identified four SDM-related factors with sufficient internal consistency, namely (1) 'guidance by clinician' (α=.741), (2) 'conduct of clinician' (α=.774); (3) 'preparation for treatment decision making' (α=.864); and (4) 'active role of patient in treatment decision making' (α=.782). Of these, clinician guidance was rated as most important by patients (M=3.61; SD=.44). Only 28.9% of patients in the survey study reported that both treatment options were discussed with them. Patients with a stage I NSCLC found clinician guidance to be important when making treatment decisions. Nevertheless, the majority of patients reported not being offered both treatment options, which might have influenced this finding.

Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of Salvage Surgery.

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Hamaji, Masatsugu; Chen, Fengshi; Matsuo, Yukinori; Ueki, Nami; Hiraoka, Masahiro; Date, Hiroshi

2015-11-01

Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) although limited data are available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. We reviewed our institutional database in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann-Whitney U test, χ2 test, or Fisher's exact test as appropriate. Survival outcomes were estimated with Kaplan-Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and eight patients received chemotherapy, whereas 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS after LR (p = 0.014), and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.

A patient perspective on shared decision making in stage I non-small cell lung cancer: a mixed methods study

NARCIS (Netherlands)

Hopmans, W.; Damman, O.C.; Senan, S.; Hartemink, K.J.; Smit, E.F.; Timmermans, D.R.M.

2015-01-01

Background: Surgery and stereotactic ablative radiotherapy (SABR) are both curative treatment options for patients with a stage I non-small cell lung cancer (NSCLC). Consequently, there is growing interest in studying the role of patients in treatment decision making. We studied how patients with

77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell...

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2012-04-25

... (e.g., details of studies conducted) from medical device industry stakeholders through public...-guidesreviews-and-reports/?pageaction=displayproduct&productid=965 . This notice is a request for industry... (clinical or biopsy) stage I (T1NOMO, T2NOMO) Non-Small Cell Lung Cancer (NSCLC) in adult patients (age 18...

Immune Responses following Stereotactic Body Radiotherapy for Stage I Primary Lung Cancer

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Yoshiyasu Maehata

2013-01-01

Full Text Available Purpose. Immune responses following stereotactic body radiotherapy (SBRT for stage I non-small cell lung cancer (NSCLC were examined from the point of view of lymphocyte subset counts and natural killer cell activity (NKA. Patients and Methods. Peripheral blood samples were collected from 62 patients at 4 time points between pretreatment and 4 weeks post-treatment for analysis of the change of total lymphocyte counts (TLC and lymphocyte subset counts of CD3+, CD4+, CD8+, CD19+, CD56+, and NKA. In addition, the changes of lymphocyte subset counts were compared between patients with or without relapse. Further, the correlations between SBRT-related parameters and immune response were analyzed for the purpose of revealing the mechanisms of the immune response. Results. All lymphocyte subset counts and NKA at post-treatment and 1 week post-treatment were significantly lower than pre-treatment (P<0.01. No significant differences in the changes of lymphocyte subset counts were observed among patients with or without relapse. The volume of the vertebral body receiving radiation doses of 3 Gy or more (VV3 significantly correlated with the changes of nearly all lymphocyte subset counts. Conclusions. SBRT for stage I NSCLC induced significant immune suppression, and the decrease of lymphocyte subset counts may be associated with exposure of the vertebral bone marrow.

Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

Science.gov (United States)

2017-07-28

Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Stereotactic radiotherapy of histologically proven inoperable stage I non-small cell lung cancer: Patterns of failure

International Nuclear Information System (INIS)

Andratschke, Nicolaus; Zimmermann, Frank; Boehm, Eva; Schill, Sabine; Schoenknecht, Christine; Thamm, Reinhard; Molls, Michael; Nieder, Carsten; Geinitz, Hans

2011-01-01

Background and purpose: To report patterns of failure of stereotactic body radiation therapy (SBRT) in inoperable patients with histologically confirmed stage I NSCLC. Materials and methods: Ninety-two inoperable patients (median age: 75 years) with clinically staged, histologically proven T1 (n = 31) or T2 (n = 61), N0, M0 non-small cell lung cancer (NSCLC) were included in this study. Treatment consisted of 3–5 fractions with 7–15 Gy per fraction prescribed to the 60% isodose. Results: Freedom from local recurrence at 1, 3 and 5 years was 89%, 83% and 83%, respectively. All 10 local failures were observed in patients with T2 tumors. Isolated regional recurrence was observed in 7.6%. The crude rate of distant progression was 20.7%. Overall survival at 1, 3, and 5 years was 79%, 38% and 17% with a median survival of 29 months. Disease specific survival at 1, 3, and 5 years was 93%, 64% and 48%. Karnofsky performance status, T stage, gross tumor volume and tumor location had no significant impact on overall and disease specific survival. SBRT was generally well tolerated and all patients completed therapy as planned. Conclusion: SBRT for stage I lung cancer is very well tolerated in this patient cohort with significant cardiopulmonal comorbidity and results in excellent local control rates, although a considerable portion develops regional and distant metastases.

Definitive radiation therapy for medically inoperable patients with stage I and II non-small cell lung cancer

International Nuclear Information System (INIS)

Hayakawa, K.; Mitsuhashi, N.; Saito, Y.; Nakayama, Y.; Katano, S.; Furuta, M.; Sakurai, H.; Takahashi, T.; Niibe, H.

1995-01-01

Purpose: To evaluate the role of definitive radiation therapy (RT) in the treatment for medically inoperable patients with stage I-II non-small cell lung cancer (NSCLC). Materials and Methods: From 1976 through 1989, 84 patients with clinical stage I and II NSCLC were treated with definitive RT alone 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 90 Gy (35 pts; 60-69 Gy, 39 pts; 70-74 Gy, 10 pts; ≥ 80 Gy) with once-daily standard fractionation. Results: The two and five-year survival rates were 74% and 31% for 28 patients with stage I disease, as compared with 40% and 19% for 56 patients with stage II respectively (p<0.05). Although there was no significant difference of survival rates by the histologic subtypes, in the patients with squamous cell carcinoma there were more long-term survivors. Fifty-three patients with tumors less than 5 cm in diameter had an infield progression rate of 14% at two years, in comparison with 38% of 31 patients with tumors greater than 5 cm (p<0.05). Overall distant failure occurred in 57% of the patients with smaller tumors and in 80% of the patients with larger tumors (p<0.05). The difference of survival rates for these two groups was statistically significant (p<0.005). Ten patients given a total dose of 80Gy or over had only 17% local progression at the time of last follow-up, however they had not been alive beyond three years because they developed pulmonary insufficiency due to severe stenosis of the proximal bronchus. For age and sex, there were no significant differences in survival, however, patients with performance status of 0-1 lived longer than those with a status of 2 or more (MST 24 versus 13 months; p=0.06). Conclusion: The tumor size was the most important factor not only for local control but also for distant failure. It was also suggested that the optimal radiation dose for medically inoperable stage I

Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance).

Science.gov (United States)

Martin, Linda W; D'Cunha, Jonathan; Wang, Xiaofei; Herzan, Debra; Gu, Lin; Abraham, Naif; Demmy, Todd L; Detterbeck, Frank C; Groth, Shawn S; Harpole, David H; Krasna, Mark J; Kernstine, Kemp; Kohman, Leslie J; Patterson, G Alexander; Sugarbaker, David J; Vollmer, Robin T; Maddaus, Michael A; Kratzke, Robert A

2016-05-01

Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation. © 2016 by American Society of Clinical Oncology.

Detection of Occult Micrometastases in Patients With Clinical Stage I Non–Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance)

Science.gov (United States)

D’Cunha, Jonathan; Wang, Xiaofei; Herzan, Debra; Gu, Lin; Abraham, Naif; Demmy, Todd L.; Detterbeck, Frank C.; Groth, Shawn S.; Harpole, David H.; Krasna, Mark J.; Kernstine, Kemp; Kohman, Leslie J.; Patterson, G. Alexander; Sugarbaker, David J.; Vollmer, Robin T.; Maddaus, Michael A.; Kratzke, Robert A.

2016-01-01

Purpose Outcomes after resection of stage I non–small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. Materials and Methods Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. Results Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. Conclusion NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation. PMID:26926677

Results of Radiation Therapy in Stage III Uterine Cervical Cancer

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Moon, Chang Woo; Shin, Byung Chul; Yum, Ha Yong; Jeung, Tae Sig; Yoo, Myung Jin [Kosin University College of Medicine, Seoul (Korea, Republic of)

1995-09-15

Purpose : The aim of this study is to analyze the survival rate, treatment failure and complication of radiation therapy alone in stage III uterine cervical cancer. Materials and Methods : From January 1980 through December 1985, 227 patients with stage II uterine cervical cancer treated with radiation therapy at Kosin Medical Center were retrospectively studied. Among 227 patients, 72 patients(31.7%) were stage IIIa, and 155 patients(68.3%) were stage IIIb according to FIGO classification. Age distribution was 32-71 years(median: 62 years). Sixty nine patients(95.8%) in stage IIIa and 150 patients(96.8%) in stage IIIb were squamous cell carcinoma. Pelvic lymph node metastasis at initial diagnosis was 8 patients (11.1%) in stage IIIa and 29 patients(18.7%) in stage IIIb. Among 72 patients with stage IIIa, 36 patients(50%) were treated with external radiation therapy alone by conventional technique (180-200 cGy/fr). And 36 patients(50%) were treated with external radiation therapy with intracavitary radiotherapy(ICR) with Cs137 sources, and among 155 patients with stage IIIb, 80 patients(51.6%) were treated with external radiation therapy alone and 75 patients(48.4%) were treated with external radiation therapy with ICR. Total radiation doses of stage IIIa and IIIb were 65-105 Gy(median : 78.5 Gy) and 65-125.5 Gy (median :83.5 Gy). Survival rate was calculated by life-table method. Results : Complete response rates were 58.3% (42 patients) in state IIIa and 56.1%(87 patients) in stage Iiib. Overall 5 year survival rates were 57% in stage IIIa and 40% in stage IIIb. Five year survival rates by radiation technique in stage IIIa and IIIb were 64%, 40% in group treated in combination of external radiation and ICR, and 50%, 40% in the group of external radiation therapy alone(P=NS). Five year survival rates by response of radiation therapy in stage IIIa and IIIb were 90%, 66% in responder group, and 10%, 7% in non-responder group (P<0.01). There were statistically no

Results of Radiation Therapy in Stage III Uterine Cervical Cancer

International Nuclear Information System (INIS)

Moon, Chang Woo; Shin, Byung Chul; Yum, Ha Yong; Jeung, Tae Sig; Yoo, Myung Jin

1995-01-01

Purpose : The aim of this study is to analyze the survival rate, treatment failure and complication of radiation therapy alone in stage III uterine cervical cancer. Materials and Methods : From January 1980 through December 1985, 227 patients with stage II uterine cervical cancer treated with radiation therapy at Kosin Medical Center were retrospectively studied. Among 227 patients, 72 patients(31.7%) were stage IIIa, and 155 patients(68.3%) were stage IIIb according to FIGO classification. Age distribution was 32-71 years(median: 62 years). Sixty nine patients(95.8%) in stage IIIa and 150 patients(96.8%) in stage IIIb were squamous cell carcinoma. Pelvic lymph node metastasis at initial diagnosis was 8 patients (11.1%) in stage IIIa and 29 patients(18.7%) in stage IIIb. Among 72 patients with stage IIIa, 36 patients(50%) were treated with external radiation therapy alone by conventional technique (180-200 cGy/fr). And 36 patients(50%) were treated with external radiation therapy with intracavitary radiotherapy(ICR) with Cs137 sources, and among 155 patients with stage IIIb, 80 patients(51.6%) were treated with external radiation therapy alone and 75 patients(48.4%) were treated with external radiation therapy with ICR. Total radiation doses of stage IIIa and IIIb were 65-105 Gy(median : 78.5 Gy) and 65-125.5 Gy (median :83.5 Gy). Survival rate was calculated by life-table method. Results : Complete response rates were 58.3% (42 patients) in state IIIa and 56.1%(87 patients) in stage Iiib. Overall 5 year survival rates were 57% in stage IIIa and 40% in stage IIIb. Five year survival rates by radiation technique in stage IIIa and IIIb were 64%, 40% in group treated in combination of external radiation and ICR, and 50%, 40% in the group of external radiation therapy alone(P=NS). Five year survival rates by response of radiation therapy in stage IIIa and IIIb were 90%, 66% in responder group, and 10%, 7% in non-responder group (P<0.01). There were statistically no

Screening and staging for non-small cell lung cancer by serum laser Raman spectroscopy.

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Wang, Hong; Zhang, Shaohong; Wan, Limei; Sun, Hong; Tan, Jie; Su, Qiucheng

2018-08-05

Lung cancer is the leading cause of cancer-related death worldwide. Current clinical screening methods to detect lung cancer are expensive and associated with many complications. Raman spectroscopy is a spectroscopic technique that offers a convenient method to gain molecular information about biological samples. In this study, we measured the serum Raman spectral intensity of healthy volunteers and patients with different stages of non-small cell lung cancer. The purpose of this study was to evaluate the application of serum laser Raman spectroscopy as a low cost alternative method in the screening and staging of non-small cell lung cancer (NSCLC). The Raman spectra of the sera of peripheral venous blood were measured with a LabRAM HR 800 confocal Micro Raman spectrometer for individuals from five groups including 14 healthy volunteers (control group), 23 patients with stage I NSCLC (stage I group), 24 patients with stage II NSCLC (stage II group), 19 patients with stage III NSCLC (stage III group), 11 patients with stage IV NSCLC (stage IV group). Each serum sample was measured 3 times at different spots and the average spectra represented the signal of Raman spectra in each case. The Raman spectrum signal data of the five groups were statistically analyzed by analysis of variance (ANOVA), principal component analysis (PCA), linear discriminant analysis (LDA), and cross-validation. Raman spectral intensity was sequentially reduced in serum samples from control group, stage I group, stage II group and stage III/IV group. The strongest peak intensity was observed in the control group, and the weakest one was found in the stage III/IV group at bands of 848 cm -1 , 999 cm -1 , 1152 cm -1 , 1446 cm -1 and 1658 cm -1 (P Raman spectroscopy can effectively identify patients with stage I, stage II or stage III/IV Non-Small Cell Lung cancer using patient serum samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Interpreting survival data from clinical trials of surgery versus stereotactic body radiation therapy in operable Stage I non-small cell lung cancer patients.

Science.gov (United States)

Samson, Pamela; Keogan, Kathleen; Crabtree, Traves; Colditz, Graham; Broderick, Stephen; Puri, Varun; Meyers, Bryan

2017-01-01

To identify the variability of short- and long-term survival outcomes among closed Phase III randomized controlled trials with small sample sizes comparing SBRT (stereotactic body radiation therapy) and surgical resection in operable clinical Stage I non-small cell lung cancer (NSCLC) patients. Clinical Stage I NSCLC patients who underwent surgery at our institution meeting the inclusion/exclusion criteria for STARS (Randomized Study to Compare CyberKnife to Surgical Resection in Stage I Non-small Cell Lung Cancer), ROSEL (Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer), or both were identified. Bootstrapping analysis provided 10,000 iterations to depict 30-day mortality and three-year overall survival (OS) in cohorts of 16 patients (to simulate the STARS surgical arm), 27 patients (to simulate the pooled surgical arms of STARS and ROSEL), and 515 (to simulate the goal accrual for the surgical arm of STARS). From 2000 to 2012, 749/873 (86%) of clinical Stage I NSCLC patients who underwent resection were eligible for STARS only, ROSEL only, or both studies. When patients eligible for STARS only were repeatedly sampled with a cohort size of 16, the 3-year OS rates ranged from 27 to 100%, and 30-day mortality varied from 0 to 25%. When patients eligible for ROSEL or for both STARS and ROSEL underwent bootstrapping with n=27, the 3-year OS ranged from 46 to 100%, while 30-day mortality varied from 0 to 15%. Finally, when patients eligible for STARS were repeatedly sampled in groups of 515, 3-year OS narrowed to 70-85%, with 30-day mortality varying from 0 to 4%. Short- and long-term survival outcomes from trials with small sample sizes are extremely variable and unreliable for extrapolation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Survival prognostic value of morphological and metabolic variables in patients with stage I and II non-small cell lung cancer

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Domachevsky, L. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Beilinson Hospital, Petah Tikva (Israel); Groshar, D.; Bernstine, H. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Galili, R. [Lady Davis-Carmel Medical Center, Department of Cardiothoracic Surgery, Haifa (Israel); Saute, M. [Rabin Medical Center, Department of Cardiothoracic Surgery, Petah Tiqva (Israel)

2015-11-15

The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. (orig.)

Long-term results of a randomized controlled trial evaluating preoperative chemotherapy in resectable non-small cell lung cancer

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Chen, Zhiwei; Luo, Qingquan; Jian, Hong; Zhou, Zhen; Cheng, Baijun; Lu, Shun; Liao, Meilin

2013-01-01

Zhiwei Chen,* Qingquan Luo,* Hong Jian, Zhen Zhou, Baijun Cheng, Shun Lu, Meilin LiaoShanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equallyObjective: We aimed to evaluate whether preoperative chemotherapy provides benefits in the survival and prognosis of patients with non-small cell lung cancer (NSCLC) in resectable stages I to IIIA, except T1N0. Methods: In this ra...

Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes

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Wang T

2016-03-01

Full Text Available Tao Wang,1 Yang Liu,1 Bin Zhou,1 Zhi Wang,1 Naichao Liang,1 Yundong Zhang,1 Zhouhuan Dong,2 Jie Li2 1Department of Thoracic Surgery, 2Department of Pathology, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Purpose: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC. Preliminary findings suggested that EGFR–TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC.Patients and methods: We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA–IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis.Results: A total of 67 patients with NSCLC were reviewed, and approximately half (38/67 of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2–4 weeks’ assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028 and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011 were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3% and dry skin (34.4%, which were tolerable.Conclusion: Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings. Keywords: non-small-cell lung cancer

Comorbidity and Karnofksy performance score are independent prognostic factors in stage III non-small-cell lung cancer: an institutional analysis of patients treated on four RTOG studies

International Nuclear Information System (INIS)

Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

2002-01-01

Purpose: To determine the prognostic role of comorbidity in Stage III non-small cell lung cancer (NSCLC) treated definitively with radiotherapy alone. Methods and Materials: A total of 112 patients with clinical Stage III NSCLC (American Joint Commission on Cancer 1997) enrolled in four Radiation Therapy Oncology Group studies (83-11, 84-03, 84-07, and 88-08 nonchemotherapy arms) at a single institution were analyzed retrospectively for overall survival (OS) and comorbidity. Of the 112 patients, 105 (94%) completed their assigned radiotherapy. The median assigned dose was 50.4 Gy to the lymphatics (range 45-50.4 Gy) and 70.2 Gy to the primary tumor (range 60-79.2 Gy). Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and Charlson scales. Karnofsky performance scores (KPSs) and weight loss were prospectively recorded. Because only 8 patients had a KPS of 70). Results: The median survival was 10.39 months (range 7.87-12.91). The 2-, 3-, and 5-year OS rate was 20.5%, 12.5%, and 7.1%, respectively. On univariate analysis, clinical stage (IIIA vs. IIIB) was found to be a statistically significant factor influencing OS (p=0.026), and the histologic features, grade, tumor size as measured on CT scans, age, tobacco use, weight loss ≥5%, and total dose delivered to the primary tumor were not. A KPS of ≤70 (p=0.001), the presence of a CIRS-G score of 4 (extremely severe; p=0.0002), and a severity index of >2 (p 2 were independently associated with inferior OS; clinical tumor stage was not found to be an independent prognostic factor. Conclusion: KPS and comorbidity are important independent prognostic factors in Stage III NSCLC. Comorbidity should be included in protocols studying advanced stage NSCLC and used for stratification

Production and characterization of monoclonal antibodies against rat platelet GPIIb/IIIa

International Nuclear Information System (INIS)

Miyazaki, H.; Tamura, S.; Sudo, T.; Suzuki, T.

1990-01-01

Four murine monoclonal antibodies against rat platelets were produced by fusion of spleen cells from mice intravenously immunized with whole rat platelets. All four antibodies immunoprecipitated two major platelet membrane proteins with apparent molecular weights of 130,000 and 82,000 (nonreduced) and of 120,000 and 98,000 (reduced), which were structurally analogous to human glycoprotein (GP) IIb/IIIa, i.e. rat GPIIb/IIIa. Two of four antibodies, named P9 and P55, strongly inhibited adenosine diphosphate (ADP)-induced aggregation of washed rat platelets and caused approximately 50% inhibition of human fibrinogen binding to ADP-stimulated rat platelets, suggesting that rat GPIIb/IIIa serves as a fibrinogen receptor in ADP-induced aggregation. In contrast, two other antibodies, named P14 and P34, themselves caused aggregation of rat platelets in platelet-rich plasma (PRP) and the secretion of 14C-serotonin from 14C-serotonin-labeled PRP. These results indicate that rat GPIIb/IIIa plays an important role in platelet aggregation

Preliminary investigation of stereotactic body radiation therapy for medically inoperable stage I/II non-small cell lung cancer

International Nuclear Information System (INIS)

Guo Jindong; Lu Changxing; Wang Jiaming; Liu Jun; Li Hongxuan; Wang Changlu; Gao Lanting; Zhao Lei

2011-01-01

Objective: To evaluate the therapeutic efficacy and treatment-related toxicity of stereotactic body radiation therapy (SBRT) in patients with medically inoperable stage I/II non-small cell lung cancer (NSCLC). Methods: SBRT was applied to 30 patients, including clinically staged T 1 , T 2 (≤5 cm) or T 3 (chest wall primary tumors only), N 0 , M 0 ,biopsy-confirmed NSCLC. All patients were precluded from lobotomy because of physical condition or comorbidity. No patients developed tumors of any T-stage in the proximal zone. SBRT was performed with the total dose of 50 Gy to 70 Gy in 10 - 11 fractions during 12 - 15 days. prescription line was set onthe edge of the PTV. Results: The follow-up rate was 100%. The number of patients who completed the 1-, and 2-year follow-up were 15, and 10, respectively. All 30 patients completed therapy as planned. The complete response (CR), partial response (PR) and stable disease (SD) rates were 37%, 53% and 3%, respectively. With a median follow-up of 16 months (range, 4-36 months), Kaplan-Meier local control at 2 years was 94%. The 2-year overall survival was 84% and the 2-year cancer specific survival was 90%. Seven patients(23%) developed Grade 2 pneumonitis, no grade > 2 acute or late lung toxicity was observed. No one developed chest wall pain. Conclusions: It is feasible to deliver 50 Gy to 70 Gy of SBRT in 10 - 11 fractions for medically inoperable patients with stage I / II NSCLC. It was associated with low incidence of toxicities and provided sustained local tumor control.The preliminary investigation indicated the cancer specific survival probability of SBRT was high. It is necessary to perform similar investigation in a larger number of patients with long-term follow-up. (authors)

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

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Lao, Louis [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Hope, Andrew J. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Maganti, Manjula [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Cho, B. C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

2014-09-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

International Nuclear Information System (INIS)

Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

2014-01-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT

Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer

International Nuclear Information System (INIS)

Langendijk, Johannes A.; Aaronson, Neil K.; Jong, Jos M.A. de; Velde, Guul P.M. ten; Muller, Martin J.; Slotman, Ben J.; Wouters, Emiel F.M.

2002-01-01

Purpose: The aim of this study was to investigate changes in quality of life (QOL) among medically inoperable Stage I non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy. Patients and Methods: The study sample was composed of 46 patients irradiated for Stage I NSCLC. Quality of life was assessed before, during, and after radiotherapy using the European Organization for the Research and Treatment of Cancer QLQ-C30 and QLQ-LC13. Changes in symptom and QOL scores over time were evaluated with a repeated measurement analysis of variance using the mixed effect modeling procedure, SAS Proc Mixed. Twenty-seven patients were treated only at the primary site, whereas for 19 patients, the regional lymph nodes were included in the target volume as well. Results: The median follow-up time of patients alive was 34 months. The median survival was 19.0 months. None of the locally treated patients developed regional recurrence. A significant, gradual increase over time was observed for dyspnea, fatigue, and appetite loss. A significant, gradual deterioration was observed also for role functioning. No significant changes were noted for the other symptoms or the functioning scales. Significantly higher levels of dysphagia, which persisted up to 12 months, were observed in those in which the regional lymph nodes were treated, as compared to the locally treated patients. Radiation-induced pulmonary changes assessed with chest radiograph were more pronounced in the group treated with locoregional radiotherapy. Conclusions: After curative radiotherapy for Stage I medically inoperable NSCLC, a gradual increase in dyspnea, fatigue, and appetite loss, together with a significant deterioration of role functioning, was observed, possibly because of pre-existing, slowly progressive chronic obstructive pulmonary disease and radiation-induced pulmonary changes. Taking into account the low incidence of regional recurrences after local irradiation, the higher incidence

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

International Nuclear Information System (INIS)

Zheng, Xiangpeng; Schipper, Matthew; Kidwell, Kelley; Lin, Jules; Reddy, Rishindra; Ren, Yanping; Chang, Andrew; Lv, Fanzhen; Orringer, Mark; Spring Kong, Feng-Ming

2014-01-01

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery

Survival Outcome After Stereotactic Body Radiation Therapy and Surgery for Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

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Zheng, Xiangpeng [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Schipper, Matthew [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Kidwell, Kelley [Department of Biostatistics, the University of Michigan, Ann Arbor, Michigan (United States); Lin, Jules; Reddy, Rishindra [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Ren, Yanping [Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai (China); Chang, Andrew [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Lv, Fanzhen [Department of Thoracic Surgery, Huadong Hospital, Fudan University, Shanghai (China); Orringer, Mark [Department of Surgery, Section of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan (United States); Spring Kong, Feng-Ming, E-mail: Fkong@gru.edu [Department of Radiation Oncology, the University of Michigan, Ann Arbor, Michigan (United States)

2014-11-01

Purpose: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). Methods and Materials: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. Results: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. Conclusions: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.

Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer

International Nuclear Information System (INIS)

Verstegen, Naomi E.; Maat, Alexander P. W. M.; Lagerwaard, Frank J.; Paul, Marinus A.; Versteegh, Michel I; Joosten, Joris J.; Lastdrager, Willem; Smit, Egbert F.; Slotman, Ben J.; Nuyttens, Joost J. M. E.; Senan, Suresh

2016-01-01

The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence following SABR for early stage non-small cell lung cancer (NSCLC). Patients who underwent surgical salvage for a local recurrence following SABR for NSCLC were identified from two Dutch institutional databases. Complications were scored using the Dindo-Clavien-classification. Nine patients who underwent surgery for a local recurrence were identified. Median time to local recurrence was 22 months. Recurrences were diagnosed with CT- and/or 18FDG-PET-imaging, with four patients also having a pre-surgical pathological diagnosis. Extensive adhesions were observed during two resections, requiring conversion from a thoracoscopic procedure to thoracotomy during one of these procedures. Three patients experienced complications post-surgery; grade 2 (N = 2) and grade 3a (N = 1), respectively. All resection specimens showed viable tumor cells. Median length of hospital stay was 8 days (range 5–15 days) and 30-day mortality was 0 %. Lymph node dissection revealed mediastinal metastases in 3 patients, all of whom received adjuvant therapy. Our experience with nine surgical procedures for local recurrences post-SABR revealed two grade IIIa complications, and a 30-day mortality of 0 %, suggesting that salvage surgery can be safely performed after SABR

Uterine cervix cancer treatment in IIB, IIIA and IIIB stages with external radiotherapy versus external radiotherapy and scintiscanning of low dose. ION SOLCA. Years 1998-2000

International Nuclear Information System (INIS)

Sanchez, Doris; Falquez, Roberto

2002-01-01

We realized study of retrospective accomplished in course of years 1998-2000, reviewing clinical charts of statistical department of ION SOLCA. We reviewed 544 cases in 1998, 603 patients in 1999, and 630 cases in 2000. In the radiotherapy service, 133 patients received treatment with external radiotherapy between February 1998 to February 1999 in IIB, IIIA, IIIB stages and only 80 patients were treated with external radiotherapy and scintiscanning of low dose rate in the same stages between March 1999 to March 2000. (The author)

Verification of Dose Distribution in Carbon Ion Radiation Therapy for Stage I Lung Cancer

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Irie, Daisuke; Saitoh, Jun-ichi, E-mail: junsaito@gunma-u.ac.jp; Shirai, Katsuyuki; Abe, Takanori; Kubota, Yoshiki; Sakai, Makoto; Noda, Shin-ei; Ohno, Tatsuya; Nakano, Takashi

2016-12-01

Purpose: To evaluate robustness of dose distribution of carbon-ion radiation therapy (C-ion RT) in non-small cell lung cancer (NSCLC) and to identify factors affecting the dose distribution by simulated dose distribution. Methods and Materials: Eighty irradiation fields for delivery of C-ion RT were analyzed in 20 patients with stage I NSCLC. Computed tomography images were obtained twice before treatment initiation. Simulated dose distribution was reconstructed on computed tomography for confirmation under the same settings as actual treatment with respiratory gating and bony structure matching. Dose-volume histogram parameters, such as %D95 (percentage of D95 relative to the prescribed dose), were calculated. Patients with any field for which the %D95 of gross tumor volume (GTV) was below 90% were classified as unacceptable for treatment, and the optimal target margin for such cases was examined. Results: Five patients with a total of 8 fields (10% of total number of fields analyzed) were classified as unacceptable according to %D95 of GTV, although most patients showed no remarkable change in the dose-volume histogram parameters. Receiver operating characteristic curve analysis showed that tumor displacement and change in water-equivalent pathlength were significant predictive factors of unacceptable cases (P<.001 and P=.002, respectively). The main cause of degradation of the dose distribution was tumor displacement in 7 of the 8 unacceptable fields. A 6-mm planning target volume margin ensured a GTV %D95 of >90%, except in 1 extremely unacceptable field. Conclusions: According to this simulation analysis of C-ion RT for stage I NSCLC, a few fields were reported as unacceptable and required resetting of body position and reconfirmation. In addition, tumor displacement and change in water-equivalent pathlength (bone shift and/or chest wall thickness) were identified as factors influencing the robustness of dose distribution. Such uncertainties should be regarded

The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

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Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

2017-02-01

The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; pcancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Hyperfractionated Radiotherapy and Concurrent Chemotherapy for Stage III Unascertainable Non Small Cell Lung Cancer : Preliminary Report for Response and Toxicity

International Nuclear Information System (INIS)

Choi, Eun Kyung; Kim, Jong Hoon; Chang, Hye Sook

1995-01-01

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy( 120 cGy/fx BID, 6480 cGY/54fx) and concurrent 2 cycles of MVP(Motomycin C 6 mg/m 2 , d2 and d29, Vinblastin 6 mg/m 2 , d2 and d29, Cisplatin 6 mg/m 2 , d1 and d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study ; 6(10%) had advanced stage IIIa and 56(90%) had IIIb disease including 1 with pleural effusion and 10 with supraclavicular metastases. Among 62 Patients, 48(77%) completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, 34(74%) showed major response including 10(22%) with complete and 24(52%) with partial responses. Of 48 patients evaluable for toxicity, 13(27%) showed grade IV hematologic toxicity but treatment delay did not exceed 5 days. Two patients died of sepsis during chemoradiotherapy. Server weight(more than 10%) occurred in 9 patients(19%) during treatment. Nine patients(19%) developed radiation pneumonitis. Six of these patients had grad I(mild) pneumonitis with radiographic changes within the treatment fields. Three other patients had grade II pneumonitis, but none of theses patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance rate(7%) in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary, supportive care will given as in patients. Longer follow-up and larger sample size is needed to

Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Yuning LIU

2016-04-01

Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

Survival of localized NSCLC patients without active treatment or treated with SBRT

DEFF Research Database (Denmark)

Jeppesen, S S; Hansen, N C G; Schytte, T

2018-01-01

BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for pati......BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment...... for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival. MATERIAL AND METHODS: From 2007 to 2013, 136 patients treated...... with SBRT at Odense University Hospital were prospectively recorded. The thoracic SBRT consisted of three fractions of 15-22 Gy delivered in 9 days. For comparison, a national group of 73 untreated patients in the same time period was extracted from the Danish Lung Cancer Registry. All patients had...

