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  1. 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...

  2. Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study.

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    Cadranel, Jacques; Park, Keunchil; Arrieta, Oscar; Pless, Miklos; Bendaly, Edmond; Patel, Dony; Sasane, Medha; Nosal, Adam; Swallow, Elyse; Galebach, Philip; Kageleiry, Andrew; Stein, Karen; Degun, Ravi; Zhang, Jie

    2016-08-01

    Second-generation ALK inhibitors are recently available for ALK+ non-small cell lung cancer (NSCLC) patients previously treated with crizotinib. This study described characteristics, treatment sequencing, and outcomes among locally advanced/metastatic crizotinib-experienced ALK+ NSCLC patients. From July 2014 to June 2015, a retrospective patient chart review was conducted among physicians from the US, EU, Korea, and Latin America. Participating clinicians identified their ALK+ NSCLC patients who received crizotinib and reported on their clinical characteristics, treatments, and survival using a pre-defined case report form. Kaplan-Meier analyses were used to describe overall survival (OS) and clinician-defined progression-free survival (PFS). Participating clinicians reviewed charts of 158 ALK+ NSCLC patients treated with crizotinib during the study period. Crizotinib was most commonly received in the second-line setting (41% of patients), though this varied across geographical regions. Roughly half (53%) of the patients who discontinued crizotinib received further antineoplastic therapy; second-generation ALK inhibitors (44%) and chemotherapy (42%) regimens were used most frequently. Following crizotinib discontinuation, median OS was 8.2 months. Among patients who did not initiate a second-generation ALK inhibitor following crizotinib, median OS was 4.9 months; among those who did, median OS was not reached. Among patients who received chemotherapy immediately following crizotinib discontinuation, time to clinician-defined PFS from post-crizotinib chemotherapy initiation was 3.6 months. Following crizotinib discontinuation, many patients received no further antineoplastic therapy, and OS was poor among patients who did not receive a second-generation ALK inhibitor. Recently available second-generation ALK inhibitors may provide important treatment options for ALK+ NSCLC patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

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    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston MA, 02215 (United States); Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States); Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States)

    2017-03-15

    Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

  4. Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

    International Nuclear Information System (INIS)

    Nishino, Mizuki; Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra; Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto; Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin

    2017-01-01

    Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

  5. EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther Larsen, Anne; Nissen, Peter Henrik; Meldgaard, Peter

    2014-01-01

    OBJECTIVES: Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription...... patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA≤16 in any allele) or long alleles (CA>16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based...

  6. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    International Nuclear Information System (INIS)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R

    2015-01-01

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  7. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

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    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

    2015-06-15

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  8. Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib

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    Winther-Larsen, Anne; Fledelius, Joan; Sorensen, Boe Sandahl

    2016-01-01

    OBJECTIVES: Accurate estimation of the prognosis of advanced non-small cell lung cancer (NSCLC) patients is essential before initiation of palliative treatment; especially in the second and third-line setting. This study was conducted in order to evaluate tumor burden measured on an 2'-deoxy-2......'-[18F] fluoro-D-glucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) scan as a marker of outcome in advanced epidermal growth factor receptor (EGFR) wild-type patients treated with second or third-line erlotinib.MATERIAL AND METHODS: Fifty-one patients were included from...... a prospectively collected cohort. An F-18-FDG-PET/CT scan was conducted prior to erlotinib treatment and tumor burden was measured in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Median values of MTV and TLG were used for dichotomization of patients. Survival outcome was compared...

  9. Pemetrexed as second-line therapy for advanced non-small-cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Enriqueta Felip

    2008-06-01

    Full Text Available Enriqueta Felip1, Rafael Rosell21Vall d’Hebron University Hospital, Barcelona, Spain; 2Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: NSCLC accounts for 80% of all cases of lung cancer, which is the leading cause of cancer mortality. The majority of NSCLC patients present with advanced, unresectable disease, which remains incurable. In advanced disease, chemotherapy with platinum (cisplatin or carboplatin in combination with a third-generation cytotoxic drug (vinorelbine, gemcitabine, paclitaxel, or docetaxel can provide a modest improvement in survival without impairing quality of life. In chemotherapy-naïve, advanced, non-squamous NSCLC patients, the combination of bevacizumab with chemotherapy was shown to produce better outcomes than chemotherapy alone. Response rates of 20%–40% can now be expected, with a median survival of 8–11 months and a 1-year survival rate of 30%–40%. In second-line treatment, docetaxel has shown superiority to best supportive care in terms of survival and quality of life. A pooled analysis comparing docetaxel administered weekly versus 3-weekly found similar survival rates between the schedules and a non-significant reduction in febrile neutropenia for the weekly regimen. Pemetrexed, a multitargeted antifolate agent, has shown clear activity in several tumors, including mesothelioma and NSCLC. In a phase III trial, second-line treatment with pemetrexed demonstrated overall survival comparable to docetaxel, with a more manageable toxicity profile.Keywords: pemetrexed, second-line therapy, NSCLC

  10. 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.

  11. Activity of crizotinib over choroidal metastases in non-small-cell lung cancer (NSCLC)-ALK rearranged: a case report.

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    Bearz, Alessandra; Santarossa, Sandra; Manfrè, Antonio; Beltrame, Giorgio; Urbani, Martina; Sartor, Ivana; Da Ros, Valentina; Tirelli, Umberto

    2014-09-02

    Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib. Despite the concerns about the efficacy of crizotinib over cerebral metastases, some reports have described its activity, although always after local treatment with radiotherapy. Recently it has been reported activity of crizotinib over choroidal metastases, again after radiotherapy. Herein we report a case of activity of crizotinib over choroidal metastases not previously treated with radiotherapy. We suggest crizotinib may be active over choroidal metastases in a patient harboring ALK translocation with no need of radiotherapy.

  12. VeriStrat (R) has prognostic value in advanced stage NSCLC patients treated with erlotinib and sorafenib

    NARCIS (Netherlands)

    Kuiper, J. L.; Lind, J. S. W.; Groen, H. J. M.; Roder, J.; Grigorieva, J.; Roder, H.; Dingemans, A. M. C.; Smit, E. F.

    2012-01-01

    BACKGROUND: The serum proteomic test VeriStrat has been shown to be able to classify advanced non-small cell lung cancer (NSCLC) patients for overall survival (OS) after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, VeriStrat was evaluated

  13. Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report

    International Nuclear Information System (INIS)

    Casadei Gardini, Andrea; Chiadini, Elisa; Faloppi, Luca; Marisi, Giorgia; Delmonte, Angelo; Scartozzi, Mario; Loretelli, Cristian; Lucchesi, Alessandro; Oboldi, Devil; Dubini, Alessandra; Frassineti, Giovanni Luca; Ulivi, Paola

    2016-01-01

    Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug. Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity. Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients

  14. Genotyping non-small cell lung cancer (NSCLC) in Latin America.

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    Arrieta, Oscar; Cardona, Andrés Felipe; Federico Bramuglia, Guillermo; Gallo, Aly; Campos-Parra, Alma D; Serrano, Silvia; Castro, Marcelo; Avilés, Alejandro; Amorin, Edgar; Kirchuk, Ricardo; Cuello, Mauricio; Borbolla, José; Riemersma, Omar; Becerra, Henry; Rosell, Rafael

    2011-11-01

    Frequency of mutations in EGFR and KRAS in non-small cell lung cancer (NSCLC) is different between ethnic groups; however, there is no information in Latin-American population. A total of 1150 biopsies of NSCLC patients from Latin America (Argentina, Colombia, Peru, and Mexico) were used extracting genomic DNA to perform direct sequencing of EGFR gene (exons 18 and 21) and KRAS gene in 650 samples. In Mexico, Scorpions ARMS was also used to obtain a genetic profile. We report the frequency of mutations in EGFR and KRAS genes in four Latin-American countries (n = 1150). Frequency of EGFR mutations in NSCLC was 33.2% (95% confidence interval [CI] 30.5-35.9) (Argentina 19.3%, Colombia 24.8%, Mexico 31.2%, and Peru 67%). The frequency of KRAS mutations was 16.6% (95% CI 13.8-19.4). EGFR mutations were independently associated with adenocarcinoma histology, older age, nonsmokers, and absence of KRAS mutations. Overall response rate to tyrosine kinase inhibitors in EGFR-mutated patients (n = 56) was 62.5% (95% CI 50-75) with a median overall survival of 16.5 months (95% CI 12.4-20.6). Our findings suggest that the frequency of EGFR mutations in Latin America lies between that of Asian and Caucasian populations and therefore support the genetic heterogeneity of NSCLC around the world.

  15. New modalities of cancer treatment for NSCLC: focus on immunotherapy

    International Nuclear Information System (INIS)

    Davies, Marianne

    2014-01-01

    Recent advances in the understanding of immunology and antitumor immune responses have led to the development of new immunotherapies, including vaccination approaches and monoclonal antibodies that inhibit immune checkpoint pathways. These strategies have shown activity in melanoma and are now being tested in lung cancer. The antibody drugs targeting cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death protein-1 immune checkpoint pathways work by restoring immune responses against cancer cells, and are associated with unconventional response patterns and immune-related adverse events as a result of their mechanism of action. As these new agents enter the clinic, nurses and other health care providers will require an understanding of the unique efficacy and safety profiles with immunotherapy to optimize potential patient benefits. This paper provides a review of the new immunotherapeutic agents in development for lung cancer, and strategies for managing patients on immunotherapy

  16. Dose to heart substructures is associated with non-cancer death after SBRT in stage I-II NSCLC patients.

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    Stam, Barbara; Peulen, Heike; Guckenberger, Matthias; Mantel, Frederick; Hope, Andrew; Werner-Wasik, Maria; Belderbos, Jose; Grills, Inga; O'Connell, Nicolette; Sonke, Jan-Jakob

    2017-06-01

    To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    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

  18. Sulforaphane attenuates EGFR signaling in NSCLC cells.

    Science.gov (United States)

    Chen, Chi-Yuan; Yu, Zhu-Yun; Chuang, Yen-Shu; Huang, Rui-Mei; Wang, Tzu-Chien V

    2015-06-03

    EGFR, a receptor tyrosine kinase (RTK), is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of many cancers, including NSCLC. However, intrinsic and acquired resistance to TKI remains a common obstacle. One strategy that may help overcome EGFR-TKI resistance is to target EGFR for degradation. As EGFR is a client protein of heat-shock protein 90 (HSP90) and sulforaphane is known to functionally regulate HSP90, we hypothesized that sulforaphane could attenuate EGFR-related signaling and potentially be used to treat NSCLC. Our study revealed that sulforaphane displayed antitumor activity against NSCLC cells both in vitro and in vivo. The sensitivity of NSCLC cells to sulforaphane appeared to positively correlate with the inhibition of EGFR-related signaling, which was attributed to the increased proteasomal degradation of EGFR. Combined treatment of NSCLC cells with sulforaphane plus another HSP90 inhibitor (17-AAG) enhanced the inhibition of EGFR-related signaling both in vitro and in vivo. We have shown that sulforaphane is a novel inhibitory modulator of EGFR expression and is effective in inhibiting the tumor growth of EGFR-TKI-resistant NSCLC cells. Our findings suggest that sulforaphane should be further explored for its potential clinical applications against NSCLC.

  19. Combination of immunotherapy with targeted therapies in advanced non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Moya-Horno, Irene; Viteri, Santiago; Karachaliou, Niki; Rosell, Rafael

    2018-01-01

    Treatment for advanced non-small cell lung cancer (NSCLC) has been significantly improved in recent years with the incorporation of drugs targeting antiangiogenesis and more specifically genomic alterations such as the EGFR mutations and ALK translocations. However, most patients invariably progress and die. The emergence of immune checkpoint inhibitors targeting the pathways involved in tumor-induced immunosuppression have redefined the management of the disease, achieving significant long-lasting responses with manageable safety profiles, regardless of histology. Still, response rates with immunotherapy are deemed suboptimal. Current efforts are focusing on new potential combination strategies with synergistic antitumor activity, using immune checkpoint blockade as a partner for targeted agents. Herein we discuss the available data on the combined use of immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, with EGFR and ALK inhibitors and comment on the current status of immunotherapy plus antiangiogenic drugs for molecularly unselected advanced NSCLC.

  20. 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.

  1. 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

  2. Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Amer Khalid

    2009-08-01

    Full Text Available Abstract Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

  3. Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) of Yunnan in southwestern China

    OpenAIRE

    Zhou, Yongchun; Yang, Yanlong; Yang, Chenggang; Chen, Yunlan; Yang, Changshao; Du, Yaxi; Zhao, Guangqiang; Ye, Lianhua; Huang, Yunchao

    2017-01-01

    To investigate the Epidermal Growth Factor Receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC) in Yunnan province in southwestern China, we detected EGFR mutation by Amplification Refractory Mutation System (ARMS) polymerase chain reaction (PCR) using DNA samples from 447 pathologically confirmed NSCLC specimens (175 tissue, 256 plasma and 16 cytologic samples). The relationship between EGFR mutations and demographic and clinical factors were further explored. Subgroup analy...

  4. 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.

  5. Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

    LENUS (Irish Health Repository)

    Cathcart, Mary Clare

    2011-06-01

    Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng\\/ml) and cell survival\\/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation\\/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis\\/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor\\/potential target in

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Acute esophagitis for patients with Local-regional Advanced NSCLC treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Y.; Brink, C.; Knap, M.

    2015-01-01

    Purpose/Objective: Esophagitis are one of the acute treatment related toxicities to definitive radiotherapy for NSCLC. Most current researches about the risk factors for acute esophagitis are based on 3DCRT. The purpose of this study was to estimate the dose-effect relationship between esophagitis...... cycles of induction chemotherapy followed by IMRT and CCT (fixed dose of vinorelbine 50 mg three times per week). The maximal esophagitis grade was prospectively scored using the Common Toxicity Criteria 3.0. Clinical and dosimetric variables were analyzed for the correlation with grade >2 esophagitis...... of esophagus and one at the end) irradiated above a certain dose. The dose variable was either maximum dose, mean dose, the physical length of esophagus irradiated above a specific dose (Lx), or the relative volume of esophagus irradiated above a specified dose (Vx). To validate the impact of the fixed dose...

  8. Feasibility of curative radiotherapy with a concomitant boost technique in 33 patients with non-small cell lung cancer (NSCLC)

    NARCIS (Netherlands)

    Schuster-Uitterhoeve, A. L.; Hulshof, M. C.; Gonzàlez Gonzàlez, D.; Koolen, M.; Sminia, P.

    1993-01-01

    Thirty-three patients with an inoperable NSCLC were treated with a dose of 60 Gy/20 fractions/25 days, using a concomitant boost technique. A dose of 40 Gy/2 Gy/25 days was given to the tumor area and a part (15 patients) or the whole (18 patients) mediastinum. During each session a simultaneous

  9. Plasma PGE-2 levels and altered cytokine profiles in adherent peripheral blood mononuclear cells in non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Hirschowitz Edward A

    2002-11-01

    Full Text Available Abstract Introduction PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile. Results Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming similar reports in the literature. Data show plasma PGE-2 levels in 38 NSCLC patients are elevated compared to normal controls. Plasma IL10 levels were not significantly elevated; however, adherent monocytes derived from NSCLC patient blood did produce significantly more IL10 in 24 hr primary culture than those from normal controls (p Conclusions Elevated plasma PGE-2 and monocyte IL10 production are associated with NSCLC. The biological significance to elevated PGE-2 levels in NSCLC are unclear. Further investigation of each as a nonspecific marker for NSCLC tumor is warranted.

  10. Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)-validation in two independent cohorts

    DEFF Research Database (Denmark)

    Buhl, Ida Kappel; Santoni-Rugiu, Eric; Ravn, Jesper

    2018-01-01

    INTRODUCTION: Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presen......INTRODUCTION: Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts...... are presented. METHODS: The profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel. An applied clinical samples filter focused the profiles to clinically relevant genes. The profiles were tested...

  11. Activity of crizotinib over choroidal metastases in Non-Small-Cell Lung Cancer (NSCLC)-ALK rearranged: a case report

    OpenAIRE

    Bearz, Alessandra; Santarossa, Sandra; Manfrè, Antonio; Beltrame, Giorgio; Urbani, Martina; Sartor, Ivana; Da Ros, Valentina; Tirelli, Umberto

    2014-01-01

    Background Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib. Despite the concerns about the efficacy of crizotinib over cerebral metastases, some reports have described its activity, although always after local treatment with radiotherapy. Recently it has been reported activity of crizotinib over choroidal metastases, again after radiotherapy. Case presentation Herei...

  12. 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

    2017-01-01

    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...

  13. Radiation pneumonitis in non.small.cell lung cancer patients treated ...

    African Journals Online (AJOL)

    Radiation pneumonitis in non.small.cell lung cancer patients treated with helical tomotherapy. B Yao, YD Wang, QZ Liu. Abstract. Objective: In this study, we investigated the incidence of radiation pneumonitis (RP) in non.small.cell lung cancer (NSCLC) patients undergoing helical tomotherapy (HT) and the clinical and ...

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

    Science.gov (United States)

    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.

  15. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.

    Science.gov (United States)

    Platt, Adam; Morten, John; Ji, Qunsheng; Elvin, Paul; Womack, Chris; Su, Xinying; Donald, Emma; Gray, Neil; Read, Jessica; Bigley, Graham; Blockley, Laura; Cresswell, Carl; Dale, Angela; Davies, Amanda; Zhang, Tianwei; Fan, Shuqiong; Fu, Haihua; Gladwin, Amanda; Harrod, Grace; Stevens, James; Williams, Victoria; Ye, Qingqing; Zheng, Li; de Boer, Richard; Herbst, Roy S; Lee, Jin-Soo; Vasselli, James

    2015-03-23

    To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment. Archival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients. The prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3-1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n = 26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4-6 copies in ≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). Of RET-rearrangement-positive patients, none had an objective response in the vandetanib arm and one patient responded in the comparator arm. Radiologic evidence of tumor shrinkage was observed in two patients treated with vandetanib and one treated with comparator drug. The objective response rate was similar in the vandetanib and comparator arms for patients positive for RET copy number gains or RET protein expression. We have identified prevalence for three RET biomarkers in a population predominated by non-Asians and smokers. RET rearrangement prevalence was lower than previously reported. We found no evidence of a differential benefit for efficacy by IHC and RET gene copy number gains. The low prevalence of RET rearrangements (0.7%) prevents firm conclusions regarding association of vandetanib treatment with

  16. EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10).

    Science.gov (United States)

    Vázquez, Sergio; Casal, Joaquín; Afonso Afonso, Francisco Javier; Fírvida, José Luis; Santomé, Lucía; Barón, Francisco; Lázaro, Martín; Pena, Carolina; Amenedo, Margarita; Abdulkader, Ihab; González-Arenas, Carmen; Fachal, Laura; Vega, Ana

    2016-01-01

    This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.

  17. Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Kong, F.-M.; Hayman, James A.; Griffith, Kent A.; Kalemkerian, Gregory P.; Arenberg, Douglas; Lyons, Susan; Turrisi, Andrew; Lichter, Allen; Fraass, Benedick; Eisbruch, Avraham; Lawrence, Theodore S.; Haken, Randall K. ten

    2006-01-01

    Purpose: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p < 0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. Conclusions: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients

  18. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Quinton, Cindy [Juravinski Cancer Centre, 699 Concession, St Hamilton, Hamilton, ON L8V 5C2 (Canada); Ellis, Peter M., E-mail: peter.ellis@jcc.hhsc.ca [Juravinski Cancer Centre, 699 Concession, St Hamilton, Hamilton, ON L8V 5C2 (Canada); Department of Oncology, McMaster University Hamilton, ON L8S 4L8 (Canada)

    2011-09-13

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

  20. XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC.

    Science.gov (United States)

    Zhang, Ying; Guessous, Fadila; Kofman, Alex; Schiff, David; Abounader, Roger

    2010-02-01

    XL-184 (BMS-907351), under development by Exelixis Inc and Bristol-Myers Squibb Co, is a pan-tyrosine kinase inhibitor for the potential oral treatment of medullary thyroid cancer, glioblastoma multiforme and NSCLC. The prinicipal targets of XL-184 are MET, VEGFR-2 and RET, but the drug is also reported to display inhibitory activity against KIT, FLT3 and TEK. Preclinical studies demonstrated that XL-184 potently inhibited multiple receptor tyrosine kinases in various cancer cell lines and animal xenograft models, and that the drug exhibited significant oral bioavailability and blood-brain barrier penetration. A phase I clinical trial in patients with advanced solid malignancies indicated that XL-184 accumulated dose-dependently in the plasma and had a long terminal half-life. A phase II trial in patients with progressive or recurrent glioblastoma revealed modest but promising median progression-free survival. Toxicity and side effects for the drug have generally been of low-to-moderate severity. At the time of publication, three additional trials of XL-184 were recruiting patients, including a phase I trial in combination with standard of care in patients with glioblastoma, a phase I/II trial in combination with erlotinib in patients with NSCLC, and a phase III trial in patients with medullary thyroid cancer.

  1. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Gerdan, L. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Section of Nuclear Medicine, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Khoa, M.T. [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, AZ (United States); Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-01-15

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  2. Current status of radiation therapy. Evidence-based medicine (EBM) of radiation therapy. Non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Sumi, Minako

    2002-01-01

    The goal of radiation therapy for non-small cell lung cancer (NSCLC) is to improve the survival rate of patients without increasing treatment-related toxicity and to improve patients' quality of life. Several prospective randomized trials have demonstrated a survival advantage in combined modality treatment over radiotherapy or chemotherapy alone when a cisplatin-based chemotherapy regimen is utilized in the treatment plan. Combined modality treatment of cisplatin-based chemotherapy and radiotherapy is standard treatment for selected patients such as those with better performance status with locally or regionally advanced lung cancer including T3-T4 or N2-N3. Determining the contribution of new agents in combined modality treatment will require carefully designed and conducted clinical trials. High-dose involved field radiation therapy using 3D-conformal radiation therapy potentially enables the use of higher doses than standard radiation therapy, because less normal tissue is irradiated, and may improve local control and survival. The combination of radiotherapy with chemotherapy and dose escalation using 3D-conformal radiation therapy is also a possibility in unresectable NSCLC. In surgery cases, the results of several Phase III trials of cisplatin-based preoperative chemotherapy have suggested survival improvement. But the concept needs to be tested in a larger Phase III trial. (author)

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

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

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

  4. Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB.

    Science.gov (United States)

    Kollipara, Pushpa Saranya; Kim, Jung Hyun; Won, Dohee; Lee, Sang Min; Sung, Ha Chang; Chang, Hyun Sok; Lee, Kang Tae; Lee, Kang Sik; Park, Mi Hee; Song, Min Jong; Song, Ho Sueb; Hong, Jin Tae

    2014-03-01

    In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC(50) value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.

  5. Role of chaperone mediated autophagy (CMA) in the degradation of misfolded N-CoR protein in non-small cell lung cancer (NSCLC) cells.

    Science.gov (United States)

    Ali, Azhar Bin; Nin, Dawn Sijin; Tam, John; Khan, Matiullah

    2011-01-01

    Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells.

  6. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC Using Two Different Schedules.

    Directory of Open Access Journals (Sweden)

    Natalia Sutiman

    Full Text Available This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV and metronomic (MSV dosing schedules in patients with advanced non-small cell lung cancer (NSCLC.This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16 and at 100 mg/week in the MSV group (N = 14. Erlotinib was administered orally daily.The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13% and hyponatremia (N = 1; 6% in the CSV group, and neutropenia (N = 5; 36% in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group.Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups.ClinicalTrials.gov NCT00702182.

  7. Sequence-dependent antiproliferative effects of gefitinib and docetaxel on non-small cell lung cancer (NSCLC cells and the possible mechanism.

    Directory of Open Access Journals (Sweden)

    Bei Chen

    Full Text Available PURPOSE: Recent clinical trials showed that the sequential combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs and chemotherapy could prolong the PFS and/or OS of advanced non-small cell lung cancer (NSCLC patients with EGFR mutation. The aim of present study was to assess the optimal combination sequence and to explore its possible mechanism. METHODS: PC-9 cells and A549 cells, the lung adenocarcinoma cells with mutant and wide-type EGFR respectively, were treated with docetaxel/gefitinib alone or in different combination schedules. The EGFR and K-ras gene status was determined by qPCR-HRM technique. Cell proliferation was detected by MTT assay. The expression and phosphorylation of EGFR, ERK, Akt and IGF-1R were detected by western blot. Cell cycle distribution was observed by flow cytometry. RESULTS: Only sequential administration of docetaxel followed by gefitinib (D → G induced significant synergistic effect in both cell lines (Combination Index1.1, whereas the concurrent administration (D+G showed additive (0.9NSCLC cells, and the phosphorylation of EGFR and ERK might contribute to this effect.

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

    Science.gov (United States)

    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.

  9. Evolution of surface-based deformable image registration for adaptive radiotherapy of non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Richter Anne

    2009-12-01

    Full Text Available Abstract Background To evaluate the performance of surface-based deformable image registration (DR for adaptive radiotherapy of non-small cell lung cancer (NSCLC. Methods Based on 13 patients with locally advanced NSCLC, CT images acquired at treatment planning, midway and the end of the radio- (n = 1 or radiochemotherapy (n = 12 course were used for evaluation of DR. All CT images were manually [gross tumor volume (GTV] and automatically [organs-at-risk (OAR lung, spinal cord, vertebral spine, trachea, aorta, outline] segmented. Contours were transformed into 3D meshes using the Pinnacle treatment planning system and corresponding mesh points defined control points for DR with interpolation within the structures. Using these deformation maps, follow-up CT images were transformed into the planning images and compared with the original planning CT images. Results A progressive tumor shrinkage was observed with median GTV volumes of 170 cm3 (range 42 cm3 - 353 cm3, 124 cm3 (19 cm3 - 325 cm3 and 100 cm3 (10 cm3 - 270 cm3 at treatment planning, mid-way and at the end of treatment. Without DR, correlation coefficients (CC were 0.76 ± 0.11 and 0.74 ± 0.10 for comparison of the planning CT and the CT images acquired mid-way and at the end of treatment, respectively; DR significantly improved the CC to 0.88 ± 0.03 and 0.86 ± 0.05 (p = 0.001, respectively. With manual landmark registration as reference, DR reduced uncertainties on the GTV surface from 11.8 mm ± 5.1 mm to 2.9 mm ± 1.2 mm. Regarding the carina and intrapulmonary vessel bifurcations, DR reduced uncertainties by about 40% with residual errors of 4 mm to 6 mm on average. Severe deformation artefacts were observed in patients with resolving atelectasis and pleural effusion, in one patient, where the tumor was located around large bronchi and separate segmentation of the GTV and OARs was not possible, and in one patient, where no clear shrinkage but more a decay of the tumor was observed

  10. Qualitative Development and Content Validity of the Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ), A Patient-reported Outcome Instrument.