Intravital Microscopy in Evaluating Patients With Primary Peritoneal, Fallopian Tube, or Stage IA-IV Ovarian Cancer

Science.gov (United States)

2018-06-04

Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage II Ovarian Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer

Residual F-18-FDG-PET Uptake 12 Weeks After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer Predicts Local Control

NARCIS (Netherlands)

Bollineni, Vikram Rao; Widder, Joachim; Pruim, Jan; Langendijk, Johannes A.; Wiegman, Erwin M.

2012-01-01

Purpose: To investigate the prognostic value of [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC). Methods and Materials: From November 2006 to February 2010, 132 medically

Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

Science.gov (United States)

2017-11-15

Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

Globo H expression is associated with driver mutations and PD-L1 expressions in stage I non-small cell lung cancer.

Science.gov (United States)

Yang, Ching-Yao; Lin, Mong-Wei; Chang, Yih-Leong; Wu, Chen-Tu

2017-12-12

Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in ⩾ 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment.

A phase II study of cisplatin, oral administration of etoposide, OK-432 and radiation therapy for inoperable stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Abe, Yoshinao; Takahashi, Jutaro; Fukuda, Hiroshi

1998-01-01

This study was designed to evaluate the feasibility and efficiency of giving cisplatin, etoposide, and OK-432 concurrently with conventional radiotherapy (RTx) for patient's with inoperable stage III, based on the TNM classification according to the International Union against Cancer staging system for lung cancer (1987) non-small cell lung cancer (NSCLC). From January 1992 to December 1994, 31 patients with cytologically or histologically confirmed stage III NSCLC were treated with RTx, to a total dose of 56-64 Gy, with concurrent daily oral administration of etoposide (25 mg) and cisplatin (20 mg) for 5 days during the third or fourth week from the start of RTx. The subcutaneous injection of 1 or 2 KE of OK-432, three times a week, for the duration of radiotherapy also started from the beginning of RTx. The number of eligible patients was 29 (26 men and 3 women). Their mean age was 66 years (range, 55-77 years). Six patients had an Eastern Cooperative Oncology Group performance status (PS) of 0; 15, 1; 8; 2. Three were stage IIIA, and 26, stage IIIB. Histologically, 2 had adenocarcinoma, 23, squamous cell carcinoma, and 4, large cell carcinoma. In 27 of the 29 patients, the RTx schedule was completed. There were no treatment-related deaths. Grade 4 toxicity (according to World Health Organisation criteria) leukopenia (700/μl) was observed in 1 patient. The response rate was 79% and the median survival was 17 months. Survival rates at 1, 2 and 3 years were 62%, 31%, and 21%, respectively. The local failure rate was 51%. The combination of cisplatin, etoposide, and OK-432, given concurrently with conventional RTx is feasible and effective for inoperable stage III NSCLC. (author)

Radiation Therapy in Treating Post-Menopausal Women With Early Stage Breast Cancer Undergoing Surgery

Science.gov (United States)

2017-06-07

Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Cribriform Breast Carcinoma; Invasive Ductal Carcinoma, Not Otherwise Specified; Lobular Breast Carcinoma In Situ; Mucinous Breast Carcinoma; Papillary Breast Carcinoma; Progesterone Receptor Positive; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer; Tubular Breast Carcinoma

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Chen, Viola J.; Oermann, Eric [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Vahdat, Saloomeh [Department of Pathology, Georgetown University Hospital, Washington, DC (United States); Rabin, Jennifer; Suy, Simeng; Yu, Xia; Collins, Sean P. [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Subramaniam, Deepa [Division of Hematology and Oncology, Georgetown University Hospital, Washington, DC (United States); Banovac, Filip [Department of Radiology, Georgetown University Hospital, Washington, DC (United States); Anderson, Eric [Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC (United States); Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States)

2012-02-01

Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4–5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21–111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3–13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12–72 months) follow-up, the 3 year Kaplan–Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1–2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

Percutaneous microwave ablation for early-stage non-small cell lung cancer (NSCLC) in the elderly: a promising outlook

International Nuclear Information System (INIS)

Acksteiner, Christian; Steinke, Karin

2015-01-01

Microwave ablation (MWA) is a relatively new minimally invasive treatment option for lung cancer with substantially lower morbidity and mortality than surgery. This retrospective study was performed to evaluate the safety, effectiveness and follow-up imaging of MWA in the elderly aged 75 years and above. Eleven percutaneous computed tomography (CT)-guided MWA of early-stage non-small cell lung cancer (NSCLC) were performed in 10 patients aged 75 years and older. All but one patient were treated with a high-powered MWA system delivering maximally 140 W. Follow-up with CT and fluorodeoxyglucose-positron emission tomography (FDG-PET) was carried out over a maximum period of 30 months and a median period of 12 months. There were no peri-procedural deaths or major complications. Seven patients were disease free at the time of manuscript submission. Three patients showed growth of the treated lesions, one patient aged 90 years deceased due to unknown cause after approximately 18 months. One patient presented with local progression and disseminated metastatic disease at 12 months; he is still alive. One patient showed increasing soft tissue at the ablation site 15 months post-treatment. Three consecutive core biopsies over 2 months failed to confirm tumour recurrence. MWA therapy is a promising option of treating early-stage NSCLC in the elderly with good treatment outcome and negligible morbidity. Determining successful treatment outcome may be challenging at times as local tissue increase and PET-CT positivity do not seem to necessarily correlate with recurrence of malignancy.

Quality of Life After Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Voort van Zyp, Noelle C. van der; Prevost, Jean-Briac; Holt, Bronno van der; Braat, Cora; Klaveren, Robertus J. van; Pattynama, Peter M.; Levendag, Peter C.; Nuyttens, Joost J.

2010-01-01

Purpose: To determine the impact of stereotactic radiotherapy on the quality of life of patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Overall survival, local tumor control, and toxicity were also evaluated in this prospective study. Methods and Materials: From January 2006 to February 2008, quality of life, overall survival, and local tumor control were assessed in 39 patients with pathologically confirmed T1 to 2N0M0 NSCLC. These patients were treated with stereotactic radiotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the QLQ LC13 lung cancer-specific questionnaire were used to investigate changes in quality of life. Assessments were done before treatment, at 3 weeks, and at 2, 4, 6, 9, and 12 months after treatment, until death or progressive disease. Toxicity was evaluated using common terminology criteria for adverse events version 3.0. Results: Emotional functioning improved significantly after treatment. Other function scores and QLQ C30 and QLQ LC13 lung symptoms (such as dyspnea and coughing) showed no significant changes. The overall 2-year survival rate was 62%. After a median follow-up of 17 months, 1 patient had a local recurrence (3%). No grade 4 or 5 treatment-related toxicity occurred. Grade 3 toxicity consisted of thoracic pain, which occurred in 1 patient within 4 months of treatment, while it occurred thereafter in 2 patients. Conclusions: Quality of life was maintained, and emotional functioning improved significantly after stereotactic radiotherapy for stage I NSCLC, while survival was acceptable, local tumor control was high, and toxicity was low.

Health related quality of life in locally advanced NSCLC treated with high dose radiotherapy and concurrent chemotherapy or cetuximab – Pooled results from two prospective clinical trials

International Nuclear Information System (INIS)

Hallqvist, Andreas; Bergman, Bengt; Nyman, Jan

2012-01-01

Background: In non-small cell lung cancer (NSCLC) stage III, data on patient reported health-related quality of life (HRQL) are scarce, especially regarding concurrent chemoradiotherapy. Aims: To evaluate HRQL in patients treated with high dose radiotherapy combined with concurrent chemotherapy or the antibody cetuximab. Methods: The study population comprised all patients enroled in either of two phase II trials in locally advanced NSCLC performed in Sweden 2002–2007. The RAKET trial investigated three different ways of increasing local control (accelerated hyperfractionated treatment or concurrent daily or weekly chemotherapy). The Satellite trial evaluated the addition of cetuximab to thoracic irradiation. HRQL was measured at four time points: At baseline, before radiotherapy, 4–6 weeks after radiotherapy and at 3 months follow-up, using the EORTC QLQ-C30 and LC14 set of questionnaires. Results: 154/220 patients (65%) who completed HRQL assessments at all time points were included in the longitudinal study. There was a significant decline over time regarding most functioning measures. Dyspnoea and fatigue gradually deteriorated without recovery after completed treatment. Chemotherapy related symptoms showed a transient deterioration, whereas radiotherapy related esophagitis had not fully recovered at 3 months. Patients with stage IIIA disease tended to recover better regarding global QL, fatigue and dyspnoea compared to patients with stage IIIB. Patients with WHO performance status (PS) 0 reported improved global QL and less fatigue over time compared with PS 1. Concurrent chemotherapy was associated with more pronounced fatigue and dysphagia, and worse global QL compared with concurrent cetuximab. Baseline physical functioning was an independent predictor of overall survival. Conclusion: Patients undergoing high dose thoracic radiotherapy combined with chemotherapy or cetuximab reported a gradual deterioration in functioning, dyspnoea and fatigue, while

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER-Medicare analysis.

Science.gov (United States)

Malhotra, J; Mhango, G; Gomez, J E; Smith, C; Galsky, M D; Strauss, G M; Wisnivesky, J P

2015-04-01

The role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly. We identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score. Overall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68-0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction. Platinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm. © The Author 2015. 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.

Comparisons of dose-volume histograms for proton-beam versus 3-D conformal X-ray therapy in patients with stage I non-small cell lung cancer

International Nuclear Information System (INIS)

Wang, Changlu; Nakayama, Hidetsugu; Sugahara, Shinji; Sakae, Takeji; Tokuuye, Koichi

2009-01-01

Dose-volume histograms (DVHs) were reviewed to determine if there is an advantage of the two modalities when treating patients with non-small cell lung cancer (NSCLC). 24 stage I NSCLC patients who underwent proton-beam therapy (PBT) from June 2003 to May 2007 were included in this study. Based on the same clinical target volumes (CTVs), treatment planning was made to cover CTV within 90% isodose lines. Each patient was evaluated by two sets of DVHs, one for PBT and the other for three-dimensional conformal X-ray therapy (3D-CRT). For all patients, the 95% isodose line covered 86.4% of the CTV for PBT, and 43.2% for 3D-CRT. PBT was associated with significantly lower mean doses to the ipsilateral lung, total lung, heart, esophagus, and spinal cord than 3D-CRT. PBT offered reduced radiation doses to the lung when evaluated in terms of percentage lung volumes receiving ≥ 5 Gy (V 5 ), ≥ 10 Gy (V 10 ), and ≥ 20 Gy (V 20 ) when compared to 3D-CRT. PBT is advantageous over 3D-CRT in reducing doses to the lung, heart, esophagus, and spinal cord in treating stage I NSCLC. (orig.)

Elucidation of the mechanisms of CryIIIA overproduction in a mutagenized strain of Bacillus thuringiensis var. tenebrionis

International Nuclear Information System (INIS)

Adams, L.F.; Mathewes, S.; O'Hara, P.; Peterson, A.; Gürtler, H.

1994-01-01

NB176 is a Bacillus thuringiensis mutant derived by λ-irradiation of NB125 Bacillus thuringiensis var. tenebrionis (Krieg). It exhibits two interesting phenotypes: (i) oligosporogeny and (ii) twofold to threefold overproduction of the CryIIIA protein. Southern profiles of the NB176 strain showed an additional copy(s) of the cryIIIA gene located on a 4 kb HindIII fragment, in addition to the expected cryIIIA gene on a 3 kb HindIII fragment. Each cryIIIA gene-bearing HindIII fragment was cloned from NB176. The restriction map of the 3 kb HindIII fragment was identical to that published by Donovan and coworkers. Sequencing of the 4 kb HindIII fragment showed no alterations in the promoter region of the cryIIIA gene but did show replacement of the region immediately following the cryIIIA open reading frame with a sequence encoding a transposase with 50% amino acid homology to that of Tn 1000. These findings suggest that the overproduction phenotype of NB176 results from extra copies of the cryIIIA gene produced from a transposition event(s) induced or stabilized by γ-irradiation. Integration of additional copies of the cryIIIA gene into the native 90MDa plasmid of the wild-type B. thuringiensis var. tenebrionis strain resulted in strains that made enormous crystals, many possessing greatly enhanced insecticidal activity

Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

Science.gov (United States)

Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

2016-08-01

To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

The ROTSE-IIIa telescope system

International Nuclear Information System (INIS)

Smith, D.; Akerlof, C.; Kehoe, R.; McKay, T.; Rykoff, E.; Ashley, M.C.B.; Phillips, M.A.; Casperson, D.; Gisler, G.; McGowan, K.; Vestrand, W.T.; Wozniak, P.; Wren, J.; Marshall, S.

2003-01-01

We report on the current operating status of the ROTSE-IIIa telescope, currently undergoing testing at Los Alamos National Laboratories in New Mexico. It will be shipped to Siding Spring Observatory, Australia, in first quarter 2002. ROTSE-IIIa has been in automated observing mode since early October, 2001, after completing several weeks of calibration and check-out observations. Calibrated lists of objects in ROTSE-IIIa sky patrol data are produced routinely in an automated pipeline, and we are currently automating analysis procedures to compile these lists, eliminate false detections, and automatically identify transient and variable objects. The manual application of these procedures has already led to the detection of a nova that rose over six magnitudes in two days to a maximum detected brightness of mR ∼ 13.9 and then faded two magnitudes in two weeks. We also readily identify variable stars, includings those suspected to be variables from the Sloan Digital Sky Survey. We report on our system to allow public monitoring of the telescope operational status in real time over the WWW

Phase II study of induction chemotherapy followed by radiotherapy combined with daily cisplatin in stage III inoperable non-small cell lung cancer (NSCLC)

Energy Technology Data Exchange (ETDEWEB)

Scolaro, T; Ardizzoni, A; Giudici, S; Grossi, F; Cosso, M; Pennucci, M C; Bacigalupo, A; Rosso, R; Vitale, V

1997-07-01

Purpose: Results of radical radiotherapy in the treatment of inoperable NSCLC can be improved by either concurrent daily low-dose Cisplatin as radiosensitizer (Shaake-Koning, N Engl J Med, 1992; 326: 524) or by using neoadiuvant chemotherapy (Dillman, N Engl J Med, 1990; 323: 940). The aim of present study was to evaluate the activity and feasibility of a new chemo-radiotherapy (CT-RT) regimen in which both strategies of RT improvement will be used. Methods: Thirty consecutive patients (pts) were treated with induction CT (Cisplatin 100 mg/m{sup 2} i.v. day 1,22 + Vinblastine 5 mg/m{sup 2} i.v. day 1,8,15,22,29) followed by RT (60 Gy/30 fractions in 6 wks) combined with Cisplatin 5 mg/m{sup 2} daily before RT. Patients' characteristics were: 29 pts were male and 1 female; median age 60.5 yrs (range 44-69); median PS 1 (range 0-1); 21 squamous cell carcinoma and 9 adenocarcinoma; stage III A in 9 pts and stage IIIB in 21 pts. Results: Twenty-three pts were evaluable for RT plus daily Cisplatin toxicity and 29 for CT toxicity (according to WHO). For RT plus daily cisplatin hematological toxicity consisted of grade III leukopenia in 22%, grade III anemia 9% and grade III thrombocytopenia in 9% of pts. Only 2 patients developed severe esophagitis. Only one case of radiation pneumonitis was reported. For induction CT hematological toxicity consisted of grade III-IV leukopenia in 31%, grade II anemia 10% and grade IV thrombocitopenia in 14% of cases. Non-hematological toxicity consisted mainly of grade I peripheral neuropaty and occured in 17% of pts. One case of minor hearing loss and 4 cases of tinnitus were observed at the end of treatment. Twenty-seven pts were evaluable for response. Response rate was 59% with 7 CRs (26%) and 9 PRs (33%); 1 patient had SD (4%), 5 pts PD (20%) and 5 pts (19%) died early (3 for early progression, 1 for toxicity and 1 for cardiac failure). All pts with CR are still alive with a median event-free survival of 23.9 months (range 12

Phase II study of induction chemotherapy followed by radiotherapy combined with daily cisplatin in stage III inoperable non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Scolaro, T.; Ardizzoni, A.; Giudici, S.; Grossi, F.; Cosso, M.; Pennucci, M.C.; Bacigalupo, A.; Rosso, R.; Vitale, V.

1997-01-01

Purpose: Results of radical radiotherapy in the treatment of inoperable NSCLC can be improved by either concurrent daily low-dose Cisplatin as radiosensitizer (Shaake-Koning, N Engl J Med, 1992; 326: 524) or by using neoadiuvant chemotherapy (Dillman, N Engl J Med, 1990; 323: 940). The aim of present study was to evaluate the activity and feasibility of a new chemo-radiotherapy (CT-RT) regimen in which both strategies of RT improvement will be used. Methods: Thirty consecutive patients (pts) were treated with induction CT (Cisplatin 100 mg/m 2 i.v. day 1,22 + Vinblastine 5 mg/m 2 i.v. day 1,8,15,22,29) followed by RT (60 Gy/30 fractions in 6 wks) combined with Cisplatin 5 mg/m 2 daily before RT. Patients' characteristics were: 29 pts were male and 1 female; median age 60.5 yrs (range 44-69); median PS 1 (range 0-1); 21 squamous cell carcinoma and 9 adenocarcinoma; stage III A in 9 pts and stage IIIB in 21 pts. Results: Twenty-three pts were evaluable for RT plus daily Cisplatin toxicity and 29 for CT toxicity (according to WHO). For RT plus daily cisplatin hematological toxicity consisted of grade III leukopenia in 22%, grade III anemia 9% and grade III thrombocytopenia in 9% of pts. Only 2 patients developed severe esophagitis. Only one case of radiation pneumonitis was reported. For induction CT hematological toxicity consisted of grade III-IV leukopenia in 31%, grade II anemia 10% and grade IV thrombocitopenia in 14% of cases. Non-hematological toxicity consisted mainly of grade I peripheral neuropaty and occured in 17% of pts. One case of minor hearing loss and 4 cases of tinnitus were observed at the end of treatment. Twenty-seven pts were evaluable for response. Response rate was 59% with 7 CRs (26%) and 9 PRs (33%); 1 patient had SD (4%), 5 pts PD (20%) and 5 pts (19%) died early (3 for early progression, 1 for toxicity and 1 for cardiac failure). All pts with CR are still alive with a median event-free survival of 23.9 months (range 12.3-41.9). Actuarial

Aggravation of dyspnea in stage I non-small cell lung cancer patients following stereotactic body radiotherapy

DEFF Research Database (Denmark)

Paludan, Merete; Traberg Hansen, Anders; Petersen, Jørgen

2006-01-01

the association of dose-volume histogram parameters with changes in dyspnea. The study concerns 28 medically inoperable stage I NSCLC patients that received SBRT at our department between 2000 and 2003. A central dose of 45 Gy/3 fractions was delivered in 5-8 days. WHO toxicity scoring of dyspnea...... consistent temporal variations of dyspnea after SBRT. We identified COPD as the factor showing the closest association with aggravation of dyspnea. The observed aggravation of dyspnea following SBRT reflects habitual exacerbations of COPD rather than treatment-related toxicity. Concern about pulmonary...

Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older

International Nuclear Information System (INIS)

Furuta, Masaya; Hayakawa, Kazushige; Katano, Susumu

1996-01-01

Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N0 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates were 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36%, respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expert a realistic probability of long-term survival with definitive radiation therapy. (author)

BLM and RMI1 Alleviate RPA Inhibition of TopoIIIa Decatenase Activity

DEFF Research Database (Denmark)

Yang, Jay; Bachrati, Csanad Z; Hickson, Ian D

2012-01-01

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIa complex. We investigated the effect of RPA on the ssDNA decatenase activity...... of topoisomerase IIIa. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIa. Complex formation between BLM, TopoIIIa, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species......-specific interactions between RPA and BLM-TopoIIIa-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIa and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIa activity, promoting...

Withholding stereotactic radiotherapy in elderly patients with stage I non-small cell lung cancer and co-existing COPD is not justified: Outcomes of a markov model analysis

International Nuclear Information System (INIS)

Louie, Alexander V.; Rodrigues, George; Hannouf, Malek; Lagerwaard, Frank; Palma, David; Zaric, Gregory S.; Haasbeek, Cornelis; Senan, Suresh

2011-01-01

Background and purpose: To model outcomes of SBRT versus best supportive care (BSC) in elderly COPD patients with stage I NSCLC. Material and methods: A Markov model was constructed to simulate the quality-adjusted and overall survival (OS) in patients ≥75 years undergoing either SBRT or BSC for a five-year timeframe. SBRT rates of local, regional and distant recurrences were obtained from 247 patients treated at the VUMC, Amsterdam. Recurrence rates were converted into transition probabilities and stratified into four groups according to T stage (1, 2) and COPD GOLD score (I-II, III-IV). Data for untreated patients were obtained from the California Cancer Registry. Tumor stage and GOLD score utilities were adapted from the literature. Results: Our model correlated closely with the source OS data for SBRT treated and untreated patients. After SBRT, our model predicted for 6.8-47.2% five-year OS and 14.9-27.4 quality adjusted life months (QALMs). The model predicted for 9.0% and 2.8% five-year OS, and 10.1 and 6.1 QALMs for untreated T1 and T2 patients, respectively. The benefit of SBRT was the least for T2, GOLD III-IV patients. Conclusion: Our model indicates that SBRT should be considered in elderly stage I NSCLC patients with COPD.

Outcomes of Stereotactic Ablative Radiotherapy in Patients With Potentially Operable Stage I Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Lagerwaard, Frank J., E-mail: fj.lagerwaard@vumc.nl [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Verstegen, Naomi E.; Haasbeek, Cornelis J.A.; Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Paul, Marinus A. [Department of Thoracic Surgery, VU University Medical Center, Amsterdam (Netherlands); Smit, Egbert F. [Department of Pulmonary Medicine, VU University Medical Center, Amsterdam (Netherlands); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)

2012-05-01

Background: Approximately two-thirds of patients with early-stage non-small-cell lung cancer (NSCLC) in The Netherlands currently undergo surgical resection. As an increasing number of fit patients have elected to undergo stereotactic ablative radiotherapy (SABR) in recent years, we studied outcomes after SABR in patients with potentially operable stage I NSCLC. Methods and Materials: In an institutional prospective database collected since 2003, 25% of lung SABR cases (n = 177 patients) were found to be potentially operable when the following patients were excluded: those with (1) synchronous lung tumors or other malignancy, (2) prior high-dose radiotherapy/pneumonectomy, (3) chronic obstructive pulmonary disease with a severity score of 3-4 according to the Global initiative for Obstructive Lung Disease classification. (4) a performance score of {>=}3, and (5) other comorbidity precluding surgery. Study patients included 101 males and 76 females, with a median age of 76 years old, 60% of whom were staged as T1 and 40% of whom were T2. Median Charlson comorbidity score was 2 (range, 0-5). A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5, or 8 fractions, depending on tumor size and location. Follow-up chest computed tomography scans were obtained at 3, 6, and 12 months and yearly thereafter. Results: Median follow-up was 31.5 months; and median overall survival (OS) was 61.5 months, with 1- and 3-year survival rates of 94.7% and 84.7%, respectively. OS rates at 3 years in patients with (n = 59) and without (n = 118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p = 0.39). Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model (Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325-332), would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each

Smoking habits of patients with newly diagnosed stage IIIA/IIIB non-small cell lung cancer

International Nuclear Information System (INIS)

Sloan, J.; Bonner, J.A.; McGinnis, W.L.; Stella, P.; Marks, R.

1997-01-01

Purpose: This study was performed to assess the smoking habits and changes in the cigarette smoking habits of patients prior to, at the time of and after the diagnosis of unresectable stage IIIA/IIIB non-small cell lung cancer. Methods: Patients with the diagnosis of unresectable stage IIIA/IIIB non-small cell lung cancer who had agreed to enter a phase III North Central Cancer Treatment Group Trial comparing twice daily thoracic radiation therapy (TRT) given with chemotherapy to once daily TRT given with chemotherapy were asked to fill out a questionnaire regarding their past and present cigarette smoking habits. This questionnaire included information regarding the number of years of smoking, number of packs of cigarettes smoked per day and the time frame of smoking history. Subsequently, patients were given questionnaires to assess changes in smoking history at the halfway point of treatment, and during follow-up visits. Results: Of the 140 patients who were entered on the above noted trial, 132 filled out baseline questionnaires and were the subject of this study. Of these 132 patients, 126 (95%) had either smoked cigarettes in the past or smoked at the time of study entry. The median pack years of smoking. (years of smoking x packs per day) was 43 with a range of 3-169 pack years. Of the 126 patients with a smoking history, 124 provided information regarding the status of their smoking at the time of entry on the study: 89 (72%) claimed to have quit smoking and, 35 (28%) reported that they continued to smoke an average of one pack per day. Of the 89 patients who had quit smoking, roughly one third had quit within the month before study entry and 45% had quit during the 8 month period prior to entry on the study. Of the 35 patients who continued to smoke at the time of entry on the study, 21 indicated that they stopped smoking during the period following randomization. Hence 10% of the original 140 patients entered on study continued to smoke an average of one

Resectable stage III lung cancer: CT, surgical, and pathologic correlation

International Nuclear Information System (INIS)

Scott, I.R.; Muller, N.L.; Miller, R.R.; Evans, K.G.; Nelems, B.

1987-01-01

Patients with stage IIIa lung cancer have improved survival following surgery. The authors reviewed the CT, surgical, and pathologic findings in 26 patients with completely resected stage IIIa lung cancer. These include examples of the different subsets of stage IIIa disease. CT correctly predicted chest-wall invasion in only two of ten patients, pericardial involvement in one of three, and tumor extension to within 2 cm of the carina in one of three patients. It detected mediastinal nodal disease in eight of 11 patients. CT is of limited value in assessing chest-wall or pericardial extension; however, such extension does not preclude complete resection. Ipsilateral nodal involvement also doses not preclude surgery

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

Science.gov (United States)

2018-02-12

Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC

Water-only fasting and an exclusively plant foods diet in the management of stage IIIa, low-grade follicular lymphoma.

Science.gov (United States)

Goldhamer, Alan C; Klaper, Michael; Foorohar, Afsoon; Myers, Toshia R

2015-12-10

Follicular lymphoma (FL), the second most common non-Hodgkin's lymphoma (NHL), is well characterised by a classic histological appearance and an indolent course. Current treatment protocols for FL range from close observation to immunotherapy, chemotherapy and/or radiotherapies. We report the case of a 42-year-old woman diagnosed by excisional biopsy with stage IIIa, grade 1 FL. In addition to close observation, the patient underwent a medically supervised, 21-day water-only fast after which enlarged lymph nodes were substantially reduced in size. The patient then consumed a diet of minimally processed plant foods free of added sugar, oil and salt (SOS), and has remained on the diet since leaving the residential facility. At 6 and 9-month follow-up visits, the patient's lymph nodes were non-palpable and she remained asymptomatic. This case establishes a basis for further studies evaluating water-only fasting and a plant foods, SOS-free diet as a treatment protocol for FL. 2015 BMJ Publishing Group Ltd.

Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

Energy Technology Data Exchange (ETDEWEB)

Varlotto, John M., E-mail: john.varlotto@umassmemorial.org [Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts (United States); Yao, Aaron N. [Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia (United States); DeCamp, Malcolm M. [Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois (United States); Northwestern University School of Medicine, Chicago, Illinois (United States); Ramakrishna, Satvik [Northwestern University School of Medicine, Chicago, Illinois (United States); Recht, Abe [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Flickinger, John [Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Andrei, Adin [Northwestern University, Chicago, Illinois (United States); Reed, Michael F. [Pennsylvania State University College of Medicine, Hershey, Pennsylvania (United States); Heart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania (United States); Toth, Jennifer W. [Pennsylvania State University College of Medicine, Hershey, Pennsylvania (United States); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania (United States); Fizgerald, Thomas J. [Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts (United States); Higgins, Kristin [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Zheng, Xiao [Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia (United States); Shelkey, Julie [Department of Anesthesiology, Columbia University, New York, New York (United States); and others

2015-03-15

Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

Science.gov (United States)

Fabera, Petr; Krijtova, Hana; Tomasek, Martin; Krysl, David; Zamecnik, Josef; Mohapl, Milan; Jiruska, Premysl; Marusic, Petr

2015-09-01

Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

Science.gov (United States)

2018-04-24

Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice.

Science.gov (United States)

Lau, Adeline A; Crawley, Allison C; Hopwood, John J; Hemsley, Kim M

2008-08-05

Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.

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

Science.gov (United States)

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.

Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

International Nuclear Information System (INIS)

Saitoh, Jun-Ichi; Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro; Sakai, Hiroshi; Kurimoto, Futoshi; Kato, Shingo; Shibuya, Kei

2012-01-01

Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m 2 , and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade ≥3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade ≥3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy With Bi-Weekly Docetaxel and Carboplatin for Stage III Unresectable, Non-Small-Cell Lung Cancer: Clinical Application of a Protocol Used in a Previous Phase II Study

Energy Technology Data Exchange (ETDEWEB)

Saitoh, Jun-Ichi, E-mail: junsaito@sannet.ne.jp [Division of Radiation Oncology, Saitama Cancer Center, Saitama (Japan); Saito, Yoshihiro; Kazumoto, Tomoko; Kudo, Shigehiro; Yoshida, Daisaku; Ichikawa, Akihiro [Division of Radiation Oncology, Saitama Cancer Center, Saitama (Japan); Sakai, Hiroshi; Kurimoto, Futoshi [Division of Respiratory Disease, Saitama Cancer Center, Saitama (Japan); Kato, Shingo [Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Shibuya, Kei [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma (Japan)

2012-04-01

Purpose: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). Methods and Materials: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m{sup 2}, and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. Results: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade {>=}3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade {>=}3 severity were observed in 2.6% and 1.7% of patients, respectively. Conclusions: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

A comparison of tumor motion characteristics between early stage and locally advanced stage lung cancers

International Nuclear Information System (INIS)

Yu, Z. Henry; Lin, Steven H.; Balter, Peter; Zhang Lifei; Dong Lei

2012-01-01

Purpose: With the increasing use of conformal radiation therapy methods for non-small cell lung cancer (NSCLC), it is necessary to accurately determine respiratory-induced tumor motion. The purpose of this study is to analyze and compare the motion characteristics of early and locally advanced stage NSCLC tumors in a large population and correlate tumor motion with position, volume, and diaphragm motion. Methods and materials: A total of 191 (94 early stage, 97 locally advanced) non-small cell lung tumors were analyzed for this study. Each patient received a four-dimensional CT scan prior to receiving radiation treatment. A soft-tissue-based rigid registration algorithm was used to track the tumor motion. Tumor volumes were determined based on the gross tumor volume delineated by physicians in the end of expiration phase. Tumor motion characteristics were correlated with their standardized tumor locations, lobe location, and clinical staging. Diaphragm motion was calculated by subtracting the diaphragm location between the expiration and the inspiration phases. Results: Median, max, and 95th percentile of tumor motion for early stage tumors were 5.9 mm, 31.0 mm, and 20.0 mm, which were 1.2 mm, 12 mm, and 7 mm more than those in locally advanced NSCLC, respectively. The range of motion at 95th percentile is more than 50% larger in early stage lung cancer group than in the locally advanced lung cancer group. Early stage tumors in the lower lobe showed the largest motion with a median motion of 9.2 mm, while upper/mid-lobe tumors exhibited a median motion of 3.3 mm. Tumor volumes were not correlated with motion. Conclusion: The range of tumor motion differs depending on tumor location and staging of NSCLC. Early stage tumors are more mobile than locally advanced stage NSCLC. These factors should be considered for general motion management strategies when 4D simulation is not performed on individual basis.

Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

Science.gov (United States)

2014-12-18

Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

Fasting blood glucose level and prognosis in non-small cell lung cancer (NSCLC) patients.

Science.gov (United States)

Luo, Juhua; Chen, Yea-Jyh; Chang, Li-Jung

2012-05-01

Diabetes has been consistently linked to many forms of cancers, such as liver, colorectal, pancreatic, and breast cancer, however, the role of diabetes in outcome among cancer patients remains unclear. In this study, we retrospectively reviewed electronic medical records of 342 inpatients newly diagnosed with NSCLC referred by a teaching hospital cancer center in southern Taiwan between 2005 and 2007 to examine the effects of fasting glucose levels at time of cancer diagnosis on overall survival in patients with non-small cell lung cancer (NSCLC). All patients were followed up until the end of 2010. The Kaplan-Meier method was used to compare survival curves for patients with and without diabetes. The Cox proportional hazards model was used to estimate hazard ratios for the association between diabetes, other prognostic factors and patient survival. We observed that significant prognostic factors for poor overall survival in patients with NSCLC included older age, smoking, poor performance status, advanced stage (stage IIIB or IV), and no cancer-directed surgery treatment. Particularly, we identified that diabetic state defined by fasting blood glucose level ≥126 mg/dl was another independent prognostic factor for these patients. Compared with those who had normal range of fasting glucose level (70-99 mg/dl), patients with high fasting glucose level (≥126 mg/dl) had 69% excess risk of all-cause mortality in patients with NSCLC. Diabetes as indicated by elevated fasting blood glucose was independently associated with a significantly higher risk of all-cause mortality in patients with NSCLC, indicating that diabetes or hyperglycemia effectively controlled may present an opportunity for improving prognosis in NSCLS patients with abnormal glucose level. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer

DEFF Research Database (Denmark)

Decaluwé, Herbert; Petersen, René Horsleben; Brunelli, Alex

2018-01-01

OBJECTIVES: Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed...

Interleukins as new prognostic genetic biomarkers in non-small cell lung cancer.

Science.gov (United States)

Pérez-Ramírez, Cristina; Cañadas-Garre, Marisa; Alnatsha, Ahmed; Molina, Miguel Ángel; Robles, Ana I; Villar, Eduardo; Delgado, Juan Ramón; Faus-Dáder, María José; Calleja-Hernández, Miguel Ángel

2017-09-01

Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients. A prospective cohorts study was performed, including 170 NSCLC patients (114 Stage IIIB-IV, 56 Stage I-IIIA). IL1B (C > T; rs1143634), IL1B (C > T; rs12621220), IL1B (C > G; rs1143623), IL1B (A > G; rs16944), IL1B (C > T; rs1143627), IL6 (C > G; rs1800795), IL12A (C > T; rs662959), IL13 (A > C; rs1881457) and IL16 (G > T; rs7170924) gene polymorphisms were analyzed by PCR Real-Time. Patients with IL16 rs7170924-GG genotype were in higher risk of death (p = 0.0139; HR = 1.82; CI 95%  = 1.13-2.94) Furthermore, carriers of the TT genotype for IL12A rs662959 presented higher risk of progression in the non-resected NSCLC patient subgroup (p = 0.0412; HR = 4.49; CI 95%  = 1.06-18.99). The rest of polymorphisms showed no effect of on outcomes. Our results suggest that IL16 rs7170924-GG and IL12A rs662959-TT genotypes predict higher risk of death and progression, respectively, in NSCLC patients. No influence of IL1B rs12621220, IL1B rs1143623, IL1B rs16944, IL1B rs1143627, IL6 rs1800795, IL13 rs1881457 on NSCLC clinical outcomes was found in our patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of a nomogram combining clinical staging with 18F-FDG PET/CT image features in non-small-cell lung cancer stage I-III

International Nuclear Information System (INIS)

Desseroit, Marie-Charlotte; Visvikis, Dimitris; Majdoub, Mohamed; Hatt, Mathieu; Tixier, Florent; Perdrisot, Remy; Cheze Le Rest, Catherine; Guillevin, Remy

2016-01-01

Our goal was to develop a nomogram by exploiting intratumour heterogeneity on CT and PET images from routine 18 F-FDG PET/CT acquisitions to identify patients with the poorest prognosis. This retrospective study included 116 patients with NSCLC stage I, II or III and with staging 18 F-FDG PET/CT imaging. Primary tumour volumes were delineated using the FLAB algorithm and 3D Slicer trademark on PET and CT images, respectively. PET and CT heterogeneities were quantified using texture analysis. The reproducibility of the CT features was assessed on a separate test-retest dataset. The stratification power of the PET/CT features was evaluated using the Kaplan-Meier method and the log-rank test. The best standard metric (functional volume) was combined with the least redundant and most prognostic PET/CT heterogeneity features to build the nomogram. PET entropy and CT zone percentage had the highest complementary values with clinical stage and functional volume. The nomogram improved stratification amongst patients with stage II and III disease, allowing identification of patients with the poorest prognosis (clinical stage III, large tumour volume, high PET heterogeneity and low CT heterogeneity). Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging 18 F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone. (orig.)

Incidence and survival from lung cancer in Greenland is comparable to survival in the Nordic countries

DEFF Research Database (Denmark)

Gelvan, Allan; Risum, Signe; Langer, Seppo W

2015-01-01

INTRODUCTION: Oncological treatment of lung cancer has been available in Greenland since 2004. We evaluated patient characteristics and survival rates for the first six years of local lung cancer treatment. METHODS: From September 2004 to August 2010, a total of 173 patients with lung cancer were...... referred to treatment at Queen Ingrid's Hospital. On 1 February 2014, treatment results, survival, and prognostic variables were analysed. RESULTS: The mean age at diagnosis was 63 years. Non-small cell lung cancer (NSCLC) was diagnosed in 145 patients (84%); 56% had squamous cell carcinoma, 34% had...... adenocarcinoma, 2% had large cell carcinoma and 8% had NSCLC not otherwise specified (NOS). In all, 28 (16%) had small cell lung cancer. A total of 142 patients (82%) received treatment; 20 underwent surgery (ten stage Ib, one stage IIa, five stage IIb, four stage IIIa); palliative chemotherapy was given to 122...

Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer.

Science.gov (United States)

Inoue, Masayoshi; Maeda, Hajime; Takeuchi, Yukiyasu; Fukuhara, Kenjiro; Shintani, Yasushi; Funakoshi, Yasunobu; Funaki, Soichiro; Nojiri, Takashi; Kusu, Takashi; Kusumoto, Hidenori; Kimura, Toru; Okumura, Meinoshin

2018-04-01

We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.

Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non–Small-Cell Lung Cancer: A Markov Model–Based Decision Analysis

International Nuclear Information System (INIS)

Louie, Alexander V.; Rodrigues, George; Hannouf, Malek; Zaric, Gregory S.; Palma, David A.; Cao, Jeffrey Q.; Yaremko, Brian P.; Malthaner, Richard; Mocanu, Joseph D.

2011-01-01

Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non–small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant! Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely with those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.

Radiological differential diagnosis between fibrosis and recurrence after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC).

Science.gov (United States)

Frakulli, Rezarta; Salvi, Fabrizio; Balestrini, Damiano; Palombarini, Marcella; Akshija, Ilir; Cammelli, Silvia; Morganti, Alessio Giuseppe; Zompatori, Maurizio; Frezza, Giovanni

2017-12-01

Parenchymal changes after stereotactic body radiation therapy (SBRT) make differential diagnosis between treatment outcomes and disease recurrence often difficult. The purpose of our study was to identify the radiographic features detectable at computed tomography (CT) scan [high-risk features (HRFs)] that allow enough specificity and sensitivity for early detection of recurrence. We retrospectively evaluated patients who underwent SBRT for inoperable early stage non-small cell lung cancer (NSCLC). The median delivered dose performed was 50 Gy in 5 fractions prescribed to 80% isodose. All patients underwent chest CT scan before SBRT and at 3, 6, 12, 18, 24 months after, and then annually. Each CT scan was evaluated and benign and HRFs were recorded. 18 F-fluorodeoxyglucose-CT was not used routinely. Forty-five patients were included (34 males, 11 females; median age: 77 years; stage IA: 77.8%, stage IB: 22.2%; median follow-up: 21.7 months). Two year and actuarial local control was 77%. HRFs were identified in 20 patients. The most significant predictor of relapse was an enlarging opacity at 12 months (P2 HRFs.

Radical hypo-fractionated radiotherapy with volumetric modulated arc therapy in lung cancer. A retrospective study of elderly patients with stage III disease

Energy Technology Data Exchange (ETDEWEB)

Franceschini, D. [Humanitas Cancer Center and Research Hospital, Radiotherapy and Radiosurgery Department, Milan (Italy); Istituto Clinico Humanitas Cancer Center, Rozzano (Milan) (Italy); De Rose, F.; Navarria, P.; Clerici, E.; Franzese, C.; Comito, T.; Tozzi, A.; Iftode, C.; D' Agostino, G. [Humanitas Cancer Center and Research Hospital, Radiotherapy and Radiosurgery Department, Milan (Italy); Cozzi, L.; Sorsetti, M. [Humanitas Cancer Center and Research Hospital, Radiotherapy and Radiosurgery Department, Milan (Italy); Humanitas University, Department of Biomedical Sciences, Milan (Italy)

2017-05-15

This study aimed to analyse the feasibility and acute toxicity of radical hypo-fractionated radiotherapy (RT) for elderly patients with non-small-cell lung cancer (NSCLC). We conducted a retrospective evaluation of treatment with volumetric modulated arc therapy (VMAT) of elderly patients affected by stage III inoperable NSCLC. The dose prescription was 56 Gy in 20 fractions, 55 Gy in 22 fractions, or 50 Gy in 20 fractions. Target volume included only the primary lesion and the infiltrated lymph nodes. The primary end point was acute and late toxicity, while secondary end points were progression-free survival (PFS), and overall survival (OS). In all, 41 patients were included in this analysis. The mean age of the patients was 78.6 years, and 22 patients had staged IIIA while 19 patients had stage IIIB disease. All but one patient had pathological nodal involvement; 15 patients received chemotherapy before RT. Acute grade 1-2 toxicity was recorded in 25 (61%) patients. Late toxicity was recorded in 13 (32%) patients. No cases of G3 or G4 toxicity were recorded. Complete response was obtained in two (5%) patients, 26 (63%) showed a partial response, and two (5%) experience disease progression. At a mean follow-up of 9.9 months (range, 1.1-25.4), 17 patients had died from disease progression, one died from other causes, and 23 were alive. Median OS was 13.7 ± 1.5 months (95% CI: 10.7-16.7), OS at 12 and 18 months was 51.3 ± 9.5% and 35.1 ± 10.1%, respectively. Median PFS was 13.7 ± 2.3 months (95% CI: 9.1-18.2), and PFS at 12 and 18 months was 50.1 ± 9.9% and 38.9 ± 10.4%, respectively. Radical hypo-fractionated VMAT is a promising treatment for locally advanced NSCLC in the elderly. The use of hypo-fractionated radiotherapy for lung cancer in older patients can be considered a valuable approach, particularly for patients with poor performance status or refusing other treatment approaches. (orig.) [German] Durchfuehrbarkeit und Nebenwirkungen der radikalen

Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

DEFF Research Database (Denmark)

Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg

2006-01-01

Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

Ultrasonographic findings of type IIIa biliary atresia

Energy Technology Data Exchange (ETDEWEB)

Kim, Seung Seob; Kim, Myung Joon; Lee, Mi Jung; Yoon, Choon Sik; Han, Seok Joo; Koh, Hong [Dept. of Radiology, Research Institute of Radiological Science, Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

2014-12-15

To describe the ultrasonographic (US) findings of type IIIa biliary atresia. We retrospectively reviewed a medical database of patients pathologically confirmed to have biliary atresia, Kasai type IIIa, between January 2002 and May 2013 (n=18). We evaluated US findings including the visible common bile duct (CBD), triangular cord thickness, gallbladder size and shape, and subcapsular flow on color Doppler US; laboratory data; and pathological hepatic fibrosis grades. We divided them into two groups-those with visible (group A) and invisible (group B) CBD on US-and compared all parameters between the two groups. CBD was visible on US in five cases (27.8%; group A) and invisible in 13 cases (72.2%; group B). US was performed at an earlier age in group A than in group B (median, 27 days vs. 60 days; P=0.027) with the maximal age of 51 days. A comparison of the US findings revealed that the triangular cord thickness was smaller (4.1 mm vs. 4.9 mm; P=0.004) and the gallbladder length was larger (20.0 mm vs. 11.7 mm; P=0.021) in group A. The gallbladder shape did not differ between the two groups, and the subcapsular flow was positive in all cases of both groups. There was no significant difference in the laboratory data between the two groups. Upon pathological analysis, group A showed low-grade and group B showed low- to high-grade hepatic fibrosis. When CBD is visible on US in patients diagnosed with type IIIa biliary atresia, other US features could have a false negative status. A subcapsular flow on the color Doppler US would be noted in the type IIIa biliary atresia patients.

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

Patterns of Care for Lung Cancer in Radiation Oncology Departments of Turkey

International Nuclear Information System (INIS)

Demiral, Ayse Nur; Alicikus, Zuemre Arican; Isil Ugur, Vahide; Karadogan, Ilker; Yoeney, Adnan; Andrieu, Meltem Nalca; Yalman, Deniz; Pak, Yuecel; Aksu, Gamze; Ozyigit, Goekhan; Ozkan, Luetfi; Kilciksiz, Sevil; Koca, Sedat; Caloglu, Murat; Yavuz, Ali Aydin; Basak Caglar, Hale; Beyzadeoglu, Murat; Igdem, Sefik

2008-01-01

Purpose: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. Methods and Materials: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. Results: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were '≥ IB' disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. Conclusion: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach

Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC

DEFF Research Database (Denmark)

Schytte, Tine; Hansen, Olfred; Stohlberg-Rohr, Thomine

2010-01-01

    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity   Backgro......    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity......   Background: Lung and oesophageal toxicity have been regarded as main toxicity in definitive radiotherapy (RT) of non-small cell lung cancer (NSCLC), whereas cardiac toxicity has not been offered much concern. This is probably due to the poor prognosis for patients with unresectable NSCLC. In this study we...

Predictive and prognostic value of preoperative serum tumor markers is EGFR mutation-specific in resectable non-small-cell lung cancer

Science.gov (United States)

Jiang, Richeng; Wang, Xinyue; Li, Kai

2016-01-01

Background The predictive and prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), squamous cell carcinoma antigen (SCCA) and neuron-specific enolase (NSE) has been investigated in non-small-cell lung cancer (NSCLC) patients. However, few studies have directly focused on the association between these markers and epidermal growth factor receptor (EGFR) mutation status or mutation subtypes. Patients and methods We retrospectively analyzed 1016 patients with stage I-IIIA NSCLC who underwent complete resection between 2008 and 2012. Correlations between serum tumor marker levels and EGFR mutations and survival parameters were analyzed and prognostic factors were identified. Results Cyfra21-1 levels (P = 0.032 for disease-free survival [DFS]; P CEA levels (P CEA (P = 0.005) and clinical stage were predictive factors of DFS, while elevated CEA (P = 0.005) and Cyfra21-1 (P = 0.027) were independent prognostic factors. Conclusion Cyfra21-1 and CEA exhibit different predictive and prognostic values between EGFR-mutated and wild-type adenocarcinomas, as well as between EGFR mutation subtypes. The prognostic impact of preoperative serum tumor markers should be evaluated together with EGFR mutation status. PMID:27072585

Ki-67 as a prognostic marker in early-stage non-small cell lung cancer in Asian patients: a meta-analysis of published studies involving 32 studies

International Nuclear Information System (INIS)

Wen, Song; Zhou, Wei; Li, Chun-ming; Hu, Juan; Hu, Xiao-ming; Chen, Ping; Shao, Guo-liang; Guo, Wu-hua

2015-01-01

Despite the large number of published papers analyzing the prognostic role of Ki-67 in NSCLC, it is still not considered an established factor for routine use in clinical practice. The present meta-analysis summarizes and analyses the associations between Ki-67 expression and clinical outcome in NSCLC patients. PubMed, Cochrane, and Embase databases were searched systematically using identical search strategies. The impacts of Ki-67 expression on survival in patients with NSCLC and NSCLC subtypes were evaluated. Furthermore, the association between Ki-67 expression and the clinicopathological features of NSCLC were evaluated. In total, 32 studies from 30 articles met the inclusion criteria, involving 5600 patients. Meta-analysis results suggested that high Ki-67 expression was negatively associated with overall survival (OS; HR = 1.59, 95 % CI 1.35-1.88, P < 0.001) and disease-free survival (DFS; HR = 2.21, 95 % CI 1.43-3.42, P < 0.001) in NSCLC patients. Analysis of the different subgroups of NSCLC suggested that the negative association between high Ki-67 expression and OS and DFS in Asian NSCLC patients was stronger than that in non-Asian NSCLC patients, particularly in early-stage (Stage I-II) adenocarcinoma (ADC) patients. Additionally, while high expression was more common in males, smokers, and those with poorer differentiation, there was no correlation between high Ki-67 expression and age or lymph node status. Importantly, significant correlations between high Ki-67 expression and clinicopathological features (males, higher tumor stage, poor differentiation) were seen only in Asian NSCLC patients. The present meta-analysis indicated that elevated Ki-67 expression was associated with a poorer outcome in NSCLC patients, particularly in early-stage Asian ADC patients. Studies with larger numbers of patients are needed to validate our findings. The online version of this article (doi:10.1186/s12885-015-1524-2) contains supplementary material, which is

Platelet glycoprotein IIb/IIIa polymorphism HPA-3 b/b is associated with increased risk of ischemic stroke in patients under 60 years of age.

Science.gov (United States)

Duan, Hao; Cai, Yan; Sun, Xiaojiang

2012-01-01

The role of genetic risk factors in ischemic stroke is unclear. Platelet glycoprotein IIb/IIIa (GpIIb-IIIa) has been implicated in the pathogenesis of ischemic stroke. We sought to evaluate the relationship between the GpIIb/IIIa complex gene polymorphism and ischemic stroke. We investigated the association of the GpIIb/IIIa complex gene polymorphism with stroke risk in 306 patients with acute ischemic stroke and 266 control subjects by determining the GpIIb and GpIIIa genotype from leukocyte DNA by polymerase chain reaction (PCR) followed by FokI and ScrFI digestion, respectively. Compared with controls, more patients presented with coronary heart disease, hypertension, smoking history, and diabetes. In addition, the patients had higher levels of cholesterol and glucose compared with the control subjects. All donors in the GpIIIa (n=572) group expressed the GpIIIa PlA1 (HPA-1 aa) phenotype. There were no significant differences between the HPA-3 genotype (GpIIb) patient distribution (aa=39.9%, ab=41.4%, bb=28.7%) and healthy control subjects (aa=36.1%, ab=35.0%, bb=28.9%) (P=0.580). Among study participants ischemic stroke >2-fold (P=0.008). The GpIIb Ile/Ser843 gene polymorphism is associated with ischemic stroke among young and middle-aged adults (ischemic stroke.

LATE-BREAKING ABSTRACT: Early relapse of non-small cell lung cancer (NSCLC) found after CNS-symptoms

DEFF Research Database (Denmark)

Hansen, Niels-Chr. G.; Laursen, Christian B.; Jeppesen, Stefan S.

2016-01-01

whether the introduction in 2010 of follow-up by CT of thorax and upper abdomen every three months has reduced the incidence of relapse suspected from CNS-symptoms.Results: All 827 NSCLC patients from Funen completing curative treatment from 2005 to 2013 were included. The total number of relapses found...... or III were found.Conclusion: CT-based follow-up has not reduced the incidence of relapse suspected from CNS-symptoms in stage II-IV, and therefore we suggest routine MR of the brain before curative treatment for this group of patients.Number, fractions(%), and [95%CI]Jan. 2005 - June 2010July 2010 - Dec...... after symptoms within 24 months decreased in the 3½ years after the introduction of CT-based follow-up, p < 0,001 (table), but the total fraction presenting with CNS-symptoms did not change, p = 0.296. Relapses after stage I cancer decreased (p = 0.025), while no differences or changes for stages II...

Gene Expression Profiling of Early Stage Non-Small Cell Lung Cancer

NARCIS (Netherlands)

J. Hou (Jun)

2010-01-01

textabstractNSCLC is a highly heterogeneous malignancy with a poor prognosis. Treatment for NSCLC is currently based on a combination of pathological staging and histological classification. Recently, gene expression-based NSCLC profiling is proven a superior approach to stratify cancer cases with

Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for stage I non-small cell lung cancer?

International Nuclear Information System (INIS)

Lagerwaard, Frank J.; Senan, Suresh; Meerbeeck, Jan P. van; Graveland, Wilfried J.

2002-01-01

Aims and background: The high local failure rates observed after radiotherapy in stage I non-small cell lung cancer (NSCLC) may be improved by the use of 3-dimensional conformal radiotherapy (3D CRT). Materials and methods: The case-records of 113 patients who were treated with curative 3D CRT between 1991 and 1999 were analysed. No elective nodal irradiation was performed, and doses of 60 Gy or more, in once-daily fractions of between 2 and 3 Gy, were prescribed. Results: The median actuarial survival of patients was 20 months, with 1-, 3- and 5-year survival of 71, 25 and 12%, respectively. Local disease progression was the cause of death in 30% of patients, and 22% patients died from distant metastases. Grade 2-3 acute radiation pneumonitis (SWOG) was observed in 6.2% of patients. The median actuarial local progression-free survival (LPFS) was 27 months, with 85 and 43% of patients free from local progression at 1 and 3 years, respectively. Endobronchial tumour extension significantly influenced LPFS, both on univariate (P=0.023) and multivariate analysis (P=0.023). The median actuarial cause-specific survival (CSS) was 19 months, and the respective 1- and 3-year rates were 72 and 30%. Multivariate analysis showed T2 classification (P=0.017) and the presence of endobronchial tumour extension (P=0.029) to be adverse prognostic factors for CSS. On multivariate analysis, T-stage significantly correlated with distant failure (P=0.005). Conclusions: Local failure rates remain substantial despite the use of 3D CRT for stage I NSCLC. Additional improvements in local control can come about with the use of radiation dose escalation and approaches to address the problem of tumour mobility

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer.

Science.gov (United States)

Decaluwé, Herbert; Petersen, René Horsleben; Brunelli, Alex; Pompili, Cecilia; Seguin-Givelet, Agathe; Gust, Lucile; Aigner, Clemens; Falcoz, Pierre-Emmanuel; Rinieri, Philippe; Augustin, Florian; Sokolow, Youri; Verhagen, Ad; Depypere, Lieven; Papagiannopoulos, Kostas; Gossot, Dominique; D'Journo, Xavier Benoit; Guerrera, Francesco; Baste, Jean-Marc; Schmid, Thomas; Stanzi, Alessia; Van Raemdonck, Dirk; Bardet, Jeremy; Thomas, Pascal-Alexandre; Massard, Gilbert; Fieuws, Steffen; Moons, Johnny; Dooms, Christophe; De Leyn, Paul; Hansen, Henrik Jessen

2017-09-27

Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed lower rate of N1 upstaging after VATS disappears after correction for central tumour location in a multivariable analysis. Consecutive patients operated for PET-CT based clinical Stage I NSCLC were selected from prospectively managed surgical databases in 11 European centres. Central tumour location was defined as contact with bronchovascular structures on computer tomography and/or visibility on standard bronchoscopy. Eight hundred and ninety-five patients underwent pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n = 196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients with central tumours. Less central tumours were operated on by VATS compared with the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed that only tumour location had a significant impact on N1 upstaging (OR 6.2, confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical technique (VATS versus open surgery) was no longer significant when accounting for tumour location. A quarter of patients with central clinical Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the only independent factor associated with N1 upstaging, undermining the evidence for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging after VATS compared with open surgery should be interpreted with caution due to possible selection bias, i.e. relatively more central tumours in the open group with a higher chance of N1 upstaging. © The Author 2017. Published by Oxford University Press on behalf of the European

FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

Institute of Scientific and Technical Information of China (English)

Matthijs; H; van; Gool; Tjeerd; S; Aukema; Koen; J; Hartemink; Renato; A; Valdés; Olmos; Houke; M; Klomp; Harm; van; Tinteren

2014-01-01

Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

PET/CT staging of T1-stage non-small cell lung cancer

International Nuclear Information System (INIS)

Salman, K. A.; Steinmann, C. H.; Von Schulthess, G. K.; Steinert, H. C.; Sukumar, V. P.

2009-01-01

Full text:Purpose: To evaluate the value of PET/CT in detecting occult metastases in patients with T 1 -stage non-small cell lung cancer (NSCLC). Method: Patients with proven NSCLC and T 1 -stage ( c m) were retrospectively analyzed. In all patients a whole-body 18 F-FDG PET/CT scan for initial staging was performed. The PET/CT findings were compared with all available clinical information, intra-operative findings and the histopathological results. Results: 95 patients (39 men, 56 women; age range, 19-85 years) were analyzed in our study. PET/CT in 68-95 patients correctly excluded mediastinal and distant metastases. In 17/95 patients (18%) mediastinal lymph-node metastases were proven (N 2 n=15; N 3 n=2). PET/CT correctly detected in 10/17 patients (58.8%) mediastinal nodal disease. The smallest mediastinal lymph-node metastasis detected by PET/CT had a size of 0.7 c m. In 7 patients PET/CT missed N 2 -stage. In three of these patients the SUVmax of the primary was c m. Only in one missed N 2 -stage metastasis was sized > 1.0 c m. The tumor histology (adenocarcinoma, squamous cell carcinoma) and location of the primary (central, periphery) did not influence the missed N 2 -stage by PET/CT. PET/CT diagnosed correctly N 3 -stage in 2 patients. 10/95 patients (10.5%) had distant metastases. PET/CT detected unknown M 1 -stage in 4/10 patients. In one patient a metastasis of the parietal pleura was missed by PET/CT. Conclusion: In our study, 28% patients with T 1 -stage NSCLC showed mediastinal or distant metastases. PET/CT was efficient in the detection of occult metastases. However, the sensitivity of PET/CT in mediastinal staging was only 64%.

Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

International Nuclear Information System (INIS)

Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

2008-01-01

Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices

A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study

Energy Technology Data Exchange (ETDEWEB)

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); Henderson, Randal [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); Pham, Dat; Cury, James D.; Bajwa, Abubakr [Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida (United States); Morris, Christopher G. [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); D' Agostino, Harry [Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida (United States); Flampouri, Stella; Huh, Soon; Li, Zuofeng [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); McCook, Barry [Department of Radiology, University of Florida College of Medicine, Jacksonville, Florida (United States); Nichols, Romaine C. [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States)

2016-05-01

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

Science.gov (United States)

Yildiz, Ferah; Zengin, Nurullah; Engin, Hüseyin; Güllü, Ibrahim; Barista, Ibrahim; Caglar, Meltem; Ozyar, Enis; Cengiz, Mustafa; Gürkaynak, Murat; Zorlu, Faruk; Caner, Biray; Atahan, I Lale; Tekuzman, Gülten

2004-11-01

To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

Mathematical modeling for Phase I cancer trials: A study of metronomic vinorelbine for advanced non-small cell lung cancer (NSCLC) and mesothelioma patients.

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Barlesi, Fabrice; Imbs, Diane-Charlotte; Tomasini, Pascale; Greillier, Laurent; Galloux, Melissa; Testot-Ferry, Albane; Garcia, Mélanie; Elharrar, Xavier; Pelletier, Annick; André, Nicolas; Mascaux, Céline; Lacarelle, Bruno; Cheikh, Raouf El; Serre, Raphaël; Ciccolini, Joseph; Barbolosi, Dominique

2017-07-18

Using mathematical modelling allows to select a treatment's regimen across infinite possibilities. Here, we report the phase I assessment of a new schedule for metronomic vinorelbine in treating refractory advanced NSCLC and mesothelioma patients. Overall, 13 patients were screened and 12 were treated (50% male, median age: 68yrs), including 9 NSCLC patients. All patients received at least one week (3 doses) of treatment. At data cut-off, the median length of treatment was 6.5 weeks (1-32+). All the patients presented with at least one adverse event (AE) and six patients with a severe AE (SAE). One partial response and 5 stable diseases were observed. The median OS was 6.4 months (95% CI, 4.8 to 12 months). The median and mean vinorelbine's AUC were 122 ng/ml*h and 159 ng/ml*h, respectively, with the higher plasmatic vinorelbine exposure associated with the best ORR (difference of AUC comparison between responders and non-responders, p-value 0.017). The mathematical modelling determined the administration of vinorelbine, 60 mg on Day 1, 30 mg on Day 2 and 60 mg on Day 4 weekly until progression, as the best schedule. Advanced NSCLC or mesothelioma patients progressing after standard treatment were eligible for the trial. NCT02555007. Responses with acceptable safety profile were observed in heavily pretreated NSCLC and mesothelioma patients using oral vinorelbine at this metronomic dosage based on a mathematic modeling. This study demonstrates the feasibility of this new type of approach, as mathematical modeling may help to rationally decide the better regimen to be clinically tested across infinite possibilities.

Arteriosclerosis and the promise of GPIIb/IIIa inhibitors in stroke Arteriosclerosis y nuevas perspectivas de los inhibidores del receptor GPIIb/IIIa en stroke

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GUSTAVO SAPOSNIK

2000-03-01

Full Text Available Ischemic mechanisms in patients with brain and heart attacks have been studied for more than 150 years. Antiplatelets agents did show benefit in secondary prevention. Aspirin is the most common antiaggregant in clinical use today. However, the benefit produced by the "best" antiplatelet regimen in stroke prevention is lower than 40%. The adherence of circulating platelets to the subendothelium is mediated by glycoprotein (GP residing on the cell's surface. GPIIb/IIIa is the most important platelet membrane receptor that mediates the process of platelet aggregation, and thrombus formation. Thus, new drugs that block the GPIIb/IIIa receptor have recently emerged. Clinical trials using these agents have shown effectiveness in acute coronary syndromes. However, the absence of studies in cerebrovascular disease and the potential hemorrhagic complications questioned their use in stroke prevention. We review the clinical trials using the new GPIIb/IIIa agents in myocardial ischemia, and consider the potential implications for cerebrovascular disease.Los mecanismos de isquemia en infarto de miocardio y enfermedad cerebrovascular (ECV han sido estudiados por mas de 150 años. Drogas antiplaquetarias mostraron un beneficio en la prevención secundaria. La aspirina es el mas común de los antiagregantes usados en la practica clínica. No obstante, el beneficio producido, aun con el "mejor" tratamiento antiagregante, en la prevención de ECV es inferior al 40%. La adhesión plaquetaria es un proceso mediado por glicoproteinas (GP de la membrana celular. GPIIb/IIIa es un receptor de membrana plaquetaria que interviene en el proceso de agregación plaquetaria y formación del trombo. Estudios clínicos con nuevos agentes que bloquean a este receptor mostraron ser efectivos en los síndromes coronarios agudos. No obstante, la falta de estudios en ECV y las potenciales complicaciones hemorrágicas, limitan su uso en la prevención de stroke. Revisamos los

Relationship Between Preoperative Sarcopenia Status and Immuno-nutritional Parameters in Patients with Early-stage Non-small Cell Lung Cancer.

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Shoji, Fumihiro; Matsubara, Taichi; Kozuma, Yuka; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

2017-12-01

Although the skeletal muscle in the region of the third lumbar vertebra (L3) is generally assessed in order to judge sarcopenia, not every patient with non-small cell lung cancer (NSCLC) undergoes computed tomography including the L3 region. We hypothesized that immuno-nutritional parameters could predict the existence of sarcopenia in patients with NSCLC. The aim of this study was to retrospectively investigate the correlation between preoperative sarcopenia and immuno-nutritional parameters in patients with early-stage NSCLC. We selected 147 of patients with pathological stage I NSCLC who underwent preoperative measurement of immuno-nutritional parameters and CT including the L3 region. Preoperative sarcopenia was significantly associated with female gender (p=0.0003) and poor prognosis (p=0.0322). In Kaplan-Meier analysis of overall survival (OS) by preoperative sarcopenia status, the sarcopenic group had significantly shorter OS than the non-sarcopenic group (5-year OS: 87.27% vs. 77.37%, p=0.0131, log-rank test). In multivariate analysis, the preoperative sarcopenia status (hazard ratio=5.138; 95% confidence interval=2.305-11.676; psarcopenia status was significantly related to controlling nutritional status score (p=0.0071) and Geriatric Nutritional Risk Index (GNRI) (psarcopenia status and GNRI (r=0.348, psarcopenia which was associated with poor outcome in patients with early-stage NSCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

NSCLC and HER2: between lights and shadows.

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Ricciardi, Giuseppina Rosaria Rita; Russo, Alessandro; Franchina, Tindara; Ferraro, Giuseppa; Zanghì, Mariangela; Picone, Antonio; Scimone, Antonino; Adamo, Vincenzo

2014-12-01

The therapeutic landscape of non-small-cell lung cancer (NSCLC) has dramatically changed in the last few years with the introduction of molecularly targeted agents, leading to unprecedented results in lung tumors with a paradigmatic shift from a "one size fits all" approach to an histologic and molecular-based approach. The discovery of epidermal growth factor receptor (EGFR) mutations in NSCLC in 2004 and the marked response to the EGFR tyrosine kinase inhibitor gefitinib, in a small subset of patients harboring these genetic abnormalities, stimulated the study of other kinase mutants involvement in NSCLC. The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors. The identification of these oncogenic drivers has dramatically changed the genetic landscape of NSCLC moving away from the old concept of a large indistinct histological entity to a combination of rare clinically relevant molecular subsets. Recently, a renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Genetic aberrations of this signaling pathway have been reported over time to be associated in NSCLC with different sensitivity to the EGFR tyrosine kinase inhibitors, to have a possible prognostic role and more recently HER2 amplification has been emerged as a possible mechanism in EGFR-mutated tumors of acquired resistance to the EGFR tyrosine kinase inhibitors. In addition, dysregulation of the HER2 pathway, in particular HER2 mutations (mostly, in-frame exon 20 insertions), may represent a possible novel therapeutic target in NSCLC, paving the way for a new generation of targeted agents in NSCLC. Since anecdotal case reports of clinical activity of anti-HER2 agents in NSCLC

FOCUS ON NIVOLUMAB IN NSCLC

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Diego Luigi Cortinovis

2016-12-01

Full Text Available Immunotherapy is changing the treatment of non-small cell lung cancer (NSCLC. The PD-1 inhibitor nivolumab has demonstrated meaningful results in terms of efficacy with a good safety profile. The novel approach of treating NSCLC using immunotherapy has still unsolved questions and challenging issues in regard to the optimal selection of the patient, its role in first line of treatment, the individualization of the correct methodology of radiologic assessment and efficacy analysis, the best management of immunomediated adverse events, and how to overcome the immunoresistance.

Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

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Songliang ZHANG

2015-06-01

Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array.

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Songliu Hu

Full Text Available To investigate the predictive role and association of nuclear survivin and the DNA double-strand breaks repair genes in non-small cell lung cancer (NSCLC: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, Ku heterodimeric regulatory complex 70-KD subunit (Ku70 and ataxia-telangiectasia mutated (ATM.The protein expression of nuclear survivin, DNA-PKcs, Ku70 and ATM were investigated using immunohistochemistry in tumors from 256 patients with surgically resected NSCLC. Furthermore, we analyzed the correlation between the expression of nuclear survivin, DNA-PKcs, Ku70 and ATM. Univariate and multivariate analyses were performed to determine the prognostic factors that inuenced the overall survival and disease-free survival of NSCLC.The expression of nuclear survivin, DNA-PKcs, Ku70 and ATM was significantly higher in tumor tissues than in normal tissues. By dichotomizing the specimens as expressing low or high levels of nuclear survivin, nuclear survivin correlated significantly with the pathologic stage (P = 0.009 and lymph node status (P = 0.004. The nuclear survivin levels were an independent prognostic factor for both the overall survival and the disease-free survival in univariate and multivariate analyses. Patients with low Ku70 and DNA-PKcs expression had a greater benefit from radiotherapy than patients with high expression of Ku70 (P = 0.012 and DNA-PKcs (P = 0.02. Nuclear survivin expression positively correlated with DNA-PKcs (P<0.001 and Ku70 expression (P<0.001.Nuclear survivin may be a prognostic factor for overall survival in patients with resected stage I-IIIA NSCLC. DNA-PKcs and Ku70 could predict the effect of radiotherapy in patients with NSCLC. Nuclear survivin may also stimulates DNA double-strand breaks repair by its interaction with DNA-PKcs and Ku70.

Perioperative rehabilitation in operation for lung cancer (PROLUCA) – rationale and design

DEFF Research Database (Denmark)

Sommer, Maja S; Trier, Karen; Vibe-Petersen, Jette

2014-01-01

postoperative rehabilitation (starting six weeks after surgery); (3) early postoperative rehabilitation alone; (4) today's standard care which is postoperative rehabilitation initiated six weeks after surgery. The preoperative rehabilitation program consists of an individually designed, 30-minute home......-based exercise program performed daily. The postoperative rehabilitation program consists of a supervised group exercise program comprising cardiovascular and resistance training two-hour weekly for 12 weeks combined with individual counseling. The primary study endpoint is VO2peak and secondary endpoints...... (Maximal Oxygen Uptake (VO2peak)), 380 patients with non-small cell lung cancer (NSCLC) stage I-IIIa referred for surgical resection will be randomly assigned to one of four groups: (1) preoperative and early postoperative rehabilitation (starting two weeks after surgery); (2) preoperative and late...

125I implantation combined with chemotherapy for treatment of local recurrent stage Ⅲ non-small cell lung cancer

International Nuclear Information System (INIS)

Luo Honglei; Yu Xiaojuan; Li Jin; Chen Xiaofei; He Jingdong

2013-01-01

Objective: To investigate the associated effect of 125 I implantation plus chemotherapy in local recurrent stage Ⅲ NSCLC patients. Methods: From January 2006 to January 2009, 34 patients documented with local recurrent stage Ⅲ NSCLC were divided into two groups by random number table. The treatment group was treated with 125 I permanent implantation combined with DP regimen (docetaxel 60 mg/m 2 + cisplatinum 75 mg/m 2 ), while the control group received only DP chemotherapy. According to the TPS, the treatment group received CT-guided percutaneous implantation of 125 I seeds with a particle activity of 2.22 ×10 7 -2.59 × 10 7 Bq. The prescribed dose was in the range of 90-110 Gy and the postoperatively matched peripheral dose (mPD) and D 90 were verified by TPS. The control group received a DP chemotherapy regime for 4 cycles after the procedure. This study was approved by the ethics committee,and all patients signed informed consents. The follow up time was up to disease progression. Kaplan-Meier survival analysis was used to describe the local lesion control (LLC) time and progression free survival (PFS). Log-rank test was used in the comparison of the survival rates between the two groups. Fisher's exact test was used to analyze the differences of CR rate and recent efficiency between two groups. Results: In the treatment group, postoperative mPD was 93.9-130.4 (M 116.7) Gy, and D 90 was 103.6-148.2 (M 130.6) Gy. The LLC time was 4.7 to 24.0 months with a median of 11.6 (95% CI: 8.7-14.6) months. In two cases, there was no recurrence during the follow-up time of 24 months.PFS was 4.7 to 24.0 months with a median of 10.5 (95% CI: 7.4-13.6) months. The recent effective rate of the treatment group was 64.7% (11/17).CR, PR, SD and PD were 41.2% (7/17), 23.5% (4/17), 23.5% (4/17) and 11.8% (2/17), respectively. In the control group, the LLC time was 4.5 to 11.4 months with a median of 7.5 (95 % CI: 6.7-8.3) months, and the median of PFS was 6.5 (4

Feasibility of four-arm robotic lobectomy as solo surgery in patients with clinical stage I lung cancer.

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Park, Seong Yong; Suh, Jee Won; Narm, Kyoung Sik; Lee, Chang Young; Lee, Jin Gu; Paik, Hyo Chae; Chung, Kyoung Young; Kim, Dae Joon

2017-06-01

This study was performed to investigate the feasibility of four-arm robotic lobectomy (FARL) as a solo surgical technique in patients with non-small cell lung cancer (NSCLC). Early outcome and long-term survival of FARL were compared with those of video-assisted thoracoscopic lobectomy (VATL). Prospective enrollment of patients with clinical stage I NSCLC undergoing FARL or VATL (20 patients in each group) was planned. Interim analysis for early postoperative outcome was performed after the initial 10 cases in each group. The study was terminated early because of safety issues in the FARL group after enrollment of 12 FARL and 17 VATL patients from 2011 to 2012. There were no differences in clinical characteristics between groups. Lobectomy time and total operation time were significantly longer in the FARL group (P=0.003). There were three life-threatening events in the FARL group (2 bleedings, 1 bronchus tear) that necessitated thoracotomy conversion in 1 patient. There were no differences in other operative outcomes including pain score, complications, or length of hospital stay. Pathologic stage and number of dissected lymph nodes (LNs) were also comparable. During a follow-up of 48.9±9.5 months, recurrence was identified in 2 (16.7%) patients in FARL group and 3 (23.5%) in VATL group. Five-year overall survival (100% vs . 87.5%, P=0.386) and disease-free survival (82.5% vs . 75.6%, P=0.589) were comparable. FARL as solo surgery could not be recommended because of safety issues. It required a longer operation time and had no benefits over VATL in terms of early postoperative outcome or long-term survival.

Electronic Monitoring Device of Patient-Reported Outcomes and Function in Improving Patient-Centered Care in Patients With Gastrointestinal Cancer Undergoing Surgery

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2018-03-05

Stage I Adult Liver Cancer; Stage I Colorectal Cancer; Stage IA Gastric Cancer; Stage IA Pancreatic Cancer; Stage IB Gastric Cancer; Stage IB Pancreatic Cancer; Stage II Adult Liver Cancer; Stage IIA Colorectal Cancer; Stage IIA Gastric Cancer; Stage IIA Pancreatic Cancer; Stage IIB Colorectal Cancer; Stage IIB Gastric Cancer; Stage IIB Pancreatic Cancer; Stage IIC Colorectal Cancer; Stage III Pancreatic Cancer; Stage IIIA Adult Liver Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Adult Liver Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Adult Liver Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer; Stage IVA Colorectal Cancer; Stage IVA Liver Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Liver Cancer; Stage IVB Pancreatic Cancer

Value of 18F-FDG PET in Clinical Staging of Non-Small Cell Lung Cancer

Institute of Scientific and Technical Information of China (English)

Suwen Liu; Jinming Yu; Ligang Xing

2005-01-01

OBJECTIVE To evaluate the feasibility of 18F-deoxyglucose positron emission tomography (18F-FDG PET) in the staging of non-small cell lung cancer(NSCLC).METHODS 105 patients with NSCLC had been examined by 18F-FDG PET before radiotherapy. The results of the 18F-FDG PET examination were compared with those of CT:RESULTS The staging was changed in 38 patients because of 18F-FDG PET findings, with PET resulting in upstaging in 31 patients and downstaging in seven patients. Because of distant metastasis detected by PET, 21 patients received palliative treatment. Six of the seven downstaged patients underwent radical surgery, among which the PET findings were concordant with the pathological findings in five patients. Distant metastasis detected by PET elevated the pre-PET stage: at stage 110.0% (2/20), stage Ⅱ 14.3% (3/21 ) and stage Ⅲ 25.0% (16/64), respectively.CONCLUSION 18F-FDG PET, by changing clinical staging in 36.2% (38/105)of NSCLC patients, has an impact on treatment strategy in NSCLC patients.

Early mortality after radical radiotherapy for non-small-cell lung cancer: comparison of PET-staged and conventionally staged cohorts treated at a large tertiary referral center

International Nuclear Information System (INIS)

Mac Manus, Michael P.; Wong, Kevin; Hicks, Rodney J.; Matthews, Jane P.; Wirth, Andrew; Ball, David L.

2002-01-01

Purpose: At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients. Methods and Materials: Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I-III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss. Results: Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss; 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p=0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival. Conclusion: Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging

Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

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Alex Langford-Smith

Full Text Available Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A, is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

Science.gov (United States)

Langford-Smith, Alex; Langford-Smith, Kia J; Jones, Simon A; Wynn, Robert F; Wraith, J E; Wilkinson, Fiona L; Bigger, Brian W

2011-01-01

Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A), is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

Lung cancer stage at diagnosis: Individual associations in the prospective VITamins and lifestyle (VITAL cohort

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Au David H

2011-06-01

Full Text Available Abstract Background Lung cancer is the leading cause of cancer death in the United States. Identifying factors associated with stage of diagnosis can improve our understanding of biologic and behavioral pathways of lung cancer development and detection. We used data from a prospective cohort study to evaluate associations of demographic, health history, and health behaviors with early versus late stage at diagnosis of non-small cell lung cancer (NSCLC. Methods We calculated odds ratios (ORs for the association of patient-level characteristics with advanced stage of diagnosis for NSCLC. The OR's were then adjusted for age, gender, race/ethnicity, smoking status, income, education, chronic obstructive pulmonary disease, and a comorbidity index. Results We identified 612 cases of NSCLC among 77,719 adults, aged 50 to 76 years from Washington State recruited in 2000-2002, with followup through December 2007. In univariate analyses, subjects who quit smoking Conclusions Smoking status, education, and a screening activity were associated with stage at diagnosis of NSCLC. These results may guide future studies of the underlying mechanisms that influence how NSCLC is detected and diagnosed.

GTV and CTV in radiation therapy: lung cancer

International Nuclear Information System (INIS)

Mornex, F.; Chapet, O.; Sentenac, I.; Loubeyre, P.; Giraud, P.; Van Houtte, P.; Bonnette, P.

2001-01-01

Radiotherapy plays a major role as a curative treatment of various stages non-small cell lung cancers (NSCLC): as an exclusive treatment in curative attempt for patients with unresectable stages I and II; as a preoperative treatment, which is often associated with chemotherapy, for patients with surgically stage IIIA NSCLC in clinical trials; in association with chemotherapy for unresectable stages IIIA and IIIB patients. Currently, three-dimensional conformal radiotherapy allows for some dose escalation, increasing radiation quality. However, the high inherent conformality of this radiotherapy technique requires a rigorous approach and an optimal quality of the preparation throughout the treatment procedure and specifically of the accurate definition of the safety margins (GTV, CTV...). Different questions remain specific to lung cancers: 1) Despite the absence of randomized trials, the irradiated lymph nodes volume should be only, for the majority of the authors, the visible macroscopically involved lymph nodal regions. However, local control remains low and solid arguments suggest the poor local control is due to an insufficient delivered dose. Therefore the goal of radiotherapy, in this particular location, is to improve local control by increasing the dose until the maximum normal tissue tolerance is achieved, which essentially depends on the dose to the organs at risk (OAR) and specifically for the lung, the esophagus and the spinal cord. For this reason, the irradiated volume should be as tiny as possible, leading to not including the macroscopically uninvolved lymph nodes regions in prophylactic view in the target volume; 2) The lung is one of the rare organs with extensive motion within the body, making lung tumors difficult to treat. This particular point is not specifically considered in the GTV and CTV definitions but it is important enough to be noted; 3) When radiation therapy starts after a good response to chemotherapy, the residual tumoral volume

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.

Science.gov (United States)

Haslett, Kate; Franks, Kevin; Hanna, Gerard G; Harden, Susan; Hatton, Matthew; Harrow, Stephen; McDonald, Fiona; Ashcroft, Linda; Falk, Sally; Groom, Nicki; Harris, Catherine; McCloskey, Paula; Whitehurst, Philip; Bayman, Neil; Faivre-Finn, Corinne

2016-04-15

The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of 'isotoxic' radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. NCT01836692; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

Directory of Open Access Journals (Sweden)

Schuette Wolfgang

2012-01-01

Full Text Available Abstract Background Second-line treatment of advanced non-small-cell lung cancer (NSCLC improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS and health-related quality of life (HR-QoL during second-line pemetrexed treatment in routine clinical practice. Methods Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI of ≥ 10% (absolute or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response". HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D. Factors potentially associated with KI benefit response were evaluated using logistic regression models. Results Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%, 471 (90.4% completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2% achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%. Conclusions In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years, physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Trial registration Registered on ClinicalTrials.gov (NCT00540241 on October 4, 2007

Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

Science.gov (United States)

Peters, Solange; Weder, Walter; Dafni, Urania; Kerr, Keith M; Bubendorf, Lukas; Meldgaard, Peter; O'Byrne, Kenneth J; Wrona, Anna; Vansteenkiste, Johan; Felip, Enriqueta; Marchetti, Antonio; Savic, Spasenija; Lu, Shun; Smit, Egbert; Dingemans, Anne-Marie; Blackhall, Fiona H; Baas, Paul; Camps, Carlos; Rosell, Rafael; Stahel, Rolf A

2014-11-01

The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.

The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

Directory of Open Access Journals (Sweden)

Chandra M Ohri

Full Text Available BACKGROUND: We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM expression of proteins associated with M1 and M2 macrophages in NSCLC. METHODS: Using immunohistochemistry, CD68(+ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14, or a non-cytotoxic M2 phenotype (CD163 and VEGF were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES (median 92.7 months and 20 patients with poor survival (PS (median 7.7 months. RESULTS: The NM expression of NM-HLA-DR (p<0.001, NM-iNOS (p = 0.02 and NM-MRP 8/14 (p = 0.02 was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001. There was more NM-CD163 expression (p = 0.04 but less NM-iNOS (p = 0.002 and MRP 8/14 (p = 0.01 expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001, 65.0% versus 14.6% (NM-iNOS p = 0.003, and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04, as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41 and 19.4% versus 59.0% (NM-VEGF p = 0.001. CONCLUSIONS: Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

Preoperative chemotherapy for operable breast cancer is associated with better compliance with adjuvant therapy in matched stage II and IIIA patients.

Science.gov (United States)

Komenaka, Ian K; Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E; Low, Boo Ghee; Salganick, Jason A; Nodora, Jesse; Hibbard, Michael L; Jha, Chandra

2011-01-01

Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy.

Endoscopic ultrasound guided biopsy performed routinely in lung cancer staging spares futile thoracotomies

DEFF Research Database (Denmark)

Larsen, Soeren S; Vilmann, Peter; Krasnik, Mark

2005-01-01

BACKGROUND: Up to 45% of operations with curative intent for non-small-cell lung cancer (NSCLC) can be regarded as futile, apparently because the stage of the disease is more advanced than expected preoperatively. During the past decade several studies have evaluated the usefulness of endoscopic...... ultrasound guided fine needle aspiration biopsy (EUS-FNA) in lung cancer staging with promising results. However, no randomised trials have been performed, in which a staging strategy with EUS-FNA performed in all patients is compared with a conventional workup. METHODS: Before surgery (i.e. mediastinoscopy...

Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer

International Nuclear Information System (INIS)

Chang, Joe Y.; Zhang Xiaodong; Wang Xiaochun; Kang Yixiu; Riley, Beverly C.; Bilton, Stephen C.; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.

2006-01-01

Purpose: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Methods and Materials: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n = 10) and 60-63 Gy, and 74 Gy in Stage III (n 15). Results: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p = 0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p = 0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Conclusions: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT

Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

International Nuclear Information System (INIS)

Palma, David; Lagerwaard, Frank; Rodrigues, George; Haasbeek, Cornelis; Senan, Suresh

2012-01-01

Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non–small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of ≤40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high (≥89%) after both treatments. Post-SBRT, actuarial OS was 79–95% at 1 year and 43–70% at 3 years. Postsurgical actuarial OS was 45–86% at 1 year and 31–66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

Energy Technology Data Exchange (ETDEWEB)

Palma, David, E-mail: david.palma@uwo.ca [VU University Medical Center, Amsterdam (Netherlands); Division of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Lagerwaard, Frank [VU University Medical Center, Amsterdam (Netherlands); Rodrigues, George [Division of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Haasbeek, Cornelis; Senan, Suresh [VU University Medical Center, Amsterdam (Netherlands)

2012-03-01

Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non-small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of {<=}40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high ({>=}89%) after both treatments. Post-SBRT, actuarial OS was 79-95% at 1 year and 43-70% at 3 years. Postsurgical actuarial OS was 45-86% at 1 year and 31-66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

Effectiveness of surgery and individualized high-dose hyperfractionated accelerated radiotherapy on survival in clinical stage I non-small cell lung cancer. A propensity score matched analysis

International Nuclear Information System (INIS)

Jimenez, Marcelo F.; Baardwijk, Angela van; Aerts, Hugo J.W.L.; De Ruysscher, Dirk; Novoa, Nuria M.; Varela, Gonzalo; Lambin, Philippe

2010-01-01

Background and purpose: Surgery is considered the treatment of choice for early-stage non-small cell lung cancer (NSCLC). Patients with poor pulmonary function or other comorbidities are treated with radiotherapy. The objective of this investigation is to compare the 3-year survival of two early-stage NSCLC populations treated in two different hospitals, either by surgical resection (lobectomy) or by individualized high-dose accelerated radiotherapy, after matching patients by propensity scoring analysis. Methods: A retrospective comparative study has been performed on two series of consecutive patients with cytohistological diagnosis of NSCLC, clinically staged IA by means of PET-scan (radiotherapy group) and pathologically staged IA (surgery group). Results: A total of 157 cases were initially selected for the analysis (110 operated and 47 treated by radiotherapy). Patients in the radiotherapy group were older, with higher comorbidity and lower FEV1% with 3-years probability of survival for operated patients higher than that found for patients treated by radiotherapy. After matching by propensity scoring (using age and FEV1%), differences disappear and 3-years probability of survival had no statistical differences. Conclusions: Although this is a non-randomized retrospective analysis, we have not found 3-years survival differences after matching cases between surgery and radiotherapy. Nevertheless, data presented here support the continuous investigation for non-surgical alternatives in this disease.

SU-F-T-112: Long-Term Follow-Up of NSCLC Patients Treated with Lung SBRT Using the Modified Conformal Arc (MDCA) Planning Technique

Energy Technology Data Exchange (ETDEWEB)

Ku, E; Desai, A [Frank H Netter, MD, School of Medicine, North Haven, CT (United States); Fang, D; Lawrence, C; Iannuzzi, C; Shi, C [St. Vincent’s Medical Center, Bridgeport, CT (United States)

2016-06-15

Purpose: To assess long-term toxicity and primary tumor changes for Stage I/II non-small cell lung carcinoma (NSCLC) patients after treatment with lung SBRT using the modified dynamic conformal arc (MDCA) planning technique. Methods: Clinical and radiograph data from electronic health records of 15 NSCLC patients treated with lung SBRT utilizing the MDCA technique between October 2011 and July 2014 were retrospectively reviewed. MDCA uses a coplanar beam arrangement, patient body center for the beam isocenter, and six partial rotation conformal arcs to target the tumor. Radiation Therapy Oncology Group (RTOG) guidelines for treatment parameters were followed. Most patients received 5 radiation fractions (Range: 3 to 7 fractions) with 48 hours between each fraction. Median total dose was 60 Gy (range: 45 to 70 Gy). Results: Median follow-up was 18 months (range: 6–51 months). Median age was 72.5 years (range: 48–90 years). Post-treatment findings included fatigue (n = 5) and chronic chest wall pain (n=1). Seven patients reported respiratory symptoms, which included: cough (n = 4), dyspnea (n = 5), and hemoptysis (n = 1). No patients deaths or grade ≥4 toxicity were recorded. Radiographic scarring was seen on computed tomography (CT) imaging in 6 patients. Local control rate was 93.3% (n = 14) and 1 patient had local recurrence. Conclusion: Our results were very similar to RTOG 0236 findings reported by Timmerman et al. – our local control rate was 93.3% compared to their 3-year primary tumor control rate of 97.6%. Toxicity rates were also similar – RTOG 0236 constitutional symptoms and pulmonary/upper respiratory symptoms rates were 36.4% and 60.0%, respectively, while ours were 33.3% and 46.7%, respectively. We were limited by a small sample size and relatively short follow-up but our findings support the use of the MDCA technique for lung SBRT treatment of Stage I/II NSCLC.

Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study

International Nuclear Information System (INIS)

Verboom, Paul; Grijseels, E.W.M; Uyl-de Groot, Carin A.; Tinteren, Harm van; Diepenhorst, Fred W.; Hoekstra, Otto S.; Smit, Egbert F.; Postmus, Pieter E.; Bergh, Jan H.A.M. van den; Velthoven, Piet C.M. van; Schreurs, Ad J.M.; Stallaert, Roland A.L.M.; Comans, Emile F.I.; Teule, Gerrit J.J.; Mourik, Johan C. van; Boers, Maarten

2003-01-01

Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between and euro;736 and and euro;1,588 depending on the (hospital) setting and the procurement of 18 FDG commercially or from on-site production. In the CWU group, 41% of the patients underwent a futile thoracotomy, whereas in the PET group 21% of the thoracotomies were considered futile (P=0.003). The average costs per patient in the CWU group were and euro;9,573 and in the PET group, and euro;8,284. The major cost driver was the number of hospital days related to recovery from surgery. Sensitivity analysis on the cost and accuracy of PET showed that the results were robust, i.e. in favour of the PET group. The addition of PET to CWU prevented futile surgery in one out of five patients with suspected NSCLC. Despite the additional PET costs, the total costs were lower in the PET group, mainly due to a reduction in the number of futile operations. The additional use of PET in the staging of patients with NSCLC is feasible, safe and cost saving from a clinical and from an economic perspective. (orig.)

A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III Non-small-cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Ishikura, Satoshi; Ohe, Yuichiro; Nihei, Keiji; Kubota, Kaoru; Kakinuma, Ryutaro; Ohmatsu, Hironobu; Goto, Koichi; Niho, Seiji; Nishiwaki, Yutaka; Ogino, Takashi

2005-01-01

Purpose: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. Methods and materials: Treatment consisted of 2 cycles of cisplatin 80 mg/m 2 on Day 1 and vinorelbine 25 mg/m 2 on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. Results: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade ≥3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). Conclusion: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed

Type IIIa cracking at 2CrMo welds in 1/2CrMoV pipework

Energy Technology Data Exchange (ETDEWEB)

Brett, S J; Smith, P A [National Power plc, Swindon (United Kingdom)

1999-12-31

The most common form of in-service defect found today on the welds of National Power`s 1/2CrMoV pipework systems is Type IV cracking which occurs in intercritically transformed material at the edge of the heat affected zone. However an alternate form of cracking, termed IIIa, which occurs close to the weld fusion line in fully grain refined heat affected zones, has also been observed. The incidence of Type IIIa cracking has increased in recent years and these defects now constitute a significant part of the total recorded crack population. This presentation describes Type IIIa cracking and compares and contrasts it with the better documented Type IV cracking. Particular reference is made to the role of carbon diffusion at the weld fusion line in promoting Type IIIa damage in preference to Type IV. (orig.) 5 refs.

Type IIIa cracking at 2CrMo welds in 1/2CrMoV pipework

Energy Technology Data Exchange (ETDEWEB)

Brett, S.J.; Smith, P.A. [National Power plc, Swindon (United Kingdom)

1998-12-31

The most common form of in-service defect found today on the welds of National Power`s 1/2CrMoV pipework systems is Type IV cracking which occurs in intercritically transformed material at the edge of the heat affected zone. However an alternate form of cracking, termed IIIa, which occurs close to the weld fusion line in fully grain refined heat affected zones, has also been observed. The incidence of Type IIIa cracking has increased in recent years and these defects now constitute a significant part of the total recorded crack population. This presentation describes Type IIIa cracking and compares and contrasts it with the better documented Type IV cracking. Particular reference is made to the role of carbon diffusion at the weld fusion line in promoting Type IIIa damage in preference to Type IV. (orig.) 5 refs.

Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

Science.gov (United States)

2018-04-06

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

Science.gov (United States)

2017-06-05

Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum.

Science.gov (United States)

Prat, Jaime

2015-10-01

Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture ("surgical spill") is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB). © 2015 American Cancer Society.

Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC.

Directory of Open Access Journals (Sweden)

Anna Durrans

Full Text Available Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor "activated/reprogrammed" stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN, chemokine (C-C motif ligand 7 (CCL7 and thrombospondin 1 (TSP1 were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.