    Science.gov (United States)

    McCarrier, Kelly P; Atkinson, Thomas M; DeBusk, Kendra P A; Liepa, Astra M; Scanlon, Michael; Coons, Stephen Joel

    2016-04-01

    The purpose of this article was to describe the process and results of the preliminary qualitative development of a new symptoms-based patient-reported outcome (PRO) measure intended for assessing treatment benefit in clinical trials of advanced non-small cell lung cancer (NSCLC). Individual qualitative interviews were conducted in adults with NSCLC (Stages I-IV) in the United States. Experienced interviewers conducted concept-elicitation (CE) and cognitive interviews using semistructured interview guides. The CE interview guide was used for eliciting spontaneous reports of symptom experiences along with probing to further explore and confirm concepts. Interview transcripts were coded and analyzed by professional qualitative coders, and were summarized by like content using an iterative coding framework. Data from the CE interviews were considered alongside existing literature and clinical expert opinion during an item-generation process, leading to the development of a preliminary version of the NSCLC Symptom Assessment Questionnaire (SAQ). Three waves of cognitive interviews were conducted to evaluate concept relevance, item interpretability, and structure of the draft items and to facilitate further instrument refinement. Fifty-one subjects (mean [SD] age, 64.9 [11.2] years; 51.0% women) participated in the CE interviews. A total of 1897 expressions of NSCLC-related symptoms were identified and coded in interview transcripts, representing ~42 distinct symptom concepts. A 9-item initial-draft instrument was developed for testing in 3 waves of cognitive interviews with additional subjects with NSCLC (n = 20), during which both paper and electronic versions of the instrument were evaluated and refined. Participant responses and feedback during cognitive interviews led to the removal of 2 items and substantial modifications to others. The NSCLC-SAQ is a 7-item PRO measure intended for use in advanced NSCLC clinical trials to support medical product labelling. The

  11. 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.

  12. Beams Arrangement in Non-Small Cell Lung Cancer (NSCLC) According to PTV and Dosimetric Parameters Predictive of Pneumonitis

    International Nuclear Information System (INIS)

    Ramella, Sara; Trodella, Lucio; Mineo, Tommaso Claudio; Pompeo, Eugenio; Gambacorta, Maria A.; Cellini, Francesco; Ciresa, Marzia; Fiore, Michele; Greco, Carlo; Gaudino, Diego; Stimato, Gerardina; Piermattei, Angelo; Cesario, Alfredo; D'Angelillo, Rolando M.

    2010-01-01

    The aim of this study is to propose and validate an original new class of solutions for three-dimensional conformal radiation therapy (3DCRT) treatment planning for non-small cell lung cancer (NSCLC) according to the different patterns of disease presentation (on the basis of tumor location and volume) and to explore beams arrangement (planar or no-planar solutions) to respect dose constraints to the lung parenchyma. Benchmarks matched to validate the new approach are interuser reproducibility and saving on planning time. Tumor location was explored and specific categories created according to the tumor volume and location. Therefore, by applying planar and no-planar 3D plans, we searched for an optimization of the beams arrangement for each category. Dose-volume histograms (DVHs) were analyzed and a plan comparison performed. Results were then validated (class solution planning confirmation) by applying the same strategy to another group of patients. This has been realized at two dose levels (50.4 and 59.4 Gy). Fifty-nine patients were enrolled in this dosimetric study. In the first 27 patients ('exploratory sample') three main planning target volume location categories were identified according to the pattern of the disease presentation: (1) centrally located; (2) peripheral T and mediastinal N (P+N); and (3) superior sulcus. Original class solutions were proposed for each location category. On the next 32 patients ('validation sample'), the treatment planning started directly with the recommended approach. Mean V 20Gy value was 18.8% (SD ± 7.25); mean V 30Gy :12% (SD ± 4.05); and mean lung dose: 11.6Gy (SD ± 5.77). No differences between the two total dose level groups were observed. These results suggest a simple and reproducible tool for treatment planning in NSCLC, allowing interuser reproducibility and cutting down on planning time.

  13. Angiogenesis Inhibitors in NSCLC

    Directory of Open Access Journals (Sweden)

    Anna Manzo

    2017-09-01

    Full Text Available Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC. Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL that demonstrated an improvement of about two months in progression-free survival (PFS in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS also. Afterwards, other antiangiogenic agents, including sunitinib, sorafenib, and vandetanib have been unsuccessfully tested in first and successive lines. Recently, two new antiangiogenic agents (ramucirumab and nintedanib produced a significant survival benefit in second-line setting. In the REVEL study, ramucirumab plus docetaxel prolonged the median OS of patients with any histology NSCLC when compared with docetaxel alone (10.4 versus 9.1 months, hazard ratio (HR 0.857, p = 0.0235. In the LUME-Lung 1 study, nintedanib plus docetaxel prolonged the median PFS of patients with any tumor histology (p = 0.0019, and improved OS (12.6 versus 10.3 months in patients with adenocarcinoma. As a result, it became a new option for the second-line treatment of patients with advanced NSCLC and adenocarcinoma histology. Identifying predictive biomarkers to optimize the benefit of antiangiogenic drugs remains an ongoing challenge.

  14. Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation

    OpenAIRE

    ISOBE, KAZUTOSHI; KAKIMOTO, ATSUSHI; MIKAMI, TETSUO; KABURAKI, KYOHEI; KOBAYASHI, HIROSHI; YOSHIZAWA, TAKAHIRO; MAKINO, TAKASHI; OTSUKA, HAJIME; SANO, GO; SUGINO, KEISHI; SAKAMOTO, SUSUMU; TAKAI, YUJIRO; TOCHIGI, NAOBUMI; IYODA, AKIRA; HOMMA, SAKAE

    2016-01-01

    Aim: This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). Patients and Methods: The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). Results: BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM ...

  15. MET gene copy number predicts worse overall survival in patients with non-small cell lung cancer (NSCLC); a systematic review and meta-analysis.

    Science.gov (United States)

    Dimou, Anastasios; Non, Lemuel; Chae, Young Kwang; Tester, William J; Syrigos, Konstantinos N

    2014-01-01

    MET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC. Two independent investigators applied parallel search strategies with the terms "MET AND lung cancer", "MET AND NSCLC", "MET gene copy number AND prognosis" in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery. Among 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2 = 72%). MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR = 1.78, 95% CI 1.22-2.60). When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23-1.94). This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97-4.90). Higher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific.

  16. EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10

    Directory of Open Access Journals (Sweden)

    Vázquez S

    2016-02-01

    Full Text Available Sergio Vázquez,1 Joaquín Casal,2 Francisco Javier Afonso Afonso,3 José Luis Fírvida,4 Lucía Santomé,5 Francisco Barón,6 Martín Lázaro,7 Carolina Pena,7 Margarita Amenedo,8 Ihab Abdulkader,9 Carmen González-Arenas,10 Laura Fachal,11 Ana Vega11 On behalf of the Galician Lung Cancer Group (GGCP1Medical Oncology Department, Lucus Augusti University Hospital, Lugo, 2Medical Oncology Department, University Hospital Complex of Vigo, Pontevedra, 3Medical Oncology Department, University Hospital Complex of Ferrol, Ferrol, 4Medical Oncology Department, University Hospital Complex of Ourense, Ourense, 5Medical Oncology Department Povisa Hospital, Vigo, 6Medical Oncology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 7Medical Oncology Department, Hospital Complex of Pontevedra, Pontevedra, 8Medical Oncology Department, Oncology Center of Galicia, A Coruña, 9Anatomical Pathology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 10AstraZeneca, Madrid, 11Galician Public Foundation of Genomic Medicine-SERGAS, Santiago de Compostela Clinic Hospital, Santiago de Compostela, Spain Purpose: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR gene in non-small-cell lung cancer (NSCLC patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. Patients and methods: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens and serum samples. Results: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6% had EGFR mutations (84% sensitizing mutations. EGFR mutation was found in serum in 14 (8.1% patients (of 174 evaluable. Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52

  17. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) Signaling Capacity and the Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC): Implications for Use of 1,25(OH)2D3 in NSCLC Treatment

    International Nuclear Information System (INIS)

    Upadhyay, Santosh Kumar; Verone, Alissa; Shoemaker, Suzanne; Qin, Maochun; Liu, Song; Campbell, Moray; Hershberger, Pamela A.

    2013-01-01

    1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) exerts anti-proliferative activity by binding to the vitamin D receptor (VDR) and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC) cells which harbor epidermal growth factor receptor (EGFR) mutations display elevated VDR expression (VDR high ) and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDR low and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT). Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH) 2 D 3 sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH) 2 D 3 induces E-cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH) 2 D 3 -mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH) 2 D 3 opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH) 2 D 3 may prevent lung cancer progression in a molecularly defined subset of NSCLC patients

  18. Knockdown of OCT4 may sensitize NSCLC cells to cisplatin.

    Science.gov (United States)

    Liu, X; Ma, M; Duan, X; Zhang, H; Yang, M

    2017-05-01

    Cisplatin is commonly used in non-small-cell lung cancer (NSCLC) chemotherapy; however, chemoresistance to cisplatin remains a great clinical challenge. Octamer-binding protein 4 (OCT4) has been reported to be overexpressed in NSCLC. In this study, we aimed to investigate the potential role of OCT4 in NSCLC with chemoresistance to cisplatin. Expressions of OCT4 was detected in NSCLC tissues and cell lines. We utilized siRNA to knock down OCT4 expression in human NSCLC cells and analyzed their phenotypic changes. We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by cisplatin, suggesting OCT4 may contribute to cisplatin resistance in NSCLC. Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity.

  19. Msi2 Regulates the Aggressiveness of Non-Small Cell Lung Cancer (NSCLC)

    Science.gov (United States)

    2016-12-01

    indicator of Notch pathway activity. TMAs will be analyzed for correlation of Msi2 expression with pathologic stage, lymph node status, presence of...identify basal -like breast cancer as a unique molecular entity. Sci Rep 2013, 3:3544. [9] Bruna A, Greenwood W, Le Quesne J, Teschendorff A, Miranda

  20. Role of interim {sup 18}F-FDG-PET/CT for the early prediction of clinical outcomes of Non-Small Cell Lung Cancer (NSCLC) during radiotherapy or chemo-radiotherapy. A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Cremonesi, Marta; Garibaldi, Cristina [European Institute of Oncology, Radiation Research Unit, Milano (Italy); Gilardi, Laura; Travaini, Laura Lavinia; Grana, Chiara Maria [European Institute of Oncology, Division of Nuclear Medicine, Milano (Italy); Ferrari, Mahila Esmeralda; Botta, Francesca [Medical Physics Unit, European Institute of Oncology, Milano (Italy); Piperno, Gaia; Ronchi, Sara; Ciardo, Delia [European Institute of Oncology, Division of Radiation Oncology, Milano (Italy); Timmerman, Robert [University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, TX (United States); Baroni, Guido [Politecnico di Milano University, Department of Electronics, Information and Bioengineering, Milano (Italy); Jereczek-Fossa, Barbara Alicja [European Institute of Oncology, Division of Radiation Oncology, Milano (Italy); University of Milan, Department of Oncology and Hemato-Oncology, Milano (Italy); Orecchia, Roberto [University of Milan, Department of Oncology and Hemato-Oncology, Milano (Italy); European Institute of Oncology, Department of Medical Imaging and Radiation Sciences, Milano (Italy)

    2017-10-15

    Non-Small Cell Lung Cancer (NSCLC) is characterized by aggressiveness and includes the majority of thorax malignancies. The possibility of early stratification of patients as responsive and non-responsive to radiotherapy with a non-invasive method is extremely appealing. The distribution of the Fluorodeoxyglucose ({sup 18}F-FDG) in tumours, provided by Positron-Emission-Tomography (PET) images, has been proved to be useful to assess the initial staging of the disease, recurrence, and response to chemotherapy and chemo-radiotherapy (CRT). In the last years, particular efforts have been focused on the possibility of using ad interim {sup 18}F-FDG PET (FDG{sub int}) to evaluate response already in the course of radiotherapy. However, controversial findings have been reported for various malignancies, although several results would support the use of FDG{sub int} for individual therapeutic decisions, at least in some pathologies. The objective of the present review is to assemble comprehensively the literature concerning NSCLC, to evaluate where and whether FDG{sub int} may offer predictive potential. Several searches were completed on Medline and the Embase database, combining different keywords. Original papers published in the English language from 2005 to 2016 with studies involving FDG{sub int} in patients affected by NSCLC and treated with radiation therapy or chemo-radiotherapy only were chosen. Twenty-one studies out of 970 in Pubmed and 1256 in Embase were selected, reporting on 627 patients. Certainly, the lack of univocal PET parameters was identified as a major drawback, while standardization would be required for best practice. In any case, all these papers denoted FDG{sub int} as promising and a challenging examination for early assessment of outcomes during CRT, sustaining its predictivity in lung cancer. (orig.)

  1. Feasibility of the use of the Active Breathing Co ordinatorTM (ABC) in patients receiving radical radiotherapy for non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    McNair, Helen A.; Brock, Juliet; Symonds-Tayler, J. Richard N.; Ashley, Sue; Eagle, Sally; Evans, Philip M.; Kavanagh, Anthony; Panakis, Niki; Brada, Michael

    2009-01-01

    Introduction: One method to overcome the problem of lung tumour movement in patients treated with radiotherapy is to restrict tumour motion with an active breathing control (ABC) device. This study evaluated the feasibility of using ABC in patients receiving radical radiotherapy for non-small cell lung cancer. Methods: Eighteen patients, median (range) age of 66 (44-82) years, consented to the study. A training session was conducted to establish the patient's breath hold level and breath hold time. Three planning scans were acquired using the ABC device. Reproducibility of breath hold was assessed by comparing lung volumes measured from the planning scans and the volume recorded by ABC. Patients were treated with a 3-field coplanar beam arrangement and treatment time (patient on and off the bed) and number of breath holds recorded. The tolerability of the device was assessed by weekly questionnaire. Quality assurance was performed on the two ABC devices used. Results: 17/18 patients completed 32 fractions of radiotherapy using ABC. All patients tolerated a maximum breath hold time >15 s. The mean (SD) patient training time was 13.8 (4.8) min and no patient found the ABC very uncomfortable. Six to thirteen breath holds of 10-14 s were required per session. The mean treatment time was 15.8 min (5.8 min). The breath hold volumes were reproducible during treatment and also between the two ABC devices. Conclusion: The use of ABC in patients receiving radical radiotherapy for NSCLC is feasible. It was not possible to predict a patient's ability to hold breath. A minimum tolerated breath hold time of 15 s is recommended prior to commencing treatment.

  2. Discovery of 2',4'-dimethoxychalcone as a Hsp90 inhibitor and its effect on iressa-resistant non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Seo, Young Ho

    2015-10-01

    Heat shock protein 90 (Hsp90) is a ATP dependent molecular chaperone and has emerged as an attractive therapeutic target in the war on cancer due to its role in regulating maturation and stabilization of numerous oncogenic proteins. In this study, we discovered that 2',4'-dimethoxychalcone (1b) disrupted Hsp90 chaperoning function and inhibited the growth of iressa-resistant non-small cell lung cancer (NSCLC, H1975). The result suggested that 2',4'-dimethoxychalcone (1b) could serve as a potential therapeutic lead to circumvent the drug resistance acquired by EGFR mutation and Met amplification.

  3. Safety and feasibility of radiotherapy treatment in elderly non-small-cell lung cancer (NSCLC) patients.

    Science.gov (United States)

    Fiorica, F; Cartei, F; Ursino, S; Stefanelli, A; Zagatti, Y; Berretta, S; Figura, S; Maugeri, D; Zanet, E; Spartà, D; La Morella, C; Tirelli, U; Berretta, M

    2010-01-01

    The purpose of this study was to evaluate the feasibility and activity of radiotherapy (RT) treatment in elderly patients with locally advanced lung cancer. From January 2002 to December 2007, 51 consecutive patients (43 men and 8 women) aged > or = 65 received RT for locally advanced lung cancer, 22 with radical intent and 16 in adjuvant setting. Thirty-six patients received chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery vs. no surgery, radiation dose and chemotherapy. The median age was 74.7 years (range 65-91). Of the patients, 15.7% had no co-morbidity, 41.2% mild, 25.5% moderate, and 17.6% had severe co-morbidities. Sixteen subjects (31.4%) underwent surgery. All patients completed the planned radiation schedule, while chemotherapy was reduced in 16 patients. At a median follow-up of 22 months, the 2- and 3-year overall survival rates were 46.5% and 35.4%, respectively. Patients with no or mild co-morbidities (p < 0.0001) and a good performance status (p < 0.0001) had a better survival. The actuarial progression-free survival at 2 and 3 years was 41.4% and 38.2%, respectively. Acute lung toxicity rates were different between patients with different ACE-27 indexes, whereas late toxicity was not influenced. In conclusion, in elderly patients, the compliance with RT is good and the rate of toxicity is acceptable. Patients with no or mild co-morbidities have a significantly better survival. The increasing severity of co-morbidities may sufficiently shorten the remaining life expectancy, cancel the gains obtained by RT and increase the acute lung toxicity. Further prospective trials are needed to confirm these results. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Comparative Survival in Patients With Postresection Recurrent Versus Newly Diagnosed Non-Small-Cell Lung Cancer Treated With Radiotherapy

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    Cai Xuwei; Xu Luying; Wang Li; Hayman, James A.; Chang, Andrew C.; Pickens, Allan; Cease, Kemp B.; Orringer, Mark B.; Kong, F.-M.

    2010-01-01

    Purpose: To compare the survival of postresection recurrent vs. newly diagnosed non-small-cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. Methods and Materials: The study population consisted of 661 consecutive patients with NSCLC registered in the radiation oncology databases at two medical centers in the United States between 1992 and 2004. Of the 661 patients, 54 had postresection recurrent NSCLC and 607 had newly diagnosed NSCLC. Kaplan-Meier and Cox regression models were used for the survival analyses. Results: The distribution of relevant clinical factors between these two groups was similar. The median survival time and 5-year overall survival rates were 19.8 months (95% confidence interval [CI], 13.9-25.7) and 14.8% (95% confidence interval, 5.4-24.2%) vs. 12.2 months (95% CI, 10.8-13.6) and 11.0% (95% CI, 8.5-13.5%) for recurrent vs. newly diagnosed patients, respectively (p = .037). For Stage I-III patients, no significant difference was observed in the 5-year overall survival (p = .297) or progression-free survival (p = .935) between recurrent and newly diagnosed patients. For the 46 patients with Stage I-III recurrent disease, multivariate analysis showed that chemotherapy was a significant prognostic factor for 5-year progression-free survival (hazard ratio, 0.45; 95% CI, 0.224-0.914; p = .027). Conclusion: Our institutional data have shown that patients with postresection recurrent NSCLC achieved survival comparable to that of newly diagnosed NSCLC patients when they were both treated with radiotherapy or chemoradiotherapy. These findings suggest that patients with postresection recurrent NSCLC should be treated as aggressively as those with newly diagnosed disease.

  5. Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells.

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    Della Corte, Carminia Maria; Ciaramella, Vincenza; Di Mauro, Concetta; Castellone, Maria Domenica; Papaccio, Federica; Fasano, Morena; Sasso, Ferdinando Carlo; Martinelli, Erika; Troiani, Teresa; De Vita, Ferdinando; Orditura, Michele; Bianco, Roberto; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-26

    Metformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene. The combination of metformin with MEK-I showed a strong anti-proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status. The combination reduced the metastatic behaviour of NSCLC cells, via a downregulation of GLI1 trascritional activity, thus affecting the transition from an epithelial to a mesenchymal phenotype. Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters. Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.

  6. Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Gu, Yuanlong; Lv, Huimin; Zhao, Juan; Li, Qi; Mu, Guannan; Li, Jiade; Wuyang, Jiazi; Lou, Ge; Wang, Ruitao; Zhang, Yanqiao; Huang, Xiaoyi

    2017-09-01

    Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P=0.0189 and P=0.0129, respectively). The median OS of the ACT≥4cycles subgroup was significantly longer than that of the ACTcells in patients who received ≥4cycles of ACT was higher than that in patients treated with cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC. Copyright © 2017. Published by Elsevier B.V.

  7. 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.

  8. 1,25-Dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) Signaling Capacity and the Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC): Implications for Use of 1,25(OH){sub 2}D{sub 3} in NSCLC Treatment

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    Upadhyay, Santosh Kumar; Verone, Alissa; Shoemaker, Suzanne [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Qin, Maochun; Liu, Song [Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Campbell, Moray; Hershberger, Pamela A., E-mail: pamela.hershberger@roswellpark.org [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States)

    2013-11-08

    1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) exerts anti-proliferative activity by binding to the vitamin D receptor (VDR) and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC) cells which harbor epidermal growth factor receptor (EGFR) mutations display elevated VDR expression (VDR{sup high}) and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDR{sup low} and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT). Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH){sub 2}D{sub 3} sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH){sub 2}D{sub 3} induces E-cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH){sub 2}D{sub 3}-mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH){sub 2}D{sub 3} opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH){sub 2}D{sub 3} may prevent lung cancer progression in a molecularly defined subset of NSCLC patients.

  9. Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS)

    International Nuclear Information System (INIS)

    Kotoula, Vassiliki; Pectasides, Dimitrios; Syrigos, Konstantinos N; Kosmidis, Paris A; Fountzilas, George; Krikelis, Dimitrios; Karavasilis, Vasilios; Koletsa, Triantafillia; Eleftheraki, Anastasia G; Televantou, Despina; Christodoulou, Christos; Dimoudis, Stefanos; Korantzis, Ippokratis

    2012-01-01

    BRCA1 (B), ERCC1 (E), RRM1 (R) and TYMS (T) mRNA expression has been extensively studied with respect to NSCLC patient outcome upon various chemotherapy agents. However, these markers have not been introduced into clinical practice yet. One of the reasons seems to be lack of a standard approach for the classification of the reported high/low mRNA expression. The aim of this study was to determine the prognostic/predictive impact of B, E, R, T in routinely-treated NSCLC patients by taking into account the expression of these genes in the normal lung parenchyma. B, E, R, T mRNA expression was examined in 276 NSCLC samples (real-time PCR). The normal range of B, E, R, T transcript levels was first determined in matched tumor – normal pairs and then applied to the entire tumor series. Four main chemotherapy categories were examined: taxanes-without-platinum (Tax); platinum-without-taxanes (Plat); taxanes/platinum doublets (Tax/Plat); and, all-other combinations. In comparison to remotely located normal lung parenchyma, B, E, R, T mRNA expression was generally increased in matched tumors, as well as in the entire tumor series. Therefore, tumors were classified as expressing normal or aberrant B, E, R, T mRNA. In general, no marker was associated with overall and progression free survival (OS, PFS). Upon multivariate analysis, aberrant intratumoral TYMS predicted for shorter PFS than normal TYMS in 1st line chemo-naïve treated patients (p = 0.012). In the same setting, specific interactions were observed for aberrant TYMS with Plat and Tax/Plat (p = 0.003 and p = 0.006, respectively). Corresponding patients had longer PFS in comparison to those treated with Tax (Plat: HR = 0.234, 95% CI:0.108-0.506, Wald’s p < 0.0001; Tax/Plat: HR = 0.242, 95% CI:0.131-0.447, Wald’s p < 0.0001). Similar results were obtained for PFS in 1st line chemo-naïve and (neo)adjuvant pre-treated patients. Adenocarcinoma, early disease stage, and treatment with Tax/Plat doublets

  10. Activation of signal transducer and activator of transcription 3 (STAT3) signaling in EGFR mutant non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Codony-Servat, Carles; Codony-Servat, Jordi; Karachaliou, Niki; Molina, Miguel Angel; Chaib, Imane; Ramirez, Jose Luis; de Los Llanos Gil, Maria; Solca, Flavio; Bivona, Trever G; Rosell, Rafael

    2017-07-18

    Gefitinib, erlotinib or afatinib are the current treatment for non-small-cell lung cancer (NSCLC) harboring an activating mutation of the epidermal growth factor receptor (EGFR), but less than 5% of patients achieve a complete response and the median progression-free survival is no longer than 12 months. Early adaptive resistance can occur as soon as two hours after starting treatment by activating signal transducer and activation of transcription 3 (STAT3) signaling. We investigated the activation of STAT3 in a panel of gefitinib-sensitive EGFR mutant cell lines, and gefitinib-resistant PC9 cell lines developed in our laboratory. Afatinib has great activity in gefitinib-sensitive as well as in gefitinib-resistant EGFR mutant NSCLC cell lines. However, afatinib therapy causes phosphorylation of STAT3 tyrosine 705 (pSTAT3Tyr705) and elevation of STAT3 and RANTES mRNA levels. The combination of afatinib with TPCA-1 (a STAT3 inhibitor) ablated pSTAT3Tyr705 and down-regulated STAT3 and RANTES mRNA levels with significant growth inhibitory effect in both gefitinib-sensitive and gefitinib-resistant EGFR mutant NSCLC cell lines. Aldehyde dehydrogenase positive (ALDH+) cells were still observed with the combination at the time that Hairy and Enhancer of Split 1 (HES1) mRNA expression was elevated following therapy. Although the combination of afatinib with STAT3 inhibition cannot eliminate the potential problem of a remnant cancer stem cell population, it represents a substantial advantage and opportunity to further prolong progression free survival and probably could increase the response rate in comparison to the current standard of single therapy.

  11. Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer.

    Science.gov (United States)

    Tanino, Ryosuke; Tsubata, Yukari; Harashima, Nanae; Harada, Mamoru; Isobe, Takeshi

    2018-03-30

    Pemetrexed (PEM) improves the overall survival of patients with advanced non-small cell lung cancer (NSCLC) when administered as maintenance therapy. However, PEM resistance often appears during the therapy. Although thymidylate synthase is known to be responsible for PEM resistance, no other mechanisms have been investigated in detail. In this study, we explored new drug resistance mechanisms of PEM-treated NSCLC using two combinations of parental and PEM-resistant NSCLC cell lines from PC-9 and A549. PEM increased the apoptosis cells in parental PC-9 and the senescent cells in parental A549. However, such changes were not observed in the respective PEM-resistant cell lines. Quantitative RT-PCR analysis revealed that, besides an increased gene expression of thymidylate synthase in PEM-resistant PC-9 cells, the solute carrier family 19 member1 ( SLC19A1) gene expression was markedly decreased in PEM-resistant A549 cells. The siRNA-mediated knockdown of SLC19A1 endowed the parental cell lines with PEM resistance. Conversely, PEM-resistant PC-9 cells carrying an epidermal growth factor receptor (EGFR) mutation acquired resistance to a tyrosine kinase inhibitor erlotinib. Although erlotinib can inhibit the phosphorylation of EGFR and Erk, it is unable to suppress the phosphorylation of Akt in PEM-resistant PC-9 cells. Additionally, PEM-resistant PC-9 cells were less sensitive to the PI3K inhibitor LY294002 than parental PC-9 cells. These results indicate that SLC19A1 negatively regulates PEM resistance in NSCLC, and that EGFR-tyrosine-kinase-inhibitor resistance was acquired with PEM resistance through Akt activation in NSCLC harboring EGFR mutations.