Treatment of stage III non-small cell lung cancer and limited-disease small-cell lung cancer

NARCIS (Netherlands)

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

Classification and Risk-factor Analysis of Postoperative Cardio-pulmonary 
Complications after Lobectomy in Patients with Stage I Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Yutian LAI

2016-05-01

Full Text Available Background and objective There are incresing lung cancer patients detected and diagnosed at the intermediate stage when the pre-malignant or early lesions are amenable to resection and cure, owing to the progress of medical technology, the renewal of detection methods, the popularity of medical screening and the improvement of social health consciousness. The aim of this study is to investigate the risk factors of the occurrence of postoperative cardio-pulmonary complications in stage I non-small cell lung cancer (NSCLC patients, based on routine laboratory tests, basic characteristics, and intraoperative variables in hospital. Methods The 421 patients after lobectomy in patients with stage I NSCLC at the West China Hospital of Sichuan University from January 2012 to December 2013 were included into the study and stratified into complication group and non-complication group, according to whether to occur postoperative cardio-pulmonary complications after lobectomy in 30 days. Results Of them, 64 (15.2% patients were finally identified and selected into the complication group, compared with 357 (84.8% in non-complication group: pneumonia (8.8%, 37/421 was the primary complication, and other main complications included atelectasis (5.9%, 25/421, pleural effusion (≥middle (5.0%, 21/421, persistent air leak (3.6%, 15/421; The operation time (P=0.007, amount of blood loss (P=0.034, preoperative chronic obstructive pulmonary disease (COPD (P=0.027, white blood cell (WBC count (P<0.001, neutrophil-lymphocyte ratio (NLR (P<0.001 were significantly different between the two groups. According to the binary logistics regression analysis, preoperative COPD (OR=0.031, 95%CI: 0.012-0.078, P<0.001 and WBC count (OR=1.451, 95%CI: 1.212-1.736, P<0.001 were independent risk factors for postoperative cardio-pulmonary complications. Conclusion Among an array of clinical variables in hospital, operation time, preoperative white blood cell count, preoperative COPD

Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC

Directory of Open Access Journals (Sweden)

Xue R

2014-10-01

Full Text Available Ruilin Xue,1 Cuili Yang,1 Fang Zhao,2 Dejia Li1 1Global Health Institute, School of Public Health, 2Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC. Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001. CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001, which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years

Optimization of radiotherapy planning for Non-Small Cell Lung Cancer (NSCLC) by {sup 18}FDG-PET; Optimierung der Bestrahlungsplanung beim nicht-kleinzelligen bronchialkarzinom (NSCLC) mit Hilfe von {sup 18}FDG-PET

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Schmidt, S.; Nestle, U.; Kirsch, C.M. [Abt. fuer Nuklearmedizin, Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Walter, K. [Abt. fuer Strahlentherapie, Marienkrankenhaus Amberg (Germany); Licht, N.; Schnabel, K. [Abt. fuer Strahlentherapie, Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Ukena, D. [Innere Medizin V, Universitaetskliniken des Saarlandes, Homburg/Saar (Germany)

2002-10-01

Aim: In recent years, FDG-PET examinations have become more important for problems in oncology, especially in staging of bronchogenic carcinoma. In the retrospective study presented here, the influence of PET on the planning of radiotherapy for patients with non-small-cell lung cancer (NSCLC) was investigated. Methods: The study involved 39 patients with NSCLC who had been examined by PET for staging. They received radiotherapy on the basis of the anterior/posterior portals including the primary tumour and the mediastinum planned according to CT- and bronchoscopic findings. The results of the PET examination were not considered in initial radiotherapy planning. The portals were retrospectively redefined on the basis of FDG uptake considering the size and localization of the primary tumour; and FDG activities outside the mediastinal part of the portals. Results: In 15 out of 39 patients, the CT/PET-planned portals differed from the CT-planned ones. In most cases (n = 12) the CT/PET field was smaller than the CT field. The median geometric field size of the portals was 179 cm{sup 2}, after redefinition using PET 166 cm{sup 2}. In 20 patients with disturbed ventilation caused by the tumour (atelectosis, dystelectosis), a correction of the portal was suggested significantly more frequently than in the other patients (p = 0.03). Conclusions: Our results demonstrate the synergism of topographical (CT) and metabolic (FDG-PET) information, which could be helpful in planning radiotherapy of bronchial carcinoma, especially for patients with disturbed ventilation. (orig.) [German] Ziel: Die FDG-PET-Untersuchung hat in den vergangenen Jahren bei onkologischen Fragestellungen insbesondere beim Staging des Bronchialkarzinoms wachsende Bedeutung erlangt. In der vorliegenden retrospektiven Untersuchung wurde der Einfluss der PET auf die Strahlentherapieplanung bei Patienten mit non-small-cell lung cancer (NSCLC) untersucht. Methoden: Die Untersuchung umfasste 39 Patienten mit

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

International Nuclear Information System (INIS)

Sher, David J.; Fidler, Mary Jo; Seder, Christopher W.; Liptay, Michael J.; Koshy, Matthew

2015-01-01

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

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Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Seder, Christopher W.; Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Koshy, Matthew [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

2015-06-01

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

Warship Radar Signatures (Ship Survivability Part III-A)

NARCIS (Netherlands)

Galle, L.F.; Heemskerk, H.J.M.; Ewijk, L.J. van

2000-01-01

Radar Cross Section (RCS) management is of paramount importance for a warships's survivability. In this first part of the paper (Part III-A), the operational benefits of low RCS will be explained. Basic RCS theory, measurement and simulation techniques will be addressed. The RCS of representative

Impact of low skeletal muscle mass on non-lung cancer mortality after stereotactic body radiotherapy for patients with stage I non-small cell lung cancer.

Science.gov (United States)

Matsuo, Yukinori; Mitsuyoshi, Takamasa; Shintani, Takashi; Iizuka, Yusuke; Mizowaki, Takashi

2018-05-17

The purpose of the present study was to retrospectively evaluate impact of pre-treatment skeletal muscle mass (SMM) on overall survival and non-lung cancer mortality after stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). One-hundred and eighty-six patients whose abdominal CT before the treatment was available were enrolled into this study. The patients were divided into two groups of SMM according to gender-specific thresholds for unilateral psoas area. Operability was judged by the treating physician or thoracic surgeon after discussion in a multi-disciplinary tumor board. Patients with low SMM tended to be elderly and underweight in body mass index compared with the high SMM. Overall survival in patients with the low SMM tended to be worse than that in the high SMM (41.1% and 55.9% at 5 years, P = 0.115). Cumulative incidence of non-lung cancer death was significantly worse in the low SMM (31.3% at 5 years compared with 9.7% in the high SMM, P = 0.006). Multivariate analysis identified SMM and operability as significant factors for non-lung cancer mortality. Impact of SMM on lung cancer death was not significant. No difference in rate of severe treatment-related toxicity was observed between the SMM groups. Low SMM is a significant risk factor for non-lung cancer death, which might lead to worse overall survival, after SBRT for stage I NSCLC. However, the low SMM does not increase lung cancer death or severe treatment-related toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

GrB TWEAK: A Potential Novel Biologic for NSCLC Therapy

Science.gov (United States)

2017-07-01

granzyme B, lung cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT...cost extension period we were able to test whether our therapeutic construct GrB-Fc-IT4 could inhibit NSCLC tumor growth in vivo using the NSCLC patient ...derived Fn14-positive cell line M2010-1005. The M2010-1005 line was established from a NSCLC patient with a tumor harboring the EGFRdel747-752

MTU engines for locomotives satisfying the EU stage IIIB emission standard; MTU-Lokomotivantriebe fuer die Emissionsstufe EU IIIB

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Wintruff, Ingo; Reich, Christian; Geiselmann, Wolfgang; Gottschalch, Harald; Jansen, Eddy [MTU Friedrichshafen GmbH, Friedrichshafen (Germany)

2011-07-01

The emission limits for diesel locomotives inside the European Union are included within the scope of Directive 97/68/EC, which is sometimes referred to as the ''non-road directive''. The pollutants limited by it are NO{sub x}, particulates, CO and HCs. The aim, through the directive, is to reduce railway emissions by a factor of ten by the year 2020. The EU stage IIIB standard is due to take effect on 1 January 2012. This envisages a further drastic reduction in limit values compared with EU stage IIIA, which is applicable today. For diesel locomotives, EU stage IIIA only came into force as recently as 2009. The manufacturers of engines and locomotives are thus having to face up to the huge challenge of getting the technologies needed for EU stage IIIB ready for the production line within a period of only three years. MTU has succeeded in developing engines for diesel locomotives that comply with the EU stage IIIB emission standard, which appreciably lower emissions compared with engines satisfying EU stage IIIA, thanks to the incorporation of the most modern technologies available, and has even gone as far as preparing them for the EU stage IV, the next one to come into force. (orig.)

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC

Directory of Open Access Journals (Sweden)

Nikaedo Sueli M

2004-09-01

Full Text Available Abstract Background Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC can be achieved with cisplatin-based chemotherapy (CT, its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. Methods In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years, younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2, and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2. We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Results Analysis was by intention to treat. Main toxicities (grade 3–4 was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP and overall survival (OS were 27.0 (95% CI: 10.1 to 43.7 weeks and 30.1 (95% CI: 24.4 to 35.8 weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%, with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Conclusion Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Pereira, José Rodrigues; Martins, Sandro J; Nikaedo, Sueli M; Ikari, Flora K

2004-01-01

Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m 2 , on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m 2 or 90 mg/m 2 ), and older patients were allocated to lower cisplatin doses (60 mg/m 2 or 70 mg/m 2 ). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

Science.gov (United States)

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Interaction of higher plant ribosomal 5S RNAs with ''Xenopus laevis'' transcriptional factor IIIA

International Nuclear Information System (INIS)

Barciszewska, M.Z.

1994-01-01

In this paper transcriptional factor IIIA (TFIIIA) has been used as a probe for identity of three-dimensional-structure of eukaryotic 5S rRNAs. I was interested in finding a common motif in plant and ''Xenopus'' 5S rRNAs for TFIIIA recognition. I found that the two eukaryotic 5S rRNAs (from wheat germ and lupin seeds) are recognized by ''X. laevis'' TFIIIA and the data clearly suggest that these 5S rRNAs have very similar if not identical three-dimensional structures. Also effects of various conditions on stability of these complexes have been studied. (author). 30 refs, 6 figs, 1 tab

Favorable prognosis of operable non-small cell lung cancer (NSCLC) patients harboring an increased expression of tumor endothelial markers (TEMs).

Science.gov (United States)

Pircher, Andreas; Fiegl, Michael; Untergasser, Gerold; Heidegger, Isabel; Medinger, Michael; Kern, Johann; Hilbe, Wolfgang

2013-08-01

Genome analyses of endothelial cells identified genes specifically expressed by tumor endothelial cells, called tumor endothelial markers (TEMs). Currently there are no data available concerning the role of TEMs in non-small cell lung cancer (NSCLC). Therefore, the aim of this study was to investigate the role of TEMs in NSCLC in vitro and in vivo. First we evaluated the expression of various TEMs (Robo4, Clec14 and ECSCR) by qRT-PCR and Western blot analyses in three NSCLC cell lines (A549, Calu1, Colo699) and compared them to human umbilical vein endothelial cells (HUVECs), endothelial colony forming cells (ECFCs) and human bronchial epithelial cells (HBEpCs). Next the expression of TEMs was measured in resected tumor tissue of NSCLC patients (n = 63) by qRT-PCR and compared to adjacent non-cancerous lung tissue (n = 52). Further, immunohistochemical analysis of Robo4 expression in tumor tissue (n = 33) and adjacent non-cancerous tissue (n = 27) was performed. We found that NSCLC cell lines and HBEpC did not express TEMs on the mRNA level compared to HUVECs (p = 0.001). In the contrary, a significant up-regulation of Robo4 and Clec14 was found in tumor samples (Robo4 p = 0.03, Clec14 p = 0.002). Both facts clearly indicate that these proteins are allocated to the tumor stromal department. Correlation with clinical data showed that increased TEM expression correlated with prolonged overall survival of operated NSCLC patients (Robo4 high 120.5 vs. Robo4 low 47.6 months, Clec14 high 108.1 vs. Clec14 low 54.5 months and ECSCR high 120.5 vs. ECSCR low 42.2 months). In summary, we found that TEMs are overexpressed in NSCLC stromal tissue and that an increased TEM expression correlated with an increased overall survival in early stage NSCLC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Emerging Therapies for Stage III Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy and Immunotherapy

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Sameera S. Kumar

2017-09-01

Full Text Available The current standard of care for locally advanced non-small cell lung cancer (NSCLC includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT has shown a high degree of safety and local control for stage I lung cancers and other localized malignancies. More recently, phase I/II studies using SBRT for dose escalation after conventional chemoradiation in locally advanced NSCLC have been promising with good apparent safety. Immunotherapy also offers opportunities to address distant disease and preclinical data suggest immunotherapy in tandem with SBRT may be a rational way to induce an “abscopal effect” although there are little clinical data as yet. By building on the proven concept of conventional chemoradiation for patients with locally advanced NSCLC with a subsequent radiation dose intensification to residual disease with SBRT concurrent with immunotherapy, we hope address the issues of metastatic and local failures. This “quadmodality” approach is still in its infancy but appears to be a safe and rational approach to the improving the outcome of NSCLC therapy.

Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

DEFF Research Database (Denmark)

Fløtten, Ø; Grønberg, B H; Bremnes, R

2012-01-01

BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin...... was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P

Screening for early lung cancer with low-dose spiral computed tomography: results of annual follow-up examinations in asymptomatic smokers

International Nuclear Information System (INIS)

Diederich, Stefan; Thomas, Michael; Semik, Michael; Lenzen, Horst; Roos, Nikolaus; Weber, Anushe; Heindel, Walter; Wormanns, Dag

2004-01-01

The aim of this study was analysis of incidence results in a prospective one-arm feasibility study of lung cancer screening with low-radiation-dose spiral computed tomography in heavy smokers. Eight hundred seventeen smokers (≥40 years, ≥20 pack years of smoking history) underwent baseline low-dose CT. Biopsy was recommended in nodules >10 mm with CT morphology suggesting malignancy. In all other lesions follow-up with low-dose CT was recommended. Annual repeat CT was offered to all study participants. Six hundred sixty-eight (81.8%) of the 817 subjects underwent annual repeat CT with a total of 1735 follow-up years. Follow-up of non-calcified nodules present at baseline CT demonstrated growth in 11 of 792 subjects. Biopsy was performed in 8 of 11 growing nodules 7 of which represented lung cancer. Of 174 new nodules, 3 represented lung cancer. The 10 screen-detected lung cancers were all non-small cell cancer (6 stage IA, 1 stage IB, 1 stage IIIA, 2 stage IV). Five symptom-diagnosed cancers (2 small cell lung cancer: 1 limited disease, 1 extensive disease, 3 central/endobronchial non-small cell lung cancer, 2 stage IIIA, 1 stage IIIB) were diagnosed because of symptoms in the 12-month interval between two annual CT scans. Incidence of lung cancer was lower than prevalence, screen-detected cancers were smaller, and stage I was found in 70% (7 of 10) of screen-detected tumors. Only 27% (4 of 15) of invasive procedures was performed for benign lesions; however, 33% (5 of 15) of all cancers diagnosed in the population were symptom-diagnosed cancers (3 central NSCLC, all stage III, 2 SCLC) demonstrating the limitations of CT screening. (orig.)

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis.

Science.gov (United States)

Janssen-Heijnen, M L G; van Erning, F N; De Ruysscher, D K; Coebergh, J W W; Groen, H J M

2015-05-01

Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during long-term follow-up. All 72 021 patients aged 45-89 years diagnosed with stage I-III NSCLC between 1989 and 2008 in the Netherlands and who died up till 2011 were derived from the Netherlands Cancer Registry and linked with the database of Statistics Netherlands for underlying causes of death. Mortality ratios and proportional distribution of causes of death were calculated during 5 time periods after diagnosis of NSCLC (up to 15 years). Median follow-up was 9.6 years (range: 0-23 years). Lung cancer was the predominant cause of death in the first 6 years after diagnosis (being 80%-85% and ∼90% up to 3 years for localized and locally advanced disease, respectively, and ∼60%-75% and ∼75%-85% during years 4-6 for both stage groups, respectively). Thereafter, lung cancer as cause of death proportionally decreased with time since diagnosis, but remained over 30%. Hence, cardiovascular diseases and chronic obstructive pulmonary diseases (COPD) became more important causes of death, especially for patients aged >60 years at diagnosis (up to 34% for cardiovascular diseases and up to 19% for COPD). With time, the relative contribution of cardiovascular and COPD causes of death increased, although the absolute contribution of lung cancer remained high in non-metastatic NSCLC. Therefore, managing morbidity of these diseases remains relevant. © The Author 2015. 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.

DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

International Nuclear Information System (INIS)

Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix; Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd; Porsch, Peter; Studnicka, Michael

2015-01-01

While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [de

Distribution of Heparan Sulfate Oligosaccharides in Murine Mucopolysaccharidosis Type IIIA

Directory of Open Access Journals (Sweden)

Kerryn Mason

2014-12-01

Full Text Available Heparan sulfate (HS catabolism begins with endo-degradation of the polysaccharide to smaller HS oligosaccharides, followed by the sequential action of exo-enzymes to reduce these oligosaccharides to monosaccharides and inorganic sulfate. In mucopolysaccharidosis type IIIA (MPS IIIA the exo-enzyme, N-sulfoglucosamine sulfohydrolase, is deficient resulting in an inability to hydrolyze non-reducing end glucosamine N-sulfate esters. Consequently, partially degraded HS oligosaccharides with non-reducing end glucosamine sulfate esters accumulate. We investigated the distribution of these HS oligosaccharides in tissues of a mouse model of MPS IIIA using high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Oligosaccharide levels were compared to total uronic acid (UA, which was used as a measure of total glycosaminoglycan. Ten oligosaccharides, ranging in size from di- to hexasaccharides, were present in all the tissues examined including brain, spleen, lung, heart, liver, kidney and urine. However, the relative levels varied up to 10-fold, suggesting different levels of HS turnover and storage. The relationship between the di- and tetrasaccharides and total UA was tissue specific with spleen and kidney showing a different disaccharide:total UA ratio than the other tissues. The hexasaccharides showed a stronger correlation with total UA in all tissue types suggesting that hexasaccharides may more accurately reflect the storage burden in these tissues.

Contribution of inhibitory receptor glycoprotein iib / iiia in coronary angioplasty and acute coronary syndrome, about 152 patients

International Nuclear Information System (INIS)

Sellami, Walid

2007-01-01

The aim of our study was to evaluate the immediate results and long-term intake of anti-GP IIb / IIIa inhibitors for patients with acute coronary syndrome treated with coronary angioplasty. The use of anti-GP IIb / IIIa is a valid therapeutic option in patients with acute coronary syndrome with signs of severity and for patients undergoing complex angioplasty. Adverse effects of anti-GP IIb / IIIa can be seen to encourage vigilance and careful monitoring during the administration of these molecules and perfect knowledge of their pharmacological properties for appropriate use.

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

International Nuclear Information System (INIS)

Wendel, Marco; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H; Marrinucci, Dena; Kuhn, Peter

2012-01-01

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL −1 (range 0–515.6) and a mean of 44.7 (±95.2) HD-CTCs mL −1 . No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0–178.2), stage III (n = 34, range 0–515.6) and stages I/II (n = 13, range 0–442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and

Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC).

Science.gov (United States)

Feng, Hongxiang; Zhang, Zhenrong; Qing, Xin; Wang, Xiaowei; Liang, Chaoyang; Liu, Deruo

2016-02-01

Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. Copyright © 2015. Published by Elsevier Inc.

Paul Scherrer Institut annual report 1994. Annex IIIA: PSI condensed matter research and material sciences

Energy Technology Data Exchange (ETDEWEB)

Baltensperger, U [ed.; Paul Scherrer Inst. (PSI), Villigen (Switzerland)

1995-10-01

This annex reports on the PSI division IIIA`s progress achieved during 1994 in the Laboratory of Ionbeam-Physics, the Laboratory of Radiochemistry; the Laboratory for Neutron Scattering and the Laboratory for Astrophysics. Progress of the spallation neutron source project (SINQ) is documented by a set of pictures. A bibliography of the department`s publications is included. figs., tabs., refs.

Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression.

Science.gov (United States)

Reguart, Noemi; Rosell, Rafael; Cardenal, Felipe; Cardona, Andres F; Isla, Dolores; Palmero, Ramon; Moran, Teresa; Rolfo, Christian; Pallarès, M Cinta; Insa, Amelia; Carcereny, Enric; Majem, Margarita; De Castro, Javier; Queralt, Cristina; Molina, Miguel A; Taron, Miquel

2014-05-01

Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to drug-induced accumulation of acetylated proteins, including the heat shock protein 90. We prospectively studied the activity of vorinostat plus erlotinib in EGFR-mutated NSCLC patients with progression to tyrosine kinase inhibitors. We conducted this prospective, non-randomized, multicenter, phase I/II trial to evaluate the maximum tolerated dose, toxicity profile and efficacy of erlotinib and vorinostat. Patients with advanced NSCLC harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included. The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. The primary end point was progression-free-survival rate at 12 weeks (PFSR12w). Pre-treatment plasma samples were required to assess T790M resistant mutation. A total of 33 patients were enrolled in the phase I-II trial. The maximum tolerated dose was erlotinib 150 mg p.o., QD, and 400mg p.o., QD, on days 1-7 and 15-21 in a 28-day cycle. Among the 25 patients treated at the RDP2, the most common toxicities included anemia, fatigue and diarrhea. No responses were observed. PFSR12w was 28% (IC 95%: 18.0-37.2); median progression-free survival (PFS) was 8 weeks (IC 95%: 7.43-8.45) and overall survival (OS) 10.3 months (95% CI: 2.4-18.1). Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFR-mutated NSCLC patients after TKI progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Loss of tumour-specific ATM protein expression is an independent prognostic factor in early resected NSCLC.

Science.gov (United States)

Petersen, Lars F; Klimowicz, Alexander C; Otsuka, Shannon; Elegbede, Anifat A; Petrillo, Stephanie K; Williamson, Tyler; Williamson, Chris T; Konno, Mie; Lees-Miller, Susan P; Hao, Desiree; Morris, Don; Magliocco, Anthony M; Bebb, D Gwyn

2017-06-13

Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry. Both malignant cell-specific ATM expression and the ratio of ATM expression within malignant tumour cells compared to that in the surrounding tumour stroma, defined as the ATM expression index (ATM-EI), were measured and correlated with clinical outcome. ATM loss was identified in 21.8% of patients, and was unaffected by clinical pathological variables. Patients with low ATM-EI tumours had worse survival outcomes compared to those with high ATM-EI (p ATM-deficient patients may derive greater benefit from guideline-recommended adjuvant chemotherapy following surgical resection. Taken together, these results indicate that ATM loss seems to be an early event in NSCLC carcinogenesis and is an independent prognostic factor associated with worse survival in stage II/III patients.

miR-151a induces partial EMT by regulating E-cadherin in NSCLC cells

DEFF Research Database (Denmark)

Daugaard, Iben; Sanders, K J; Idica, A

2017-01-01

mortality. Here, we demonstrate that miR-151a is overexpressed in non-small cell lung cancer (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a overexpression promotes proliferation, epithelial-to-mesenchymal transition (EMT) and induces tumor cell migration and invasion of NSCLC......-cadherin in miR-151a NSCLC cell lines potently repressed miR-151a-induced partial EMT and cell migration of NSCLC cells. In conclusion, our findings suggest that miR-151a functions as an oncomiR in NSCLC by targeting E-cadherin mRNA and inducing proliferation, migration and partial EMT....

Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

Directory of Open Access Journals (Sweden)

Pranshu eBansal

2016-05-01

Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

A Novel Inflammation-Based Stage (I Stage in Patients with Resectable Esophageal Squamous Cell Carcinoma

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Peng-Cheng Chen

2016-01-01

Full Text Available Background. Inflammation plays a key role in cancer. In the current study, we proposed a novel inflammation-based stage, named I stage, for patients with resectable esophageal squamous cell carcinoma (ESCC. Methods. Three hundred and twenty-three patients with resectable ESCC were enrolled in the current study. The I stage was calculated as follows: patients with high levels of C-reactive protein (CRP (>10 mg/L, neutrophil-to-lymphocyte ratio (NLR (>3.5, and platelet-count-to-lymphocyte ratio (PLR (>150 were defined as I3. Patients with two, one, or no abnormal value were defined as I2, I1, or I0, respectively. The prognostic factors were evaluated by univariate and multivariate analyses. Results. There were 112 patients for I0, 97 patients for I1, 66 patients for I2, and 48 patients for I3, respectively. The 5-year cancer-specific survival (CSS in patients with I0, I1, I2, and I3 was 50.0%, 30.9%, 18.2%, and 8.3%, respectively (I0 versus I1, P=0.002; I1 versus I2, P=0.012; I2 versus I3, P=0.020. Multivariate analyses revealed that I stage was an independent prognostic factor in patients with resectable ESCC (P<0.001. Conclusion. The inflammation-based stage (I stage is a novel and useful predictive factor for CSS in patients with resectable ESCC.

Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.

Science.gov (United States)

Zhang, Hongjie; Garcia, Jose M

2015-06-01

Cancer anorexia-cachexia syndrome (CACS) is associated with increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin receptor agonist in clinical development for the treatment of CACS in NSCLC. The aim of this review is to summarize preclinical and clinical studies evaluating anamorelin as a potential promising treatment for CACS in NSCLC. Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed. Anamorelin administration may lead to increases in food intake, body weight and lean body mass, and a stimulatory effect on growth hormone secretion in NSCLC patients. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. Targeting ghrelin receptors presents the advantage of potentially addressing multiple mechanisms of CACS simultaneously including appetite, muscle protein balance, adipose tissue metabolism, energy expenditure and inflammation. Clinical data suggest that anamorelin is well tolerated and it effectively increases appetite, body weight and lean mass in patients with advanced NSCLC. Long-term safety remains unknown at this time. The potential synergistic effects of anamorelin with nutritional support or exercise as well as its efficacy/safety in other tumor types are also unknown.

76 FR 13643 - FDA Food Safety Modernization Act: Title III-A New Paradigm for Importers; Public Meeting

Science.gov (United States)

2011-03-14

... Act: Title III--A New Paradigm for Importers; Public Meeting AGENCY: Food and Drug Administration, HHS... announcing a public meeting entitled ``FDA Food Safety Modernization Act: Title III--A New Paradigm for... provided. Request special accommodations due By March 22, 2011.... Patricia M. Kuntze, 301- to disability...

Effectiveness of accelerated radiotherapy for patients with inoperable non-small cell lung cancer (NSCLC) and borderline prognostic factors without distant metastasis: a retrospective review

International Nuclear Information System (INIS)

Nguyen, Linh N.; Komaki, Ritsuko; Allen, Pamela; Schea, Randi A.; Milas, Luka

1999-01-01

Purpose: The standard treatment for patients with unresectable or medically inoperable non-small cell lung cancer (NSCLC) and good prognostic factors (e.g., weight loss [WL] ≤5% and Karnofsky performance status [KPS] ≥70) is induction chemotherapy followed by definitive radiotherapy to the primary site at 1.8-2.0 Gy per fraction with a total dose of 60-63 Gy to the target volume. Patients with poor prognostic factors usually receive radiotherapy alone, but the fractionation schedule and total dose have not been standardized. To attempt to optimize irradiation doses and schedule, we compared the effectiveness of accelerated radiotherapy (ACRT) alone to 45 Gy at 3 Gy per fraction with standard radiation therapy (STRT) of 60-66 Gy at 2 Gy per fraction in regard to tumor response, local control, distant metastasis, toxicity, and survival. Methods and Materials: Fifty-five patients treated with radiation for NSCLC at The University of Texas M. D. Anderson Cancer Center between 1990 and 1994 were identified. All 55 patients had node-positive, and no distant metastasis (N+, M0) of NSCLC. Two cohorts were identified. One cohort (26 patients) had borderline poor prognostic factors (KPS less than 70 but higher than 50, and/or WL of more than 5%) and was treated with radiotherapy alone to 45 Gy over 3 weeks at 3 Gy/fraction (ACRT). The second cohort (29 patients) had significantly better prognostic factors (KPS ≥70 and WL ≤5%) and was treated to 60-66 Gy over 6 to 6((1)/(2)) weeks at 2 Gy per fraction (STRT) during the same period. Results: In the first cohort treated by ACRT, the distribution of patients by AJCC stage was IIB 8%, IIIA 19%, and IIIB 73%. Sixty-two percent had KPS 5%. The maximum response rate as determined by chest X-ray was 60% among 45 of 55 patients who were evaluable for response: combined complete responses (20%) and partial responses (40%). Overall survival in these patients was 13% at 2 and 5 years, with a locoregional control rate of 42% and a

A retrospective analysis of delays in the diagnosis of lung cancer and associated costs

Directory of Open Access Journals (Sweden)

Gildea TR

2017-05-01

IV disease and lowest among patients diagnosed at Stage I disease ($7,239 Stage I, $9,484 Stage II, $11,193 Stage IIIa, $17,415 Stage IIIb, and $21,441 Stage IV. Conclusion: This study showed that most patients experienced long periods of delay between their first diagnostic test for lung cancer and a definitive diagnosis, and the majority were diagnosed at advanced stages of disease. Costs associated with the management of lung cancer increased substantially with higher stages at diagnosis. Procedures that diagnose lung cancer at earlier stages may allow for less resource use and costs among patients with lung cancer. Keywords: biopsy (lung, cost, health care utilization, pulmonary nodule, staging

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

2015-01-01

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Lindsay, WD [University of Pennsylvania, Philadelphia, PA (United States); Oncora Medical, LLC, Philadelphia, PA (United States); Berlind, CG [Georgia Institute of Technology, Atlanta, GA (Georgia); Oncora Medical, LLC, Philadelphia, PA (United States); Gee, JC; Simone, CB [University of Pennsylvania, Philadelphia, PA (United States)

2015-06-15

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

Seventh edition (2010) of the AJCC/UICC staging system for gastric adenocarcinoma: is there room for improvement?

Science.gov (United States)

Patel, Manali I; Rhoads, Kim F; Ma, Yifei; Ford, James M; Visser, Brendan C; Kunz, Pamela L; Fisher, George A; Chang, Daniel T; Koong, Albert; Norton, Jeffrey A; Poultsides, George A

2013-05-01

The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database. California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method. Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory ability In this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma

Science.gov (United States)

2018-04-26

Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC).

Science.gov (United States)

Cedrés, Susana; Nuñez, Isaac; Longo, Marina; Martinez, Pablo; Checa, Eva; Torrejón, Davis; Felip, Enriqueta

2011-05-01

Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases. Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Changes in pulmonary function after definitive radiotherapy for NSCLC

DEFF Research Database (Denmark)

Schytte, Tine; Bentzen, Søren M; Brink, Carsten

2015-01-01

a negative impact on FVC. Long-term FEV1 and FVC were analyzed using linear regression. Treatment year and V60 had a significant impact on loss of FEV1. V60 had a significant impact on FVC changes. CONCLUSION: In this study, early PF change reached a plateau at 6months after the start of radiotherapy......INTRODUCTION: The objective of this study was to identify factors associated with early and long-term pulmonary function (PF) changes after definitive radiotherapy for NSCLC patients. PF was measured by spirometry i.e. forced expiratory volume in 1s (FEV1), and forced vital capacity (FVC...