  12. Comparison of Survival Rate in Primary Non-Small-Cell Lung Cancer Among Elderly Patients Treated With Radiofrequency Ablation, Surgery, or Chemotherapy

    International Nuclear Information System (INIS)

    Lee, Heon; Jin, Gong Yong; Han, Young Min; Chung, Gyung Ho; Lee, Yong Chul; Kwon, Keun Sang; Lynch, David

    2012-01-01

    Purpose: We retrospectively compared the survival rate in patients with non-small-cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA), surgery, or chemotherapy according to lung cancer staging. Materials and Methods: From 2000 to 2004, 77 NSCLC patients, all of whom had WHO performance status 0–2 and were >60 years old, were enrolled in a cancer registry and retrospectively evaluated. RFA was performed on patients who had medical contraindications to surgery/unsuitability for surgery, such as advanced lung cancer or refusal of surgery. In the RFA group, 40 patients with inoperable NSCLC underwent RFA under computed tomography (CT) guidance. These included 16 patients with stage I to II cancer and 24 patients with stage III to IV cancer who underwent RFA in an adjuvant setting. In the comparison group (n = 37), 13 patients with stage I to II cancer underwent surgery; 18 patients with stage III to IV cancer underwent chemotherapy; and 6 patients with stage III to IV cancer were not actively treated. The survival curves for RFA, surgery, and chemotherapy in these patients were calculated using Kaplan–Meier method. Results: Median survival times for patients treated with (1) surgery alone and (2) RFA alone for stage I to II lung cancer were 33.8 and 28.2 months, respectively (P = 0.426). Median survival times for patients treated with (1) chemotherapy alone and (2) RFA with chemotherapy for stage III to IV cancer were 29 and 42 months, respectively (P = 0.03). Conclusion: RFA can be used as an alternative treatment to surgery for older NSCLC patients with stage I to II inoperable cancer and can play a role as adjuvant therapy with chemotherapy for patients with stage III to IV lung cancer.

  13. 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.

  14. Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST).

    Science.gov (United States)

    Kawamura, Masafumi; Gika, Masatoshi; Abiko, Tomohiro; Inoue, Yoshimasa; Oyama, Takahiko; Izumi, Yotaro; Kobayashi, Hisayuki; Kobayashi, Koichi

    2007-03-01

    In the present study, we prospectively evaluated the clinical feasibility and efficacy of collagen gel droplet embedded culture drug sensitivity test (CD-DST) in unresectable non-small cell lung cancer (NSCLC) without previous treatment. Eighty patients with unresectable NSCLC, aged less than 81 years old, PS 0-1, and with evaluable tumor lesions, entered the study. If the patient had CD-DST active drugs, more than three cycles of chemotherapy containing these drugs were administered. If the patient did not have CD-DST active drugs, the patient could choose any treatment including best supportive care. Of the 80 patients in this study, CD-DST yielded results successfully in 49 patients (61.3%). CD-DST active drugs were present in 22 patients, and significantly more female patients had in vitro active anticancer agents than male (P=0.0008). All of the patients with CD-DST active agents received chemotherapy including these agents. In these patients, the response rate was 72.7%, and median survival was 15.0 months. In the patients without CD-DST active agents, 11 patients received standard, empirical chemotherapy. In these patients, response rate was 0%, and median survival was 6.0 months. The results show that CD-DST is capable of selecting the responders and the respective optimal regimens, and also delineating the patients less likely benefit from treatment.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  16. Accuracy of diffusion-weighted (DW) MRI with background signal suppression (MR-DWIBS) in diagnosis of mediastinal lymph node metastasis of nonsmall-cell lung cancer (NSCLC).

    Science.gov (United States)

    Xu, Liang; Tian, Jiakai; Liu, Yuhui; Li, Chuanfu

    2014-07-01

    To prospectively evaluate the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging with background signal suppression (MR-DWIBS) for detecting mediastinal lymph node metastasis of nonsmall-cell lung cancer (NSCLC). MR-DWIBS was performed in 42 consecutive patients (27 men, 15 women; age range, 42-78 years; median age, 55 years) with histologically proven NSCLC. The visualization rate of metastatic lymph node (MLN) and benign lymph node (BLN) of enlarged lymph nodes (ELN) and normal-sized lymph nodes (NLN) was compared by using a chi-square test or Fisher's exact test on a per-nodal basis. Apparent diffusion coefficient (ADC) of MLN and BLN was measured and compared by using two-tailed unpaired Student's t-test. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of ADC for ELN and NLN. The optimal cutoff value was determined and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy was calculated. Thirty-five out of 119 lymph resected nodes were confirmed to be metastatic by histologic examination. The visualization rate of MLN was significantly higher than that of BLN for ELN (P accuracy were 75.0%, 90.9%, 66.7%, 93.8%, and 87.8%, respectively. MR-DWIBS may be clinically useful to visually detect mediastinal lymph nodes and ADC measurement can aid in malignant node discrimination. © 2013 Wiley Periodicals, Inc.

  17. Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC: new insights on the role of phosphatydil-inositol-3 kinase.

    Directory of Open Access Journals (Sweden)

    Marianna Scrima

    Full Text Available Aberrant activation of PI3K/AKT signalling represents one of the most common molecular alterations in lung cancer, though the relative contribution of the single components of the cascade to the NSCLC development is still poorly defined. In this manuscript we have investigated the relationship between expression and genetic alterations of the components of the PI3K/AKT pathway [KRAS, the catalytic subunit of PI3K (p110α, PTEN, AKT1 and AKT2] and the activation of AKT in 107 surgically resected NSCLCs and have analyzed the existing relationships with clinico-pathologic features. Expression analysis was performed by immunohistochemistry on Tissue Micro Arrays (TMA; mutation analysis was performed by DNA sequencing; copy number variation was determined by FISH. We report that activation of PI3K/AKT pathway in Italian NSCLC patients is associated with high grade (G3-G4 compared with G1-G2; n = 83; p<0.05 and more advanced disease (TNM stage III vs. stages I and II; n = 26; p<0.05. In addition, we found that PTEN loss (41/104, 39% and the overexpression of p110α (27/92, 29% represent the most frequent aberration observed in NSCLCs. Less frequent molecular lesions comprised the overexpression of AKT2 (18/83, 22% or AKT1 (17/96, 18%, and KRAS mutation (7/63, 11%. Our results indicate that, among all genes, only p110α overexpression was significantly associated to AKT activation in NSCLCs (p = 0.02. Manipulation of p110α expression in lung cancer cells carrying an active PI3K allele (NCI-H460 efficiently reduced proliferation of NSCLC cells in vitro and tumour growth in vivo. Finally, RNA profiling of lung epithelial cells (BEAS-2B expressing a mutant allele of PIK3 (E545K identified a network of transcription factors such as MYC, FOS and HMGA1, not previously recognised to be associated with aberrant PI3K signalling in lung cancer.

  18. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    Dillman, R.O.

    1989-01-01

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

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

    International Nuclear Information System (INIS)

    Zimmermann, Frank B.; Geinitz, Hans; Schill, Sabine; Thamm, Reinhard; Nieder, Carsten; Schratzenstaller, Ulrich; Molls, Michael

    2006-01-01

    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

  20. 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.

  1. The Use of the Active Breathing Coordinator Throughout Radical Non-Small-Cell Lung Cancer (NSCLC) Radiotherapy

    International Nuclear Information System (INIS)

    Brock, Juliet; McNair, Helen A.; Panakis, Niki; Symonds-Tayler, Richard; Evans, Phil M.; Brada, Michael

    2011-01-01

    Purpose: To assess feasibility and reproducibility of an Active Breathing Coordinator (ABC) used throughout radical radiotherapy for non-small-cell lung cancer, and compare lung dosimetric parameters between free-breathing and ABC plans. Methods and Materials: A total of 18 patients, recruited into an approved study, had free-breathing and ABC breath-hold treatment plans generated. Lung volume, the percentage volume of lung treated to a dose of ≥20 Gy (V 20 ), and mean lung dose (MLD) were compared. Treatment (64 Gy in 32 fractions, 5 days/week) was delivered in breath-hold. Repeat breath-hold computed tomography scans were used to assess change in gross tumor volume (GTV) size and position. Setup error was also measured and potential GTV-planning target volume (PTV) margins calculated. Results: Seventeen of 18 patients completed radiotherapy using ABC daily. Intrafraction tumor position was consistent, but interfraction variation had mean (range) values of 5.1 (0-25), 3.6 (0-9.7), and 3.5 (0-16.6) mm in the superoinferior (SI), right-left (RL), and anteroposterior (AP) directions, respectively. Tumor moved partially outside the PTV in 5 patients. Mean reduction in GTV from planning to end of treatment was 25% (p = 0.003). Potentially required PTV margins were 18.1, 11.9, and 11.9 mm in SI, RL, and AP directions. ABC reduced V 20 by 13% (p = 0.0001), V 13 by 12% (p = 0.001), and MLD by 13% (p < 0.001) compared with free-breathing; lung volume increased by 41% (p < 0.001). Conclusions: Clinically significant movements of GTV were seen during radiotherapy for non-small-cell lung cancer using ABC. Image guidance is recommended with ABC. The use of ABC can reduce dose volume parameters determining lung toxicity, and might allow for equitoxic radiotherapy dose escalation.

  2. Prognostic factors of three dimensional conformal radiation therapy in treating non-small lung cancer

    International Nuclear Information System (INIS)

    Liu Fei; Li Guang; Dang Jun; Cai Feng; Xia Bing; Zhang Shuo; Yao Lei

    2007-01-01

    Objective: To analyze the prognosis of patients with non-small lung cancer (NSCLC) treated with three -dimension conformal radiation therapy(3DCRT). Methods: From January 2003 to December 2004, 178 patients with NSCLC were treated, including 136 males and 42 females. Their median age was 65. Radiotherapy was delivered at 2 - 3 Gy per fraction, 6 fractions per week with a total dose of 60 -75 Gy. The impact of related prognostic factors on survival was evaluated by univariate and multivariate analyses. The treatment outcome was analyzed by prognostic index model. Results: With a median follow-up of 16 months, the 1 - and 2 -year survival rates were 62.4% and 39.7%, respectively. Logrank analysis showed that gender, weight loss, histology, tumor stage, tumor diameter, Gross tumor volume (GTV) and total irradiation dose were prognostic factors for the survival. COX model multivariate analysis showed that weight loss, histology, GTV and total dose were independent prognostic factors. Conclusions: Weight loss, histology, total dose and gross tumor volume are independent prognostic factors of patients with non-small lung cancer treated with radiation therapy. Prognostic index model is able to predict the prognosis more effectively than single variable. (authors)

  3. WE-AB-207B-02: A Bayesian Network Approach for Joint Prediction of Tumor Control and Radiation Pneumonitis (RP) in Non-Small-Cell Lung Cancer (NSCLC)

    International Nuclear Information System (INIS)

    Luo, Y; McShan, D; Matuszak, M; Hobson, S; Jolly, S; Ten Haken, R; El Naqa, I

    2016-01-01

    Purpose: NSCLC radiotherapy treatment is a trade-off between controlling the tumor while limiting radiation-induced toxicities. Here we identify hierarchical biophysical relationships that could simultaneously influence both local control (LC) and RP by using an integrated Bayesian Networks (BN) approach. Methods: We studied 79 NSCLC patients treated on prospective protocol with 56 cases of LC and 21 events of RP. Beyond dosimetric information, each patient had 193 features including 12 clinical factors, 60 circulating blood cytokines before and during radiotherapy, 62 microRNAs, and 59 single-nucleotide polymorphisms (SNPs). The most relevant biophysical predictors for both LC and RP were identified using a Markov blanket local discovery algorithm and the corresponding BN was constructed using a score-learning algorithm. The area under the free-response receiver operating characteristics (AU-FROC) was used for performance evaluation. Cross-validation was employed to guard against overfitting pitfalls. Results: A BN revealing the biophysical interrelationships jointly in terms of LC and RP was developed and evaluated. The integrated BN included two SNPs, one microRNA, one clinical factor, three pre-treatment cytokines, relative changes of two cytokines between pre and during-treatment, and gEUDs of the GTV (a=-20) and lung (a=1). On cross-validation, the AUC prediction of independent LC was 0.85 (95% CI: 0.75–0.95) and RP was 0.83 (0.73–0.92). The AU-FROC of the integrated BN to predict both LC/RP was 0.81 (0.71–0.90) based on 2000 stratified bootstrap, indicating minimal loss in joint prediction power. Conclusions: We developed a new approach for multiple outcome utility application in radiotherapy based on integrated BN techniques. The BN developed from large-scale retrospective data is able to simultaneously predict LC and RP in NSCLC treatments based on individual patient characteristics. The joint prediction is only slightly compromised compared to

  4. Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations.

    Science.gov (United States)

    Tan, Pui San; Bilger, Marcel; de Lima Lopes, Gilberto; Acharyya, Sanchalika; Haaland, Benjamin

    2017-08-01

    Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed

  5. Factors which influence quality of life in patients with non-small cell lung cancer (NSCLC): A radiation therapy oncology group study (RTOG 89-01)

    International Nuclear Information System (INIS)

    Scott, C.B.; Sause, W.T.; Johnson, D.; Dar, A.R.; Wasserman, T.H.; Rubin, P.; Khandekar, J.; Byhardt, R.B.; Taylor, S.; McDonald, A.

    1997-01-01

    Purpose: Prospectively evaluate the quality of life (QOL) of patients with NSCLC participating in a randomized phase III study conducted by the RTOG and Eastern Cooperative Oncology Group. Determine the factors which influence QOL during and post therapy. Materials and Methods: From (4(90)) to (4(94)) to 75 patients (pts) were randomized on RTOG 89-01 between a regimen containing radiation therapy (RT) versus a regimen containing surgery (S). All pts received induction vinblastine and cisplatin, followed by either S or RT and consolidation chemotherapy (CT). Pts were given the self-assessment QOL forms prior to the start of therapy, post induction CT, post RT or S, and periodically during follow-up. Two questionnaires were used: Functional Assessment of Cancer Therapy for lung cancer patients (FACT-L) and Functional Living Index-Cancer (FLIC). The FACT-L consists of 44 questions covering 6 domains (physical, social, and emotional well-being, relationship with physician, fulfilment, and lung cancer specific concerns), FLIC contains 22 questions summing to one total score. Results: 51 pts participated in the QOL endpoint, 24 were excluded: 3 pts refused, institution did not administer QOL questionnaires in 9 pts, 3 completed QOL after start of therapy, 1 institution refused to participate, 5 questionnaires were incomplete/unusable, 1 pt could not read English, and 2 were ineligible for treatment. Participation in QOL was not predicted by any pretreatment characteristic. Women had worse pretreatment QOL (p<0.005, by FLIC) and more problems with disease-related symptoms (p<0.005, by FACT) than men. Pts with KPS 90-100 had better pretreatment QOL than pts with KPS 60-80 (p<0.025, FLIC). Neither race, marital status, education level, age, prior weight loss, nor disease symptoms statistically significantly influenced pretreatment QOL. Initial QOL did not predict overall survival. FACT-L was reported on 25 pts post induction CT. Follow-up FACT-L was available on 12 pts

  6. Ipsilateral lung dose volume parameters predict radiation pneumonitis in addition to classical dose volume parameters in locally advanced NSCLC treated with combined modality therapy

    Directory of Open Access Journals (Sweden)

    Sushma Agrawal

    2014-01-01

    Full Text Available Purpose: The purpose was to determine the correlation of clinical factors and lung dose volume parameters with significant radiation pneumonitis (RP in non-small cell lung cancer patients treated with combined modality therapy. Materials and Methods: Between January 2008 and December 2010, 52 patients of non-small cell lung cancer were treated with combined modality therapy with radical intent. Radiation pneumonitis was correlated with ipsilateral (V 20 ipsi, V 5 ipsi and MLD ipsi and whole lung (V 20 , V 5 , and MLD dose volume parameters. Clinical factors like pulmonary function tests (PFT, site of tumor, planning target volume, and type of treatment were also correlated with incidence of significant pneumonitis. Results: Out of 52 patients, 35.3% developed grade 2 or more pneumonitis. On univariate analysis, factors significantly correlating with radiation pneumonitis were V 5 (P = 0.002, V 5 ipsi (P = 0.000, V 20 (P = 0.019, V 20 ipsi (P = 0.004, MLD (P = 0.008 and MLD ipsi (P = 0.008. On multivariate analysis, V 5 ipsi was retained as the most significant factor. Concurrent chemoradiation caused significantly more RP than neoadjuvant chemoradiation (P = 0.004. A cutoff of 65% for V 5 ipsi had a sensitivity of 65% and a specificity of 91%. Conclusion: The correlation between pneumonitis and dosimetric constraints has been validated. Adding ipsilateral V 20 , V 5 , and MLD to the classical total lung constraints identifies patients likely to develop pulmonary toxicity in patients undergoing chemoradiation.

  7. Adding Ipsilateral V20 and V30 to Conventional Dosimetric Constraints Predicts Radiation Pneumonitis in Stage IIIA-B NSCLC Treated With Combined-Modality Therapy

    International Nuclear Information System (INIS)

    Ramella, Sara; Trodella, Lucio; Mineo, Tommaso Claudio; Pompeo, Eugenio; Stimato, Gerardina; Gaudino, Diego; Valentini, Vincenzo; Cellini, Francesco; Ciresa, Marzia; Fiore, Michele; Piermattei, Angelo; Russo, Patrizia; Cesario, Alfredo; D'Angelillo, Rolando M.

    2010-01-01

    Purpose: To determine lung dosimetric constraints that correlate with radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional radiation therapy and concurrent chemotherapy. Methods and Materials: Between June 2002 and December 2006, 97 patients with locally advanced non-small-cell lung cancer were treated with concomitant radiochemotherapy. All patients underwent complete three-dimensional treatment planning (including dose-volume histograms), and patients were treated only if the percentage of total lung volume exceeding 20 Gy (V 20 ) and 30 Gy (V 30 ), and mean lung dose (MLD) had not exceeded the constraints of 31%, 18%, and 20 Gy, respectively. The total and ipsilateral lung dose-volume histogram parameters, planning target volume, and total dose delivered were analyzed and correlated with pneumonitis incidence. Results: If dose constraints to the total lung were respected, the most statistically significant factors predicting pneumonitis were the percentage of ipsilateral lung volume exceeding 20 Gy (V 20 ipsi), percentage of ipsilateral lung volume exceeding 30 Gy (V 30 ipsi), and planning target volume. These parameters divided the patients into low- and high-risk groups: if V 20 ipsi was 52% or lower, the risk of pneumonitis was 9%, and if V 20 ipsi was greater than 52%, the risk of pneumonitis was 46%; if V 30 ipsi was 39% or lower, the risk of pneumonitis was 8%, and if V 30 ipsi was greater than 39%, the risk of pneumonitis was 38%. Actuarial curves of the development of pneumonitis of Grade 2 or higher stratified by V 20 ipsi and V 30 ipsi were created. Conclusions: The correlation between pneumonitis and dosimetric constraints has been validated. Adding V 20 ipsi and V 30 ipsi to the classical total lung constraints could reduce pulmonary toxicity in concurrent chemoradiation treatment. V 20 ipsi and V 30 ipsi are important if the V 20 to the total lung, V 30 to the total lung, and mean lung dose have not exceeded

  8. The Influence of Tissue Ischemia Time on RNA Integrity and Patient-Derived Xenografts (PDX) Engraftment Rate in a Non-Small Cell Lung Cancer (NSCLC) Biobank.

    Science.gov (United States)

    Guerrera, Francesco; Tabbò, Fabrizio; Bessone, Luca; Maletta, Francesca; Gaudiano, Marcello; Ercole, Elisabetta; Annaratone, Laura; Todaro, Maria; Boita, Monica; Filosso, Pier Luigi; Solidoro, Paolo; Delsedime, Luisa; Oliaro, Alberto; Sapino, Anna; Ruffini, Enrico; Inghirami, Giorgio

    2016-01-01

    Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs). One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical) and cold (ex-vivo) ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs) values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted. RNAs with a RIN>7 were detected in 51% of the sample (70/135), with values of RIN significantly lower (OR 0.08, P = 0.01) in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma) were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours) and ex-vivo ischemia time (>10 hours) were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively). RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted.

  9. 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.

  10. Histone deacetylation, as opposed to promoter methylation, results in epigenetic BIM silencing and resistance to EGFR TKI in NSCLC.

    Science.gov (United States)

    Zhao, Mingchuan; Zhang, Yishi; Li, Jiayu; Li, Xuefei; Cheng, Ningning; Wang, Qi; Cai, Weijing; Zhao, Chao; He, Yayi; Chang, Jianhua; Zhou, Caicun

    2018-01-01

    Drug resistance remains a major challenge in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Bcl-2-like protein 11 (BIM), a B-cell lymphoma 2 family pro-apoptotic protein, is a prime target for specific anti-cancer therapeutics. However, the epigenetic regulation of BIM in non-small cell lung cancer (NSCLC) cell lines and patients with NSCLC in association with EGFR-TKI resistance requires investigation. Methylation-specific PCR (MSP), pyrosequencing, and nested quantitative (q)-MSP were conducted to explore the methylation status of BIM in NSCLC cell lines. In addition, the methylation profile of BIM in patients with NSCLC was assessed by nested q-MSP using circulating free DNA. Cell lines, treated with methylation inhibitor 5-Aza-2'-deoxycytidine (AZA) or histone deacetylation inhibitor trichostatin A (TSA) prior to gefitinib treatment, were examined for BIM gene expression and resistance to gefitinib. All cell lines used in the present study presented with hypo-methylated BIM . Treatment with AZA had no effect on BIM RNA expression in PC9 cells or the gefitinib-resistant cell lines PC9/R and PC9/G2, nor did it reverse their resistance to gefitinib. In contrast, TSA treatment produced the opposite result. In the present study, 25 (78.1%) patients with hypo-methylated BIM and 7 patients (21.9%) with partial or hyper-methylated BIM were identified. The clinicopathological data revealed a random hypo-methylated BIM distribution amongst patients with NSCLC. In the overall study group and EGFR mutant group, hypo-methylated BIM carriers presented with no significant differences in progression free survival compared with patients with partial or hyper-methylated BIM . All cell lines in the present study and the majority of patients with NSCLC carried hypo-methylated BIM . Histone deacetylation, as opposed to promoter methylation, may contribute to the epigenetic silencing of BIM and lead to EGFR TKI resistance in NSCLC.

  11. 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

  12. A retrospective quality of life analysis using the lung cancer symptom scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Lutz, Stephen T.; Huang, David T.; Ferguson, Catherine L.; Kavanagh, Brian D.; Tercilla, Oscar F.; Lu Jiandong

    1997-01-01

    Purpose: To measure symptom palliation in patients treated with radiation therapy for advanced nonsmall cell lung cancer (NSCLC). Methods and Materials: Five hundred thirty patients with NSCLC were treated at the Medical College of Virginia between 1988 and 1993. Sixty-three patients with the least favorable prognostic features received palliative radiation to 30 Gy in 10 or 12 fractions for symptoms related to the presence of intrathoracic tumor. The observer portion of the Lung Cancer Symptom Scale (LCSS) was employed in a retrospective chart review, scoring measures of appetite, fatigue, cough, dyspnea, hemoptysis, and pain. Results: In 54 evaluable patients, median survival was 4 months and was independent of age, stage, performance status, or histology. Ninety-six percent of the patients had at least one LCSS symptom at presentation. Fatigue was unaffected by therapy. Improvements in appetite (p = 0.68) and pain (p = 0.61) were not statistically significant. There was, however, a statistically significant reduction in cough (p = 0.01), hemoptysis (p = 0.001), and dyspnea (p 0.0003). Self-limiting acute side effects included transient esophagitis in 37% of patients, though no severe toxicities were noted. Conclusions: These results suggest symptomatic benefit from radiotherapy even in those NSCLC patients with advanced disease and a limited life expectancy. Treatment should be given to patients whose symptoms are most amenable to palliation. A site-specific quality of life instrument such as the LCSS should be included within any future clinical trial of NSCLC management so that symptom control may be scored as a treatment outcome in addition to disease-free survival

  13. Impact of tumor attachment to the pleura measured by a pretreatment CT image on outcome of stage I NSCLC treated with stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    Yamamoto, Takaya; Kadoya, Noriyuki; Shirata, Yuko; Koto, Masashi; Sato, Kiyokazu; Matsushita, Haruo; Sugawara, Toshiyuki; Umezawa, Rei; Kubozono, Masaki; Ishikawa, Yojiro; Kozumi, Maiko; Takahashi, Noriyoshi; Ito, Kengo; Katagiri, Yu; Takeda, Ken; Jingu, Keiichi

    2015-01-01

    Pleural invasion status is known to be a predictor of survival after pulmonary resection for non-small cell lung cancer. Our goal was to determine whether the length of tumor attachment to the pleura on a pretreatment CT image has prognostic value as an alternative to pleural invasion status for stage I non-small cell lung cancer treated with stereotactic body radiotherapy (SBRT). A total of 90 tumors in 87 patients (males: 68, females: 19) who received SBRT between March 2005 and September 2011 in our institution were reviewed. The median age of the patients was 78 years (range, 48-90 years). The median tumor diameter was 2.2 cm (range, 0.9-4.2 cm). The prescribed dose was typically 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions to the isocenter with 6 MV X-ray using 4 non-coplanar and 3 coplanar static beams. The lengths of attachment were measured using pretreatment CT images at the lung window. Cumulative incidence rates were calculated using Kaplan-Meier curves, and univariate and multivariate analyses for in-field tumor control, locoregional control (LRC), freedom from distant metastasis and freedom from progression (FFP) were performed using a Cox proportional hazards model. Of the 90 tumors, 42 tumors were attached to the pleura (median, 14.7 mm; range, 4.3-36.0 mm), 21 tumors had pleural indentation and 27 tumors had no attachment. The median follow-up period for survivors was 46.1 months. The 3-year in-field control, LRC, FFP and overall survival rates were 91.2%, 75.3%, 63.8% and 68.6%, respectively. SBRT dose and tumor diameter were independently significant predictors of in-field control (p = 0.02 and p = 0.04, respectively). Broad attachment to the pleura, the length being more than 14.7 mm, was a negative independent predictor of LRC and FFP (p = 0.02 and p = 0.01, respectively). Pleural attachment status on a pretreatment CT image might be an important predictor of LRC and FFP

  14. A phase II trial of erlotinib as maintenance treatment after concurrent chemoradiotherapy in stage III non-small-cell lung cancer (NSCLC): a Galician Lung Cancer Group (GGCP) study.

    Science.gov (United States)

    Casal Rubio, J; Fírvida-Pérez, J L; Lázaro-Quintela, M; Barón-Duarte, F J; Alonso-Jáudenes, G; Santomé, L; Afonso-Afonso, F J; Amenedo, M; Huidobro, G; Campos-Balea, B; López-Vázquez, M D; Vázquez, S

    2014-03-01

    This single arm, phase II study aims to evaluate the role of epidermal growth factor receptor-tyrosine-kinase inhibitor erlotinib as maintenance therapy following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients with unresectable stage IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a standard cCRT regimen with curative intent were included. Oral erlotinib 150 mg/day was administered within 4-6 weeks after the end of the cCRT for a maximum of 6 months if no disease progression or intolerable toxicity occurred. Primary end point was the progression-free rate (PFR) at 6 months. Secondary end points included time to progression (TTP) and overall survival (OS). Sixty-six patients were enrolled and received maintenance treatment with erlotinib [average: 4.5 months (95 % CI 4.0-5.0)]. PFR at 6 months was 63.5 % (41/66). With a median follow-up of 22.7 months (95 % CI 13.5-37.1), the median TTP was 9.9 months (95 % CI 6.2-12.1), and the median OS was 24.0 months (95 % CI 17.3-48.6). Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 % grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3), anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients (7.6 %) were withdrawn due to AEs. Erlotinib as maintenance therapy is an active treatment after cCRT in unselected patients with stage III NSCLC, reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile of maintenance erlotinib was as expected and manageable.

  15. Metabolic activity by {sup 18}F-FDG-PET/CT is predictive of early response after nivolumab in previously treated NSCLC

    Energy Technology Data Exchange (ETDEWEB)

    Kaira, Kyoichi; Altan, Bolag [Gunma University Graduate School of Medicine, Department of Oncology Clinical Development, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Arisaka, Yukiko; Tokue, Azusa [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Naruse, Ichiro [Hidaka Hospital, Department of Respiratory Medicine, Hidaka (Japan); Suda, Satoshi [Hidaka Hospital, Department of Radiology, Hidaka (Japan); Mogi, Akira; Shimizu, Kimihiro [Gunma University Graduate School of Medicine, Department of General Surgical Science, Maebashi, Gunma (Japan); Sunaga, Noriaki [Gunma University Hospital, Oncology Center, Maebashi, Gunma (Japan); Hisada, Takeshi [Gunma University Hospital, Department of Respiratory Medicine, Maebashi, Gunma (Japan); Kitano, Shigehisa [National Cancer Center Hospital, Department of Experimental Therapeutics, Tokyo (Japan); Obinata, Hideru; Asao, Takayuki [Gunma University Initiative for Advanced Research, Big Data Center for Integrative Analysis, Maebashi, Gunma (Japan); Yokobori, Takehiko [Gunma University Initiative for Advanced Research, Division of Integrated Oncology Research, Research Program for Omics-based Medical Science, Maebashi, Gunma (Japan); Mori, Keita [Clinical Research Support Center, Shizuoka Cancer Center, Suntou-gun (Japan); Nishiyama, Masahiko [Gunma University Graduate School of Medicine, Department of Molecular Pharmacology and Oncology, Maebashi, Gunma (Japan); Tsushima, Yoshihito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gunma University Initiative for Advanced Research (GIAR), Research Program for Diagnostic and Molecular Imaging, Division of Integrated Oncology Research, Maebashi, Gunma (Japan)

    2018-01-15

    Nivolumab, an anti-programmed death-1 (PD-1) antibody, is administered in patients with previously treated non-small cell lung cancer. However, little is known about the established biomarker predicting the efficacy of nivolumab. Here, we conducted a preliminary study to investigate whether {sup 18}F-FDG-PET/CT could predict the therapeutic response of nivolumab at the early phase. Twenty-four patients were enrolled in this study. {sup 18}F-FDG-PET/CT was carried out before and 1 month after nivolumab therapy. SUV{sub max}, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were calculated. Immunohistochemical analysis of PD-L1 expression and tumour-infiltrating lymphocytes was conducted. Among all patients, a partial metabolic response to nivolumab was observed in 29% on SUV{sub max}, 25% on MTV, and 33% on TLG, whereas seven (29%) patients achieved a partial response (PR) based on RECIST v1.1. The predictive probability of PR (100% vs. 29%, p = 0.021) and progressive disease (100% vs. 22.2%, p = 0.002) at 1 month after nivolumab initiation was significantly higher in {sup 18}F-FDG on PET/CT than in CT scans. Multivariate analysis confirmed that {sup 18}F-FDG uptake after administration of nivolumab was an independent prognostic factor. PD-L1 expression and nivolumab plasma concentration could not precisely predict the early therapeutic efficacy of nivolumab. Metabolic response by {sup 18}F-FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment. (orig.)

  16. Practical integration of [18F]-FDG-PET and PET-CT in the planning of radiotherapy for non-small cell lung cancer (NSCLC): the technical basis, ICRU-target volumes, problems, perspectives.

    Science.gov (United States)

    Nestle, Ursula; Kremp, Stephanie; Grosu, Anca-Ligia

    2006-11-01

    The value of positron emission tomography using [18F]-fluoro-deoxy-glucose (FDG-PET) for pretherapeutic evaluation of patients with non-small cell lung cancer (NSCLC) is beyond doubt. Due to the increasing availability of PET and PET-CT scanners the method is now widely available, and its technical integration has become possible for radiotherapy planning systems. Due to the depiction of malignant tissue with high diagnostic accuracy, the use of FDG-PET in radiotherapy planning of NSCLC is very promising. However, by uncritical application, PET could impair rather than improve the prognosis of patients. Therefore, in the present paper we give an overview of technical factors influencing PET and PET-CT data, and their consequences for radiotherapy planning. We further review the relevant literature concerning the diagnostic value of FDG-PET and on the integration of FDG-PET data in RT planning for NSCLC. We point out the possible impact in gross tumor volume (GTV) definition and describe methods of target volume contouring of the primary tumor, as well as concepts for the integration of diagnostic information on lymph node involvement into the clinical target volume (CTV), and the possible implications of PET data on the definition of the planning target volume (PTV). Finally, we give an idea of the possible future use of tracers other than [18F]-FDG in lung cancer.

  17. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

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    Hellevik Turid

    2012-04-01

    Full Text Available Abstract Background Cancer-Associated Fibroblasts (CAFs are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR, equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART for medically inoperable stage-I/II non-small-cell lung cancers. Methods CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs and their endogenous inhibitors (TIMPs were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining. Results Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.

  18. Improved outcome of treating locally advanced lung cancer with the use of Lattice Radiotherapy (LRT: A case report

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    Beatriz E. Amendola

    2018-02-01

    Full Text Available The Lattice Radiotherapy (LRT technique is mainly based on the GRID technology with the improved feature of the 3D treatment delivery. A 72 year old male presented with left shoulder pain due to a 6 cm pulmonary mass in the left upper lobe (LUL histologically proven Non-Small Cell Lung Cancer (NSCLC stage IIIA. In July 2011 he was treated in our center with LRT followed by conventional fractionated Volumetric Modulated Arc Therapy (VMAT combined with chemotherapy. Clinical and imaging follow up of 6 years demonstrated continued improvement and the patient is currently with no evidence of disease (NED. This outstanding result obtained in our first lung cancer patient treated with this approach corroborates its potential in the treatment of locally advanced lung cancer. In a period of 7 years we have treated more than 30 patients with LRT for different diagnosis and sites; 12 of them NSCLC patients, with markedly improved local control and minimal toxicity.

  19. [The short-term observation of Shenqifuzheng injection combined with NP chemotherapy in treating elder patients with advanced non-small cell lung cancer].

    Science.gov (United States)

    Wang, Xiuyun; Huang, Zongqiong; Li, Hong; Cai, Xuebin

    2007-06-20

    About 80% lung cancer is non-small cell lung cancer (NSCLC) and 70%-80% are in advanced stage. Chemotherapy is main treatment method. The aim of this study is to compare the therapeutic effects and toxicity of NP regimen combined with Shenqifuzheng injection on elder patients with advanced NSCLC. Totally 69 patients enrolled into this study and were randomized into two groups: treatment group (35 patients) and control group (34 patients). Each patient received NVB 25mg/m² intravenously at days 1 and 8 and DDP 30mg intravenously from 1st day to 4th day. Shenqifuzheng injection was used in the treatment group by 250mL per day for 10 days. There was no significant difference of the response rate between two groups (45.7% vs 41.2%, P > 0.05). The hematological toxicity, nausea and vomiting in the treatment group were lower than those in the control group with significant difference (P NP regimen combined with Shenqifuzheng injection on elder patients with advanced NSCLC is effective and safe. Shenqifuzheng injection has definite toxicity relieving effect on treating elder patients with advanced NSCLC.

  20. The management impact of clinically significant incidental lesions detected on staging FDG PET-CT in patients with non-small cell lung cancer (NSCLC): an analysis of 649 cases.

    Science.gov (United States)

    Lin, Michael; Ambati, Chaitanya

    2012-06-01

    To evaluate FDG PET-CT in the detection of unexpected pre-malignancy or second malignancy at the initial staging of patients with histologically proven non-small cell lung cancer (NSCLC) and its impact on management. Staging FDG PET-CT scans acquired between February 2006 and July 2010 in 649 patients (M=389; F=260) with NSCLC were reviewed for the presence of unexpected pre-malignancy or second primary. A "True-Positive" lesion represented a second primary or pre-malignant lesion. A "False-Positive" lesion was due to benign causes or an atypical site of metastasis from NSCLC. 77 (12%) patients were identified on PET-CT as having a potential pre-malignancy or second primary. 39 out of 77 (51%) patients had diagnostic verification where histopathology served as reference standard in 33 patients (85%) and the rest had endoscopy and progress PET-CT scans. 20 patients (3.1%) had a second primary (n=11) or pre-malignant lesions comprising dysplastic colorectal polyps (n=9), and additional therapy and/or management change for the index tumour was instigated in 17 patients (85%). In patients with a second primary, 3 (27%) patients had a high impact change in management from an initial curative intent to palliative. Staging FDG PET-CT is highly valuable in identifying second primary cancers or pre-malignant lesions in patients with NSCLC. When a second primary is detected on PET-CT, there is a high impact change in management in 27% of patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. TNFRSF1B +676 T>G polymorphism predicts survival of non-Small cell lung cancer patients treated with chemoradiotherapy

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    Komaki Ritsuko

    2011-10-01

    Full Text Available Abstract Background The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC. Furthermore, functional polymorphisms in TNF-α and TNFRSF1B genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both TNF-α and TNFRSF1B and prognosis of NSCLC patients treated with chemoradiotherapy. Methods We genotyped five potentially functional polymorphisms of TNF-α and TNFRSF1B genes [TNF-α -308 G>A (rs1800629 and -1031 T>C (rs1799964; TNFRSF1B +676 T>G (rs1061622, -1709A>T(rs652625 and +1663A>G (rs1061624] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS. Results We found that the TNFRSF1B +676 GG genotype was associated with a significantly better OS of NSCLC (GG vs. TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG vs. GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88. Further stepwise multivariate Cox regression analysis showed that the TNFRSF1B +676 GG was an independent prognosis predictor in this NSCLC cohort (GG vs. GT/TT: HR = 0.35, 95% CI = 0.14-0.85, in the presence of node status (N2-3 vs. N0-1: HR = 1.60, 95% CI = 1.09-2.35 and tumor stage (T3-4 vs. T0-2: HR = 1.48, 95% CI = 1.08-2.03. Conclusions Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of TNFRSF1B +676 T>G (rs1061622 in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.

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

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

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

  3. ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy.

    Science.gov (United States)

    Das, Millie; Riess, Jonathan W; Frankel, Paul; Schwartz, Erich; Bennis, Robyn; Hsieh, H Ben; Liu, Xiaohe; Ly, Janey C; Zhou, Lisa; Nieva, Jorge J; Wakelee, Heather A; Bruce, Richard H

    2012-08-01

    To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation. PFS decreased with increasing ERCC1 expression (ptest, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, ptest (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging. Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Prognostic role of a comprehensive geriatric assessment on the management of elderly patients with advanced non-small cell lung cancer (NSCLC): a pooled analysis of two prospective phase II trials by the GFPC Group

    Science.gov (United States)

    Le Caer, Hervé; Borget, Isabelle; Corre, Romain; Locher, Chrystele; Raynaud, Christine; Decroisette, Chantal; Berard, Henri; Audigier-Valette, Clarisse; Dujon, Cecile; Auliac, Jean Bernard; Crequit, Jacquy; Monnet, Isabelle; Vergnenegre, Alain

    2017-01-01

    Background The prognostic role of a comprehensive geriatric assessment (CGA) on the management of elderly patients with advanced-stage non-small cell lung cancer (NSCLC) remains to be established. The objective of this analysis was to determine the prognostic role of each CGA domain on overall survival (OS) among elderly patients with advanced-stage NSCLC. Methods We pooled individual data from two prospective, randomized phases II trials in patients over 65 years old with advanced-stage NSCLC, who were considered fit (0405 trial) or no-fit (0505 trial) based on a CGA. Both trials compared first-line chemotherapy followed by second-line erlotinib with the reverse strategy in terms of progression-free survival (PFS) and OS. Factors prognostic of OS were sought by using the Kaplan-Meier method and the log rank test for univariate analysis, and a Cox model for multivariate analysis. Results Analysis performed on 194 patients (mean age: 77 years, male gender: 70%, never- or ex-smokers: 56%) showed, in univariate analysis that performance status (PS), smoking status, Charlson, simplified Charlson, nutritional scores, and a mobility score were prognostics of OS. In multivariate analysis, PS [HR: 1.4 (1.02–1.9), P=0.04] and the Charlson score [HR: 1.46 (1.07–1.99), P=0.02] were independently prognostic of OS, while the nutritional score [HR: 0.69 (0.46–1.04), P=0.07] and the mobility score [HR: 0.25 (0.06–1.01), P=0.06] were close to significance. Conclusions PS and comorbidities appear to be the main predictors of OS in elderly advanced NSCLC patients selected on the basis of CGA. PMID:29268382

  5. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1)

    DEFF Research Database (Denmark)

    Reck, Martin; Kaiser, Rolf; Mellemgaard, Anders

    2014-01-01

    BACKGROUND: The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer (NSCLC). METHODS: Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy...... to treat after 714 events in all patients. The key secondary endpoint was overall survival, analysed by intention to treat after 1121 events had occurred, in a prespecified stepwise order: first in patients with adenocarcinoma who progressed within 9 months after start of first-line therapy, then in all...... a median follow-up of 31·7 months (IQR 27·8-36·1), overall survival was significantly improved for patients with adenocarcinoma histology who progressed within 9 months after start of first-line treatment in the docetaxel plus nintedanib group (206 patients) compared with those in the docetaxel plus...

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

    Science.gov (United States)

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

    2017-12-10

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

  7. Phase I study of combined therapy with vorinostat and gefitinib to treat BIM deletion polymorphism-associated resistance in EGFR-mutant lung cancer (VICTROY-J): a study protocol.

    Science.gov (United States)

    Takeuchi, Shinji; Yoshimura, Kenichi; Fujiwara, Tadami; Ando, Masahiko; Shimizu, Shinobu; Nagase, Katsuhiko; Hasegawa, Yoshinori; Takahashi, Toshiaki; Katakami, Nobuyuki; Inoue, Akira; Yano, Seiji

    2017-01-01

    The BIM deletion polymorphism is reported to be associated with poor outcomes of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR-TKIs, including gefitinib. We have shown that a histone deacetylase inhibitor, vorinostat, can epigenetically restore BIM function and apoptosis sensitivity to EGFR-TKIs in EGFR-mutant NSCLC cells with BIM deletion polymorphisms. The purpose of this study is to determine the feasibility of combined treatment of vorinostat with gefitinib in BIM deletion polymorphism positive EGFR-mutant NSCLC patients. BIM deletion polymorphism positive EGFR-mutant NSCLC patients treated with at least one EGFR-TKI and one regimen of chemotherapy are being recruited to this study. Vorinostat (200-400 mg) will be administered orally once daily on days 1-7, and gefitinib 250 mg orally once daily on days 1-14. With a fixed dose of gefitinib, the dose of vorinostat will be escalated following a conventional 3+3 design. The primary endpoint is to define the maximum tolerated dose (MTD) of vorinostat combined with 250 mg of gefitinib. This is the first phase I study of combined therapy with vorinostat and gefitinib for NSCLC patients double selected for an EGFR mutation and BIM deletion polymorphism. J. Med. Invest. 64: 321-325, August, 2017.

  8. Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Eblan, Michael J.; Corradetti, Michael N.; Lukens, J. Nicholas; Xanthopoulos, Eric [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Grover, Surbhi; Fernandes, Annemarie T. [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Langer, Corey J.; Evans, Tracey L.; Stevenson, James [Department of Medical Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Rengan, Ramesh [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Apisarnthanarax, Smith, E-mail: apisarns@uphs.upenn.edu [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2013-01-01

    Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received {>=}50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received {<=}78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving {>=}1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of

  9. Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

    International Nuclear Information System (INIS)

    Eblan, Michael J.; Corradetti, Michael N.; Lukens, J. Nicholas; Xanthopoulos, Eric; Mitra, Nandita; Christodouleas, John P.; Grover, Surbhi; Fernandes, Annemarie T.; Langer, Corey J.; Evans, Tracey L.; Stevenson, James; Rengan, Ramesh; Apisarnthanarax, Smith

    2013-01-01

    Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received ≥50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received ≤78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving ≥1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of

  10. 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.

  11. Cost-effective analysis of PET application in NSCLC

    International Nuclear Information System (INIS)

    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)

  12. Comparison of RECIST to immune-related response criteria in patients with non-small cell lung cancer treated with immune-checkpoint inhibitors.

    Science.gov (United States)

    Kim, Hee Kyung; Heo, Mi Hwa; Lee, Han Sang; Sun, Jong-Mu; Lee, Se-Hoon; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung-Ju

    2017-09-01

    Given that immune-related response in non-small cell lung cancer (NSCLC) has not been well evaluated, we assessed tumor response using the response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1) and immune-related response criteria (irRC) to identify atypical responses in patients with advanced NSCLC treated with immunotherapeutic agents. Patients received immune-checkpoint inhibitors (pembrolizumab, atezolizumab, nivolumab, and durvalumab plus tremelimumab) to treat metastatic or recurrent NSCLC after failed platinum-based chemotherapy. Tumor response was assessed according to both RECIST v1.1 and irRC. Responses by 41 patients were analyzed. The overall response rate (ORR) was 29.2% (95% CI 17.6-44.5) assessed by RECIST v1.1 and 34.1% (95% CI 21.6-49.4) by irRC, showing similar results from the two methods (p = 0.923). Two patients (4.9%) were defined as having progressive disease as assessed by RECIST but not by irRC. The patients eventually experienced tumor regression, suggesting delayed pseudoprogression. For all patients, the median PFS was 5.1 months (95% CI 3.4-6.7) and OS was 18.3 months (95% CI 6.7-29.8). In multivariate analysis, ex- or current smokers (HR 0.34, p = 0.14) and EGFR mutation negativity (HR 0.16, p = 0.05) were associated with significantly longer PFS. Our study found that pseudoprogression was not frequently observed in NSCLC. Conventional RECIST v1.1 might underestimate the benefit of immune-checkpoint inhibitors. Given the small number of patients studied, further study is warranted on whether treatment with immune-checkpoint inhibitors beyond RECIST progression benefits patients with advanced NSCLC.

  13. Combined Targeted DNA Sequencing in Non-Small Cell Lung Cancer (NSCLC) Using UNCseq and NGScopy, and RNA Sequencing Using UNCqeR for the Detection of Genetic Aberrations in NSCLC

    Science.gov (United States)

    Walter, Vonn; Patel, Nirali M.; Eberhard, David A.; Hayward, Michele C.; Salazar, Ashley H.; Jo, Heejoon; Soloway, Matthew G.; Wilkerson, Matthew D.; Parker, Joel S.; Yin, Xiaoying; Zhang, Guosheng; Siegel, Marni B.; Rosson, Gary B.; Earp, H. Shelton; Sharpless, Norman E.; Gulley, Margaret L.; Weck, Karen E.

    2015-01-01

    The recent FDA approval of the MiSeqDx platform provides a unique opportunity to develop targeted next generation sequencing (NGS) panels for human disease, including cancer. We have developed a scalable, targeted panel-based assay termed UNCseq, which involves a NGS panel of over 200 cancer-associated genes and a standardized downstream bioinformatics pipeline for detection of single nucleotide variations (SNV) as well as small insertions and deletions (indel). In addition, we developed a novel algorithm, NGScopy, designed for samples with sparse sequencing coverage to detect large-scale copy number variations (CNV), similar to human SNP Array 6.0 as well as small-scale intragenic CNV. Overall, we applied this assay to 100 snap-frozen lung cancer specimens lacking same-patient germline DNA (07–0120 tissue cohort) and validated our results against Sanger sequencing, SNP Array, and our recently published integrated DNA-seq/RNA-seq assay, UNCqeR, where RNA-seq of same-patient tumor specimens confirmed SNV detected by DNA-seq, if RNA-seq coverage depth was adequate. In addition, we applied the UNCseq assay on an independent lung cancer tumor tissue collection with available same-patient germline DNA (11–1115 tissue cohort) and confirmed mutations using assays performed in a CLIA-certified laboratory. We conclude that UNCseq can identify SNV, indel, and CNV in tumor specimens lacking germline DNA in a cost-efficient fashion. PMID:26076459

  14. Combined Targeted DNA Sequencing in Non-Small Cell Lung Cancer (NSCLC Using UNCseq and NGScopy, and RNA Sequencing Using UNCqeR for the Detection of Genetic Aberrations in NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiaobei Zhao

    Full Text Available The recent FDA approval of the MiSeqDx platform provides a unique opportunity to develop targeted next generation sequencing (NGS panels for human disease, including cancer. We have developed a scalable, targeted panel-based assay termed UNCseq, which involves a NGS panel of over 200 cancer-associated genes and a standardized downstream bioinformatics pipeline for detection of single nucleotide variations (SNV as well as small insertions and deletions (indel. In addition, we developed a novel algorithm, NGScopy, designed for samples with sparse sequencing coverage to detect large-scale copy number variations (CNV, similar to human SNP Array 6.0 as well as small-scale intragenic CNV. Overall, we applied this assay to 100 snap-frozen lung cancer specimens lacking same-patient germline DNA (07-0120 tissue cohort and validated our results against Sanger sequencing, SNP Array, and our recently published integrated DNA-seq/RNA-seq assay, UNCqeR, where RNA-seq of same-patient tumor specimens confirmed SNV detected by DNA-seq, if RNA-seq coverage depth was adequate. In addition, we applied the UNCseq assay on an independent lung cancer tumor tissue collection with available same-patient germline DNA (11-1115 tissue cohort and confirmed mutations using assays performed in a CLIA-certified laboratory. We conclude that UNCseq can identify SNV, indel, and CNV in tumor specimens lacking germline DNA in a cost-efficient fashion.

  15. Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

    Science.gov (United States)

    Yamamoto, Masaaki; Serizawa, Toru; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Nagano, Osamu; Barfod, Bierta E; Ono, Junichi; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-02-01

    We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

  16. 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...... year was 64%, 35% and 14%, respectively. In a Cox regression analyses of time to CE, age > 65 year, + induction chemotherapy, smoking, high mean dose to left + right ventricles or whole heart was not a statistically significant factor, whereas low FEV-1, large GTV, low Hb, poor PS, high V20 to lunge...

  17. Survival Outcomes According to TIMP1 and EGFR Expression in Heavily Treated Patients with Advanced Non-small Cell Lung Cancer who Received Biweekly Irinotecan Plus Bevacizumab.

    Science.gov (United States)

    Wills, Beatriz; Cardona, Andrés F; Rojas, Leonardo; Ruiz-Patiño, Alejandro; Arrieta, Oscar; Reguart, Noemí; Carranza, Hernán; Vargas, Carlos; Otero, Jorge; Corrales, Luis; Martín, Claudio; Cuello, Mauricio; Pino, Luis Eduardo; Rolfo, Christian; Rosell, Rafael; Zatarain-Barrón, Zyanya Lucia

    2017-11-01

    Heavily treated patients with non-small cell lung cancer (NSCLC) have few treatment options, while irinotecan and bevacizumab have proven synergistic action in preclinical studies. A total of 49 patients with heavily treated NSCLC were enrolled from 2011-2014 and treated with irinotecan and bevacizumab. Treatment response along with mutational status of epidermal growth factor receptor (EGFR), and tissue inhibitor of metalloproteinases-1 (TIMP1) and EGFR expression were evaluated. Progression-free (PFS) and overall (OS) survival were monitored. Median follow-up was 13.2 months. Twenty-three patients had received three or more prior therapy lines. Overall response rate was 32% [95% confidence interval (CI)=22%-39%] and 26% of patients achieved stable disease. Median PFS was 4.4 (95% CI=2.8-8.3) months and median OS 18.0 (95% CI=16.2-30.7) months. Nine patients harboring EGFR mutations had a long-lasting partial response. A shorter OS was found in patients with a higher TIMP1 expression (p=0.006). Irinotecan combined with bevacizumab had favorable antitumor activity in heavily pretreated patients with NSCLC. These results suggest this is a reasonable strategy, particularly for patients with low TIMP1 expression. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Serum proteomic patterns of patients with non-small cell lung cancer treated by radiochemotherapy

    International Nuclear Information System (INIS)

    Li Xianglan; You Qingshan; Yang Yanmei; Ma Yuyan; Tang Yali; Cai Huilong

    2007-01-01

    Objective:To detect the serum proteomic patterns of patients with non-small cell lung (NSCLC) treated with radiochemotherapy by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) protein chip array techniques, and to screen differential expression protein and observe the changes between the patterns before and after the treatment. Methods: SELDI-TOF-MS and CM-10 protein chips were used to detect the serum proteomic patterns of 35 healthy persons (normal control) and 35 patients with NSCLC before radiochemotherapy. Twenty-six out of the 35 patients after the treatment were also studied. BioMarker Wizard 3.01 and BioMarker Pattern System 5. 01 were used in combination to analyze the data and to develop diagnostic models. Results: Sixteen differential expression protein peaks from a total of 251 protein peaks were automatically chosen, including 8 high expressions and 8 low expressions in patients with NSCLC. Of the 16 protein peaks, 6 protein peak patterns ( M 2 572.1, M 2 885.8, M 3 870.4, M 4 161.4, M 5 739.7 and M 8 164.3 mass/charge ratio [ m/z] ) were observed in model that could be used to distinguish lung cancer' from non-cancer diseases. The sensitivity and specificity results were 91% (32/35)and 83% (29/35). When the SELDI marker pattern was tested with the blinded test set, the sensitivity and specificity were 80% (28/35) and 71% (25/35). The 16 differential expression protein peaks of patients before and after the treatment were obviously different. But the peaks of patients after the treatment trended to those of the normal control. Of the 16 protein peaks, M 2 572.1, M 2 885.8, M 4 664.78, M 9 228.39 and M 9 396.42 were significantly changed. Conclusions: SELDI-TOF-MS is possibly significant for screening differential expression proteins and assessing the treatment efficacy and prognosis of patients, which needs to be demonstrated by further study. (authors)

  19. The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Lee, Ji Yun; Ku, Bo Mi; Lim, Sung Hee; Lee, Min-Young; Kim, Haesu; Kim, Moonjin; Kim, Sungmin; Jung, Hyun Ae; Sun, Jong-Mu; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung-Ju

    2015-06-01

    A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib). The BIM deletion polymorphism was present in 15.6% (32 of 205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were younger than 65 years (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar objective response rates (91 vs. 84%, p = 0.585). Progression-free survival and overall survival did not differ significantly between patients with and without the BIM deletion polymorphism (median progression-free survival 12 vs. 11 months, p = 0.160; median overall survival 31 vs. 30 months, p = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including Eastern Cooperative Oncology Group performance status 0-1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients. It remains to be determined whether the BIM deletion polymorphism

  20. Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives

    DEFF Research Database (Denmark)

    Vilmar, A C; Sorensen, J B

    2011-01-01

    Treating patients with advanced nonsmall cell lung cancer (NSCLC) is a daunting task but during recent years new options have emerged. By tailoring treatment using either information on histological subtypes of NSCLC or biomarkers it is now possible to improve outcome and maintain stable quality...

  1. Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

    2016-10-01

    Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. 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

  3. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer ... because of timely detection and treatment of his prostate cancer. He participated in an NIH-sponsored clinical trial. ...

  4. 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.

  5. Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

    Directory of Open Access Journals (Sweden)

    Ming Yin

    Full Text Available The repair of DNA double-strand breaks (DSBs is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC patients treated with definitive radio(chemotherapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs (i.e., RAD51 -135G>C/rs1801320 and -172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794 and estimated their associations with overall survival (OS and radiation pneumonitis (RP in 228 NSCLC patients. We found a predictive role of RAD51 -135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31-0.86, P = 0.010 for CG/CC vs. GG. We also found that RAD51 -135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14-2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02-2.85, P = 0.043 for AG vs. GG, respectively and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 -135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemotherapy. Large studies are needed to confirm our findings.