The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

Science.gov (United States)

Ohri, Chandra M; Shikotra, Aarti; Green, Ruth H; Waller, David A; Bradding, Peter

2011-01-01

We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC. Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months). The NM expression of NM-HLA-DR (pMRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (pMRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR pMRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001). Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

Preoperative staging of lung cancer with PET/CT: cost-effectiveness evaluation alongside a randomized controlled trial

DEFF Research Database (Denmark)

Søgaard, Rikke; Fischer, Barbara Malene B; Mortensen, Jann

2011-01-01

PURPOSE: Positron emission tomography (PET)/CT has become a widely used technology for preoperative staging of non-small cell lung cancer (NSCLC). Two recent randomized controlled trials (RCT) have established its efficacy over conventional staging, but no studies have assessed its cost-effective......PURPOSE: Positron emission tomography (PET)/CT has become a widely used technology for preoperative staging of non-small cell lung cancer (NSCLC). Two recent randomized controlled trials (RCT) have established its efficacy over conventional staging, but no studies have assessed its cost......-effectiveness. The objective of this study was to assess the cost-effectiveness of PET/CT as an adjunct to conventional workup for preoperative staging of NSCLC. METHODS: The study was conducted alongside an RCT in which 189 patients were allocated to conventional staging (n = 91) or conventional staging + PET/CT (n = 98......) and followed for 1 year after which the numbers of futile thoracotomies in each group were monitored. A full health care sector perspective was adapted for costing resource use. The outcome parameter was defined as the number needed to treat (NNT)-here number of PET/CT scans needed-to avoid one futile...

Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells.

Science.gov (United States)

Filosto, Simone; Baston, David S; Chung, Samuel; Becker, Cathleen R; Goldkorn, Tzipora

2013-08-01

The EGF receptor (EGFR) is a proto-oncogene commonly dysregulated in several cancers including non-small cell lung carcinoma (NSCLC) and, thus, is targeted for treatment using tyrosine kinase inhibitors (TKI) such as erlotinib. However, despite the efficacy observed in patients with NSCLC harboring oncogenic variants of the EGFR, general ineffectiveness of TKIs in patients with NSCLC who are current and former smokers necessitates identification of novel mechanisms to overcome this phenomenon. Previously, we showed that NSCLC cells harboring either wild-type (WT) EGFR or oncogenic mutant (MT) L858R EGFR become resistant to the effects of TKIs when exposed to cigarette smoke, evidenced by their autophosphorylation and prolonged downstream signaling. Here, we present Src as a target mediating cigarette smoke-induced resistance to TKIs in both WT EGFR- and L858R MT EGFR-expressing NSCLC cells. First, we show that cigarette smoke exposure of A549 cells leads to time-dependent activation of Src, which then abnormally binds to the WT EGFR causing TKI resistance, contrasting previous observations of constitutive binding between inactive Src and TKI-sensitive L858R MT EGFR. Next, we show that Src inhibition restores TKI sensitivity in cigarette smoke-exposed NSCLC cells, preventing EGFR autophosphorylation in the presence of erlotinib. Furthermore, we show that overexpression of a dominant-negative Src (Y527F/K295R) restores TKI sensitivity to A549 exposed to cigarette smoke. Importantly, the TKI resistance that emerges even in cigarette smoke-exposed L858R EGFR-expressing NSCLC cells could be eliminated with Src inhibition. Together, these findings offer new rationale for using Src inhibitors for treating TKI-resistant NSCLC commonly observed in smokers.

Can Laws Be a Potential PET Image Texture Analysis Approach for Evaluation of Tumor Heterogeneity and Histopathological Characteristics in NSCLC?

Science.gov (United States)

Karacavus, Seyhan; Yılmaz, Bülent; Tasdemir, Arzu; Kayaaltı, Ömer; Kaya, Eser; İçer, Semra; Ayyıldız, Oguzhan

2018-04-01

We investigated the association between the textural features obtained from 18 F-FDG images, metabolic parameters (SUVmax , SUVmean, MTV, TLG), and tumor histopathological characteristics (stage and Ki-67 proliferation index) in non-small cell lung cancer (NSCLC). The FDG-PET images of 67 patients with NSCLC were evaluated. MATLAB technical computing language was employed in the extraction of 137 features by using first order statistics (FOS), gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), and Laws' texture filters. Textural features and metabolic parameters were statistically analyzed in terms of good discrimination power between tumor stages, and selected features/parameters were used in the automatic classification by k-nearest neighbors (k-NN) and support vector machines (SVM). We showed that one textural feature (gray-level nonuniformity, GLN) obtained using GLRLM approach and nine textural features using Laws' approach were successful in discriminating all tumor stages, unlike metabolic parameters. There were significant correlations between Ki-67 index and some of the textural features computed using Laws' method (r = 0.6, p = 0.013). In terms of automatic classification of tumor stage, the accuracy was approximately 84% with k-NN classifier (k = 3) and SVM, using selected five features. Texture analysis of FDG-PET images has a potential to be an objective tool to assess tumor histopathological characteristics. The textural features obtained using Laws' approach could be useful in the discrimination of tumor stage.

Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells.

Science.gov (United States)

Pan, Mengwu; Hou, Lingling; Zhang, Jingsi; Zhao, Diandian; Hua, Jilei; Wang, Ziling; He, Jinsheng; Jiang, Hong; Hu, Honggang; Zhang, Lishu

2018-04-01

Non-small-cell lung cancer (NSCLC) is still the main threat of cancer-associated death. Current treatment of NSCLC has limited effectiveness, and unfortunately, the prognosis of NSCLC remains poor. Therefore, a novel strategy for cancer therapy is urgently needed. Stem cell therapy has significant potential for cancer treatment. Mesenchymal stem cells (MSCs) with capacity for self-renewal and differentiation into various cells types exhibit the feature of homing to tumor site and immunosuppression, have been explored as a new treatment for various cancers. Studies revealed that the broad repertoire of trophic factors secreted by MSCs extensively involved in the interplay between MSCs and tumor cells. In this study, we confirmed that MSCs do have the paracrine effect on proliferation and migration of NSCLC cells (A549, NCI-H460, and SK-MES-1). Co-culture system and conditioned medium experiments results showed that soluble factors secreted by MSCs inhibited the proliferation of NSCLC cells in vitro. The scratch assay showed that conditioned medium of MSCs could suppress the migration of NSCLC cells in vitro. Western blot results showed that the expression of proteins relevant to cell proliferation, anti-apoptosis, and migration was remarkably decreased via MAPK/eIF4E signaling pathway. We speculated that soluble factors secreted by MSCs might be responsible for inhibitory mechanism of NSCLC cells. By Human Gene Expression Microarray Assay and recombinant Vascular Endothelial Growth Factor 165 (VEGF165) neutralizing experiment, we verified that VEGF might be responsible for the down-regulation of proteins related to cell proliferation, anti-apoptosis, and migration by suppressing translation initiation factor eIF4E via MAPK signaling pathway. Taken together, our study demonstrated that a possible trophic factor secreted by MSCs could manipulate translation initiation of NSCLC cells via MAPK signaling pathway, and significantly affect the fate of tumor cells, which

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

DEFF Research Database (Denmark)

Helbekkmo, N; Sundstrøm, S H; Aasebø, U

2007-01-01

This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB....../IV and WHO performance status 0-2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m(-2) or gemcitabine 1000 mg m(-2) on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy...... and every 8 weeks until 49 weeks. During 14 months, 432 patients were included (VC, n=218; GC, n=214). Median survival was 7.3 vs 6.4 months, 1-year survival 28 vs 30% and 2-year survival 7 vs 7% in the VC and GC arm, respectively (P=0.89). HRQOL, represented by global QOL, nausea/vomiting, dyspnoea...

Positron emission tomography/computed tomography (PET/CT) and CT for N staging of non-small cell lung cancer.

Science.gov (United States)

Vegar Zubović, Sandra; Kristić, Spomenka; Hadžihasanović, Besima

2017-08-01

Aim The aim of this study is to investigate the possibilities of non-invasive diagnostic imaging methods, positron emission tomography/computed tomography (PET/CT) and CT, in clinical N staging of non-small cell lung cancer (NSCLC). Methods Retrospective clinical study included 50 patients with diagnosed NSCLC who have undergone PET/CT for the purpose of disease staging. The International association for the study of lung cancer (IASLC) nodal mapping system was used for analysis of nodal disease. Data regarding CT N-staging and PET/CT Nstaging were recorded. Two methods were compared using χ2 test and Spearman rank correlation coefficient. Results Statistical analysis showed that although there were some differences in determining the N stage between CT and PET/CT, these methods were in significant correlation. CT and PET/CT findings established the same N stage in 74% of the patients. In five patients based on PET/CT findings the staging was changed from operable to inoperable, while in four patients staging was changed from inoperable to operable. Conclusion PET/CT and CT are noninvasive methods that can be reliably used for N staging of NSCLC. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

International Nuclear Information System (INIS)

Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

2002-01-01

Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

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Crawford Jeffrey

2010-04-01

Full Text Available Abstract Background The Lung Cancer Exercise Training Study (LUNGEVITY is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak, patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC patients. Methods/Design Using a single-center, randomized design, 160 subjects (40 patients/study arm with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1 aerobic training alone, (2 resistance training alone, (3 the combination of aerobic and resistance training, or (4 attention-control (progressive stretching. The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks, social interaction (participants will receive one-on-one instruction, and duration (30-45 mins/session. The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs (e.g., quality of life, fatigue, depression, etc. and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function. All endpoints will be assessed at baseline and postintervention (16 weeks. Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes

Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Science.gov (United States)

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

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Ayakawa Shiho

2009-05-01

Full Text Available Abstract Background In stereotactic body radiotherapy (SBRT for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2 levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC, 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. Results By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. Conclusion Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

Residual {sup 18}F-FDG-PET Uptake 12 Weeks After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer Predicts Local Control

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Bollineni, Vikram Rao, E-mail: v.r.bollineni@umcg.nl [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Widder, Joachim [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Pruim, Jan [Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A.; Wiegman, Erwin M. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

2012-07-15

Purpose: To investigate the prognostic value of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC). Methods and Materials: From November 2006 to February 2010, 132 medically inoperable patients with proven Stage I NSCLC or FDG-PET-positive primary lung tumors were analyzed retrospectively. SABR consisted of 60 Gy delivered in 3 to 8 fractions. Maximum standardized uptake value (SUV{sub max}) of the treated lesion was assessed 12 weeks after SABR, using FDG-PET. Patients were subsequently followed at regular intervals using computed tomography (CT) scans. Association between post-SABR SUV{sub max} and local control (LC), mediastinal failure, distant failure, overall survival (OS), and disease-specific survival (DSS) was examined. Results: Median follow-up time was 17 months (range, 3-40 months). Median lesion size was 25 mm (range, 9-70 mm). There were 6 local failures: 15 mediastinal failures, 15 distant failures, 13 disease-related deaths, and 16 deaths from intercurrent diseases. Glucose corrected post-SABR median SUV{sub max} was 3.0 (range, 0.55-14.50). Using SUV{sub max} 5.0 as a cutoff, the 2-year LC was 80% versus 97.7% for high versus low SUV{sub max}, yielding an adjusted subhazard ratio (SHR) for high post-SABR SUV{sub max} of 7.3 (95% confidence interval [CI], 1.4-38.5; p = 0.019). Two-year DSS rates were 74% versus 91%, respectively, for high and low SUV{sub max} values (SHR, 2.2; 95% CI, 0.8-6.3; p = 0.113). Two-year OS was 62% versus 81% (hazard ratio [HR], 1.6; 95% CI, 0.7-3.7; p = 0.268). Conclusions: Residual FDG uptake (SUV{sub max} {>=}5.0) 12 weeks after SABR signifies increased risk of local failure. A single FDG-PET scan at 12 weeks could be used to tailor further follow-up according to the risk of failure, especially in patients potentially eligible for salvage surgery.

The role of positron-emission-tomography (F-18-FDG-PET) in the staging and follow-up of lung cancer and in the evaluation of focal pulmonary abnormalities

International Nuclear Information System (INIS)

Baum, R.P.; Bonnet, R.B.; Presselt, N.; Leonhardi, J.

2001-01-01

For lymph node staging (especially for the detection of mediastinal lymph node involvement, i.e. N2 or N3 metastases) of non-small cell lung cancer (NSCLC), FDG PET and spiral CT were compared head to head in prospective studies. A significantly higher diagnostic accuracy was shown for FDG-PET, which is able to detect metastases (up-staging) even in normal sized lymph nodes (in CT 80%. (orig.) [de

Early tumor shrinkage served as a prognostic factor for patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

Science.gov (United States)

Wei, Min; Ye, Qingqing; Wang, Xuan; Wang, Men; Hu, Yan; Yang, Yonghua; Yang, Jiyuan; Cai, Jun

2018-05-01

Lung cancer is the most common cause of cancer death. About 80% of patients are diagnosed at stage III in the non-small cell lung cancer (NSCLC). It is extremely important to understand the progression of this disease which has low survival times despite the advancing treatment modalities. We aimed to investigate the relationship between early tumor shrinkage (ETS) after initial concurrent chemoradiotherapy (C-CRT) and survival outcome in patients with stage III (NSCLC). A retrospective review of 103 patients with stage III NSCLC who had received C-CRT from January 2006 to October 2011 was performed. Patients were treated with systemic chemotherapy regimen of Cisplatin/Vp-16 and concurrent thoracic radiotherapy at a median dose of 66 Gy (range 60-70 Gy). All patients received a computed tomography (CT) examination before treatment. Also subsequently, chest CT scans were performed with the same imaging parameters at approximately 5 weeks after the initiation of treatment. ETS is here stratified by a decrease in tumor size ≥30% and cancer-related death (P < .05) in stage IIINSCLC. ETS may be served as a useful prognostic factor to predict the outcome of stage III NSCLC patients treated with CCRT.

DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

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Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Paracelsus Medizinische Privatuniversitaet, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria); Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria); Porsch, Peter; Studnicka, Michael [Landeskrankenhaus Salzburg, Univ.-Klinik fuer Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen Privatuniversitaet, Salzburg (Austria)

2014-09-23

While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for < 2.5 cm, 79.2 Gy for 2.5-4.5 cm, 84.6 Gy for 4.5-6 cm, 90 Gy for > 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [German] Die Standardbehandlung fuer nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie fuer Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative

Value of dual time point F-18 FDG-PET/CT imaging for the evaluation of prognosis and risk factors for recurrence in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

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Satoh, Yoko, E-mail: pecampecam@yahoo.co.jp [PET Center, Kofu Neurosurgical Hospital, ZIP Code 400-0805, Sakaori 1-16-18, Kofu city, Yamanashi Prefecture (Japan); Nambu, Atsushi, E-mail: nambu-a@gray.plala.or.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Onishi, Hiroshi, E-mail: honishi@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Sawada, Eiichi, E-mail: e_sawaday_61674@ybb.ne.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Tominaga, Licht, E-mail: lichtt@gmail.com [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Kuriyama, Kengo, E-mail: kuriyama@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); Komiyama, Takafumi, E-mail: takafumi-ymu@umin.ac.jp [Department of Radiology, Kofu Municipal Hospital, ZIP Code 400-0832, Masutsubo-cho 366, Kofu City, Yamanashi Prefecture (Japan); Marino, Kan, E-mail: marino-akrf@ych.pref.yamanashi.jp [Department of Radiology, Yamanashi Prefectural Hospital, ZIP Code 400-8506, Fujimi 1-1-1, Kofu City, Yamanashi Prefecture (Japan); Aoki, Shinichi, E-mail: aokis@yamanashi.ac.jp [Department of Radiology, University of Yamanashi, ZIP Code 409-3898, Yamanashi University Faculty of Medicine, Shimokato 1110, Chuo City, Yamanashi Prefecture (Japan); and others

2012-11-15

Purpose: To investigate prognostic and risk factors for recurrence after stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung carcinoma (NSCLC), focusing on dual time point [18]F-fluorodeoxyglucose positron emission tomography (FDG PET). Materials and methods: We prospectively evaluated 57 patients with stage I NSCLC (45 T1N0M0 and 12 T2N0M0) who had undergone pretreatment FDG-PET/CT and were subsequently treated with SBRT. All patients received a whole-body PET/CT scan at 60 min and a whole-lung at 120 min after the injection. The maximum standardized uptake value (SUV) and retention index (RI) of the lesions were calculated. Local recurrence, regional lymph node metastasis, distant metastasis, and the recurrence pattern were evaluated. Cox proportional hazard regression analyses were performed to evaluate prognostic factors or risk factors of recurrence. Results: During the median follow-up period of 27 months, local recurrence, regional lymph node metastasis, and distant metastasis were seen in 17 (30%), 12 (21%), and 17 (30%) of the 57 patients, respectively. The 3-year overall survival rate was 63.4%. SUV{sub max} did not affect any recurrence, DFS, OS, or CSS. RI significantly predicted higher distant metastasis (HR 47.546, p = 0.026). In contrast, RI tended to predict lower local recurrence (HR 0.175, p = 0.246) and regional lymph node metastasis (HR 0.109, p = 0.115). Conclusions: SUV{sub max} at staging FDG-PET does not predict any recurrence, DFS, OS or CSS. In contrast, higher RI predicts higher distant metastasis and tended to predict lower local or regional lymph node metastasis.

Clinical and prognostic significance of plasma fibrinogen in lung cancer

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Chen YS

2014-01-01

Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

Percutaneous thermal ablation for stage IA non-small cell lung cancer: long-term follow-up.

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Narsule, Chaitan K; Sridhar, Praveen; Nair, Divya; Gupta, Avneesh; Oommen, Roy G; Ebright, Michael I; Litle, Virginia R; Fernando, Hiran C

2017-10-01

Surgical resection is the most effective curative therapy for non-small cell lung cancer (NSCLC). However, many patients are unable to tolerate resection secondary to poor reserve or comorbid disease. Radiofrequency ablation (RFA) and microwave ablation (MWA) are methods of percutaneous thermal ablation that can be used to treat medically inoperable patients with NSCLC. We present long-term outcomes following thermal ablation of stage IA NSCLC from a single center. Patients with stage IA NSCLC and factors precluding resection who underwent RFA or MWA from July 2005 to September 2009 were studied. CT and PET-CT scans were performed at 3 and 6 month intervals, respectively, for first 24 months of follow-up. Factors associated with local progression (LP) and overall survival (OS) were analyzed. Twenty-one patients underwent 21 RFA and 4 MWA for a total of 25 ablations. Fifteen patients had T1a and six patients had T1b tumors. Mean follow-up was 42 months, median survival was 39 months, and OS at three years was 52%. There was no significant difference in median survival between T1a nodules and T1b nodules (36 vs . 39 months, P=0.29) or for RFA and MWA (36 vs . 50 months, P=0.80). Ten patients had LP (47.6%), at a median time of 35 months. There was no significant difference in LP between T1a and T1b tumors (22 vs . 35 months, P=0.94) or RFA and MWA (35 vs . 17 months, P=0.18). Median OS with LP was 32 months compared to 39 months without LP (P=0.68). Three patients underwent repeat ablations. Mean time to LP following repeat ablation was 14.75 months. One patient had two repeat ablations and was disease free at 40-month follow-up. Thermal ablation effectively treated or controlled stage IA NSCLC in medically inoperable patients. Three-year OS exceeded 50%, and LP did not affect OS. Therefore, thermal ablation is a viable option for medically inoperable patients with early stage NSCLC.

A Novel Inflammation-Based Stage (I Stage Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma

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Jian-Pei Li

2016-11-01

Full Text Available Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS, modified GPS (mGPS and C-reactive protein/Albumin (CRP/Alb ratio, platelet–lymphocyte ratio (PLR, and neutrophil–lymphocyte ratio (NLR, have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC. In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR. The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03 and PLR (>146.2 were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves analyzed by receiver operating characteristics (ROC curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR = 2.093; 95% Confidence interval (CI: 1.222–3.587; p = 0.007 and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010 were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001. The I stage had a higher area under the curve value (0.670 compared with other systemic inflammation

Detection of EGFR somatic mutations in non-small cell lung cancer (NSCLC) using a novel mutant-enriched liquidchip (MEL) technology.

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Zhang, Li; Yang, Huiyi; Zhao, Yanwei; Liu, Wenchao; Wu, Shiyang; He, Jiaying; Luo, Xiaodi; Zhu, Zeyao; Xu, Jiasen; Zhou, Qinghua; Ren-Heidenreich, Lifen

2012-09-01

We have developed and standardized a novel technology, mutant-enriched liquidchip (MEL), for clinical detection of EGFR mutations. The MEL integrates a mutant-enriched PCR procedure with liquidchip technology for detections of EGFR exon 19 deletions and L858R mutation on both formalin-fixed and paraffin-embedded (FFPE) slides and plasma samples from patients with non-small cell lung cancer (NSCLC). The detection sensitivity was 0.1% of mutant DNA in the presence of its wild-type DNA. The cross-reaction rate was lower than 5%. To evaluate the MEL platform, the EGFR mutation status of 59 patients with advanced NSCLC treated with EGFRTKIs (Tyrosine Kinase Inhibitors) were tested on their FFPE samples. EGFR exon 19 deletions and L858R were detected in 21 patients (21/59) and 76.2% (16/21) of them had partial response to the EGFR-TKIs, while by sequencing method, only 4 (4/59) mutations were detected. Plasma samples from 627 patients with various stages of NSCLC were examined with the MEL and 22% of EGFR exon 19 deletions and L858R were detected. Furthermore, in patients with advanced disease there are more mutations detected in plasma samples than in patients with less advanced disease. In conclusion, the MEL is a sensitive, stable, and robust technology for detecting EGFR DNA mutations from both FFPE and plasma samples from patients with NSCLC and is now routinely used for clinical diagnosis.

Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

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Kishi, Takahiro; Matsuo, Yukinori, E-mail: ymatsuo@kuhp.kyoto-u.ac.jp; Ueki, Nami; Iizuka, Yusuke; Nakamura, Akira; Sakanaka, Katsuyuki; Mizowaki, Takashi; Hiraoka, Masahiro

2015-07-01

Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

Female Mucopolysaccharidosis IIIA Mice Exhibit Hyperactivity and a Reduced Sense of Danger in the Open Field Test

OpenAIRE

Langford-Smith, Alex; Langford-Smith, Kia J.; Jones, Simon A.; Wynn, Robert F.; Wraith, J. E.; Wilkinson, Fiona L.; Bigger, Brian W.

2011-01-01

Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A), is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive lo...

[Optimization of radiotherapy planning for non-small cell lung cancer (NSCLC) using 18FDG-PET].

Science.gov (United States)

Schmidt, S; Nestle, U; Walter, K; Licht, N; Ukena, D; Schnabel, K; Kirsch, C M

2002-10-01

In recent years, FDG-PET examinations have become more important for problems in oncology, especially in staging of bronchogenic carcinoma. In the retrospective study presented here, the influence of PET on the planning of radiotherapy for patients with non-small-cell lung cancer (NSCLC) was investigated. The study involved 39 patients with NSCLC who had been examined by PET for staging. They received radiotherapy on the basis of the anterior/posterior portals including the primary tumour and the mediastinum planned according to CT- and bronchoscopic findings. The results of the PET examination were not considered in initial radiotherapy planning. The portals were retrospectively redefined on the basis of FDG uptake considering the size and localization of the primary tumour; and FDG activities outside the mediastinal part of the portals. In 15 out of 39 patients, the CT/PET-planned portals differed from the CT-planned ones. In most causes (n = 12) the CT/PET field was smaller than the CT field. The median geometric field size of the portals was 179 cm2, after redefinition using PET 166 cm2. In 20 patients with disturbed ventilation caused by the tumour (atelectasis, dystelectosis), a correction of the portal was suggested significantly more frequently than in the other patients (p = 0.03). Our results demonstrate the synergism of topographical (CT) and metabolic (FDG-PET) information, which could be helpful in planning radiotherapy of bronchial carcinoma, especially for patients with disturbed ventilation.

Results of paclitaxel (day 1 and 8 and carboplatin given on every three weeks in advanced (stage III-IV non-small cell lung cancer

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Salepci Taflan

2005-01-01

Full Text Available Abstract Background Both paclitaxel (P and carboplatin (C have significant activity in non-small cell lung cancer (NSCLC. The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT regimen in advanced stage NSCLC to evaluate the efficacy and toxicity. Methods Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS ECOG 0–2 were given P 112.5 mg/m2 intravenously (IV over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles. Results Median age was 58 (age range 39–77 and 41 patients (80% were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6. Seven patients (14% did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR in 45% and stable disease (SD in 18%. Twelve patients (24% received local RT. Thirteen patients (25% received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20, 25 (49% patients died and 35 patients (69% progressed. Median overall survival (OS was 11 ± 2 months (95% CI; 6 to 16, 1-year OS ratio was 44%. Median time to progression (TTP was 6 ± 1 months (95% CI; 4 to 8, 1-year progression free survival (PFS ratio was 20%. We observed following grade 3 toxicities: asthenia (10%, neuropathy (4%, anorexia (4%, anemia (4%, hypersensitivity to P (2%, nausea/vomiting (2%, diarrhea (2% and neutropenia (2%. Two patients (4% died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%. Conclusions P on day 1 and 8 and C every three weeks is practical and fairly

Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

International Nuclear Information System (INIS)

Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

2011-01-01

Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

Correlation between Pre-treatment Anemia and Prognosis in Non-small Cell Lung Cancer Patients

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Qiuhua DENG

2010-07-01

Full Text Available Background and objective The patients with non-small cell lung cancer (NSCLC might contract anemia, however, whether anemia is one of the independent prognostic factors to the patients with NSCLC is still controversial. So the aim of this study is to investigate the correlation between anemia and overall survival (OS in patients with NSCLC. Methods 1 018 patients with operable NSCLC were retrospectively analyzed in our hospital from January 2000 to December 2008. Results The occurrence of anemia before operation was 252/1 018 (24.1%. The OS in NSCLC patients without anemia was (2 425.98±50.03 days, and the OS in patients with anemia was (2 107.15±93.86 days. There was significant difference in the OS between them (P=0.001. The patients with anemia in stage I had shorter survival time than those without anemia (P < 0.001. But there was no difference in other stage patients. TNM stage, gender, tumor size and lymph nodes metastasis were correlated with OS using Cox regression analysis. Conclusion Anemia is correlated with survival in operable NSCLC patients. Moreover, it is an independent prognostic factor in NSCLC patients with stage I.

Appendectomy in primary and secondary staging operations for ovarian malignancy.

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Rose, P G; Reale, F R; Fisher, A; Hunter, R E

1991-01-01

Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures.

FDG PET evaluation of therapeutic response and toxicity after radiotherapy for NSCLC

International Nuclear Information System (INIS)

Hicks, R.J.; MacManus, M.P.; Matthews, J.P.; Rischin, D.; Binns, D.; McKenzie, A.F.; Ball, D.L.

2002-01-01

Full text: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is recognised for staging and therapeutic planning of patients with non-small cell carcinoma of the lung (NSCLC). The potential for this technique to be used in the assessment of therapeutic response has also been highlighted but may be limited by false positive results due to inflammatory response, particularly early after radiotherapy (RT). To evaluate the utility of FEX PET for therapeutic monitoring early (<12 weeks) after completion of radical RT we prospectively evaluated metabolic response and radiation toxicity using a standardised scoring system in 73 consecutive patients. All 73 had evaluable PET scans but 6 of the CT scan results were considered non-evaluable for therapeutic response using WHO criteria. PET therapeutic response category differed from that by CT in 40/67 (60%) cases and in 80% of such cases suggested a more marked response than suggested by CT (p 0.0002). Multifactor analysis including PET response, CT response, performance status, weight loss and stage revealed that PET response was the only significant predictor of survival (p 0.0001). Radiation toxicity scores were inversely related to therapeutic response on both PET (p = 0.022) and CT (p =0.029). In particular, more severe (grade 2 or 3) radiotoxicity scores on PET were associated with a greater proportion of partial or complete responses on both PET and CT than were lower (grade 0 and 1) scores (p =0.0044 and 0.041 respectively) consistent with the known relationship between the radiosensitivity of normal host and tumoral tissues. Early after completion of radiotherapy for NSCLC, PET response provides better prognostic stratification than CT response. PET can also identify typical radiation toxicity changes which are associated with response to treatment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression analysis as potential prognostic or differentiating markers for NSCLC patients in the Polish population.

Science.gov (United States)

Kordiak, Jacek; Czarnecka, Karolina H; Pastuszak-Lewandoska, Dorota; Antczak, Adam; Migdalska-Sęk, Monika; Nawrot, Ewa; Domańska-Senderowska, Daria; Kiszałkiewicz, Justyna; Brzeziańska-Lasota, Ewa

2017-06-01

According to the latest data, lung cancer is one of the most common cancer worldwide, men contributing nearly 21.2% and women 8.6% of all diagnosed cancers. Late detection of tumour drastically reduces the chance for a cure. Thus, it is important to search for candidate biomarkers for screening of early stage nonsmall cell lung carcinoma (NSCLC). Tumour suppressor genes, DLEC1, TUSC4 and MLH1, localized on 3p21 are recognized to play a role in NSCLC carcinogenesis. The aim of this study was to assess the relationship between the DLEC1, TUSC4 and MLH1 mRNA expression, and clinical features of NSCLC patients, tobacco addiction, and tumour histopathological characteristics. The DLEC1, TUSC4 and MLH1 expression was analysed in lung tumour tissue samples obtained from 69 patients diagnosed with NSCLC: squamous cell carcinoma (n = 34), adenocarcinoma (n = 24), large cell carcinoma (n = 5), carcinoma adenosquamosum (n = 5). A decreased gene expression (RQ MLH1 in 50.7% and for TUSC4 in 26% of NSCLC samples. DLEC1 was decreased in more aggressive subtypes: large cell carcinoma and adenocarcinoma-squamous cell carcinoma. The simultaneous downregulation of two of the studied genes, DLEC1 andMLH1,was observed in 30.4% of NSCLCsamples, highlighting the importance of these two genes in lung carcinogenesis. We found no correlation between the DLEC1, TUSC4 and MLH1 gene expression and NSCLC patient characteristics (gender, age and smoking) or cancer histopathology. No significant differences in the gene expression among NSCLC subtypes indicate the weakness of DLEC1, TUSC4 and MLH1 expression analysis as potential differentiating markers of NSCLC subtypes in the Polish population.

Mortality in asymptomatic vs. symptomatic patients surgically treated for non-small cell lung cancer (NSCLC)

DEFF Research Database (Denmark)

Madsen, Kirsten Riis; Bødtger, Uffe

, tobacco pack years, or FEV1. Former malignancy was significantly more prevalent among asymptomatic than symptomatic subjects (33 % vs. 11%), with insignificant differences in prevalence of other co-morbidities or in post-surgical TNM (82% vs 85% in stages IA-IIB). 12-months mortality was insignificantly...... higher in asymptomatic than symptomatic subjects (23% vs. 12%), and in patients with former malignancy compared to patients with no former cancer (17% vs. 16%). Discussion: Symptoms at diagnosis per se appear unrelated to mortality in patients with NSCLC referred for surgery. Asymptomatic patients were...

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

[Significance and mechanism of MSCT perfusion scan on differentiation of NSCLC].