  6. A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus.

    Science.gov (United States)

    Bang, Sun-Hwi; Yoon, Jeung-Won; Cho, Chong-Kwan; Shin, Ji-Eun; Lee, Yeon-Weol; Yoo, Hwa-Seung

    2012-06-01

    Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus(HAP) has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. The study involved six patients treated at the East- West Cancer Center (EWCC) from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT) scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS) and progression-free survival (PFS). Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD), and the other three showed progressive disease (PD). The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

  7. 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.

  8. Functional promoter rs2868371 variant of HSPB1 associates with radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with radio(chemo)therapy

    International Nuclear Information System (INIS)

    Lopez Guerra, Jose Luis; Wei Qingyi; Yuan Xianglin; Gomez, Daniel; Liu Zhensheng; Zhuang Yan; Yin Ming; Li Minghuan; Wang, Li-E; Cox, James D.; Liao Zhongxing

    2011-01-01

    Purpose: We investigated the association between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and the risk of radiation-induced esophageal toxicity (RIET) in patients with non-small-cell lung cancer (NSCLC). Materials and methods: The experimental dataset comprised 120 NSCLC patients who were treated with radio(chemo)therapy between 2005 and 2009, when novel radiation techniques were implemented at MD Anderson. The validation dataset comprised 181 NSCLC patients treated between 1998 and 2004. We genotyped two SNPs of the HSPB1 gene (rs2868370 and rs2868371) by TaqMan assay. Results: Univariate and multivariate analyses of the experimental dataset showed that the CG/GG genotypes of HSPB1 rs2868371 were associated with significantly lower risk of grade ⩾3 RIET than the CC genotype (univariate hazard ratio [HR] 0.30; 95% confidence interval [CI], 0.10–0.91; P = 0.033; multivariate HR 0.29; 95% CI, 0.09–0.97; P = 0.045). This difference in risk was replicated in the validation cohort despite the different radiation techniques used during that period. Conclusions: The CG/GG genotypes of HSPB1 rs2868371 were associated with lower risk of RIET, compared with the CC genotype in patients with NSCLC treated with radio(chemo)therapy. This finding should be validated in large multi-institutional prospective trials.

  9. Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Yoneshima, Yasuto; Morita, Satoshi; Ando, Masahiko; Miura, Satoru; Yoshioka, Hiroshige; Abe, Tetsuya; Kato, Terufumi; Kondo, Masashi; Hosomi, Yukio; Hotta, Katsuyuki; Yamamoto, Nobuyuki; Kishimoto, Junji; Nakanishi, Yoichi; Okamoto, Isamu

    2017-01-01

    Nanoparticle albumin-bound (nab) paclitaxel is a promising new therapeutic agent for all histologic types of non-small-cell lung cancer (NSCLC). We recently performed a phase 2 study of weekly nab-paclitaxel in patients with previously treated advanced NSCLC, finding promising activity and acceptable toxicity for this regimen. We have now designed a randomized phase 3 intergroup study (J-AXEL, UMIN000017487) to examine the clinical benefit and safety of nab-paclitaxel compared to docetaxel in patients with previously treated advanced NSCLC. Patients are randomized to receive either docetaxel (60 mg/m 2 on day 1 every 3 weeks, control arm) or nab-paclitaxel (100 mg/m 2 on days 1, 8, and 15 every 3 weeks, experimental arm), with each drug being administered until disease progression or unacceptable toxicity. The study will evaluate the noninferiority of nab-paclitaxel relative to docetaxel for the primary end point of overall survival. If the primary objective is achieved, this study will provide evidence for a new alternative treatment option for patients with previously treated advanced NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Correlation of the apparent diffusion coefficient (ADC with the standardized uptake value (SUV in lymph node metastases of non-small cell lung cancer (NSCLC patients using hybrid 18F-FDG PET/MRI.

    Directory of Open Access Journals (Sweden)

    Benedikt Michael Schaarschmidt

    Full Text Available To compare the apparent diffusion coefficient (ADC in lymph node metastases of non-small cell lung cancer (NSCLC patients with standardized uptake values (SUV derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI.38 patients with histopathologically proven NSCLC (mean age 60.1 ± 9.5 y received whole-body PET/CT (Siemens mCT™ 60 min after injection of a mean dose of 280 ± 50 MBq 18F-FDG and subsequent PET/MRI (mean time after tracer injection: 139 ± 26 min, Siemens Biograph mMR. During PET acquisition, simultaneous diffusion-weighted imaging (DWI, b values: 0, 500, 1000 s/mm² was performed. A maximum of 10 lymph nodes per patient suspicious for malignancy were analyzed. Regions of interest (ROI were drawn covering the entire lymph node on the attenuation-corrected PET-image and the monoexponential ADC-map. According to histopathology or radiological follow-up, lymph nodes were classified as benign or malignant. Pearson's correlation coefficients were calculated for all lymph node metastases correlating SUVmax and SUVmean with ADCmean.A total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUVmax was 9.1 ± 3.8 and mean SUVmean was 6.0 ± 2.5 while mean ADCmean was 877.0 ± 128.6 x10(-5 mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUVmax and ADCmean as well as SUVmean and ADCmean (r = -0.30, p<0.05 and r = -0.36, p<0.05 existed.The present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.

  11. Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study.

    Science.gov (United States)

    Huang, Chu-Ying; Wang, Li; Feng, Cheng-Jun; Yu, Ping; Cai, Xiao-Hong; Yao, Wen-Xiu; Xu, Yong; Liu, Xiao-Ke; Zhu, Wen-Jiang; Wang, Yan; Zhou, Jin; Lu, You; Wang, Yong-Sheng

    2016-10-11

    Bisphosphonates have exhibited anti-tumor activity in non-small cell lung cancer (NSCLC). We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations. Between January 2008 and October 2013, 114 advanced EGFR mutations NSCLC patients who received EGFR-TKIs as first-line therapy were recruited from two cancer centers. Patients were separated into EGFR-TKIs alone or EGFR-TKIs plus bisphosphonates (combination) group. Median progression free survival (mPFS), median overall survival (mOS) distributions and survival curves were analyzed. Among the 114 patients, 62 had bone metastases (19 patients treated with EGFR-TKIs, 43 patients treated with EGFR-TKIs + bisphosphonates). Median PFS and OS were significantly improved in combination group compared with EGFR-TKIs group (mPFS: 15.0 vs 7.3 months, P = 0.0017; mOS: 25.2 vs 10.4 months, P = 0.0015) in patients with bone metastases. Among the 71 patients (19 patients with bone metastases) treated with EGFR-TKIs alone, patients with bone metastases had poor survival prognosis (mPFS:7.3 vs 12.1 months, P = 0.0434; mOS:10.4 vs 22.0 months, P = 0.0036). The survival of patients with bone metastases who received EGFR-TKIs plus bisphosphonates therapy was non-inferior to patients without bone metastases treated with EGFR-TKIs alone (mPFS: 15.0 vs 12.1 months, p = 0.1871; mOS: 25.2 vs 22.0 months, p = 0.9798). Concomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases.

  12. Non-Small Cell Lung Cancer as a Second Primary Among Patients With Previous Malignancy: Who Is at Risk?

    Science.gov (United States)

    Wu, Geena X; Nelson, Rebecca A; Kim, Jae Y; Raz, Dan J

    2017-09-01

    Patients with previous malignancies could be at increased risk of non-small cell lung cancer (NSCLC). However, the extent of the risk is unknown for many cancer types; thus, it is unclear who might benefit from screening. The Surveillance, Epidemiology, and End Results data set from 1992 to 2012 was used to identify patients with previous malignancies who received a diagnosis of NSCLC ≥ 6 months after their initial cancer diagnosis. Standardized incidence ratios (SIRs) for NSCLC were calculated as a ratio of the observed to expected cases adjusted by person-years at risk. Cancers with a SIR > 1.0 had a risk of NSCLC greater than expected. The analyses were stratified by sex, radiation therapy use, and histologic type. Among the cancer survivors, 32,058 developed NSCLC. Smoking-related (lung, head and neck, bladder) and hematologic malignancies, regardless of previous radiation therapy, had the greatest SIR for NSCLC (range, 1.97-4.88). Colorectal and renal cancer survivors also had an increased SIR for NSCLC (1.16 and 1.21, respectively). Women with previous pancreatic cancer treated with radiation, breast cancer with or without radiation therapy, and those with thyroid cancer demonstrated a greater SIR for lung adenocarcinoma. Men with previous irradiated prostate cancer also had an elevated SIR (1.08; 99% confidence interval, 1.01-1.15) for lung adenocarcinoma. Patients with melanoma, prostate or uterine cancer had a lower SIR for NSCLC than expected. Smoking-related malignancies had the greatest risk of NSCLC. Radiation therapy conferred an elevated risk of NSCLC for certain cancers. Melanoma, prostate, and uterine cancer survivors had a low risk of NSCLC. These results could help identify high-risk screening candidates in the growing population of cancer survivors. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Combining Drugs to Treat Ovarian Cancer - Annual Plan

    Science.gov (United States)

    Approximately 70 percent of women diagnosed with ovarian cancer will die from the disease. Read about the NCI-funded combination drug trial that has successfully treated Betsy Brauser's recurrent cancer.

  14. Development and External Validation of Prognostic Model for 2-Year Survival of Non-Small-Cell Lung Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Dehing-Oberije, Cary; Yu Shipeng; De Ruysscher, Dirk; Meersschout, Sabine; Van Beek, Karen; Lievens, Yolande; Van Meerbeeck, Jan; De Neve, Wilfried; Rao, Bharat Ph.D.; Weide, Hiska van der; Lambin, Philippe

    2009-01-01

    Purpose: Radiotherapy, combined with chemotherapy, is the treatment of choice for a large group of non-small-cell lung cancer (NSCLC) patients. Recent developments in the treatment of these patients have led to improved survival. However, the clinical TNM stage is highly inaccurate for the prediction of survival, and alternatives are lacking. The objective of this study was to develop and validate a prediction model for survival of NSCLC patients, treated with chemoradiotherapy. Patients and Methods: The clinical data from 377 consecutive inoperable NSCLC patients, Stage I-IIIB, treated radically with chemoradiotherapy were collected. A prognostic model for 2-year survival was developed, using 2-norm support vector machines. The performance of the model was expressed as the area under the curve of the receiver operating characteristic and assessed using leave-one-out cross-validation, as well as two external data sets. Results: The final multivariate model consisted of gender, World Health Organization performance status, forced expiratory volume in 1 s, number of positive lymph node stations, and gross tumor volume. The area under the curve, assessed by leave-one-out cross-validation, was 0.74, and application of the model to the external data sets yielded an area under the curve of 0.75 and 0.76. A high- and low-risk group could be clearly identified using a risk score based on the model. Conclusion: The multivariate model performed very well and was able to accurately predict the 2-year survival of NSCLC patients treated with chemoradiotherapy. The model could support clinicians in the treatment decision-making process.

  15. University of Texas Southwestern Medical Center: High-Throughput siRNA Screening of a Non-Small Cell Lung Cancer (NSCLC) Cell Line Panel | Office of Cancer Genomics

    Science.gov (United States)

    The goal of this project is to use siRNA screens to identify NSCLC-selective siRNAs from two genome-wide libraries that will allow us to functionally define genetic dependencies of subtypes of NSCLC. Using bioinformatics tools, the CTD2 center at the University of Texas Southwestern Medical Center are discovering associations between this functional data (siRNAs) and NSCLC mutational status, methylation arrays, gene expression arrays, and copy number variation data that will help us identify new targets and enrollment biomarkers. 

  16. Dual-Energy CT in Patients Treated with Anti-Angiogenic Agents for Non-Small Cell Lung Cancer: New Method of Monitoring Tumor Response?

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na; Lee, Ho Yun; Lee, Kyung Soo; Chung, Myung Jin; Ahn, Myung Ju; Park, Keun Chil; Kim, Tae Sung; Yi, Chin A [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Seo, Joon Beom [Dept. of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    To evaluate tumor responses in patients treated with anti-angiogenic agents for non-small cell lung cancer (NSCLC) by assessing intratumoral changes using a dual-energy CT (DECT) (based on Choi's criteria) and to compare it to traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Ten NSCLC patients treated with bevacizumab underwent DECT. Tumor responses to anti-angiogenic therapy were assessed and compared with the baseline CT results using both RECIST (size changes only) and Choi's criteria (reflecting net tumor enhancement). Kappa statistics was used to evaluate agreements between tumor responses assessed by RECIST and Choi's criteria. The weighted {kappa} value for the comparison of tumor responses between the RECIST and Choi's criteria was 0.72. Of 31 target lesions (21 solid nodules, 8 lymph nodes, and two ground-glass opacity nodules [GGNs]), five lesions (16%) showed discordant responses between RECIST and Choi's criteria. Iodine-enhanced images allowed for a distinction between tumor enhancement and hemorrhagic response (detected in 14% [4 of 29, excluding GGNs] of target lesions on virtual nonenhanced images). DECT may serve as a useful tool for response evaluation after anti-angiogenic treatment in NSCLC patients by providing information on the net enhancement of target lesions without obtaining non-enhanced images.

  17. Targeting the Circadian Clock to Treat Cancer

    Science.gov (United States)

    Two compounds that target components of the circadian clock killed several types of cancer cells in the lab and slowed the growth of brain cancer in mice without harming healthy cells, as this Cancer Currents post reports.

  18. Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study. European Organization for Research and Treatment of Cancer

    NARCIS (Netherlands)

    Uitterhoeve, A. L.; Belderbos, J. S.; Koolen, M. G.; van der Vaart, P. J.; Rodrigus, P. T.; Benraadt, J.; Koning, C. C.; González González, D.; Bartelink, H.

    2000-01-01

    The purpose of this work was to study the feasibility of concurrent chemoradiation in patients with inoperable non-small cell lung cancer (NSCLC). 40 patients with inoperable NSCLC were treated with escalating doses of radiotherapy and cisplatin (cDDP). The radiation dose was increased step by step

  19. Optimised Pre-Analytical Methods Improve KRAS Mutation Detection in Circulating Tumour DNA (ctDNA) from Patients with Non-Small Cell Lung Cancer (NSCLC)

    Science.gov (United States)

    Sherwood, James L.; Corcoran, Claire; Brown, Helen; Sharpe, Alan D.; Musilova, Milena; Kohlmann, Alexander

    2016-01-01

    Introduction Non-invasive mutation testing using circulating tumour DNA (ctDNA) is an attractive premise. This could enable patients without available tumour sample to access more treatment options. Materials & Methods Peripheral blood and matched tumours were analysed from 45 NSCLC patients. We investigated the impact of pre-analytical variables on DNA yield and/or KRAS mutation detection: sample collection tube type, incubation time, centrifugation steps, plasma input volume and DNA extraction kits. Results 2 hr incubation time and double plasma centrifugation (2000 x g) reduced overall DNA yield resulting in lowered levels of contaminating genomic DNA (gDNA). Reduced “contamination” and increased KRAS mutation detection was observed using cell-free DNA Blood Collection Tubes (cfDNA BCT) (Streck), after 72 hrs following blood draw compared to EDTA tubes. Plasma input volume and use of different DNA extraction kits impacted DNA yield. Conclusion This study demonstrated that successful ctDNA recovery for mutation detection in NSCLC is dependent on pre-analytical steps. Development of standardised methods for the detection of KRAS mutations from ctDNA specimens is recommended to minimise the impact of pre-analytical steps on mutation detection rates. Where rapid sample processing is not possible the use of cfDNA BCT tubes would be advantageous. PMID:26918901

  20. Optimised Pre-Analytical Methods Improve KRAS Mutation Detection in Circulating Tumour DNA (ctDNA from Patients with Non-Small Cell Lung Cancer (NSCLC.

    Directory of Open Access Journals (Sweden)

    James L Sherwood

    Full Text Available Non-invasive mutation testing using circulating tumour DNA (ctDNA is an attractive premise. This could enable patients without available tumour sample to access more treatment options.Peripheral blood and matched tumours were analysed from 45 NSCLC patients. We investigated the impact of pre-analytical variables on DNA yield and/or KRAS mutation detection: sample collection tube type, incubation time, centrifugation steps, plasma input volume and DNA extraction kits.2 hr incubation time and double plasma centrifugation (2000 x g reduced overall DNA yield resulting in lowered levels of contaminating genomic DNA (gDNA. Reduced "contamination" and increased KRAS mutation detection was observed using cell-free DNA Blood Collection Tubes (cfDNA BCT (Streck, after 72 hrs following blood draw compared to EDTA tubes. Plasma input volume and use of different DNA extraction kits impacted DNA yield.This study demonstrated that successful ctDNA recovery for mutation detection in NSCLC is dependent on pre-analytical steps. Development of standardised methods for the detection of KRAS mutations from ctDNA specimens is recommended to minimise the impact of pre-analytical steps on mutation detection rates. Where rapid sample processing is not possible the use of cfDNA BCT tubes would be advantageous.

  1. Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Alvarez-Fernandez, Carlos; Perez-Arnillas, Quionia; Ruiz-Echeverria, Lucrecia; Rodriguez-Rubi, David; Sanchez-Lorenzo, Luisa; Li-Torres, Walter; Izquierdo-Manuel, Marta; Berros, Jose P; Luque-Cabal, Maria; Jimenez-Fonseca, Paula; Villanueva-Palicio, Noemi; Esteban-Gonzalez, Emilio

    2014-04-01

    RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC. The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples. RFC expression was detected in 16 (33 %) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p = 0.926) and median OS (11.7 vs 4.8; p = 0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p = 0.039). These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.

  2. Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC.

    Science.gov (United States)

    Mak, Raymond H; Doran, Elizabeth; Muzikansky, Alona; Kang, Josephine; Neal, Joel W; Baldini, Elizabeth H; Choi, Noah C; Willers, Henning; Jackman, David M; Sequist, Lecia V

    2011-01-01

    Epidermal growth factor receptor (EGFR) mutations identify a unique biological subtype of non-small cell lung cancer (NSCLC). Treatment outcomes for EGFR-mutant locally advanced NSCLC patients have not been well described. We retrospectively examined outcomes after combined modality therapy including thoracic radiation therapy (RT) in 123 patients with locally advanced NSCLC and known EGFR mutation status. Outcomes were compared using Kaplan-Meier analysis, the log-rank test, and multivariate Cox regression models. All 123 patients underwent thoracic RT; 25% had tumors with EGFR mutations and 94% had stage III disease. Overall, 81% received chemotherapy concurrent with RT and 55% underwent surgical resection. With a median follow-up of 27.5 months, the overall survival (OS) rate was significantly higher in patients with EGFR-mutant tumors than in those with wild-type EGFR tumors (2-year estimate: 92.6% versus 69.0%; p = .04). The 2-year relapse-free survival and distant recurrence rates did not differ significantly by genotype. The 2-year locoregional recurrence rate (LRR) was significantly lower in EGFR-mutant than in wild-type EGFR patients (17.8% versus 41.7%; p = .005). EGFR-mutant genotype was associated with a lower risk for LRR on multivariate analysis, but not OS, after adjusting for surgery and other potential confounders. We observed that EGFR-mutant patients with locally advanced NSCLC treated with RT had lower rates of LRR than wild-type EGFR patients, raising the hypothesis that EGFR mutations may confer sensitivity to RT and/or chemotherapy. The association between mutation status and OS after combined modality therapy was less robust. Our data may serve as a useful baseline estimate of outcomes by EGFR genotype for future prospective studies.

  3. Emerging treatments and combinations in the management of NSCLC

    DEFF Research Database (Denmark)

    Reck, Martin; Mellemgaard, Anders

    2015-01-01

    There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast...... investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led...... to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC...

  4. Prognostic implications of survivin and lung resistance protein in advanced non-small cell lung cancer treated with platinum-based chemotherapy

    Science.gov (United States)

    HUANG, WENFENG; MAO, YAN; ZHAN, YONGZI; HUANG, JIANFENG; WANG, XIANGPING; LUO, PENGHUI; LI, LI; MO, DUNCHANG; LIU, QIONG; XU, HUIMIN; HUANG, CHANGJIE

    2016-01-01

    Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but the chemotherapy often results in the development of chemoresistance. The present study aimed to explore the prognostic implications of survivin and lung resistance protein (LRP) in advanced NSCLC treated with platinum-based chemotherapy. Tumor samples were collected from 61 hospitalized patients with stage IIIB-IV NSCLC that underwent platinum-based chemotherapy. All patient samples were collected in the Oncology Department of the Third Affiliated Hospital of Guangxi Medical University between January 2006 and January 2011. Cytoplasmic survivin and LRP expression were evaluated using immunohistochemistry. The expression of LRP and survivin reached 77% (47/61) and 76% (45/61), respectively. Positive expression of survivin was associated with a lower median progression-free survival (PFS) time (4 vs. 9 months; P=0.038) and a lower median overall survival (OS) time compared with the absence of survivin expression (9 vs. 16 months; P=0.039). Patients with LRP and survivin expression (n=41) demonstrated a median PFS time of 4 months. However, patients with either LRP or survivin expression (n=10) demonstrated a median PFS time of 8 months, which is similar to the median PFS time of the 10 patients with no expression of LRP and survivin (9 months; P=0.022). Either the expression of survivin or the combined expression of LRP and survivin is associated with a poor prognosis in advanced NSCLC treated with platinum-based chemotherapy. PMID:26870274

  5. KLF4 promotes c-Met amplification-mediated gefitinib resistance in NSCLC.

    Science.gov (United States)

    Feng, Wei; Xie, Qianyi; Liu, Suo; Ji, Ying; Li, Chunyun; Wang, Chunle; Jin, Longyu

    2018-04-06

    Gefitinib have been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-Catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    International Nuclear Information System (INIS)

    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

  7. Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

    International Nuclear Information System (INIS)

    Lopci, Egesta; Olivari, Laura; Toschi, Luca; Marchetti, Silvia; Pistillo, Daniela; Grizzi, Fabio; Castino, Giovanni Francesco; Cortese, Nina; Qehajaj, Dorina; Rahal, Daoud; Alloisio, Marco; Roncalli, Massimo; Allavena, Paola; Santoro, Armando; Marchesi, Federica; Chiti, Arturo

    2016-01-01

    Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months. Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1

  8. Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Olivari, Laura [Humanitas Clinical and Research Hospital, Nuclear Medicine Department, Rozzano, MI (Italy); Toschi, Luca; Marchetti, Silvia; Pistillo, Daniela [Humanitas Clinical and Research Hospital, Oncology, Rozzano, Milan (Italy); Grizzi, Fabio; Castino, Giovanni Francesco; Cortese, Nina; Qehajaj, Dorina [Humanitas Clinical and Research Hospital, Department of Immunology and Inflammation, Rozzano, Milan (Italy); Rahal, Daoud [Humanitas Clinical and Research Hospital, Department of Pathology, Rozzano, Milan (Italy); Alloisio, Marco [Humanitas Clinical and Research Hospital, Thoracic Surgery, Rozzano, Milan (Italy); Roncalli, Massimo [Humanitas Clinical and Research Hospital, Department of Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Allavena, Paola [Humanitas University, Rozzano, Milan (Italy); Santoro, Armando [Humanitas Clinical and Research Hospital, Oncology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Marchesi, Federica [Humanitas Clinical and Research Hospital, Department of Immunology and Inflammation, Rozzano, Milan (Italy); University of Milan, Department of Medical Biotechnologies and Translational Medicine, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine Department, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

    2016-10-15

    Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months. Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1

  9. Detecting and treating breast cancer resistance to EGFR inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Moonlee, Sun-Young; Bissell, Mina J.; Furuta, Saori; Meier, Roland; Kenny, Paraic A.

    2016-04-05

    The application describes therapeutic compositions and methods for treating cancer. For example, therapeutic compositions and methods related to inhibition of FAM83A (family with sequence similarity 83) are provided. The application also describes methods for diagnosing cancer resistance to EGFR inhibitors. For example, a method of diagnosing cancer resistance to EGFR inhibitors by detecting increased FAM83A levels is described.

  10. Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.

    Science.gov (United States)

    Remon, J; Caramella, C; Jovelet, C; Lacroix, L; Lawson, A; Smalley, S; Howarth, K; Gale, D; Green, E; Plagnol, V; Rosenfeld, N; Planchard, D; Bluthgen, M V; Gazzah, A; Pannet, C; Nicotra, C; Auclin, E; Soria, J C; Besse, B

    2017-04-01

    Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue. © The Author 2017. 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.

  11. 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

  12. Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

    Science.gov (United States)

    Holgersson, Georg; Bergström, Stefan; Liv, Per; Nilsson, Jonas; Edlund, Per; Blomberg, Carl; Nyman, Jan; Friesland, Signe; Ekman, Simon; Asklund, Thomas; Henriksson, Roger; Bergqvist, Michael

    2015-10-01

    To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000. Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group

    DEFF Research Database (Denmark)

    Thunnissen, Erik; Kerr, Keith M; Herth, Felix J F

    2012-01-01

    Until recently, the division of pulmonary carcinomas into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was adequate for therapy selection. Due to the emergence of new treatment options subtyping of NSCLC and predictive testing have become mandatory. A practical approach to...

  14. Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC.

    Science.gov (United States)

    Chaib, Imane; Karachaliou, Niki; Pilotto, Sara; Codony Servat, Jordi; Cai, Xueting; Li, Xuefei; Drozdowskyj, Ana; Servat, Carles Codony; Yang, Jie; Hu, Chunping; Cardona, Andres Felipe; Vivanco, Guillermo Lopez; Vergnenegre, Alain; Sanchez, Jose Miguel; Provencio, Mariano; de Marinis, Filipo; Passaro, Antonio; Carcereny, Enric; Reguart, Noemi; Campelo, Charo Garcia; Teixido, Christina; Sperduti, Isabella; Rodriguez, Sonia; Lazzari, Chiara; Verlicchi, Alberto; de Aguirre, Itziar; Queralt, Cristina; Wei, Jia; Estrada, Roger; Puig de la Bellacasa, Raimon; Ramirez, Jose Luis; Jacobson, Kirstine; Ditzel, Henrik J; Santarpia, Mariacarmela; Viteri, Santiago; Molina, Migual Angel; Zhou, Caicun; Cao, Peng; Ma, Patrick C; Bivona, Trever G; Rosell, Rafael

    2017-09-01

    The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response. We used MTT and clonogenic assays, immunoblotting, and quantitative polymerase chain reaction to evaluate the efficacy of EGFR TKI alone and in combination with STAT3 and Src inhibition in three EGFR-mutant NSCLC cell lines. The Chou-Talalay method was used for the quantitative determination of drug interaction. We examined tumor growth inhibition in one EGFR-mutant NSCLC xenograft model (n = 4 mice per group). STAT3 and YAP1 expression was evaluated in tumors from 119 EGFR-mutant NSCLC patients (64 in an initial cohort and 55 in a validation cohort) by quantitative polymerase chain reaction. Kaplan-Meier and Cox regression analyses were used to assess the correlation between survival and gene expression. All statistical tests were two-sided. We discovered that lung cancer cells survive initial EGFR inhibitor treatment through activation of not only STAT3 but also Src-YAP1 signaling. Cotargeting EGFR, STAT3, and Src was synergistic in two EGFR-mutant NSCLC cell lines with a combination index of 0.59 (95% confidence interval [CI] = 0.54 to 0.63) for the PC-9 and 0.59 (95% CI = 0.54 to 0.63) for the H1975 cell line. High expression of STAT3 or YAP1 predicted worse progression-free survival (hazard ratio [HR] = 3.02, 95% CI = 1.54 to 5.93, P = .001, and HR = 2.57, 95% CI = 1.30 to 5.09, P = .007, respectively) in an initial cohort of 64 EGFR-mutant NSCLC patients treated with firstline EGFR TKIs. Similar results were observed in a validation cohort. Our study uncovers a coordinated signaling network centered on both STAT3 and Src-YAP signaling

  15. k-RAS mutations in non-small cell lung cancer patients treated with TKIs among smokers and non-smokers: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Ai-Gui Jiang

    2016-06-01

    Full Text Available Aim of the study : Recent studies have suggested that k-RAS mutations are related to the response to epidermal growth factor receptor (EGFR tyrosine-kinase inhibitions (TKIs in advanced non-small cell lung cancer (NSCLC treatment. The aim of this meta-analysis was to assess the relationship between smoking history and k-RAS mutations in NSCLC treated with TKIs. Material and methods : We searched MEDLINE and Web of Science up to 15 March 2014. The pooled relative risk (RR was estimated by using fixed effect model or random effect model, according to heterogeneity between studies. We also carried out power analyses. Results : We identified 12 studies with 1193 patients, including 196 patients (16.4% with k-RAS mutations. The pooled k-RAS mutations incidence was 22.8% (174/764 in patients with smoke expose vs. 5.4% (23/429 in those with no smoke exposure. The pooled RR was 2.991 (95% CI: 1.884–4.746; Z = 4.65, p = 0.000. No publication bias was found (Begg’s test: z = 1.09, p = 0.274 and Egger’s test: t = 1.38, p = 0.201. In subgroup analyses, the pooled RR was 3.336 (95% CI: 1.925–5.779; Z = 4.30, p = 0.000 in the Caucasian subgroup, while in the Asian subgroup the pooled RR was 2.093 (95% CI: 0.909–4.822; Z = 1.73, p = 0.083, but the sample size was underpowered (0.465. Conclusions : The current meta-analysis found that smoking was related to increased incidence of k-RAS mutations in non-small cell lung cancer treated with TKIs. This may be further evidence that smoking will lead to a worse prognosis in NSCLC patients treated with TKIs.

  16. Brain accumulation of the EML4-ALK inhibitor ceritinib is restricted by P-glycoprotein (P-GP/ABCB1) and breast cancer resistance protein (BCRP/ABCG2)

    NARCIS (Netherlands)

    Kort, Anita; Sparidans, Rolf|info:eu-repo/dai/nl/075047144; Wagenaar, Els; Beijnen, Jacob|info:eu-repo/dai/nl/071919570; Schinkel, Alfred H.

    2015-01-01

    We aimed to clarify the roles of the multidrug transporters ABCB1 and ABCG2 in oral availability and brain accumulation of ceritinib, an oral anaplastic lymphoma kinase (ALK) inhibitor used to treat metastatic non-small cell lung cancer (NSCLC) after progression on crizotinib. Importantly, NSCLC is

  17. MiR-488 inhibits proliferation and cisplatin sensibility in non-small-cell lung cancer (NSCLC) cells by activating the eIF3a-mediated NER signaling pathway.

    Science.gov (United States)

    Fang, Chao; Chen, Yi-Xin; Wu, Na-Yiyuan; Yin, Ji-Ye; Li, Xiang-Ping; Huang, Hsuan-Shun; Zhang, Wei; Zhou, Hong-Hao; Liu, Zhao-Qian

    2017-01-11

    Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3'UTR of eIF3a. In addition, the overexpression of miRNA-488 inhibited cell migration and invasion in A549 cells, and also inhibited cell proliferation, cell cycle progression by elevated P27 expression. Compared to the parental cell line, A549/cisplatin (DDP) resistant cells exhibited a higher level of miRNA-488. Moreover, we found that miRNA-488 was associated with cisplatin resistance in three NSCLC cells (A549, H1299 and SK-MES-1). The mechanism of miRNA-488 induced cisplatin resistance was that miRNA-488 activated nucleotide excision repair (NER) by increasing the expression of Replication Protein A (RPA) 14 and Xeroderma pigmentosum group C (XPC). In conclusion, our results demonstrated that miRNA-488 is a tumor suppressor miRNA that acts by targeting eIF3a. Moreover, miRNA-488 also participates in eIF3a mediated cisplatin resistance in NSCLC cells.

  18. Using Oncolytic Viruses to Treat Cancer

    Science.gov (United States)

    Cancer treatments known as oncolytic viruses are being tested in clinical trials, and one, T-VEC or Imlygic®, has been approved by the FDA. Research now suggests that these treatments work not only by infecting and killing tumor cells, but that they may also be a form of cancer immunotherapy.

  19. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

    DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...... that govern replicative stress, thus providing ample opportunities to enhance replicative stress for therapeutic purposes. Rather than trying to halt cell cycle progression, cancer therapeutics could aim to increase replicative stress by further loosening the checkpoints that remain available to cancer cells...

  20. Nanotechnology for sensing, imaging, and treating cancer.

    Science.gov (United States)

    Panchapakesan, Balaji; Wickstrom, Eric

    2007-04-01

    Nanotechnology encompasses the creation and use of materials, devices, and systems at the level of atoms, molecules, and supramolecular structures. Nanotechnology for cancer consists of three main areas: (1) nanodetectors for sensing proteins and cancer cells, (2) nanoparticle or nanovector formulations for high-contrast imaging, and (3) nanotechnology-based drug delivery and therapeutic formulations. Although there are tremendous challenges facing nanotechnologists, nanotechnology, if properly integrated with established cancer research, can make laboratory-to-clinic transfer of technology successful, which can result in breakthrough potential for patient care.

  1. Cardiac toxicity and radiation dose to the heart in definitive treated non-small cell lung cancer

    International Nuclear Information System (INIS)

    Schytte, Tine; Hansen, Olfred; Stolberg-Rohr, Thomine; Brink, Carsten

    2010-01-01

    In this retrospective analysis of a consecutive series of NSCLC patients treated with definitive radiotherapy, we did not find a correlation between high mean-dose to three different volumes of the heart (left ventricle, both ventricles or whole heart) and cardiac toxicity defined as having an cardiac event after radiotherapy start. This is not as shown in studies with other diseases treated with radiotherapy. Darby et al. recently published a review concerning radiation related heart disease. They reported a significantly worse survival beyond ten years for breast cancer patients receiving radiotherapy. Some studies reported mortality from heart disease increased by 27%. In Hodgkin lymphoma patients an increased risk value of three to five for cardiac morbidity in general compared to general population and relative risk of death from myocardial infarction compared with general population in range 2 to 4. There may be several possible reasons why we did not experience a significant toxicity despite the high doses we delivered to the heart compared with patients receiving RT for breast cancer and lymphoma. Only relative few NSCLC patients live long enough to experience cardiac disease either due to lung cancer itself or comorbidity as a competitive risk factor. In our study the five year survival was 15% leaving very few patients at risk for developing cardiac disease. Without long-term survivors cardiac toxicity does not seem to be a problem, and this suggests that we should aim to increase tumour control by administrating larger doses of radiotherapy to the tumour and/or by adding concurrent chemotherapy. However, the latter may increase the risk of cardiac toxicity by itself, and the results given in present study, may not be extrapolated to this situation. Another reason might be that if NSCLC patients develop dyspnoea, chest pain, etc. it is interpreted as being due to a relapse of lung cancer and not cardiac disease. There are several studies indicating that

  2. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  3. SU-F-J-64: Comparison of Dosimetric Robustness Between Proton Therapy and IMRT Plans Following Tumor Regression for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Teng, C; Ainsley, C; Teo, B; Burgdorf, B; Berman, A; Levin, W; Xiao, Y; Lin, L; Simone, C; Solberg, T [University of Pennsylvania, Philadelphia, PA (United States); Janssens, G [IBA, Louvain-la-Neuve (Belgium)

    2016-06-15

    Purpose: In the light of tumor regression and normal tissue changes, dose distributions can deviate undesirably from what was planned. As a consequence, replanning is sometimes necessary during treatment to ensure continued tumor coverage or to avoid overdosing organs at risk (OARs). Proton plans are generally thought to be less robust than photon plans because of the proton beam’s higher sensitivity to changes in tissue composition, suggesting also a higher likely replanning rate due to tumor regression. The purpose of this study is to compare dosimetric deviations between forward-calculated double scattering (DS) proton plans with IMRT plans upon tumor regression, and assesses their impact on clinical replanning decisions. Methods: Ten consecutive locally advanced NSCLC patients whose tumors shrank > 50% in volume and who received four or more CT scans during radiotherapy were analyzed. All the patients received proton radiotherapy (6660 cGy, 180 cGy/fx). Dosimetric robustness during therapy was characterized by changes in the planning objective metrics as well as by point-by-point root-mean-squared differences for the entire PTV, ITV, and OARs (heart, cord, esophagus, brachial plexus and lungs) DVHs. Results: Sixty-four pairs of DVHs were reviewed by three clinicians, who requested a replanning rate of 16.7% and 18.6% for DS and IMRT plans, respectively, with a high agreement between providers. Robustness of clinical indicators was found to depend on the beam orientation and dose level on the DVH curve. Proton dose increased most in OARs distal to the PTV along the beam path, but these changes were primarily in the mid to low dose levels. In contrast, the variation in IMRT plans occurred primarily in the high dose region. Conclusion: Robustness of clinical indicators depends where on the DVH curves comparisons are made. Similar replanning rates were observed for DS and IMRT plans upon large tumor regression.

  4. Metronomic Chemotherapy - A New Path to Treat Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shuang ZHANG

    2015-04-01

    Full Text Available Metronomic chemotherapy is an emerging strategy to fight cancer. Unlike traditional chemotherapy, metronomic chemotherapy is defined by the frequent, repetitive administration of chemotherapeutic drugs at relatively low doses, and without prolonged drug-free break. Initially thought to play a role inhibiting tumor angiogenesis by targeting activated endothelial cells in tumors, metronomic chemotherapy is a multi-targeted therapy,including activation of immunity, effect on tumour initiating cells, induction of tumor dormancy. It is from eradicateing tumor cells to improve effect, reduce the toxicity and improve quality of life for treatment of advanced non-small cell lung cancer (NSCLC. Metronomic chemotherapy which can avoid the toxicity of traditional chemotherapy and rebounding is explored in clinical studies of advanced NSCLC, as a promising treatment strategy.

  5. 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

  6. Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Atallah, Soha; Cho, B.C. John; Allibhai, Zishan; Taremi, Mojgan; Giuliani, Meredith [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Brade, Anthony; Sun, Alexander; Bezjak, Andrea [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Hope, Andrew J., E-mail: andrew.hope@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2014-07-01

    Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from

  7. [How to treat an elderly person's cancer?].

    Science.gov (United States)

    Mäkelä, Siru; Nevala, Riikka

    2013-01-01

    Among the elderly having cancer, many are in good condition and wish for active treatment. Although elderly people have been shown to benefit from oncological treatments, they are more susceptible than the young to the adverse effects of treatment. Comprehensive geriatric assessment has been utilized in predicting the capability of an elderly patient to tolerate treatment. A functional status questionnaire completed by the patient her/himself has been used in the oncological unit of Helsinki University Hospital in support of a cancer drug therapy assessment. The consultations with an oncologist have been centralized and the patients have had a possibility to meet a geriatrist.

  8. Targetting in atelectatic lung by positron emission tomography in non-small cell lung cancer patients treated with three-dimensional conformal radiation therapy

    International Nuclear Information System (INIS)

    Wang Kai; Wang Luhua; Liang Jun; Ou Guangfei; Lu Jima

    2006-01-01

    Objective: To investigate the potential benefit of incorporating fluorodeoxyglucose positron e- mission tomography (FDG PET) to delineate tire gross tumor volume(GTV) in patients with non-small cell lung cancer (NSCLC) complicated with atelectasis who are to be treated with three-dimensional conformal radiation therapy (3DCRT). Methods: Fourteen patients histopathologically proven as having NSCLC with image diagnosed as complicated with various degrees were studied in this study. All patients were scanned with both thoracic CT and thoracic or whole body PET. The GTV was delineated basing on both CT image and PET image (CT-GTV, PET- GTV) and the volume of each GTV(designated CT-GTV and PET-GTV) was compared by 3DCRT plan. Results: Each paired CT-GTV and PET-GTV was different from each other. All patients' GTV was reduced to an average of 27 cm 3 (20.4%) with median CT-PET of 133 cm 3 (90-180 cm 3 ) and median PET-GTV of 106 cm 3 , with a in- crease of 16.9%, 22 cm 3 ). The reduction of PET-GTV was due to PET could so differ cancer-induced atelectasis from gross tumor that it reduced the tarbet volume and spared more surrounding normal tissues. Conclusions: The incorporation of FDG PET data with gross tumor delineation is able to improve the accuracy of 3DCRT for non-small cell lung cancer patients complicated with atelectasis. (authors)

  9. Feasibility of Using Real-time Cine-MRI for Treating Moving & Deforming Tumors

    Science.gov (United States)

    2012-12-05

    Pancreatic Cancer; Liver Cancer; Lung Cancer; Lung Cancer Non-Small Cell Cancer (NSCLC); Lung Cancer Small Cell Lung Cancer (SCLC); Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Hepatobiliary Cancers Hepatocellular Carcinoma (Hepatoma); Hepatobiliary Cancers Gallbladder; Hepatobiliary Cancers Bile Duct

  10. Personalizing Therapy in Advanced Non–Small Cell Lung Cancer

    Science.gov (United States)

    Villaruz, Liza C.; Burns, Timothy F.; Ramfidis, Vasilis S.; Socinski, Mark A.

    2016-01-01

    The recognition that non–small cell lung cancer (NSCLC) is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms, has permanently shifted the therapeutic landscape of NSCLC to a personalized approach. This personalization of NSCLC therapy is typified by the dramatic response rates seen in EGFR mutant NSCLC when treated with targeted tyrosine kinase inhibitor therapy and in ALK translocation–driven NSCLC when treated with ALK inhibitors. Targeted therapeutic approaches in NSCLC necessitate consideration of more invasive biopsy techniques aimed at providing sufficient tissue for both histological determination and molecular profiling in all patients with stage IV disease both at the time of diagnosis and at the time of disease progression. Comprehensive genotyping efforts have identified oncogenic drivers in 62% lung adenocarcinomas and an increasing proportion of squamous cell carcinomas of the lung. The identification of these oncogenic drivers and the triage of patients to clinical trials evaluating novel targeted therapeutic approaches will increasingly mold a landscape of personalized lung cancer therapy where each genotype has an associated targeted therapy. This review outlines the state of personalized lung cancer therapy as it pertains to individual NSCLC genotypes. PMID:24258572

  11. PSF1 (Partner of SLD Five 1) is a Prognostic Biomarker in Patients with Non-small Cell Lung Cancer Treated with Surgery Following Preoperative Chemotherapy or Chemoradiotherapy.

    Science.gov (United States)

    Kanzaki, Ryu; Naito, Hisamichi; Kise, Kazuyoshi; Takara, Kazuhiro; Eino, Daisuke; Minami, Masato; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Kimura, Toru; Okumura, Meinoshin; Takakura, Nobuyuki

    2016-11-01

    PSF1 (Partner of SLD Five 1) is an evolutionarily conserved DNA replication factor that is part of the GINS (Go, Ichi, Nii, and San) complex . The objective of this study was to evaluate the relationship between PSF1 expression and prognosis in patients with non-small cell lung cancer (NSCLC) treated with surgery following preoperative chemotherapy or chemoradiotherapy. Sixty-nine patients with NSCLC treated with surgery following preoperative chemotherapy or chemoradiotherapy who did not achieve pathologic complete response were enrolled. The status of PSF1 expression was evaluated by immunohistochemistry, and the relationship between expression of PSF1 and Ki-67 was determined, as well as correlations between PSF1 expression and prognosis. We found that 27 of 69 patients' tumors (39 %) were positive for PSF1 expression. The Ki-67 index was significantly higher in the PSF1-positive versus the PSF1-negative group (p = 0.0026). Five-year, disease-free survival of the PSF1-positive group was significantly worse (17.7 vs. 44.3 %, p = 0.0088), and the 5-year overall survival also was worse (16.6 vs. 47.2 %, p = 0.0059). Moreover, PSF1 expression was found to be a significant independent prognostic factor for shorter survival by Cox multivariate analysis (hazard ratio 2.43, 95 % confidence interval 1.27-4.60, p = 0.0076). PSF1 is a useful prognostic biomarker to stratify NSCLC patients treated with surgery following preoperative chemotherapy or chemoradiotherapy.

  12. Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

    Directory of Open Access Journals (Sweden)

    Kyung Eun Choi

    2014-07-01

    Full Text Available Our previous findings have demonstrated that bee venom (BV has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB activity assay. BV (1–5 μg/mL inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

  13. 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

  14. Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Milicic, Biljana; Dagovic, Aleksandar; Acimovic, Ljubisa; Milisavljevic, Slobodan

    2006-01-01

    Purpose: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Patients and Methods: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n = 72). Results: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. Conclusions: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy

  15. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Anderson, H; Hopwood, P; Stephens, R J; Thatcher, N; Cottier, B; Nicholson, M; Milroy, R; Maughan, T S; Falk, S J; Bond, M G; Burt, P A; Connolly, C K; McIllmurray, M B; Carmichael, J

    2000-08-01

    Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year

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

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek

    2010-01-01

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

  17. Peripheral Blood Biomarkers Associated with Clinical Outcome in Non-Small Cell Lung Cancer Patients Treated with Nivolumab.

    Science.gov (United States)

    Tanizaki, Junko; Haratani, Koji; Hayashi, Hidetoshi; Chiba, Yasutaka; Nakamura, Yasushi; Yonesaka, Kimio; Kudo, Keita; Kaneda, Hiroyasu; Hasegawa, Yoshikazu; Tanaka, Kaoru; Takeda, Masayuki; Ito, Akihiko; Nakagawa, Kazuhiko

    2018-01-01

    The aim of this study was to identify baseline peripheral blood biomarkers associated with clinical outcome in patients with NSCLC treated with nivolumab. Univariable and multivariable analyses were performed retrospectively for 134 patients with advanced or recurrent NSCLC treated with nivolumab to evaluate the relationship between survival and peripheral blood parameters measured before treatment initiation, including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count, and absolute eosinophil count (AEC), as well as serum C-reactive protein and lactate dehydrogenase levels. Progression-free survival, overall survival, and response rate were determined. Among the variables selected by univariable analysis, a low ANC, high ALC, and high AEC were significantly and independently associated with both better progression-free survival (p = 0.001, p = 0.04, and p = 0.02, respectively) and better overall survival (p = 0.03, p = 0.03, and p = 0.003, respectively) in multivariable analysis. Categorization of patients according to the number of favorable factors revealed that those with only one factor had a significantly worse outcome than those with two or three factors. A similar trend was apparent for patients with a programmed death 1 ligand tumor proportion score less than 50%, whereas all patients with a score of 50% or higher had at least two favorable factors. A baseline signature of a low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab treatment, with the number of favorable factors identifying subgroups of patients differing in survival and response rate. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  18. Association of microRNA-33a Molecular Signature with Non-Small Cell Lung Cancer Diagnosis and Prognosis after Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Li-Kun Hou

    Full Text Available This study aims to explore the expression pattern and prognostic significance of miR-33a in non-small cell lung cancer (NSCLC treated with adjuvant chemotherapy.MiR-33aexpression in NSCLC was analyzed in silico using the GEO database and was subsequently confirmed by quantitative RT-PCR in 147 NSCLC biopsies. Among these, 32 of these biopsies were paired with adjacent non-neoplastic tissues. The survival analysis of NSCLC by Kaplan-Meier estimates was stratified based on miR-33a expression. In addition, multivariate survival analysis in corresponding groups of NSCLC patients was conducted by Cox proportional hazards regression model.The in silico analysis of miR-33a expression in NSCLC resulted to its down-regulation in different tumor types. The expression level of miR-33a was lower in each grade of NSCLC tumor biopsies than in normal lung tissues. Univariate and multivariate survival analysis further established that low miR-33a expression was an important risk factor for overall survival and disease free survival in NSCLC patients.Our study implied that miR-33a expression levels may have an essential role in NSCLC progression, and could act as a specific and sensitive biomarker for NSCLC patients who have undergone adjuvant chemotherapy.

  19. The Role of Epigenetics in Resistance to Cisplatin Chemotherapy in Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    O' Byrne, Kenneth J.; Barr, Martin P.; Gray, Steven G., E-mail: sgray@stjames.ie [Trinity College Dublin, Department of Clinical Medicine, Trinity Centre for Health Sciences, St James Hospital, James Street, Dublin 8 (Ireland)

    2011-03-17

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC.

  20. The Role of Epigenetics in Resistance to Cisplatin Chemotherapy in Lung Cancer

    International Nuclear Information System (INIS)

    O'Byrne, Kenneth J.; Barr, Martin P.; Gray, Steven G.

    2011-01-01

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-30

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

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

    Directory of Open Access Journals (Sweden)

    Melissa Bersanelli

    2014-09-01

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

  3. Novel Therapeutic Approaches Toward Treating Prostate Cancer

    Science.gov (United States)

    2013-05-01

    or acting in concert regulate different biological processes and under what cellular circumstances. The question of the activity of Pim iso - forms...Gibbons JJ, Abraham RT, Yu K (2009) Mammalian target of rapamycin: Discovery of rapamydn reveals a signaling pathway important for norma ! and cancer cell...Cells were harvested in lysis buffer A consisting of 50 mmol/L Tris, pH 7.4, ISO mmoi/L NaCI, I% NP-40, aad 5 mmoi/L EDTA. Protein concentrations

  4. Consultations with Women Treated for Breast Cancer

    Directory of Open Access Journals (Sweden)

    Moyez Jiwa

    2011-01-01

    Full Text Available Background. Health professionals, including general practitioners involved in followup of breast cancer patients, need to systematically assess opportunities to offer patients support with ongoing or new problems. Methods. A self-administered needs assessment questionnaire was developed with reference to a multidisciplinary team. Short, evidence-based, readable questions were emphasized, and questions were tested for face validity. The questions flowed across three domains: physical, social, and psychological. Content validity and user friendliness were assessed. Results. A final set of 30 questions was rated as easy to read and comprehend (Flesch Reading Ease score 65.8 and Flesch-Kincaid Grade Level 6.9. When piloted with twenty-one patients the self-administered questionnaire detected 121 items of unmet need encompassing all three domains. Conclusions. This self-administered questionnaire has the potential to assist in the holistic assessment of breast cancer patient after treatment. The clinical value of the self-administered questionnaire will need to be further tested before it can be widely adopted.

  5. Serial assessment of FDG-PET FDG uptake and functional volume during radiotherapy (RT) in patients with non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Edet-Sanson, Agathe; Dubray, Bernard; Doyeux, Kaya; Back, Adeline; Hapdey, Sebastien; Modzelewski, Romain; Bohn, Pierre; Gardin, Isabelle; Vera, Pierre

    2012-01-01

    Objectives: The objectives were (i) to confirm that diagnostic FDG-PET images could be obtained during thoracic radiotherapy, (ii) to verify that significant changes in FDG uptake or volume could be measured early enough to adapt the radiotherapy plan and (iii) to determine an optimal time window during the radiotherapy course to acquire a single FDG-PET examination that would be representative of tumour response. Methods: Ten non-small cell lung carcinoma (NSCLC) patients with significant PET/CT-FDG tumour radioactivity uptake (versus the background level), candidates for curative radiotherapy (RT, n = 4; 60–70 Gy, 2 Gray per fraction, 5 fractions per week) or RT plus chemotherapy (CT-RT, n = 6), were prospectively evaluated. Using a Siemens Biograph, 5 or 6 PET/CT scans (PET n , n = 0–5) were performed for each patient. Each acquisition included a 15-min thoracic PET with respiratory gating (RG) 60 ± 5 min post-injection of the FDG (3.5 MBq/kg), followed by a standard, 5-min non-gated (STD) thoracic PET. PET 0 was performed before the first RT fraction. During RT, PET 1–5 were performed every 7 fractions, i.e., at 14 Gy total dose increment. FDG uptake was measured as the variation of SUV max,PETn versus SUV max,PET0 . Each lesions’ volume was measured by (i) visual delineation by an experienced nuclear physician, (ii) 40% SUV max fixed threshold and (iii) a semi-automatic adaptive threshold method. Results: A total of 53 FDG-PET scans were acquired. Seventeen lesions (6 tumours and 11 nodes) were visible on PET 0 in the 10 patients. The lesions were located either in or near the mediastinum or in the apex, without significant respiratory displacements at visual inspection of the gated images. Healthy lung did not cause motion artefacts in the PET images. As measured on 89 lesions, both the absolute and relative SUV max values decreased as the RT dose increased. A 50% SUV max decrease was obtained around a total dose of 45 Gy. Out of the 89 lesions, 75

  6. 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 95% increased by 1.1% ± 1.1%), higher dose conformity (R 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.) [de

  7. Metabolic activity measured by FDG PET predicts pathological response in locally advanced superior sulcus NSCLC.

    Science.gov (United States)

    Bahce, I; Vos, C G; Dickhoff, C; Hartemink, K J; Dahele, M; Smit, E F; Boellaard, R; Hoekstra, O S; Thunnissen, E

    2014-08-01

    Pathological complete response and tumor regression to less than 10% vital tumor cells after induction chemoradiotherapy have been shown to be prognostically important in non-small cell lung cancer (NSCLC). Predictive imaging biomarkers could help treatment decision-making. The purpose of this study was to assess whether postinduction changes in tumor FDG uptake could predict pathological response and to evaluate the correlation between residual vital tumor cells and post-induction FDG uptake. NSCLC patients with sulcus superior tumor (SST), planned for trimodality therapy, routinely undergo FDG PET/CT scans before and after induction chemoradiotherapy in our institute. Metabolic end-points based on standardized uptake values (SUV) were calculated, including SUV(max) (maximum SUV), SUV(TTL) (tumor-to-liver ratio), SUV(peak) (SUV within 1 cc sphere with highest activity), and SUV(PTL) (peak-to-liver ratio). Pathology specimens were assessed for residual vital tumor cell percentages and scored as no (grade 3), 10% vital tumor cells (grade 2a/1). 19 and 23 patients were evaluated for (1) metabolic change and (2) postinduction PET-pathology correlation, respectively. Changes in all parameters were predictive for grade 2b/3 response. ΔSUV(TTL) and ΔSUV(PTL) were also predictive for grade 3 response. Remaining vital tumor cells correlated with post-induction SUV(peak) (R=0.55; P=0.007) and postinduction SUV(PTL) (R=0.59; P=0.004). Postinduction SUV(PTL) could predict both grades 3 and 2b/3 response. In NSCLC patients treated with chemoradiotherapy, changes in SUV(max), SUV(TTL), SUV(peak), and SUV(PTL) were predictive for pathological response (grade 2b/3 and for SUV(TTL) and SUV(PTL) grade 3 as well). Postinduction SUV(PTL) correlated with residual tumor cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Metachronous Esophageal Cancer and Colon Cancer Treated by Endoscopic Mucosal Resection

    Directory of Open Access Journals (Sweden)

    Chun-Chao Chang

    2007-01-01

    Full Text Available Most cases of esophageal cancer and colorectal cancer in Taiwan are diagnosed in the advanced stage and treated by surgery or concurrent chemoirradiation. The detection rates of early esophageal cancer and early colorectal cancer are still low in Taiwan. Metachronous early esophageal cancer and early colorectal cancer have rarely been reported. Endoscopic mucosal resection (EMR is a well-established method for treatment of early gastrointestinal cancer in Japan. We report a 77-year-old man with metachronous early esophageal cancer and early colorectal cancer detected by chromoendoscopy with 3% Lugol's iodine and 0.2% indigo carmine, respectively. These two lesions were successfully treated by EMR. Endoscopic mucosal resection of early cancer in the gastrointestinal tract may be considered in patients who are not suitable for open surgery. [J Formos Med Assoc 2007;106(3 Suppl:S5-S9

  9. Ursolic acid sensitizes radioresistant NSCLC cells expressing HIF-1α through reducing endogenous GSH and inhibiting HIF-1α.