Science.gov (United States)

Liu, Jin-Kang; Hu, Cheng-Ping; Zhou, Mo-Ling; Zhou, Hui; Xiong, Zeng; Xia, Yu; Chen, Wei

2009-06-01

To determine the significance of MSCT perfusion scan on differentiation of NSCLC and to investigate its possible mechanisms. Forty four NSCLC patients underwent CT perfusion scan by MSCT. Among them, 22 cases were selected to detected the two-dimensional tumor microvascular architecture phenotype (2D-TMAP), the relationships between CT perfusion parameters (BF, BV, PEI, TIP), and the differentiation of NSCLC were analysed by using the correlation analysis and trend test. Spearman correlation analysis was used to study the relationships between CT perfusion parameters, differentiation, and 2D-TMAP. The total BF, BV and PEI decreased with decreasing differentiation of NSCLC (P<0.05). The total PEI showed a positive correlation with the total MVD (P<0.05). There were negative correlations between the surrounding area BF, the total BF, BV, and PEI, the uncomplete lumen of the surrounding area MVD, and expression of PCNA, respectively (P<0.05). There were positive correlations between degree of differentiation and the uncomplete lumen of the surrounding area MVD (P<0.05). It was the same as degree of differentiation and expression of PCNA, VEGF, respectively. There were positive correlations between the uncomplete lumen of the surrounding area MVD and expression of VEGF, ephrinB2, EphB4, and PCNA, respectively (P<0.05). Perfusion parameters reflect the difference of density of vassels with mature functional lumen. Careful evaluation of the differences of blood flow pattern in pulmonary space-occupying lesions by MSCT perfusion scan can be used to identify the degree of NSCLC differentiation.

Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

International Nuclear Information System (INIS)

Nguyen, Xuan Canh; Nguyen, Van Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

2014-01-01

To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUV pt ), maxSUV of whole-body tumors (maxSUV wb ) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSCLC were enrolled. Seventeen patients had Stage IIIA, 21 Stage IIIB, and 45 Stage IV. maxSUV pt , maxSUV wb , sumaxSUV, age, gender, tumor-cell type, T stage, N stage, overall stage, primary tumor size, and specific treatment were analyzed for correlation with overall survival. Median follow-up duration was 13 months. Fifty patients were dead during a median follow-up time of 11 months and 33 patients were alive with a median time of 15 months. Univariate analysis revealed that overall survival was significantly correlated with sumaxSUV (≥35 vs. <35, P = 0.004), T stage (T4 vs. T1-T3, P = 0.025), overall stage (IV vs. III, P = 0.002), gender (male vs. female, P = 0.029) and specific treatment (no vs. yes, P = 0.011). maxSUV pt and maxSUV wb were not correlated with overall survival with P value of 0.139 and 0.168, respectively. Multivariate analysis identified sumaxSUV, T stage, gender, and specific treatment as independent prognostic indicators. Patients with a sumaxSUV of ≥35 were 1.921 times more likely to die than those with a sumaxSUV of < 35 (P = 0.047). Median survival time was 14 months for patients with sumaxSUV ≥ 35 compared with 20 months for those with sumaxSUV < 35. In patients with metastatic NSCLC, sumaxSUV with cut-off of 35 was much more significant for survival prognosis (P = 0.021). sumaxSUV is a new prognostic measure, independent of tumor stage, gender, and specific treatment in advanced NSCLC. sumaxSUV may be better than maxSUV pt and maxSUV wb in

Current Status of Stereotactic Ablative Radiotherapy (SABR for Early-stage 
Non-small Cell Lung Cancer

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Anhui SHI

2016-06-01

Full Text Available High level evidence from randomized studies comparing stereotactic ablative radiotherapy (SABR to surgery is lacking. Although the results of pooled analysis of two randomized trials for STARS and ROSEL showed that SABR is better tolerated and might lead to better overall survival than surgery for operable clinical stage I non-small cell lung cancer (NSCLC, SABR, however, is only recommended as a preferred treatment option for early stage NSCLC patients who cannot or will not undergo surgery. We, therefore, are waiting for the results of the ongoing randomized studies [Veterans affairs lung cancer surgery or stereotactic radiotherapy in the US (VALOR and the SABRTooth study in the United Kingdom (SABRTooths]. Many retrospective and case control studies showed that SABR is safe and effective (local control rate higher than 90%, 5 years survival rate reached 70%, but there are considerable variations in the definitions and staging of lung cancer, operability determination, and surgical approaches to operable lung cancer (open vs video-assisted. Therefore, it is difficult to compare the superiority of radiotherapy and surgery in the treatment of early staged lung cancer. Most studies demonstrated that the efficacy of the two modalities for early staged lung cancer is equivalent; however, due to the limited data, the conclusions from those studies are difficult to be evidence based. Therefore, the controversies will be focusing on the safety and invasiveness of the two treatment modalities. This article will review the ongoing debate in light of these goals.

Health-related quality of life in end-stage COPD and lung cancer patients.

Science.gov (United States)

Habraken, Jolanda M; ter Riet, Gerben; Gore, Justin M; Greenstone, Michael A; Weersink, Els J M; Bindels, Patrick J E; Willems, Dick L

2009-06-01

Historically, palliative care has been developed for cancer patients and is not yet generally available for patients suffering from chronic life-limiting illnesses, such as chronic obstructive pulmonary disease (COPD). To examine whether COPD patients experience similar or worse disease burden in comparison with non-small cell lung cancer (NSCLC) patients, we compared the health-related quality of life (HRQOL) scores of severe COPD patients with those of advanced NSCLC patients. We also formally updated previous evidence in this area provided by a landmark study published by Gore et al. in 2000. In updating this previous evidence, we addressed the methodological limitations of this study and a number of confounding variables. Eighty-two GOLD IV COPD patients and 19 Stage IIIb or IV NSCLC patients completed generic and disease-specific HRQOL questionnaires. We used an individual patient data meta-analysis to integrate the new and existing evidence (total n=201). Finally, to enhance between-group comparability, we performed a sensitivity analysis using a subgroup of patients with a similar degree of "terminality," namely those who had died within one year after study entry. Considerable differences in HRQOL were found for physical functioning, social functioning, mental health, general health perceptions, dyspnea, activities of daily living, and depression. All differences favored the NSCLC patients. The sensitivity analysis, using only terminal NSCLC and COPD patients, confirmed these findings. In conclusion, end-stage COPD patients experience poor HRQOL comparable to or worse than that of advanced NSCLC patients. We discuss these findings in the light of the notion that these COPD patients may have a similar need for palliative care.

Differential effect of age on survival in advanced NSCLC in women versus men: analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab.

Science.gov (United States)

Wakelee, H A; Dahlberg, S E; Brahmer, J R; Schiller, J H; Perry, M C; Langer, C J; Sandler, A B; Belani, C P; Johnson, D H

2012-06-01

The impact of age on prognosis in advanced stage non-small cell lung cancer (NSCLC) may differ by sex. Eligible patients (N=1590) from E1594, a 4-arm platinum-based chemotherapy trial, and E4599 (carboplatin/paclitaxel ± bevacizumab) chemotherapy arm were divided into male and female cohorts and separated into age groups of women ≥60 years old treated with chemotherapy alone on E1594 and E4599 was 11.6 months versus 9.0 months for women women (younger had greater benefit), with no age effect in men. In this unplanned, exploratory subgroup analysis of advanced stage NSCLC ECOG trials, women ≥60 years old treated with chemotherapy live longer than men and younger women. In contrast, bevacizumab survival benefit was more pronounced in men of any age and in younger women on E4599. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Adjuvant chemotherapy for stage I non-seminomatous testicular ...

African Journals Online (AJOL)

Adjuvant chemotherapy for stage I non-seminomatous testicular cancer. R. P. Abratt, A. R. Pontin, R. D. Barnes, B. V. Reddi. Developments in the treatment of stage I ... taxing for patients.·. Analysis of tumour histology in the orchidectomy specimen in patients entered into surveillance studies led to the identification of risk ...

Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer

DEFF Research Database (Denmark)

Konge, Lars; Vilmann, P; Clementsen, P

2012-01-01

Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliabilit...... and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC....

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

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Chien-Hung Huang

2014-01-01

Full Text Available Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

Effect of PlA1/A2 glycoprotein IIIa gene polymorphism on the long-term outcome after successful coronary stenting

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Riddell John

2007-11-01

Full Text Available Abstract Aim To prospectively determine the role of platelet glycoprotein IIIa (GP IIIa gene PlA1/PlA2 polymorphism on the long-term clinical outcome in patients with coronary artery disease undergoing coronary stenting. Design and setting Prospective observational study in the University Hospital of Caen (France. Patients and methods 1 111 symptomatic consecutive Caucasian patients treated with percutaneous coronary intervention including stent implantation underwent genotyping for GP IIIa PlA1/A2. Main outcome measures Long-term clinical outcome in terms of the rate of major adverse cardiac events (MACE, ie death from any cause, non-fatal Q wave or non Q wave myocardial infarction, and need for coronary revascularisation was obtained and subsequently stratified according to the GP IIIa PlA1/A2 polymorphism. Results Three groups of patients were determined according to the GP IIIa PlA1/A2 polymorphism (71.6% had the A1/A1, 25.8% had the A1/A2 and 2.6% had the A2/A2 genotype. These three groups were comparable for all clinical characteristics including sex ratio, mean age, vascular risk factors, previous coronary events, baseline angiographic exam, indication for the percutaneous coronary intervention and drug therapy. The incidence of MACE was similar in these 3 groups of patients during a mean follow-up period of 654+/-152 days. Independent risk factors for MACE were a left ventricular ejection fraction Conclusion The GP IIIa PlA1/A2 polymorphism does not influence the clinical long-term outcome in patients with symptomatic coronary disease undergoing percutaneous coronary intervention with stent implantation.

Characterization of a canine model of glycogen storage disease type IIIa

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Haiqing Yi

2012-11-01

Glycogen storage disease type IIIa (GSD IIIa is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR. The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT, aspartate transaminase (AST and alkaline phosphatase (ALP activities; serum creatine phosphokinase (CPK activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.

Time and dose-related changes in lung perfusion after definitive radiotherapy for NSCLC

DEFF Research Database (Denmark)

Farr, Katherina P; Khalil, Azza A; Møller, Ditte S

2018-01-01

BACKGROUND AND PURPOSE: To examine radiation-induced changes in regional lung perfusion per dose level in 58 non-small-cell lung cancer (NSCLC) patients treated with intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: NSCLC patients receiving chemo-radiotherapy (RT) of minimum 60 Gy we...

Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

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Margherita Iaboni

2016-01-01

Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is a promising antitumor agent for its remarkable ability to selectively induce apoptosis in cancer cells, without affecting the viability of healthy bystander cells. The TRAIL tumor suppressor pathway is deregulated in many human malignancies including lung cancer. In human non-small cell lung cancer (NSCLC cells, sensitization to TRAIL therapy can be restored by increasing the expression levels of the tumor suppressor microRNA-212 (miR-212 leading to inhibition of the anti-apoptotic protein PED/PEA-15 implicated in treatment resistance. In this study, we exploited a previously described RNA aptamer inhibitor of the tyrosine kinase receptor Axl (GL21.T expressed on lung cancer cells, as a means to deliver miR-212 into human NSCLC cells expressing Axl. We demonstrate efficient delivery of miR-212 following conjugation of the miR to GL21.T (GL21.T-miR212 chimera. We show that the chimera downregulates PED and restores TRAIL-mediate cytotoxicity in cancer cells. Importantly, treatment of Axl+ lung cancer cells with the chimera resulted in (i an increase in caspase activation and (ii a reduction of cell viability in combination with TRAIL therapy. In conclusion, we demonstrate that the GL21.T-miR212 chimera can be employed as an adjuvant to TRAIL therapy for the treatment of lung cancer.

The CT Findings and the Peak SUV on PET/CT according to the Levels of Cyfra 21-1 and CEA in Patients with Non-Small Cell Lung Carcinoma

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Jou, Sung Shick; Kim, Young Tong; Han, Jong Kyu; Kim, Hyung Hwan; Park, Jeong Mi; Park, Jai Soung; Hwang, Jung Hwa

2009-01-01

We wanted to evaluate the CT findings and the peak SUV according to the levels of cyfra 21-1 and CEA in patients with non-small cell lung carcinoma (NSCLC). We evaluated the TNM staging, cell types, the CT findings and peak SUV of the NSCLC in 234 patients with NSCLC according to the tumor marker levels. The correlations of the CT findings and the peak SUV with the tumor markers were evaluated in 35 patients with stage I disease. The sensitivities of the combined tumor markers cyfra 21-1 and CEA in the NSCLC for each TNM staging (I-IV) were 48.5%, 66.7%, 78.3% and 84.3%, respectively (p<0.05). Cyfra 21-1 was more sensitive for squamous cell carcinoma and CEA was more sensitive for adenocarcinoma. The tumor size, tumor necrosis and peak SUV were greater in the NSCLC with an elevated cyfra 21-1 level than that in the NSCLC without an elevated cyfra 21-1 level (p<0.05). For stage I disease, the level of cyfra 21-1 was linearly correlated with the tumor size (r=0.54) and the peak SUV (r=0.46), and the level of CEA was high in the spiculated masses (p<0.05). The NSCLC with an elevated cyfra 21-1 level shows larger, more frequently necrosis and a higher peak SUV than the NSCLC without an elevated Cyfra 21-1 level. For stage 1 disease, the tumor size and peak SUV correlate with the level of cyfra 21-1, and spiculated masses show an elevated level of CEA

The CT Findings and the Peak SUV on PET/CT according to the Levels of Cyfra 21-1 and CEA in Patients with Non-Small Cell Lung Carcinoma

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Jou, Sung Shick; Kim, Young Tong; Han, Jong Kyu; Kim, Hyung Hwan [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of); Park, Jeong Mi; Park, Jai Soung [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Hwang, Jung Hwa [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

2009-10-15

We wanted to evaluate the CT findings and the peak SUV according to the levels of cyfra 21-1 and CEA in patients with non-small cell lung carcinoma (NSCLC). We evaluated the TNM staging, cell types, the CT findings and peak SUV of the NSCLC in 234 patients with NSCLC according to the tumor marker levels. The correlations of the CT findings and the peak SUV with the tumor markers were evaluated in 35 patients with stage I disease. The sensitivities of the combined tumor markers cyfra 21-1 and CEA in the NSCLC for each TNM staging (I-IV) were 48.5%, 66.7%, 78.3% and 84.3%, respectively (p<0.05). Cyfra 21-1 was more sensitive for squamous cell carcinoma and CEA was more sensitive for adenocarcinoma. The tumor size, tumor necrosis and peak SUV were greater in the NSCLC with an elevated cyfra 21-1 level than that in the NSCLC without an elevated cyfra 21-1 level (p<0.05). For stage I disease, the level of cyfra 21-1 was linearly correlated with the tumor size (r=0.54) and the peak SUV (r=0.46), and the level of CEA was high in the spiculated masses (p<0.05). The NSCLC with an elevated cyfra 21-1 level shows larger, more frequently necrosis and a higher peak SUV than the NSCLC without an elevated Cyfra 21-1 level. For stage 1 disease, the tumor size and peak SUV correlate with the level of cyfra 21-1, and spiculated masses show an elevated level of CEA.

Programmable type III-A CRISPR-Cas DNA targeting modules.

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H Travis Ichikawa

Full Text Available The CRISPR-Cas systems provide invader defense in a wide variety of prokaryotes, as well as technologies for many powerful applications. The Type III-A or Csm CRISPR-Cas system is one of the most widely distributed across prokaryotic phyla, and cleaves targeted DNA and RNA molecules. In this work, we have constructed modules of Csm systems from 3 bacterial species and heterologously expressed the functional modules in E. coli. The modules include a Cas6 protein and a CRISPR locus for crRNA production, and Csm effector complex proteins. The expressed modules from L. lactis, S. epidermidis and S. thermophilus specifically eliminate invading plasmids recognized by the crRNAs of the systems. Characteristically, activation of plasmid targeting activity depends on transcription of the plasmid sequence recognized by the crRNA. Activity was not observed when transcription of the crRNA target sequence was blocked, or when the opposite strand or a non-target sequence was transcribed. Moreover, the Csm module can be programmed to recognize plasmids with novel target sequences by addition of appropriate crRNA coding sequences to the module. These systems provide a platform for investigation of Type III-A CRISPR-Cas systems in E. coli, and for introduction of programmable transcription-activated DNA targeting into novel organisms.

Treatment of Early Stage Non-Small Cell Lung Cancer: Surgery or Stereotactic Ablative Radiotherapy?

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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.

Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

Science.gov (United States)

2017-10-16

Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB 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

Exercise and Low-Dose Ibuprofen for Cognitive Impairment in Colorectal Cancer Patients Receiving Chemotherapy

Science.gov (United States)

2018-03-13

Cognitive Impairment; Stage 0 Colorectal Cancer; Stage I Colorectal Cancer; Stage II Colorectal Cancer; Stage IIA Colorectal Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage III Colorectal Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer

Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

International Nuclear Information System (INIS)

Dyke, A. L. V.

2009-01-01

In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotype in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

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Waters, Eugenie; Dingle, Brian; Rodrigues, George; Vincent, Mark; Ash, Robert; Dar, Rashid; Inculet, Richard; Kocha, Walter; Malthaner, Richard; Sanatani, Michael; Stitt, Larry; Yaremko, Brian; Younus, Jawaid; Yu, Edward

2010-07-01

The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Effects of multidisciplinary team care on the survival of patients with different stages of non-small cell lung cancer: a national cohort study.

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Chien-Chou Pan

Full Text Available In Taiwan, cancer is the top cause of death, and the mortality rate of lung cancer is the highest of all cancers. Some studies have demonstrated that multidisciplinary team (MDT care can improve survival rates of non-small cell lung cancer (NSCLC patients. However, no study has discussed the effect of MDT care on different stages of NSCLC. The target population for this study consisted of patients with NSCLC newly diagnosed in the 2005-2010 Cancer Registry. The data was linked with the 2002-2011 National Health Insurance Research Database and the 2005-2011 Cause of Death Statistics Database. The multivariate Cox proportional hazards model was used to explore whether the involvement of MDT care had an effect on survival. This study applied the propensity score as a control variable to reduce selection bias between patients with and without involvement of MDT care. The adjusted hazard ratio (HR of death of MDT participants with stage III & IV NSCLC was significantly lower than that of MDT non-participants (adjusted HR = 0.87, 95% confidence interval = 0.84-0.90. This study revealed that MDT care are significantly associated with higher survival rate of patients with stage III and IV NSCLC, and thus MDT care should be used in the treatment of these patients.

GAS5 modulated autophagy is a mechanism modulating cisplatin sensitivity in NSCLC cells.

Science.gov (United States)

Zhang, N; Yang, G-Q; Shao, X-M; Wei, L

2016-06-01

In this study, we investigated the association between lncRNA GAS5 and cisplatin (DDP) resistance in NSCLC and further studied the regulative effect of GAS5 on autophagy and DDP resistance. GAS5 expression in cancerous and adjacent normal tissues from 15 NSCLC patients received neoadjuvant chemotherapy and the following surgery were measured using qRT-PCR analysis. GAS5 gain-and-loss study was performed using A549 and A549/DDP cells as an in-vitro model to investigate the effect of GAS5 on autophagy and cisplatin sensitivity. NSCLC tissues had a substantially lower expression of GAS5 than adjacent normal tissues. The NSCLC tissues from patients with progressive disease (PD) had even lower GAS5 expression. GAS5 knockdown increased DDP IC50 of A549 cells, while GAS5 overexpression decreased DDP IC50 of A549/DDP cells. A549/DDP cells had significantly higher basal autophagy than A549 cells. GAS5 knockdown resulted in decreased autophagy in A549 cells, while GAS5 overexpression led to increased autophagy in A549/DDP cells. Treatment with 3-MA, an autophagy inhibitor, significantly decreased DDP IC50 and promoted DDP-induced cell apoptosis in A549 cells. In addition, 3-MA also partly reversed the effect of GAS5 knockdown. In A549/DDP cells, GAS5 showed the similar effect as 3-MA in reducing DPP IC50 and promoting DDP-induced apoptosis and also presented synergic effect with 3-MA. GAS5 downregulation is associated with cisplatin resistance in NSCLC. GAS5 can inhibit autophagy and therefore enhance cisplatin sensitivity in NSCLC cells.

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

International Nuclear Information System (INIS)

Sidhu, Navdeep S.; Schreiber, Kathrin; Pröpper, Kevin; Becker, Stefan; Usón, Isabel; Sheldrick, George M.; Gärtner, Jutta; Krätzner, Ralph; Steinfeld, Robert

2014-01-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

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Sidhu, Navdeep S. [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Schreiber, Kathrin [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); Pröpper, Kevin [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Usón, Isabel [Instituto de Biologia Molecular de Barcelona (IBMB–CSIC), Barcelona Science Park, Baldiri Reixach 15, 08028 Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), (Spain); Sheldrick, George M. [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Gärtner, Jutta; Krätzner, Ralph, E-mail: rkraetz@gwdg.de; Steinfeld, Robert, E-mail: rkraetz@gwdg.de [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany)

2014-05-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.

Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - A first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study

International Nuclear Information System (INIS)

Baumann, Pia; Nyman, Jan; Hoyer, Morten; Gagliardi, Giovanna; Lax, Ingmar; Wennberg, Berit; Drugge, Ninni; Ekberg, Lars; Friesland, Signe; Johansson, Karl-Axel; Lund, Jo-Asmund; Morhed, Elisabeth; Nilsson, Kristina; Levin, Nina; Paludan, Merete; Sederholm, Christer; Traberg, Anders; Wittgren, Lena; Lewensohn, Rolf

2008-01-01

Background and Aims: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15 Gy x 3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). Material and methods: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45 Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. Results: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. Conclusion: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity

Definition of stereotactic body radiotherapy. Principles and practice for the treatment of stage I non-small cell lung cancer

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Guckenberger, M.; Sauer, O. [University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Andratschke, N. [University of Rostock, Department of Radiotherapy and Radiation Oncology, Rostock (Germany); Alheit, H. [Distler Radiation Oncology, Bautzen/Pirna (Germany); Holy, R. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Moustakis, C. [University of Muenster, Department of Radiation Oncology, Muenster (Germany); Nestle, U. [University of Freiburg, Department of Radiation Oncology, Freiburg (Germany)

2014-01-15

This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft fuer Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy. (orig.) [German] Die Arbeitsgruppe ''Stereotaktische Radiotherapie'' der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) erarbeitete eine Definition der Koerperstereotaxie (SBRT), die sich an vorhandene internationale Definitionen anlehnt: Die SBRT ist eine Form der perkutanen Strahlentherapie, die mit hoher Praezision eine hohe Bestrahlungsdosis in einer oder wenigen Bestrahlungsfraktionen in einem extrakraniellen Zielvolumen appliziert. Zur Praxis der SBRT beim nichtkleinzelligen Bronchialkarzinom (NSCLC) im fruehen Stadium werden detaillierte Empfehlungen gegeben, die den gesamten Ablauf der Behandlung von der Indikationsstellung, Staging, Behandlungsplanung und Applikation sowie Nachsorge umfassen. Die Koerperstereotaxie wurde als Methode der Wahl im Vergleich zu Best Supportive Care, zur konventionell fraktionierten Strahlentherapie sowie zur Radiofrequenzablation identifiziert. Die Ergebnisse nach SBRT und sublobaerer Resektion

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

Science.gov (United States)

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.

Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer

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Grutsch James F

2009-01-01

Full Text Available Abstract Background A frequent manifestation of advanced lung cancer is malnutrition, timely identification and treatment of which can lead to improved patient outcomes. Bioelectrical impedance analysis (BIA is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated the prognostic role of BIA-derived phase angle in advanced non-small cell lung cancer (NSCLC. Methods A case series of 165 stages IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle, independent of stage at diagnosis and prior treatment history. Results 93 were males and 72 females. 61 had stage IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3 degrees (range = 2.9 – 8. Patients with phase angle 5.3 had 12.4 months (95% CI: 10.5 to 18.7; n = 84; (p = 0.02. After adjusting for age, stage at diagnosis and prior treatment history we found that every one degree increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64 to 0.97, P = 0.02. Conclusion We found BIA-derived phase angle to be an independent prognostic indicator in patients with stage IIIB and IV NSCLC. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with advanced NSCLC.

Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

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Fadi Kayali

2011-02-01

Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis

NARCIS (Netherlands)

Janssen-Heijnen, M. L. G.; van Erning, F. N.; De Ruysscher, D. K.; Coebergh, J. W. W.; Groen, H. J. M.

Background: Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during

Impact of the new international association for the study of lung cancer staging system in non-small cell lung cancer: With comparison to the union for international cancer control 6th tumor, node, metastasis edition

International Nuclear Information System (INIS)

Lee, Myung Jae; Lee, So Won; Shim, Sung Shine; Ryu, Yon Ju; Kim, Yoo Kyung

2014-01-01

To investigate the impact of the proposed International Association for the Study of Lung Cancer (IASLC) tumor, node, metastasis (TNM) system on staging and outcome of non small cell lung cancer (NSCLC). With a total of 501 NSCLC patients with staging according to Union for International Cancer Control (UICC), 6th TNM (TNM-6) were reclassified according to the IASLC proposed TNM staging (TNM-7). The impact of TNM-7 in comparison with TNM-6 was evaluated at three levels: change in substage, staging, and outcome. The outcome measure was to compare the stage-specific overall survival of NSCLC between the two groups of patients. A total of 214 (42.7%) patients had changed TNM staging, and 101 (20.2%) patients had changed stage groupings in TNM-7 compared to TNM-6. Among 100 patients showing changed stage grouping, 72 (14.4%) showed upstage and 29 (5.8%) demonstrated downstage. The TNM-7 system resulted in better separation of survival curves among stage-specific NSCLC than TNM-6 system, especially in separation of stage IIA vs. IIB (p 0.023) and stage IIIB vs. IV (p < 0.001). TNM-7 for lung cancer appears to be superior in defining stage-specific survival groups than TNM-6, especially between stage IIA vs. stage IIB and stage IIIB vs. stage IV.

Genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC

International Nuclear Information System (INIS)

Liu Xiaolan; Wang Weili; Zhang Xueying; Hao Ming; Liu Linlin; Wu Zhenfeng; Jiang Hongwei

2008-01-01

Objective: To investigate the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of non-small cell lung cancer (NSCLC). Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to identify mdm2 genotypes. The Pearson Chi square test and Woolf statistic method were used to analyze the relative risk and 95% confidence interval (CI) in order to find the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC. Results: In the SNP rs1196337 (a G to A base change) AA genotype showed association with cough of NSCLC (P<0.05). Conclusion: The polymorphism of mdm2 gene may be associated with symptom as cough of NSCLC. (authors)

The IASLC Lung Cancer Staging Project

DEFF Research Database (Denmark)

Chansky, Kari; Detterbeck, Frank C; Nicholson, Andrew G

2017-01-01

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally...... demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity...... validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC...

A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

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Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-07-15

Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

Dual time point FDG PET/CT:Is it useful for lymph node staging in patients with non small cell lung cancer?

Energy Technology Data Exchange (ETDEWEB)

Kim, Dae Weung; Kim, Woo Hyoung; Kim, Chang Guhn [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

2012-09-15

Dual time point (DTP)FDG PET/CT has been shown to be useful for lymph node (LN)staging in patients with non small cell lung cancer (NSCLC). The aim of this study was to evaluate the LN staging ability of DTP FDG PET/CT in the predominant area of pulmonary tuberculosis. Sixty nine NSCLC patients underwent DTP PET/CT. Regions of interest were placed on each LN of each station, and the maximum SUVs were measured. Three variables were obtained: (1)the SUV on the early scan (SUV{sup early}), (2)the SUV on the delayed scan (SUV{sup delayed}), and (3)the retention index of the SUV (RI). Each patient had one final LN stage and three other LN stages according to the cutoff values of SUV{sup early}, SUV{sup delayed}, and RI. In the LN based analysis, the area under the ROC curve of SUV{sup delayed} (0.884)was significantly larger (p<0.01)than those of SUV{sup early} (0.868)and RI (0.717). Among the three variables, SUV{sup delayed} was more accurate (P<0.01)for detecting the mediastinal LN metastasis than SUV{sup early} and RI. In the patient based analysis, SUV{sup delayed} had correctly determined LN stages in 55 of 69 patients (sensitivity, specificity, and accuracy=88.7%, 50.0%, and 79.7%), whereas SUV{sup early} and RI correctly determined LN stages in 53 and 52 patients, respectively. In this study, comparing the diagnostic efficacy of SUV{sup early}, SUV{sup delayed}, and RI for LN staging in patients with NSCLC, SUV{sup delayed} was the most accurate variable for LN staging. DTP PET/CT could provide improved diagnostic accuracy for the LN staging of NSCLC.

Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer: report of a phase I/II dose-escalating study.

Science.gov (United States)

Thomas, A L; Cox, G; Sharma, R A; Steward, W P; Shields, F; Jeyapalan, K; Muller, S; O'Byrne, K J

2000-12-01

The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis.

Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs.

Directory of Open Access Journals (Sweden)

Chengjuan Zhang

Full Text Available Epidermal growth factor receptor (EGFR specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC. However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients.A total of forty-five (45 NSCLC patients who received EGFR-TKI therapy were enrolled. We identified the changes of EGFR mutations in plasma ctDNA by Amplification Refractory Mutation System (ARMS PCR technology.In the 45 cases of NSCLC with EGFR mutations, the EGFR mutation status changed in 26 cases, in which, 12 cases (26.7% from positive to negative, and 14 cases (31.1% from T790M mutation negative to positive after TKI targeted therapy. The T790M occurance group had a shorter Progression -Free-Survival (PFS than the groups of EGFR mutation undetected and EGFR mutation turned out to have no change after EGFR-TKI therapy (p < 0.05.According to this study, it's necessary to closely monitor EGFR mutations during follow-up to predict the prognosis of NSCLC patients who are to receive the TKI targeted therapy.

Thoracic staging with {sup 18}F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to {sup 18}F-FDG PET/CT?

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Schaarschmidt, Benedikt M. [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Grueneisen, Johannes; Umutlu, Lale [University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Metzenmacher, Martin [University Duisburg-Essen, Medical Faculty, Department of Medical Oncology, Essen (Germany); Gomez, Benedikt; Ruhlmann, Verena [University Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Gauler, Thomas [University Duisburg-Essen, Medical Faculty, Radiation and Tumour Clinic, Essen (Germany); Roesel, Christian [University Duisburg-Essen, Ruhrlandklinik, Thoracic Surgery and Endoscopy, Essen (Germany); Heusch, Philipp; Antoch, Gerald; Buchbender, Christian [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany)

2017-02-15

To investigate whether differences in thoracic tumour staging between {sup 18}F-FDG PET/CT and PET/MR imaging lead to different therapeutic decisions in Non-Small Cell Lung Cancer (NSCLC). Seventy-seven NSCLC patients that underwent whole-body {sup 18}F-FDG PET/CT from the base of skull to the upper thighs and thoracic PET/MR were enrolled in this retrospective study. Thoracic PET/CT and PET/MR images were staged according to the 7th edition of the AJCC staging manual. Staging results of both modalities were discussed separately in a simulated interdisciplinary tumour board and therapeutic decisions based on both imaging modalities were recorded. Descriptive statistics were used to compare the results and reasons for changes in the therapeutic decision were investigated. Staging results differed in 35 % of patients (27 patients) between thoracic PET/CT and PET/MR. Differences were detected when assessing the T-stage in 18 % (n = 14), the N-stage in 23 % (n = 18), and the M-stage in 1 % (n = 1). However, patient therapy management was changed in only six patients (8 %). Despite the variability of thoracic {sup 18}F-FDG PET/CT and PET/MR in TNM-staging, both modalities lead to comparable therapeutic decisions in patients suffering from NSCLC. Hence, {sup 18}F-FDG PET/MR can be considered an possible alternative to {sup 18}F-FDG PET/CT for clinical NSCLC staging. (orig.)

Stage I carcinoma of the endometrium: Some prognostic factors

International Nuclear Information System (INIS)

Perry, H.; Lefkofsky, M.M.; Chang, H.S.; Mantel, J.

1987-01-01

A total of 446 patients with FIGO stage I adenocarcinoma of the endometrium were treated from 1953 to 1980. The overall actuarial survival was 80.77% at 5 years and 72.16% at 10 years. The 5- and 10-year actuarial survivals for various stages are as follows: stage IA: 82.33% and 73.12%; stage IB: 79.80% and 71.55% (P = .4045); stage IB, grade I: 87l.34% and 79.29%; grade II, 83.11% and 75.52%; grade III, 53.62% and 48.53% (P = .0000); stage IC: for patients receiving preoperative radiation therapy with residual carcinoma in the operative specimen, 86.26% and 79.76%; for specimens containing residual tumor, 76.41% and 68.31% (P = .0802). Patient selection appeared to influence survival

Phase I study of cisplatin, vinorelbine, and concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Sekine, Ikuo

2004-01-01

To determine the recommended phase II dose of vinorelbine in combination with cisplatin and thoracic radiotherapy (TRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC), 18 patients received cisplatin (80 mg/m 2 ) on day 1 and vinorelbine (20 mg/m 2 in level 1, and 25 mg/m 2 in level 2) on days 1 and 8 every 4 weeks for 4 cycles. TRT consisted of a single dose of 2 Gy once daily for 3 weeks followed by a rest of 4 days, and then the same TRT for 3 weeks to a total dose of 60 Gy. Fifteen (83%) patients received 60 Gy of TRT and 14 (78%) patients received 4 cycles of chemotherapy. Ten (77%) of 13 patients at level 1 and all 5 patients at level 2 developed grade 3-4 neutropenia. Four (31%) patients at level 1 and 3 (60%) patients at level 2 developed grade 3-4 infection. None developed ≥grade 3 esophagitis or lung toxicity. Dose-limiting toxicity was noted in 33% of the patients in level 1 and in 60% of the patients in level 2. The overall response rate (95% confidence interval) was 83% (59-96%) with 15 partial responses. The median survival time was 30.4 months, and the 1-year, 2-year, and 3-year survival rates were 72%, 61%, and 50%, respectively. In conclusion, the recommended dose is the level 1 dose, and this regimen is feasible and promising in patients with stage III NSCLC. (author)

Radiotherapy following bronchial artery infusion (BAI) chemotherapy for lung cancer. Analysis of long-term treatment results of 168 patients

International Nuclear Information System (INIS)

Miyaji, Noriaki

1995-01-01

Local control is known to contribute to a better survival for non-small cell lung cancer (NSCLC). Radiotherapy with bronchial artery infusion (BAI) of anticancer agents was employed to improve the response rate and prognosis of lung cancer. One hundred and sixty-eight patients of lung cancer were treated by this combined therapy. There were 138 with NSCLC and 30 with small cell lung cancer (SCLC). The overall cumulative 5-year survival rate of NSCLC was 11.3% and median survival time (MST) was 12 months. The response rate of 84% was obtained by this combined therapy. CR cases showed a better result of 35% of 5-year survival. Histology did not influence survival. Stage IIIA patients showed a significantly better survival than stage IIIB patients (p<0.05). No significant difference in survival was observed in the MMC/ADM group and the CDDP group. In SCLC patients, the overall cumulative 5-year survival was 4% and MST was 12 months. In limited disease (LD) group, MST was 13 months and extensive disease (ED) showed 11 months of MST. Two-year survival of LD was 18%. The response rate of this combined therapy was 94% and CR rate was 31%. On patterns of failure, the lower local recurrence rate of 6% (1/18) suggested contribution of BAI in SCLC. However, the long-term survival of SCLC was not greatly improved by radiotherapy combined with BAI. Thus these results suggest that it is necessary for improvement of survival to achieve CR in NSCLC patients, but local control may not contribute to it in SCLC patients. (author)

Textural features in pre-treatment [F18]-FDG-PET/CT are correlated with risk of local recurrence and disease-specific survival in early stage NSCLC patients receiving primary stereotactic radiation therapy.

Science.gov (United States)

Pyka, Thomas; Bundschuh, Ralph A; Andratschke, Nicolaus; Mayer, Benedikt; Specht, Hanno M; Papp, Laszló; Zsótér, Norbert; Essler, Markus

2015-04-22

Textural features in FDG-PET have been shown to provide prognostic information in a variety of tumor entities. Here we evaluate their predictive value for recurrence and prognosis in NSCLC patients receiving primary stereotactic radiation therapy (SBRT). 45 patients with early stage NSCLC (T1 or T2 tumor, no lymph node or distant metastases) were included in this retrospective study and followed over a median of 21.4 months (range 3.1-71.1). All patients were considered non-operable due to concomitant disease and referred to SBRT as the primary treatment modality. Pre-treatment FDG-PET/CT scans were obtained from all patients. SUV and volume-based analysis as well as extraction of textural features based on neighborhood gray-tone difference matrices (NGTDM) and gray-level co-occurence matrices (GLCM) were performed using InterView Fusion™ (Mediso Inc., Budapest). The ability to predict local recurrence (LR), lymph node (LN) and distant metastases (DM) was measured using the receiver operating characteristic (ROC). Univariate and multivariate analysis of overall and disease-specific survival were executed. 7 out of 45 patients (16%) experienced LR, 11 (24%) LN and 11 (24%) DM. ROC revealed a significant correlation of several textural parameters with LR with an AUC value for entropy of 0.872. While there was also a significant correlation of LR with tumor size in the overall cohort, only texture was predictive when examining T1 (tumor diameter 3 cm) subgroups. No correlation of the examined PET parameters with LN or DM was shown. In univariate survival analysis, both heterogeneity and tumor size were predictive for disease-specific survival, but only texture determined by entropy was determined as an independent factor in multivariate analysis (hazard ratio 7.48, p = .016). Overall survival was not significantly correlated to any examined parameter, most likely due to the high comorbidity in our cohort. Our study adds to the growing evidence that tumor

Textural features in pre-treatment [F18]-FDG-PET/CT are correlated with risk of local recurrence and disease-specific survival in early stage NSCLC patients receiving primary stereotactic radiation therapy

International Nuclear Information System (INIS)

Pyka, Thomas; Bundschuh, Ralph A; Andratschke, Nicolaus; Mayer, Benedikt; Specht, Hanno M; Papp, Laszló; Zsótér, Norbert; Essler, Markus

2015-01-01

Textural features in FDG-PET have been shown to provide prognostic information in a variety of tumor entities. Here we evaluate their predictive value for recurrence and prognosis in NSCLC patients receiving primary stereotactic radiation therapy (SBRT). 45 patients with early stage NSCLC (T1 or T2 tumor, no lymph node or distant metastases) were included in this retrospective study and followed over a median of 21.4 months (range 3.1–71.1). All patients were considered non-operable due to concomitant disease and referred to SBRT as the primary treatment modality. Pre-treatment FDG-PET/CT scans were obtained from all patients. SUV and volume-based analysis as well as extraction of textural features based on neighborhood gray-tone difference matrices (NGTDM) and gray-level co-occurence matrices (GLCM) were performed using InterView Fusion™ (Mediso Inc., Budapest). The ability to predict local recurrence (LR), lymph node (LN) and distant metastases (DM) was measured using the receiver operating characteristic (ROC). Univariate and multivariate analysis of overall and disease-specific survival were executed. 7 out of 45 patients (16%) experienced LR, 11 (24%) LN and 11 (24%) DM. ROC revealed a significant correlation of several textural parameters with LR with an AUC value for entropy of 0.872. While there was also a significant correlation of LR with tumor size in the overall cohort, only texture was predictive when examining T1 (tumor diameter < = 3 cm) and T2 (>3 cm) subgroups. No correlation of the examined PET parameters with LN or DM was shown. In univariate survival analysis, both heterogeneity and tumor size were predictive for disease-specific survival, but only texture determined by entropy was determined as an independent factor in multivariate analysis (hazard ratio 7.48, p = .016). Overall survival was not significantly correlated to any examined parameter, most likely due to the high comorbidity in our cohort. Our study adds to the growing evidence

Adjuvant radiotherapy for stage I endometrial cancer.

Science.gov (United States)

Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H

2007-04-18

The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

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

Directory of Open Access Journals (Sweden)

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.

Hypofractionated three-dimensional conformal radiotherapy for medically inoperable early stage

Energy Technology Data Exchange (ETDEWEB)

Lee, Joo Ho; Wu, Hong Gyun; KIm, Hak Jae; Park, Charn Il; Lee, Se Hoon; Kim, Dong Wan; Heo, Dae Seong [Seoul National University College of Medicine, Seou (Korea, Republic of)

2013-01-15

The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. {<=}90 Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.

Adenovirus structural protein IIIa is involved in the serotype specificity of viral DNA packaging.

Science.gov (United States)

Ma, Hsin-Chieh; Hearing, Patrick

2011-08-01

The packaging of the adenovirus (Ad) genome into a capsid displays serotype specificity. This specificity has been attributed to viral packaging proteins, the IVa2 protein and the L1-52/55K protein. We previously found that the Ad17 L1-52/55K protein was not able to complement the growth of an Ad5 L1-52/55K mutant virus, whereas two other Ad17 packaging proteins, IVa2 and L4-22K, could complement the growth of Ad5 viruses with mutations in the respective genes. In this report, we investigated why the Ad17 L1-52/55K protein was not able to complement the Ad5 L1-52/55K mutant virus. We demonstrate that the Ad17 L1-52/55K protein binds to the Ad5 IVa2 protein in vitro and the Ad5 packaging domain in vivo, activities previously associated with packaging function. The Ad17 L1-52/55K protein also associates with empty Ad5 capsids. Interestingly, we find that the Ad17 L1-52/55K protein is able to complement the growth of an Ad5 L1-52/55K mutant virus in conjunction with the Ad17 structural protein IIIa. The same result was found with the L1-52/55K and IIIa proteins of several other Ad serotypes, including Ad3 and Ad4. The Ad17 IIIa protein associates with empty Ad5 capsids. Consistent with the complementation results, we find that the IIIa protein interacts with the L1-52/55K protein in vitro and associates with the viral packaging domain in vivo. These results underscore the complex nature of virus assembly and genome encapsidation and provide a new model for how the viral genome may tether to the empty capsid during the encapsidation process.

Thoracic staging in lung cancer: prospective comparison of 18F-FDG PET/MR imaging and 18F-FDG PET/CT.

Science.gov (United States)

Heusch, Philipp; Buchbender, Christian; Köhler, Jens; Nensa, Felix; Gauler, Thomas; Gomez, Benedikt; Reis, Henning; Stamatis, Georgios; Kühl, Hilmar; Hartung, Verena; Heusner, Till A

2014-03-01

Therapeutic decisions in non-small cell lung cancer (NSCLC) patients depend on the tumor stage. PET/CT with (18)F-FDG is widely accepted as the diagnostic standard of care. The purpose of this study was to compare a dedicated pulmonary (18)F-FDG PET/MR imaging protocol with (18)F-FDG PET/CT for primary and locoregional lymph node staging in NSCLC patients using histopathology as the reference. Twenty-two patients (12 men, 10 women; mean age ± SD, 65.1 ± 9.1 y) with histopathologically confirmed NSCLC underwent (18)F-FDG PET/CT, followed by (18)F-FDG PET/MR imaging, including a dedicated pulmonary MR imaging protocol. T and N staging according to the seventh edition of the American Joint Committee on Cancer staging manual was performed by 2 readers in separate sessions for (18)F-FDG PET/CT and PET/MR imaging, respectively. Results from histopathology were used as the standard of reference. The mean and maximum standardized uptake value (SUV(mean) and SUV(max), respectively) and maximum diameter of the primary tumor was measured and compared in (18)F-FDG PET/CT and PET/MR imaging. PET/MR imaging and (18)F-FDG PET/CT agreed on T stages in 16 of 16 of patients (100%). All patients were correctly staged by (18)F-FDG PET/CT and PET/MR (100%), compared with histopathology. There was no statistically significant difference between (18)F-FDG PET/CT and (18)F-FDG PET/MR imaging for lymph node metastases detection (P = 0.48). For definition of thoracic N stages, PET/MR imaging and (18)F-FDG PET/CT were concordant in 20 of 22 patients (91%). PET/MR imaging determined the N stage correctly in 20 of 22 patients (91%). (18)F-FDG PET/CT determined the N stage correctly in 18 of 22 patients (82%). The mean differences for SUV(mean) and SUV(max) of NSCLC in (18)F-FDG PET/MR imaging and (18)F-FDG PET/CT were 0.21 and -5.06. These differences were not statistically significant (P > 0.05). The SUV(mean) and SUV(max) measurements derived from (18)F-FDG PET/CT and (18)F-FDG PET

Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

2009-01-01

Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived ≥ 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

Therapy for stage I aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

Kluin-Nelemans, Hanneke

2002-01-01

Although radiotherapy was considered sufficient for stage I and limited stage II aggressive non-Hodgkin's lymphoma in the past, new data from randomized studies have shown that intensified chemotherapy or combined modality therapy (multiagent chemotherapy followed by involved field radiotherapy) can

Prognostic and predictive role of FOXP3 positive tumor infiltrating lymphocytes (TILs in curatively resected non small cell lung cancer other than stage IA

Directory of Open Access Journals (Sweden)

Fatih Kose

2017-12-01

Full Text Available Lung cancer is the leading cause of cancer-related mortality and responsible for 1.6 million deaths per year through world-wide. Surgical resection with negative margin combined with the adjuvant therapy [except for stage IA and IB (<4 cm] is the Standard treatment for early-stage Non-small cell lung cancer (NSCLC. Early-stage NSCLC, however, has relapse rate over 40% mostly at distant sites. Therefore, high relapse rate necessitates urgent novel biomarker for these patients. In this study, we aim to evaluate the predictive and prognostic role of FOXP3+ Treg cells along with well defined Clinicohistopathological factors in early-stage non-small cell lung cancer (NSCLC. FOXP3 expression in tumor infiltrating lymphocytes (TIL was examined by immunohistochemical staining from resected early-stage 48 NSCLC patients. Data of patients and FOXP3 expression status along with common clinicohistopathological prognostic factors were evaluated retrospectively. Median age of patients was 62 years-old (range 43–78. Mean follow-up, median overall survival (OS, and disease-free survival (DFS were 49, 49 and 30 months, respectively. FOXP3 expression was positive in 23 (47.9% patients. Adjuvant chemotherapy (4 cycles of cisplatin-vinorelbine was given to 16 patients (33.3% at physician discretion. Patients with a FOXP3 expression of 25% or higher significantly lower OS and DFS when compared with patients with a FOXP3 staining lower than 25% with p-value of 0.016 and 0.032, respectively. In the patients with high FOXP3 expression, platin-based adjuvant chemotherapy had showed a detrimental effect on DFS and OS. These results suggest that FOXP3 expression may be used as useful prognostic biomarker in resected NSCLC. Our findings also suggest that resected NSCLC patients with FOXP3 expression of 25% or higher staining intensity may not get any benefit even disfavor from adjuvant platin chemotherapy.

Evaluation of therapeutic response with 18-FDG PET-CT for non-small cell lung cancer: case report and literature review

International Nuclear Information System (INIS)

Bitencourt, Almir G.V.; Lima, Eduardo N.P.; Chojniak, Rubens; Haddad, Fabio J.; Dettino, Aldo L.A.; Cavicchioli, Marcelo; Torres, Ivone C.G.

2010-01-01

Positron Emission Tomography / Computed Tomography (PET-CT) is increasingly being used as to complement conventional imaging methods and improve the management of patients with non-small cells lung cancer (NSCLC). The objective of this work is to report on a case in which PET-CT was used as a complementary method to evaluate the therapeutic response in a patient with NSCLC, and to carry out a literature review of the theme. Female patient, 65 years-old, with NSCLC, stage IIIA (T2N2M0), was submitted to exclusive neoadjuvant chemotherapy and presented good response to the treatment, classified by the morphological criteria of the RECIST (Response Evaluation Criteria in Solid Tumors) as a partial response (reduction equal to or greater than 30% in the sum of the widest diameter of all the target lesions in the computed tomography). The metabolic evaluation by PET-CT showed a complete response (reduction equal to or higher than 80% at maximum SUV of the lesions), which was confirmed in the histopathological analysis of the surgical samples. In the case presented, and through the literature review, we show that the evaluation of response with metabolic criteria, associated with morphological criteria, may be more accurate than the use of morphological criteria alone. (author)

[The progressive reduction of functioning in the course of mucopolysaccharidosis type IIIA - longitudinal study of two siblings].

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Michalska, Agata; Nawrocka, Małgorzata; Znój, Dorota

2013-01-01

This paper presents a description of changes in the functioning of two siblings diagnosed with mucopolysaccharidosis type III A. Both are under specialist care exercised by the Rehabilitation, Care and Education Centre in the city Kielce, including care of a oligophrenopedagogue, a psychologist, a speech therapist and a physiotherapist. Evaluation of changes in functioning of two siblings diagnosed with mucopolysaccharidosis type IIIA. The longitudinal study covered two children with MPS type IIIA. During the 29 months of observation, there were six measurements on the basis of PPAC Gunzburg Inventory in the Polish adaptation by Tadeusz Witkowski. The results are shown in the form of PPAC diagrams and profiles of functioning. Despite the differences in the presence and severity of somatic and neurocognitive symptoms, functioning both of the boy and the girl does not differ from functioning described in the literature. Therapeutic interventions have produced short-term improvements in its area of self-service, communication and activities. Despite the similar trend of changes in functioning, there is an inter-individual variability in the quality of patterns and dynamics of progress. The progressive decrease in the level of functioning in patients with MPS IIIA does not preclude the acquisition of new skills. They are not permanent, however. There is a need for functional assessment in order to learn more about the specificity of the disease and to assume an individualised therapeutic approach aimed at improving the quality of life of patients with MPS IIIA and, indirectly, the quality of life of their families.

A potential to reduce pulmonary toxicity: The use of perfusion SPECT with IMRT for functional lung avoidance in radiotherapy of non-small cell lung cancer

International Nuclear Information System (INIS)

Lavrenkov, Konstantin; Christian, Judith A.; Partridge, Mike; Niotsikou, Elena; Cook, Gary; Parker, Michelle; Bedford, James L.; Brada, Michael

2007-01-01

Background and purpose: The study aimed to examine specific avoidance of functional lung (FL) defined by a single photon emission computerized tomography (SPECT) lung perfusion scan, using intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3-DCRT) in patients with non-small cell lung cancer (NSCLC). Materials and methods: Patients with NSCLC underwent planning computerized tomography (CT) and lung perfusion SPECT scan in the treatment position using fiducial markers to allow co-registration in the treatment planning system. Radiotherapy (RT) volumes were delineated on the CT scan. FL was defined using co-registered SPECT images. Two inverse coplanar RT plans were generated for each patient: 4-field 3-DCRT and 5-field step-and-shoot IMRT. 3-DCRT plans were created using automated AutoPlan optimisation software, and IMRT plans were generated employing Pinnacle 3 treatment planning system (Philips Radiation Oncology Systems). All plans were prescribed to 64 Gy in 32 fractions using data for the 6 MV beam from an Elekta linear accelerator. The objectives for both plans were to minimize the volume of FL irradiated to 20 Gy (fV 20 ) and dose variation within the planning target volume (PTV). A spinal cord dose was constrained to 46 Gy. Volume of PTV receiving 90% of the prescribed dose (PTV 90 ), fV 20 , and functional mean lung dose (fMLD) were recorded. The PTV 90 /fV 20 ratio was used to account for variations in both measures, where a higher value represented a better plan. Results: Thirty-four RT plans of 17 patients with stage I-IIIB NSCLC suitable for radical RT were analysed. In 6 patients with stage I-II disease there was no improvement in PTV 90 , fV 20 , PTV/fV 20 ratio and fMLD using IMRT compared to 3-DCRT. In 11 patients with stage IIIA-B disease, the PTV was equally well covered with IMRT and 3-DCRT plans, with IMRT producing better PTV 90 /fV 20 ratio (mean ratio - 7.2 vs. 5.3, respectively, p = 0.001) and reduced f

SSX2-4 expression in early-stage non-small cell lung cancer

DEFF Research Database (Denmark)

Greve, K B V; Pøhl, M; Olsen, K E

2014-01-01

The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; Systematic review and comparison with a surgical cohort

International Nuclear Information System (INIS)

Soldà, Francesca; Lodge, Mark; Ashley, Sue; Whitington, Alastair; Goldstraw, Peter; Brada, Michael

2013-01-01

Background and purpose: To assess the efficacy of stereotactic ablative radiotherapy (SABR) for the treatment of non-small cell lung cancer (NSCLC) through a systematic review of all relevant publications from 2006 to the present compared to controls treated with surgery. In the absence of Grade I evidence, the objective outcome data should form the basis for planning future studies and commissioning SABR services. Materials and methods: Standard systematic review methodology extracting patient and disease characteristics, treatment and outcome data from published articles reporting patient data from populations of 20 or more Stage I NSCLC patients treated with SABR with a median follow up of minimum of 1 year. The individual outcome measures were corrected for stage and summary weighted outcome data were compared to outcome data from a large International Association for the Study of Lung Cancer (IASLC) cohort matched for stage of disease with survival as the principal endpoint and local control (local progression free survival – local PFS) as the secondary endpoint. Results: Forty-five reports containing 3771 patients treated with SABR for NSCLC were identified that fulfilled the selection criteria; both survival and staging data were reported in 3171 patients. The 2 year survival of the 3201 patients with localized stage I NSCLC treated with SABR was 70% (95% CI: 67–72%) with a 2 year local control of 91% (95% CI: 90–93%). This was compared to a 68% (95% CI: 66–70) 2 year survival of 2038 stage I patients treated with surgery. There was no survival or local PFS difference with different radiotherapy technologies used for SABR. Conclusions: Systematic review of a large cohort of patients with stage I NSCLC treated with SABR suggests that survival outcome in the short and medium term is equivalent to surgery for this population of patients regardless of co-morbidity. As selection bias cannot be assessed from the published reports and treatment related

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

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Jin, Hyeon-Ok [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Hong, Sung-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Kim, Chang Soon [Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143–701 (Korea, Republic of); Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Park, In-Chul, E-mail: parkic@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Lee, Jin Kyung, E-mail: jklee@kirams.re.kr [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of)

2015-08-15

Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.

Fluorine F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for restaging of non small cell lung cancer (NSCLC): analysis of management change and survival in 63 consecutive patients

International Nuclear Information System (INIS)

Hicks, R.J.; Binns, D.J.; Kalff, V.; Ware, R.E.; Hogg, A.; MacManus, M.P.; Ball, D.L.; Suter, M.E.; Matthews, J.

2000-01-01

Full text: Following treatment with curative intent for non small cell lung cancer (NSCLC), assessment of disease status using conventional techniques is often difficult. We evaluated management impact and prognostic value of FDG PET in 63 consecutive patients undergoing restaging of NSCLC between 11/96 and 12/98. All patients were >6 months from primary treatment with curative intent. Salvage therapy with curative intent was being contemplated in 18 patients. Conventional imaging was abnormal 61/63 patients, two others had recurrent symptoms only. Compared to conventional restaging, 33% of patients were down-staged, and 35% were upstaged by PET. PET led to more aggressive treatment than planned in 7 patients (11%), a change from planned curative to palliative treatment in 8 patients (13%) and 17 patients (27%) thought to have recurrent disease had no further investigation or treatment after negative PET studies. Cox proportional hazards analysis indicated that a positive PET scan had a hazard ratio of 2.95 (95% CI 1.038.50, p = 0.012) compared to negative PET. Extent of active disease on PET was also prognostically significant with each incremental extent category (no disease, local recurrence, limited locoregional, extensive locoregional and systemic) having an estimated 60% increase in the rate of death (95% Cl 24% to 107%, p<0.0001). Stage of disease at initial diagnosis, primary treatment used and disease extent on conventional restaging were not predictive of survival. Thus, PET provided a high impact on management for NSCLC patients with suspected recurrence and more accurate prognostic stratification than conventional staging. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

Penetration of Recommended Procedures for Lung Cancer Staging and Management in the United States Over 10 Years: A Quality Research in Radiation Oncology Survey

Energy Technology Data Exchange (ETDEWEB)

Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Khalid, Najma [American College of Radiology, Philadelphia, Pennsylvania (United States); Langer, Corey J. [Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Kong, Feng-Ming [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Owen, Jean B.; Crozier, Cheryl L. [American College of Radiology, Philadelphia, Pennsylvania (United States); Wilson, J. Frank [Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wei, Xiong [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Movsas, Benjamin [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States)

2013-03-15

Purpose: To document the penetration of clinical trial results, practice guidelines, and appropriateness criteria into national practice, we compared the use of components of staging and treatment for lung cancer among patients treated in 2006-2007 with those used in patients treated in 1998-1999. Methods and Materials: Patient, staging work-up, and treatment characteristics were extracted from the process survey database of the Quality Research in Radiation Oncology (QRRO), consisting of records of 340 patients with locally advanced non-small cell lung cancer (LA-NSCLC) at 44 institutions and of 144 patients with limited-stage small cell lung cancer (LS-SCLC) at 39 institutions. Data were compared for patients treated in 2006-2007 versus those for patients treated in 1998-1999. Results: Use of all recommended procedures for staging and treatment was more common in 2006-2007. Specifically, disease was staged with brain imaging (magnetic resonance imaging or computed tomography) and whole-body imaging (positron emission tomography or bone scanning) in 66% of patients with LA-NSCLC in 2006-2007 (vs 42% in 1998-1999, P=.0001) and in 84% of patients with LS-SCLC in 2006-2007 (vs 58.3% in 1998-1999, P=.0011). Concurrent chemoradiation was used for 77% of LA-NSCLC patients (vs 45% in 1998-1999, P<.0001) and for 90% of LS-SCLC patients (vs 62.5% in 1998-1999, P<.0001). Use of the recommended radiation dose (59-74 Gy for NSCLC and 60-70 Gy as once-daily therapy for SCLC) did not change appreciably, being 88% for NSCLC in both periods and 51% (2006-2007) versus 43% (1998-1999) for SCLC. Twice-daily radiation for SCLC was used for 21% of patients in 2006-2007 versus 8% in 1998-1999. Finally, 49% of patients with LS-SCLC received prophylactic cranial irradiation (PCI) in 2006-2007 (vs 21% in 1998-1999). Conclusions: Although adherence to all quality indicators improved over time, brain imaging and recommended radiation doses for stage III NSCLC were used in <90% of cases. Use

Treatment selection of early stage non-small cell lung cancer: the role of the patient in clinical decision making.

Science.gov (United States)

Mokhles, S; Nuyttens, J J M E; de Mol, M; Aerts, J G J V; Maat, A P W M; Birim, Ö; Bogers, A J J C; Takkenberg, J J M

2018-01-15

The objective of this study is to investigate the role and experience of early stage non-small cell lung cancer (NSCLC) patient in decision making process concerning treatment selection in the current clinical practice. Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68) were included in this prospective study and completed a questionnaire that explored: (1) perceived patient knowledge of the advantages and disadvantages of the treatment options, (2) experience with current clinical decision making, and (3) the information that the patient reported to have received from their treating physician. This was assessed by multiple-choice, 1-5 Likert Scale, and open questions. The Decisional Conflict Scale was used to assess the decisional conflict. Health related quality of life (HRQoL) was measured with SF-36 questionnaire. In 19% of patients, there was self-reported perceived lack of knowledge about the advantages and disadvantages of the treatment options. Seventy-four percent of patients felt that they were sufficiently involved in decision-making by their physician, and 81% found it important to be involved in decision making. Forty percent experienced decisional conflict, and one-in-five patients to such an extent that it made them feel unsure about the decision. Subscores with regard to feeling uninformed and on uncertainty, contributed the most to decisional conflict, as 36% felt uninformed and 17% of patients were not satisfied with their decision. HRQoL was not influenced by patient experience with decision-making or patient preferences for shared decision making. Dutch early-stage NSCLC patients find it important to be involved in treatment decision making. Yet a substantial proportion experiences decisional conflict and feels uninformed. Better patient information and/or involvement in treatment-decision-making is needed in order to improve patient knowledge and hopefully reduce decisional conflict.

Design Guidelines and Criteria for User/Operator Transactions with Battlefield Automated Systems. Volume III-A. Human Factors Analyses of User/ Operator Transactions with TACFIRE - The Tactical Fire Direction System

Science.gov (United States)

1981-02-01

7. Reseaarch Product 81-26 - DESIGN GUIDELINES AND CRITERIA FOR USER/ I;. I’OPERATOR TRANSACTIONS WITH BATTLEFIELD AUTOMIATED SYSTEMS I’ /HVtAN...FACTORS XWLYSES :’F K~R/ OPERATOR TRANSACTIONS WTHT TACFIRE - THE TACTICAL FIRE DiRECTION SY2T3EM A HUMAN FACTORS TECHNICAL AREA L~h~h K L-J 1’ U~~i~ ll...Battlefield Auto- Inter : Oct 1979-Feb 1981 mated Systems Volume III-A: Human Factors 4t C/ Analyses of User/Operator Transactions with 6. PERFORMING

Efficacy and adverse effects of icotinib in treatment of 30 NSCLC patients with brain metastases

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Yu-hong DAI

2016-06-01

Full Text Available Objective 　To evaluate the efficacy and adverse effects of icotinib in the treatment for non-small cell lung cancer (NSCLC patients with brain metastases. Methods 　This study was performed at Tongji Hospital Cancer Center over the period between September 2011 and November 2015. Thirty cases of advanced NSCLC patients with icotinib monotherapy were enrolled, all with brain metastases, the median follow-up time being 24 months (5.5-49.0 months, with no case censored. The follow-up rate was 100%, and the data of efficacy and adverse effects were collected. Results 　The intracranial progression-free survival (iPFS was 9.6 months, while no patient exhibited complete remission (CR, 8 patients showed partial remission (PR and 14 showed stable disease (SD in the intracranial foci. The intracranial disease control rate (DCR was 73.3%, and the objective remission rate (ORR was 26.7%. The extracranial progression-free survival (ePFS was 10.1 months, while no patient exhibited CR, 11 patients showed PR and 11 patients showed SD in the extracranial foci. The extracranial DCR was 73.3%, and the ORR was 36.7%. The one-year survival rate was 63.8% in all the 30 patients. Twelve (40.0% of the total 30 patients developed rash, five (16.7% developed grade 1 diarrhea, one (3.3% developed grade 2 transaminase elevation. None of the patients experienced headache, nausea, vomiting, fatigue, etc. Conclusion 　Icotinib hydrochloride is effective and safe for NSCLC patients with brain metastasis. DOI: 10.11855/j.issn.0577-7402.2016.06.11