    Science.gov (United States)

    Song, Bing; Zhang, Qian; Yu, Maohu; Qi, Xinrong; Wang, Gang; Xiao, Linlin; Yi, Qiyi; Jin, Wensen

    2017-02-01

    In previous studies, the present authors demonstrated that effective sensitization of ionizing radiation-induced death of tumor cells, including non-small cell lung cancer (NSCLC) cells, could be produced by oleanolic acid (OA), a pentacyclic triterpenoid present in plants. In the present study, it was investigated whether ursolic acid (UA), an isomer of OA, had also the capacity of sensitizing radioresistant NSCLC cells. The radioresistant cell line H1299/M-hypoxia inducible factor-1α (HIF-1α) was established by transfection with a recombinant plasmid expressing mutant HIF-1α (M-HIF-1α). Compared with parental H1299 cells and H1299 cells transfected with empty plasmid, H1299/M-HIF-1α cells had lower radiosensitivity. Following the use of UA to treat NSCLC cells, elevation of the radiosensitivity of cells was observed by MTT assay. The irradiated H1299/M-HIF-1α cells were more sensitive to UA pretreatment than the irradiated cells with empty plasmid and control. The alteration of DNA damage in the irradiated cells was further measured using micronucleus (MN) assay. The combination of UA treatment with radiation could induce the increase of cellular MN frequencies, in agreement with the change in the tendency observed in the cell viability assay. It was further shown that the endogenous glutathione (GSH) contents were markedly attenuated in the differently irradiated NSCLC cells with UA (80 µmol/l) pretreatment through glutathione reductase/5,5'-dithiobis-(2-nitrob-enzoic acid) (DTNB) recycling assay. The results revealed that UA treatment alone could effectively decrease the GSH content in H1299/M-HIF-1α cells. In addition, the inhibition of HIF-1α expression in radioresistant cells was confirmed by western blotting. It was then concluded that UA could upregulate the radiosensitivity of NSCLC cells, and in particular reduce the refractory response of cells expressing HIF-1α to ionizing radiation. The primary mechanism is associated with reduction of

  10. Intracellular Protein Delivery for Treating Breast Cancer

    Science.gov (United States)

    2014-08-01

    apoptosis; T PO NC after and cellul g the encap uclei of th ocess, the M n yielded s etrated the c elative amo potentials o afficking of lization usi ith...60 and e detected by wn as purple y calculating ; b) confoca La and MCF and MCF-7 -APO NC o ained in the lded by the the transpor orescence o odamine...ernalization tion of LHR opy images o sule synthes B-231 treate ted with GFP La cells trea . The scale b ure 2b, the p psules, eithe GFP nanoc osol. To

  11. Mammographic changes in breast cancer patients treated with tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Keun; Oh, Ki Keun; Kim, Tae Hoon; Lee, Hy De [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-09-01

    To evaluate the efficacy of tamoxifen, as shown by mammographic changes. We studied the mammograms of 20 breast cancer patients treated with tamoxifen(20mg/day) and 20 patients treated with tamoxifen(20mg/day) in combination with chemothrapy. Control groups consisted of 20 breast cancer patients treated with chemotherapy and 20 healthy women;the patterns of age distribution and menstrual cycle among these participants were similar to these of the study groups. Two radiologists determined parenchymal changes as seen on follow-up mammogram, of the contralateral breast in patients with breast cancer, and of the left breast in healthy women. Follow-up mammogram showed decreased breast parenchyma in 75% of patients treated with tamoxifen, and in 70% of patients treated with tamoxifen and chemotherapy. Mammographic changes were not noted in 85% of patients treated with chemotherapy and in 90% of healthy women. On follow-up mammogram, breast parenchyma was seen to have been decreased by tamoxifen, used to prevent the recurrence of breast cancer and for its antiproliferative effect. Mammography might be a suitable method for determining the effect of tamoxifen.=20.

  12. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  13. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Villarreal-Garza, Cynthia; Zamora, Jesús; Blake-Cerda, Mónika; Mata, María D de la; Zavala, Diego G; Muñiz-Hernández, Saé; Garza, Jaime de la

    2011-01-01

    Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038). Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment

  14. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  15. Mutant KRAS associated malic enzyme 1 expression is a predictive marker for radiation therapy response in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Chakrabarti, Gaurab

    2015-01-01

    Advanced non-small cell lung cancer (NSCLC) is an aggressive tumor that is treated with a combination of chemotherapy and radiation if the patient is not a candidate for surgery. Predictive biomarkers for response to radiotherapy are lacking in this patient population, making it a non-tailored therapy regimen with unknown outcome. Twenty to 30 % of NSCLC harbor an activating mutation in KRAS that may confer radioresistance. We hypothesized that mutant KRAS can regulate glutamine metabolism genes in NSCLC and maintain tumor redox balance through transamination reactions that generate cytosolic NADPH via malic enzyme 1 (ME1), which may contribute to radioresistance. A doxycycline-inducible mouse model of KRAS G12D driven NSCLC and patient data was analyzed from multiple publicly accessible databases including TCGA, CCLE, NCBI GEO and Project Achilles. ME1 expression was found to be mutant KRAS associated in both a NSCLC mouse model and human NSCLC cancer cell lines. Perturbing glutamine metabolism sensitized mutant KRAS, but not wild-type KRAS NSCLC cell lines to radiation treatment. NSCLC survival analysis revealed that patients with elevated ME1 and GOT1 expression had significantly worse outcomes after radiotherapy, but this was not seen after chemotherapy alone. KRAS driven glutamine metabolism genes, specifically ME1 and GOT1 reactions, may be a predictive marker and potential therapeutic target for radiotherapy in NSCLC. The online version of this article (doi:10.1186/s13014-015-0457-x) contains supplementary material, which is available to authorized users

  16. Brain metastasis from male breast cancer treated 12 years ago ...

    African Journals Online (AJOL)

    Male breast cancer is an uncommon disease that has been the focus of limited researches. Its etiology is unclear, but hormonal levels may play a role in the development of this disease. Our case is a 84 year old patient treated for breast cancer 12 years ago, it was an infiltrating ductal carcinoma classified pT2 N0 M0 with ...

  17. Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation.

    Science.gov (United States)

    Isobe, Kazutoshi; Kakimoto, Atsushi; Mikami, Tetsuo; Kaburaki, Kyohei; Kobayashi, Hiroshi; Yoshizawa, Takahiro; Makino, Takashi; Otsuka, Hajime; Sano, G O; Sugino, Keishi; Sakamoto, Susumu; Takai, Yujiro; Tochigi, Naobumi; Iyoda, Akira; Homma, Sakae

    This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023). Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  18. A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

    Directory of Open Access Journals (Sweden)

    Bang Sun-Hwi

    2012-06-01

    Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

  19. A pilot study of a metronomic chemotherapy regimen with weekly low-dose docetaxel for previously treated non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yokoi T

    2012-05-01

    Full Text Available Takashi Yokoi, Takeshi Tamaki, Toshiki Shimizu, Shosaku NomuraFirst Department of Internal Medicine, Kansai Medical University, Moriguchi City, Osaka, JapanBackground: Low-dose metronomic (LDM chemotherapy is a novel approach that involves frequent administration of a low dose of chemotherapeutic agent without a long interval.Purpose: The aim of this clinical pilot study was to evaluate the toxicity and efficacy of LDM chemotherapy with weekly low-dose docetaxel for previously treated non-small cell lung cancer (NSCLC.Patients and methods: The enrolled patients received 15 mg/m2 of docetaxel intravenously on a weekly basis without any interval.Results: Twenty-seven patients were enrolled in the study; 20 were men, and seven were women. The median age was 62 years (range: 32–75. Eleven patients were stage IIIB, and 16 were stage IV. The Eastern Cooperative Oncology Group performance status was 0 or 1. There was no severe hematological adverse effect; importantly, there was no neutropenia or thrombocytopenia. The objective response rate was 7.4% and the disease control rate was 51.9%. The median survival time was 16.4 months (95% CI: 5.7–36.4.Conclusion: Our preliminary results indicate that our metronomic regimen was well tolerated and active in patients with previously treated NSCLC. Thus, further investigation of this LDM regimen is warranted.Keywords: optimal biological dose, metronomic chemotherapy, docetaxel

  20. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    International Nuclear Information System (INIS)

    Niu, Nifang; Cunningham, Julie M; Li, Liang; Sun, Zhifu; Yang, Ping; Wang, Liewei; Schaid, Daniel J; Abo, Ryan P; Kalari, Krishna; Fridley, Brooke L; Feng, Qiping; Jenkins, Gregory; Batzler, Anthony; Brisbin, Abra G

    2012-01-01

    Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10 -4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

  1. Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices.

    Science.gov (United States)

    Martín, Claudio; Cardona, Andrés F; Zatarain-Barrón, Zyanya Lucia; Ruiz-Patiño, Alejandro; Castillo, Omar; Oblitas, George; Corrales, Luis; Lupinacci, Lorena; Pérez, María Angelina; Rojas, Leonardo; González, Lisde; Chirinos, Luis; Ortíz, Carlos; Lema, Mauricio; Vargas, Carlos; Puparelli, Carmen; Carranza, Hernán; Otero, Jorge; Arrieta, Oscar

    2018-03-06

    This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice. © 2018 S. Karger AG, Basel.

  2. Erlotinib in previously treated non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Smrdel, U.; Kovac, V.

    2006-01-01

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

  3. Current practice when treating lung cancer in Australasia

    International Nuclear Information System (INIS)

    Holloway, L.

    2007-01-01

    A multidisciplinary meeting was held by the radiation oncology department of South Western Sydney Area Cancer Services in March 2003. This meeting was advertised in all radiation oncology departments in Australia and New Zealand. As a precursor to this meeting, a survey was undertaken on the use of radiotherapy for treating lung cancer. All departments in Australia and New Zealand were asked to participate. The survey considered planning techniques, delivery set-up and prescription doses for non-small-cell and small-cell lung cancer and palliative and radical treatments. A wide range in the techniques used was seen across departments, particularly when prescription doses and fractionation were considered

  4. Evaluation of QOL in cancer patients treated with radiation therapy

    International Nuclear Information System (INIS)

    Takahashi, Takeo; Machida, Kikuo; Honda, Norinari; Hosono, Makoto; Murata, Osamu; Osada, Hisato; Omichi, Masahide

    2002-01-01

    Evaluation of quality of life (QOL) in cancer patients is an important theme. However, we do not have an established method to assess QOL in cancer patients during radiotherapy in Japan. We evaluated both the changes of QOL and the factors affecting QOL in radiotherapy patients. Three hundred fifty-five cancer patients, who filled in a questionnaire at the beginning, middle, and end of radiotherapy between 1998 and 2001, were studied. We used The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD)'' devised by Kurihara et al, the Ministry of Health and Welfare. The QOL Questionnaire had five categories: physical activity, physical condition, mental state, social interaction, and face scale. The total score, sum of the score of five categories, were established synthetically (maximum score is 110). The mean of total QOL scores were 75.8, 77.6, and 78.2 at the beginning, middle, and end of radiotherapy respectively. Patients with symptoms related to cancer had apparent improvement of QOL score. Patients receiving chemotherapy had a decreased QOL score at the end of radiotherapy. The score of physical condition was reduced improvement. It was suggested that radiotherapy could be performed without losing QOL of cancer patients, including older patients. However, patients receiving chemotherapy and those with head and neck cancer may lose their QOL, therefore, we should treat such patients carefully. (author)

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

    Directory of Open Access Journals (Sweden)

    Richard PJ

    2016-11-01

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

  6. The role of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in non small cell lung cancer (NSCLC) patients: SEED-SEPD-AEG Joint Guideline.

    Science.gov (United States)

    Vázquez-Sequeiros, Enrique; González-Panizo-Tamargo, Fernando; Barturen, Ángel; Calderón, Ángel; Esteban, José Miguel; Fernández-Esparrach, Gloria; Gimeno-García, Antonio; Ginés, Angels; Lariño, José; Pérez-Carreras, Mercedes; Romero, Rafael; Súbtil, José Carlos; Vila, Juan

    2013-04-01

    Lung cancer is one of the most frequent neoplasms in our environment, and represents the first cause of cancer related death in western countries. Diagnostic and therapeutic approach to these patients may be complicated, with endoscopic ultrasound guided fine needle aspiration (EUS-FNA), classically performed by gastroenterologists, playing a very important role. As this disease is not closely related to the "digestive tract", gastroenterologists have been forced to update their knowledge on this field o adequately diagnose this significant group of patients. The recent advent of modern and promising techniques like endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) have prompted new approaches for diagnosis and staging of this type of patients. In this clinical guideline, the "Sociedad Española de Endoscopia Digestiva" (SEED), "Sociedad Española de Patología Digestiva" (SEPD) and the "AsociaciónEspañola de Gastroenterología", have jointed efforts to update the existing knowledge on the field and provide their members with evidence based recommendations.

  7. Pattern and experience with cancers treated with the chinese ...

    African Journals Online (AJOL)

    Conclusion: The Chinese GWGP80 Cobalt unit has effectively treated a large number of cancer patients but the failures of the “force back system” of its radioactive source compromise its radiation safety and ideally would require a change in the engineering design to decrease on the associated radiation hazards.

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

    Directory of Open Access Journals (Sweden)

    Liang JL

    2014-05-01

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

  9. Characteristics of Real-World Metastatic Non-Small Cell Lung Cancer Patients Treated with Nivolumab and Pembrolizumab During the Year Following Approval.

    Science.gov (United States)

    Khozin, Sean; Abernethy, Amy P; Nussbaum, Nathan C; Zhi, Jizu; Curtis, Melissa D; Tucker, Melisa; Lee, Shannon E; Light, David E; Gossai, Anala; Sorg, Rachael A; Torres, Aracelis Z; Patel, Payal; Blumenthal, Gideon Michael; Pazdur, Richard

    2018-03-01

    Evidence from cancer clinical trials can be difficult to generalize to real-world patient populations, but can be complemented by real-world evidence to optimize personalization of care. Further, real-world usage patterns of programmed cell death protein 1 (PD-1) inhibitors following approval can inform future studies of subpopulations underrepresented in clinical trials. We performed a multicenter analysis using electronic health record data collected during routine care of patients treated in community cancer care clinics in the Flatiron Health network. Real-world metastatic non-small cell lung cancer (NSCLC) patients who received nivolumab or pembrolizumab in the metastatic setting ( n  = 1,344) were selected from a starting random sample of 55,969 NSCLC patients with two or more documented visits from January 1, 2011, through March 31, 2016. The primary study outcome measurement was demographic and treatment characteristics of the cohort. Median age at PD-1 inhibitor initiation was 69 years (interquartile range 61-75). Patients were 56% male, 88% smokers, 65% nonsquamous histology, and 64% diagnosed at stage IV. Of 1,344 patients, 112 (8%) were tested for programmed death-ligand 1 expression. Overall, 50% received nivolumab or pembrolizumab in the second line, with a substantial proportion of third and later line use that began to decline in Q4 2015. During the year following U.S. regulatory approval of PD-1 inhibitors for treatment of NSCLC, real-world patients receiving nivolumab or pembrolizumab were older at treatment initiation and more had smoking history relative to clinical trial cohorts. Studies of outcomes in underrepresented subgroups are needed to inform real-world treatment decisions. Evidence gathered in conventional clinical trials used to assess safety and efficacy of new therapies is not necessarily generalizable to real-world patients receiving these drugs following regulatory approval. Real-world evidence derived from electronic health

  10. Prognostic and Predictive Value of Carcinoembryonic Antigen and Cytokeratin-19 Fragments Levels in Advanced Non-Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib

    Science.gov (United States)

    Jung, Minkyu; Kim, Se Hyun; Hong, Soojung; Kang, Young Ae; Kim, Se Kyu; Chang, Joon; Rha, Sun Young; Kim, Joo Hang

    2012-01-01

    Purpose The prognostic and predictive value of pretreatment serum levels of carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) were assessed in advanced non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib. Materials and Methods Pretreatment CEA and CYFRA 21-1 were measured in 123 advanced NSCLC patients receiving gefitinib or erlotinib. High CEA levels (h-CEA) were significantly associated with females, patients with adenocarcinoma, and non-smokers. Results Low CYFRA 21-1 levels (l-CYFRA) were significantly associated with a good performance status (ECOG PS 0-1). The overall response rate (RR) was 27.6%, and higher RR was associated with adenocarcinoma, h-CEA, and epidermal growth factor receptor (EGFR) mutation. Patients with h-CEA had significantly longer progression-free survival (PFS) (p=0.021). Patients with l-CYFRA had significantly longer PFS and overall survival (p=0.006 and p<0.001, respectively). Of note, h-CEA and l-CYFRA had good prognosis in patients with unknown EGFR mutation status or patients with squamous cell carcinoma (p=0.021 and p=0.015, respectively). A good ECOG PS (HR=0.45, p=0.017), h-CEA (HR=0.41, p=0.007), l-CYFRA 21-1 (HR=0.52, p=0.025), and an EGFR mutation (HR=0.22, p<0.001) were independently predictive of a longer PFS. Conclusion h-CEA and l-CYFRA 21-1 may be prognostic and predictive serum markers for higher response and longer survival in patients with advanced NSCLC receiving gefitinib or erlotinib, especially in patients with unknown EGFR mutation status or patients with squamous cell carcinoma. PMID:22869475

  11. Natural ways to prevent and treat oral cancer

    Directory of Open Access Journals (Sweden)

    Shweta Danaraddi

    2014-01-01

    Full Text Available Oral cancer is one of the usual causes of mortality all over the world, with a five-year survival rate of only 50%. Oral cancers are treated primarily by surgery with / without adjuvant radiotherapy and / or chemotherapy. However, there is significant post-treatment morbidity and mortality secondary to recurrences. Dietary supplements like fruits and vegetables are rich in phytochemicals and provide a variety of antioxidants like vitamin A, C, E. Spirulina, Selenium, Green tea (EGCG, Neem, Tomatoes (lycopene, Turmeric (curcumin, and some medicinal mushrooms are also used as chemopreventive and chemotherapeutic agents. This overview emphasizes on natural therapies to fight against oral cancer. Thus, there are several natural compounds that can enhance the prevention of oral cancer.

  12. High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis.

    Science.gov (United States)

    Ding, Cheng-Zhi; Guo, Xu-Feng; Wang, Guo-Lei; Wang, Hong-Tao; Xu, Guang-Hui; Liu, Yuan-Yuan; Wu, Zhen-Jiang; Chen, Yu-Hang; Wang, Jiao; Wang, Wen-Guang

    2018-01-24

    Despite the growing number of studies exhibited an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. This study was to investigate whether and how high glucose (HG) contribute to the proliferation and migration of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC. ©2018 The Author(s).

  13. 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

  14. Adoption of Robotic Technology for Treating Colorectal Cancer.

    Science.gov (United States)

    Schootman, Mario; Hendren, Samantha; Ratnapradipa, Kendra; Stringer, Lisa; Davidson, Nick O

    2016-11-01

    Debate exists regarding the role of robotic-assisted surgery in colorectal cancer. Robotic-assisted surgery has been promoted as a strategy to increase the availability of minimally invasive surgery, which is associated with improved short-term morbidity; however, robotic-assisted surgery is much more expensive than laparoscopic surgery. We aimed to understand hospital and patient trends in the adoption of robotic-assisted surgery. The study used cross-sectional and longitudinal designs. The study included 2010 and 2012 American Hospital Association surveys, as well as the 2010-2012 Nationwide Inpatient Sample. US hospitals responding to the American Hospital Association survey were included to measure patients with colorectal cancer who were undergoing elective minimally invasive surgery or open resection. Robotic-assisted surgery adoption by US hospitals was measured, regarding specifically patients with colorectal cancer who were treated with robotic surgery. In 2010, 20.1% of hospitals adopted robotic-assisted surgery, increasing to 27.4% by 2012. Hospitals more likely to adopt robotic-assisted surgery included teaching hospitals, those with more advanced imaging services, those in metropolitan rather than rural areas, and those performing the highest inpatient surgery volume. Robotic-assisted surgery only accounted for 1.3% of colorectal cancer operations during 2010-2012, but patient probability of robotic-assisted surgery ranged from 0.1% to 15.2%. The percentage of patients with colorectal cancer who were treated robotically among those undergoing minimally invasive surgery increased over time (2010, 1.5%; 2012, 3.6%). Robotic-assisted surgery is increasing more rapidly for patients with rectal cancer with minimally invasive surgery (2010, 5.5%; 2012, 13.3%) versus patients with colon cancer treated with minimally invasive surgery (2010, 1.3%; 2012, 3.3%). The study was limited by its observational study design. Robotic-assisted surgery uptake remains low

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

    OpenAIRE

    Fung, Simon Fung Fee; Warren, Graham W.; Singh, Anurag K.

    2012-01-01

    Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality. The majority of patients present with advanced (stage III-IV) disease. Such patients are treated with a variety of therapies including surgery, radiation, and chemotherapy. Despite decades of work, however, overall survival in this group has been resistant to any substantial improvement. This review briefly details the evolution to the current standard of care for advanced NSCLC, advances in systemic therapy, and ...

  16. Ultrasound elastography in patients with rectal cancer treated with chemoradiation

    DEFF Research Database (Denmark)

    Rafaelsen, S R; Vagn-Hansen, C; Sørensen, T

    2013-01-01

    OBJECTIVE: The current literature has described several predictive markers in rectal cancer patients treated with chemoradiation, but so far none of them have been validated for clinical use. The purpose of the present study was to compare quantitative elastography based on ultrasound measurements...... in the course of chemoradiation with tumor response based on T stage classification and the Mandard tumor regression grading (TRG). MATERIALS AND METHODS: We prospectively examined 31 patients with rectal cancer planned for high dose radiochemotherapy. The tumor and the mesorectal fat elasticity were measured...

  17. Sexual dysfunctions in men treated for testicular cancer

    DEFF Research Database (Denmark)

    Rosendal, Susanne; Kristensen, Ellids; Giraldi, Annamaria G E

    2008-01-01

    Patients treated for testicular cancer have increased risk of ejaculatory, orgasmic and erectile dysfunction compared with healthy men. The underlying relations are unclear. This review describes sexual dysfunctions that are associated with various treatment modalities. One meta-analysis and 11...... original works were examined. About one third of the patients experience one or more sexual problems in relation to the treatment. Only retroperitoneal surgery can cause a specific sexual dysfunction, namely loss of ejaculation ability or ejaculatory functioning. Psychosexual causes are important...... for understanding sexual dysfunctions in patients with testicular cancer....

  18. 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

  19. Mimicking the BIM BH3 domain overcomes resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer.

    Science.gov (United States)

    Xia, Jinjing; Bai, Hao; Yan, Bo; Li, Rong; Shao, Minhua; Xiong, Liwen; Han, Baohui

    2017-12-12

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied to treat EGFR-mutant non-small cell lung cancer (NSCLC). BIM is a BH3 domain-containing protein encoded by BCL2L11. Some EGFR-mutant NSCLC patients showing BIM deletion polymorphism are resistant to EGFR TKIs. We retrospectively investigated BIM deletion polymorphism in NSCLC patients, its correlation with EGFR TKI (erlotinib) resistance, and the mechanism underlying the drug resistance. Among 245 EGFR-mutant NSCLC patients examined, BIM deletion polymorphism was detected in 43 (12.24%). Median progression-free and overall survival was markedly shorter in patients with BIM deletion polymorphism than with BIM wide-type. Moreover, NSCLC cells expressing EGFR-mutant harboring BIM polymorphism were more resistant to erlotinib-induced apoptosis than BIM wide-type cells. However, combined use of erlotinib and the BH3-mimetic ABT-737 up-regulated BIM expression and overcame erlotinib resistance in EGFR-mutant NSCLC cells harboring BIM deletion polymorphism. In vivo , erlotinib suppressed growth of BIM wide-type NSCLC cell xenographs by inducing apoptosis. Combined with ABT-737, erlotinib also suppressed NSCLC xenographs expressing EGFR-mutant harboring BIM deletion polymorphism. These results indicate that BIM polymorphism is closely related to a poor clinical response to EGFR TKIs in EGFR-mutant NSCLC patients, and that the BH3-mimetic ABT-737 restores BIM functionality and EGFR-TKI sensitivity.

  20. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  1. The clinical characteristics and prognostic analysis of Chinese advanced NSCLC patients based on circulating tumor DNA sequencing

    Directory of Open Access Journals (Sweden)

    Rao C

    2018-01-01

    Full Text Available Chuangzhou Rao,1 Liangqin Nie,1 Xiaobo Miao,1 Yunbao Xu,1 Bing Li,2 Tengfei Zhang2 1Radiotherapy & Chemotherapy Dept 2, Ningbo No. 2 Hospital, Zhejiang, 2Burning Rock Biotech, Guangzhou, People’s Republic of China Purpose: Circulating tumor DNA (ctDNA is a noninvasive and real-time marker for tumor diagnosis, prognosis, and prediction. However, further investigations about ctDNA prognostic and predictive value are still needed, and conclusions from several studies were inconsistent.Experimental design: We performed capture-based targeted ultradeep sequencing on liquid biopsies from a cohort of 34 advanced Chinese non-small-cell lung cancer (NSCLC patients and analyzed the clinical use of ctDNA in this study.Results: On the basis of clinical characteristics of the 34 NSCLC patients, we found that brain metastasis correlated with shorter progression-free survival (PFS and is more prone to happen in younger patients. After ctDNA sequencing, we analyzed the prognostic value of baseline ctDNA. In osimertinib-treated group, high max allelic fraction (maxAF correlated with shorter PFS. But for the cohort of 34 patients, no correlation can be observed between maxAF and PFS. We also presented two cases to demonstrate the value of disease progression prediction by ctDNA, which can be detected earlier than clinical response.Conclusion: In this study, we demonstrated that ctDNA is a prognostic marker for evaluating treatment response and predicting recurrence in advanced NSCLC. Further investigations with larger cohort and uniformed patient background are still needed to validate our findings. Keywords: circulating tumor DNA, non-small-cell lung cancer, prognosis 

  2. Blood group antigen A type 3 expression is a favorable prognostic factor in advanced NSCLC.

    Science.gov (United States)

    Schmidt, L H; Kuemmel, A; Schliemann, C; Schulze, A; Humberg, J; Mohr, M; Görlich, D; Hartmann, W; Bröckling, S; Marra, A; Hillejan, L; Goletz, S; Karsten, U; Berdel, W E; Spieker, T; Wiewrodt, R

    2016-02-01

    Several blood group-related carbohydrate antigens are prognosis-relevant markers of tumor tissues. A type 3 (repetitive A) is a blood group antigen specific for A1 erythrocytes. Its potential expression in tumor tissues has so far not been examined. We have evaluated its expression in normal lung and in lung cancer using a novel antibody (A69-A/E8). For comparison an anti-A antibody specific to A types 1 and 2 was used, because its expression on lung cancer tissue has been previously reported to be of prognostic relevance. Resected tissue samples of 398 NSCLC patients were analyzed in immunohistochemistry using tissue microarrays. Expression of A type 3 was not observed in non-malignant lung tissues. A type 3 was expressed on tumor cells of around half of NSCLC patients of blood group A1 (ptype 1/2 antigen was observed (p=0.562), the expression of A type 3 by tumor cells indicated a highly significant favorable prognosis among advanced NSCLC patients (p=0.011) and in NSCLC patients with lymphatic spread (p=0.014). Univariate prognostic results were confirmed in a Cox proportional hazards model. In this study we present for the first time prognostic data for A type 3 antigen expression in lung cancer patients. Prospective studies should be performed to confirm the prognostic value of A type 3 expression for an improved risk stratification in NSCLC patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Prognosis was not deteriorated by multiple primary cancers in esophageal cancer patients treated by radiotherapy

    International Nuclear Information System (INIS)

    Shirai, Katsuyuki; Tamaki, Yoshio; Kitamoto, Yoshizumi

    2013-01-01

    Esophageal cancer patients are often associated with multiple primary cancers (MPC). The aim of this study is to evaluate the effect of MPC on prognosis in esophageal cancer patients treated by radiotherapy. Between 2001 and 2008, esophageal cancer patients treated by definitive radiotherapy at Gunma Cancer Center were retrospectively reviewed. Exclusion criteria were preoperative or postoperative radiotherapy, palliative radiotherapy, follow-up of <6 months, radiation dose of <50 Gy and no information on MPC. We analyzed 167 esophageal cancer patients and 56 (33.5%) were associated with MPC. Gastric cancer was the most frequent tumor (38.2%), followed by head and neck cancer (26.5%). Median follow-up time was 31.5 months (range 6.1-87.3 months). Patients with MPC included more stage I/II esophageal cancer than those without MPC (66.1% vs. 36.9%, P<0.01). The 5-year overall survival rate for esophageal cancer with MPC was relatively better than those without MPC (46.1% vs. 26.7%), although the difference did not reach statistical significance in univariate analysis (P=0.09). Stage I/II esophageal cancer patients had a significantly better overall survival than stage III/IV patients (P<0.01). Among esophageal cancer patients with MPC, there was no difference in overall survival between antecedent and synchronous cancer (P=0.59). Our study indicated that the prognosis of esophageal cancer patients treated by radiotherapy was primarily determined by the clinical stage itself, but not the presence of MPC. (author)

  4. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

  5. Resveratrol raisesin vitroanticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression.

    Science.gov (United States)

    Kong, Fanhua; Zhang, Runqi; Zhao, Xudong; Zheng, Guanlin; Wang, Zhou; Wang, Peng

    2017-09-01

    The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The 10 µg/ml of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or 10 µg/ml of PA also had no effect on MRC-5 normal cells. PA-L (5 µg/ml) and PA-H (10 µg/ml) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res (5 µg/ml)+PA-H (10 µg/ml) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, NF-κB, Bcl-2, Bcl-xL, procollagen I, collagen I, collagen III and CTGF, TNF-α, IL-1β, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, IκB-α, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

  6. Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    2015-03-11

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

  7. The rapidly escalating cost of treating colorectal cancer in Australia.

    Science.gov (United States)

    Ananda, Sumitra; Kosmider, Suzanne; Tran, Ben; Field, Kathryn; Jones, Ian; Skinner, Iain; Guerrieri, Mario; Chapman, Michael; Gibbs, Peter

    2016-03-01

    Considerable progress in cancer treatment is leading to better outcomes, but the cost of therapy is placing increasing pressure on the health system. Understanding the real-world cost of therapies for each stage will become increasingly important in informing treatment selection and health policy. To explore the cost of treating colorectal cancer in the modern era, data were entered onto a prospective database at four hospitals. We estimated the impact of bevacizumab by using data from July 2009, and projected the likely impact of the recent listing of cetuximab. The utility of these data for estimating the cost-effectiveness of treatment was explored. Cancer stage and age at diagnosis were major determinants of treatment received and the associated cost. The cost of early stage disease has not substantially changed whereas therapies such as oxaliplatin and irinotecan were significant contributors to substantial increases in stage IV disease, now $71,156 per patient. Bevacizumab has added at least $10,247 per patient and we estimate that cetuximab will add a further $12,022. An exploratory analysis of the cost-effectiveness of oxaliplatin for adjuvant therapy of stage III colon cancer suggests that this is well within the accepted range. These data suggest that recent progress in the treatment of later stages of colorectal cancer is being achieved at significant financial cost. The increased costs of managing later stages of disease make an investment in prevention and early detection ever more attractive. © 2015 Wiley Publishing Asia Pty Ltd.

  8. Long Intergenic Noncoding RNA 00511 Acts as an Oncogene in Non–small-cell Lung Cancer by Binding to EZH2 and Suppressing p57

    Directory of Open Access Journals (Sweden)

    Cheng-Cao Sun

    2016-01-01

    Full Text Available Long noncoding RNAs (lncRNAs play crucial roles in carcinogenesis. However, the function and mechanism of lncRNAs in human non–small-cell lung cancer (NSCLC are still remaining largely unknown. Long intergenic noncoding RNA 00511 (LINC00511 has been found to be upregulated and acts as an oncogene in breast cancer, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Herein, we identified LINC00511 as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found LINC00511 was upregulated and associated with oncogenesis, tumor size, metastasis, and poor prognosis in NSCLC. Moreover, LINC00511 affected cell proliferation, invasiveness, metastasis, and apoptosis in multiple NSCLC cell lines. Mechanistically, LINC00511 bound histone methyltransferase enhancer of zeste homolog 2 ((EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2, a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3, and acted as a modular scaffold of EZH2/PRC2 complexes, coordinated their localization, and specified the histone modification pattern on the target genes, including p57, and consequently altered NSCLC cell biology. Thus, LINC00511 is mechanistically, functionally, and clinically oncogenic in NSCLC. Targeting LINC00511 and its pathway may be meaningful for treating patients with NSCLC.

  9. Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC

    DEFF Research Database (Denmark)

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

    2014-01-01

    be analysed in plasma and may increase the scientific use of such measurements. In the present study, we investigated: i) the dynamics of cfDNA and plasma mutated KRAS (pmKRAS) during the treatment of patients with advanced NSCLC; and ii) the prognostic value of baseline cfDNA and pmKRAS. Sixty‑nine patients......Non-small cell lung cancer (NSCLC) is one of the most common malignant tumours in the western world and is associated with a poor prognosis. Biomarkers predicting prognosis and therapeutic effects are highly required, and cell-free DNA (cfDNA) may be a feasible option. Genetic mutations can...... were included in a prospective biomarker trial. Inclusion criteria included advanced NSCLC, candidate for first-line treatment, no previous cancer within the five years prior to this study. Blood samples were drawn at baseline, day 8 and at progression. Analyses of cfDNA and KRAS mutations in plasma...

  10. NSCLC molecular testing in Central and Eastern European countries.

    Science.gov (United States)

    Ryska, Ales; Berzinec, Peter; Brcic, Luka; Cufer, Tanja; Dziadziuszko, Rafal; Gottfried, Maya; Kovalszky, Ilona; Olszewski, Włodzimierz; Oz, Buge; Plank, Lukas; Timar, Jozsef

    2018-03-09

    The introduction of targeted treatments for subsets of non-small cell lung cancer (NSCLC) has highlighted the importance of accurate molecular diagnosis to determine if an actionable genetic alteration is present. Few data are available for Central and Eastern Europe (CEE) on mutation rates, testing rates, and compliance with testing guidelines. A questionnaire about molecular testing and NSCLC management was distributed to relevant specialists in nine CEE countries, and pathologists were asked to provide the results of EGFR and ALK testing over a 1-year period. A very high proportion of lung cancer cases are confirmed histologically/cytologically (75-100%), and molecular testing of NSCLC samples has been established in all evaluated CEE countries in 2014. Most countries follow national or international guidelines on which patients to test for EGFR mutations and ALK rearrangements. In most centers at that time, testing was undertaken on request of the clinician rather than on the preferred reflex basis. Immunohistochemistry, followed by fluorescent in situ hybridization confirmation of positive cases, has been widely adopted for ALK testing in the region. Limited reimbursement is a significant barrier to molecular testing in the region and a disincentive to reflex testing. Multidisciplinary tumor boards are established in most of the countries and centers, with 75-100% of cases being discussed at a multidisciplinary tumor board at specialized centers. Molecular testing is established throughout the CEE region, but improved and unbiased reimbursement remains a major challenge for the future. Increasing the number of patients reviewed by multidisciplinary boards outside of major centers and access to targeted therapy based on the result of molecular testing are other major challenges.

  11. Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

    Science.gov (United States)

    Amir, Gail; Demma, Jonathan; Vernea, Fiona; Beider, Katia; Shlomai, Zippora; Wald, Hanna; Zamir, Gideon; Shapira, Oz M.; Peled, Amnon; Wald, Ori

    2011-01-01

    Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations. PMID:21949768

  12. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  13. XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC

    OpenAIRE

    Qin, Sida; Yang, Chengcheng; Zhang, Boxiang; Li, Xiang; Sun, Xin; Li, Gang; Zhang, Jing; Xiao, Guodong; Gao, Xiao; Huang, Guanghong; Wang, Peili; Ren, Hong

    2016-01-01

    X-linked inhibitor of apoptosis protein (XIAP) and second mitochondrial-derived activator of caspase (Smac) are two important prognostic biomarkers for cancer. They are negatively correlated in many types of cancer. However, their relationship is still unknown in lung cancer. In the present study, we found that there was a negative correlation between Smac and XIAP at the level of protein but not mRNA in NSCLC patients. However, XIAP overexpression had no effect on degrading endogenous Smac i...

  14. Potential use of custirsen to treat prostate cancer

    Directory of Open Access Journals (Sweden)

    Higano CS

    2013-06-01

    Full Text Available Celestia S Higano Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Over the last few years, five agents have demonstrated a survival benefit over a comparator treatment or placebo in the treatment of metastatic castration-resistant prostate cancer and have been approved by the US Food and Drug Administration: sipuleucel-T (a dendritic cell immunotherapy; cabazitaxel; abiraterone acetate and enzalutamide (both hormonal agents; and radium 223 (an alpha emitter. The development of these agents pivoted on whether patients had been treated with docetaxel, which remains the first-line chemotherapy of choice. To date, no combination of docetaxel and another active agent has demonstrated superiority to docetaxel alone despite numerous Phase III trials. Clusterin is a cytoprotective chaperone protein that is upregulated in response to various anticancer therapies. When overexpressed, clusterin interferes with apoptotic signaling, thereby promoting cell survival and conferring broad-spectrum resistance in cancer cell lines. Custirsen (OGX-011 is a second-generation 2´-methoxyethyl modified phosphorothioate antisense oligonucleotide that inhibits expression of clusterin. This review presents the preclinical and clinical data that provided the rationale for the combination of custirsen with chemotherapy in ongoing Phase III trials. Keywords: castration-resistant prostate cancer, clusterin, custirsen, OGX-011, antisense, OGX-427, apoptosis

  15. Psychological distress and intervention in cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Sostaric, M.; Sprah, L.

    2004-01-01

    Background. Common side effects of treatment with radiation therapy (RT) often cause psychophysical distress in cancer patients. Anxiety, adjustment disorders and depression (which are according to many studies experienced in about half of the oncological population) might originate some serious psychiatric forms of mood disorders and can even culminate in suicide, if not treated appropriately. There are some groups of cancer patients who are especially vulnerable and among them are cancer patients undergoing RT - they should receive special attention from medical staff. The purpose of this review is to present a variety of psychosocial interventions and illustrate some methods that are (or could be) used in psycho-oncology practice. Conclusions. A large body of literature suggests that the first intervention step should be effective screening for patients in distress. In regard to these proposals the development of (computerized) screening programmes is the first measure that ought to be taken. Moreover, further systematical research of traditional, non-traditional and complementary intervention strategies in cancer patients in distress would be necessary in order to provide reliable empirical results about the effectiveness of different approaches. (author)

  16. New Therapeutics to Treat Castrate-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Ömer Acar

    2013-01-01

    Full Text Available The effective treatment of castrate-resistant prostate cancer (CRPC has proven to be very challenging. Until recently, docetaxel was the only therapeutic demonstrated to extend overall patient survival. Yet recently, a considerable number of new therapeutics have been approved to treat CRPC patients. These remarkable advances now give new tools for the therapeutic management of late-stage prostate cancer. In this review, we will examine mechanistic and clinical data of several newly approved therapeutics including the chemotherapeutic cabazitaxel, antiandrogen enzalutamide, endocrine disruptor abiraterone acetate, immunotherapy sipuleucel-T, and bone-targeting radiopharmaceutical alpharadin. In addition, we will examine other promising therapeutics that are currently in Phase III trials.

  17. Perfusion CT allows prediction of therapy response in non-small cell lung cancer treated with conventional and anti-angiogenic chemotherapy.

    Science.gov (United States)

    Tacelli, Nunzia; Santangelo, Teresa; Scherpereel, Arnaud; Duhamel, Alain; Deken, Valérie; Klotz, Ernst; Cortot, Alexis; Lafitte, Jean-Jacques; Wallyn, Frédéric; Remy, Jacques; Remy-Jardin, Martine

    2013-08-01

    To determine whether CT can depict early perfusion changes in lung cancer treated by anti-angiogenic drugs, allowing prediction of response. Patients with non-small cell lung cancer, treated by conventional chemotherapy with (Group 1; n = 17) or without (Group 2; n = 23) anti-vascular endothelial growth factor (anti-VEGF) drug (bevacizumab) underwent CT perfusion before (TIME 0) and after 1 (TIME 1), 3 (TIME 2) and 6 (TIME 3) cycles of chemotherapy. The CT parameters evaluated included: (1) total tumour vascular volume (TVV) and total tumour extravascular flow (TEF); (2) RECIST (Response Evaluation Criteria in Solid Tumours) measurements. Tumour response was also assessed on the basis of the clinicians' overall evaluation. In Group 1, significant reduction in perfusion was identified between baseline and: (1) TIME 1 (TVV, P = 0.0395; TEF, P = 0.015); (2) TIME 2 (TVV, P = 0.0043; TEF, P Perfusion CT demonstrates early changes in lung cancer vascularity under anti-angiogenic chemotherapy that may help predict therapeutic response. • Perfusion CT has the potential of providing in vivo information about tumour vasculature. • CT depicts early and specific perfusion changes in NSCLC under anti-angiogenic drugs. • Specific therapeutic effects of anti-angiogenic drugs can be detected before tumour shrinkage. • Early perfusion changes can help predict therapeutic response to anti-angiogenic treatment. • Perfusion CT could be a non-invasive tool to monitor anti-angiogenic treatment.

  18. Antitumor effects of a novel chromosome region maintenance 1 (CRM1 inhibitor on non-small cell lung cancer cells in vitro and in mouse tumor xenografts.

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    Shuai Wang

    Full Text Available BACKGROUND: Chromosome Region Maintenance 1 (CRM1 is a nuclear exporter and its inhibitor has anti-tumor activity in various cancers. This study assessed the therapeutic efficiency of the novel CRM1 inhibitor KPT-185 on non-small cell lung cancer (NSCLC. METHODS: NSCLC cell lines were treated with KPT-185 to assess changes in cell viability, cell cycle, apoptosis, and protein expression. NOD-SCID mice carrying NSCLC cell xenografts were orally treated with KPT-276, a clinical analog of KPT-185, to examine the efficacy and side effects of KPT-276 in vivo. RESULTS: KPT-185 significantly reduced the viability of six NSCLC cell lines in a time- and dose-dependent manner, including epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI-resistant H1975 and H1650GR cell lines. In addition, KPT-185 induced these NSCLC cells to arrest at G1 phase of the cell cycle and caused apoptosis in a dose-dependent manner. KPT-185 treatment also reduced CRM1 protein levels in six NSCLC cell lines, and the reduction could be completely abolished by the proteasome inhibitor bortezomib. KPT-185 activated caspase 3, 8, and 9, but inhibited survivin expression in NSCLC cells. In a mouse H1975 cell xenograft model, tumor growth was significantly inhibited by oral KPT-276 administration, and there was no significant mouse body weight loss or other side effects. CONCLUSIONS: The current study demonstrated the anti-tumor effects of KPT-185 in NSCLC cells, including EGFR-TKI-resistant NSCLC cell lines. Further studies will assess anti-tumor activity of KPT-185 in a clinical trial for NSCLC patients.

  19. Do Hospital Characteristics Influence Cancer-Specific Survival for Early Stage Lung Cancer?

    Science.gov (United States)

    David, Elizabeth A; Chen, Yingjia; Cooke, David T; Perry, Andrew; Canter, Robert J; Cress, Rosemary

    2015-01-01

    Background Quality of oncologic outcomes is of paramount importance in the care of patients with non-small cell lung cancer (NSCLC). We sought to evaluate the relationship of hospital volume for lobectomy on cancer-specific survival in NSCLC patients treated in California, as well as the influence of Committee on Cancer (CoC) accreditation. Methods The California Cancer Registry was queried from 2004–2011 for cases of Stage I NSCLC and 8,345 patients were identified. Statistical analysis was used to determine prognostic factors for cancer-specific survival. Results 7,587 patients were treated surgically. CoC accreditation was not significant for cancer-specific survival, but treatment in high volume centers was associated with longer survival when compared to low and medium volume centers (HR 1.77, 1.474–2.141 and HR 1.23, 1.058–1.438). Conclusions These data suggest that surgical treatment in high volume hospitals is associated with longer cancer-specific survival for early-stage NSCLC, but that CoC accreditation is not. PMID:26193801

  20. Combination phenylbutyrate/gemcitabine therapy effectively inhibits in vitro and in vivo growth of NSCLC by intrinsic apoptotic pathways

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    Schniewind Bodo

    2006-11-01

    Full Text Available Abstract Background Standard chemotherapy protocols in NSCLC are of limited clinical benefit. Histone deacetylase (HDAC inhibitors represent a new strategy in human cancer therapy. In this study the combination of the HDAC inhibitor phenylbutyrate (PB and the nucleoside analogue gemcitabine (GEM was evaluated and the mechanisms underlying increased cell death were analyzed. Methods Dose escalation studies evaluating the cytotoxicity of PB (0.01–100 mM, GEM (0.01–100 μg/ml and a combination of the two were performed on two NSCLC cell lines (BEN and KNS62. Apoptotic cell death was quantified. The involvement of caspase-dependent cell death and MAP-kinase activation was analyzed. Additionally, mitochondrial damage was determined. In an orthotopic animal model the combined effect of PB and GEM on therapy was analyzed. Results Applied as a single drug both GEM and PB revealed limited potential to induce apoptosis in KNS62 and Ben cells. Combination therapy was 50–80% (p = 0.012 more effective than either agent alone. On the caspase level, combination therapy significantly increased cleavage of the pro-forms compared to single chemotherapy. The broad spectrum caspase-inhibitor zVAD was able to inhibit caspase cleavage completely, but reduced the frequency of apoptotic cells only by 30%. Combination therapy significantly increased changes in MTP and the release of cyto-c, AIF and Smac/Diabolo into the cytoplasm. Furthermore, the inhibitors of apoptosis c-IAP1 and c-IAP2 were downregulated and it was shown that in combination therapy JNK activation contributed significantly to induction of apoptosis. The size of the primary tumors growing orthotopically in SCID mice treated for 4 weeks with GEM and PB was significantly reduced (2.2–2.7 fold compared to GEM therapy alone. The Ki-67 (KNS62: p = 0.015; Ben: p = 0.093 and topoisomerase IIα (KNS62: p = 0.008; Ben: p = 0.064 proliferation indices were clearly reduced in tumors treated by combination

  1. ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, E; Sørensen, J B

    2010-01-01

    Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participa...

  2. Influenza vaccination in children being treated with chemotherapy for cancer.

    Science.gov (United States)

    Goossen, Ginette M; Kremer, Leontien C M; van de Wetering, Marianne D

    2013-08-01

    Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear. 1. To assess the efficacy of influenza vaccination in stimulating an immunological response in children with cancer during chemotherapy, compared with control groups.2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or in stimulating immunological response in children with cancer treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.3. To identify the adverse effects associated with influenza vaccines in children with cancer treated with chemotherapy, compared with other control groups. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2012) and EMBASE (1980 to 2012) up to August 2012. We also searched reference lists of relevant articles and conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Infectious Diseases Society of America (IDSA), the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Paediatric Oncology (SIOP). We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serological response to influenza vaccination of children with cancer was compared with that of control groups. We also considered RCTs and CCTs that compared the effects of influenza vaccination on clinical response and/or immunological response in children with cancer being treated with chemotherapy, compared with placebo, no intervention or different dosage schedules. Two independent review authors assessed the methodological quality of included studies and extracted the data. We included 1 RCT and 9 CCTs

  3. 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

    miR-151a and its host gene, focal adhesion kinase, FAK, are located in a region of chromosome 8q that is frequently amplified in solid tumors, including lung cancer. Lung cancer is the leading cause of cancer deaths worldwide and metastasis remains the major challenge in battling lung cancer...... 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...... cells. Blocking miR-151a expression using anti-miR-151a approaches significantly reduced NCSLC cell proliferative and motility potential. Furthermore, we determined that miR-151a significantly regulates E-cadherin expression. Finally, functional rescue experiments determined that overexpression of E...

  4. The analysis of prognostic factors affecting post-radiation acute reaction after conformal radiotherapy for non-small cell lung cancer

    OpenAIRE

    Spych, Michał; Gottwald, Leszek; Klonowicz, Małgorzata; Biegała, Michał; Bibik, Robert; Fijuth, Jacek

    2010-01-01

    Introduction The aim was to evaluate the risk of acute side effects in the lung after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non-small cell lung cancer (NSCLC). An attempt was made to single out clinical factors and factors related to treatment technique which may induce acute post-radiation pneumonitis. Material and methods The analysis concerned 34 consecutive patients who underwent radical radiation therapy for NSCLC. Intensity of early toxicity was evaluated...

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

    Directory of Open Access Journals (Sweden)

    Xingsheng Hu

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

  6. Focus on Nintedanib in NSCLC and other tumors

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    Anna Manzo

    2016-12-01

    Full Text Available Nintedanib is a new triple angiokinase inhibitor that potently blocks the proangiogenic pathways mediated by vascular endothelial growth factor (VEGF receptors, platelet-derived growth factor (PDGF receptors and fibroblast growth factor (FGF receptors. Evidence about its efficacy in addition to second-line chemotherapy in non-small-cell-lung-cancer (NSCLC has been produced by two large randomized phase III clinical trials (LUME-Lung-1 and LUME-Lung-2, conducted in patients with pretreated NSCLC, without major risk factors for bleeding. In the LUME-Lung-1, the addition of nintedanib to docetaxel significantly improved progression-free survival (PFS, that was the primary endpoint of the trial (3.4 vs 2.7 months, HR 0.79; p=0.0019. Furthermore, a significant improvement in median overall survival (OS (from 10.3 to 12.6 months was observed in patients with adenocarcinoma histology, with a greater advantage in patients with adenocarcinoma who progressed within 9 months after start of first line treatment (from 7.9 to 10.9 months, and in patients with adenocarcinoma most refractory to first line chemotherapy (from 6.3 to 9.8 months. Adverse events were more common in the docetaxel plus nintedanib group and they included diarrhea and increased liver enzymes, while no statistically significant increase in the incidence of bleeding and hypertension events by the addition of nintedanib was observed. On these bases, the combination of docetaxel and nintedanib can be considered a new option for the second-line treatment for patients with advanced NSCLC with adenocarcinoma histology. Future challenges are the identification of predictive factors to help the decision of using nintedanib in eligible patients.

  7. Nanotechnology for delivery of gemcitabine to treat pancreatic cancer.

    Science.gov (United States)

    Birhanu, Gebremariam; Javar, Hamid Akbari; Seyedjafari, Ehsan; Zandi-Karimi, Ali

    2017-04-01

    Pancreatic cancer (PC) is one of the most deadly and quickly fatal human cancers with a 5-year mortality rate close to 100%. Its prognosis is very poor, mainly because of its hostile biological behavior and late onset of symptoms for clinical diagnosis; these bring limitations on therapeutic interventions. Factors contributing for the difficulties in treating PC include: high rate of drug resistance, fast metastasis to different organs, poor prognosis and relapse of the tumor after therapy. After being approved by US FDA 1997, Gemcitabine (Gem) is the first line and the gold standard drug for all stages of advanced PC till now. However, its efficacy is unsatisfactory, mainly due to; its chemical instability and poor cellular uptake, resulting in an extremely short half-life and low bioavailability. To solve this drawbacks and increase the therapeutic outcome important progress has been achieved in the field of nanotechnology and offers a promising and effective alternative. This review mainly focus on the most commonly investigated nanoparticle (NP) delivery systems of Gem for PC treatment and the latest progresses achieved. Novel nanocarriers with better tumor targeting efficiencies and maximum treatment outcome to treat this deadly due are given much attention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Developing and Validating a Survival Prediction Model for NSCLC Patients Through Distributed Learning Across 3 Countries.

    Science.gov (United States)

    Jochems, Arthur; Deist, Timo M; El Naqa, Issam; Kessler, Marc; Mayo, Chuck; Reeves, Jackson; Jolly, Shruti; Matuszak, Martha; Ten Haken, Randall; van Soest, Johan; Oberije, Cary; Faivre-Finn, Corinne; Price, Gareth; de Ruysscher, Dirk; Lambin, Philippe; Dekker, Andre

    2017-10-01

    Tools for survival prediction for non-small cell lung cancer (NSCLC) patients treated with chemoradiation or radiation therapy are of limited quality. In this work, we developed a predictive model of survival at 2 years. The model is based on a large volume of historical patient data and serves as a proof of concept to demonstrate the distributed learning approach. Clinical data from 698 lung cancer patients, treated with curative intent with chemoradiation or radiation therapy alone, were collected and stored at 2 different cancer institutes (559 patients at Maastro clinic (Netherlands) and 139 at Michigan university [United States]). The model was further validated on 196 patients originating from The Christie (United Kingdon). A Bayesian network model was adapted for distributed learning (the animation can be viewed at https://www.youtube.com/watch?v=ZDJFOxpwqEA). Two-year posttreatment survival was chosen as the endpoint. The Maastro clinic cohort data are publicly available at https://www.cancerdata.org/publication/developing-and-validating-survival-prediction-model-nsclc-patients-through-distributed, and the developed models can be found at www.predictcancer.org. Variables included in the final model were T and N category, age, performance status, and total tumor dose. The model has an area under the curve (AUC) of 0.66 on the external validation set and an AUC of 0.62 on a 5-fold cross validation. A model based on the T and N category performed with an AUC of 0.47 on the validation set, significantly worse than our model (PLearning the model in a centralized or distributed fashion yields a minor difference on the probabilities of the conditional probability tables (0.6%); the discriminative performance of the models on the validation set is similar (P=.26). Distributed learning from federated databases allows learning of predictive models on data originating from multiple institutions while avoiding many of the data-sharing barriers. We believe that

  9. Radiosensitization of NSCLC cells by EGFR inhibition is the result of an enhanced p53-dependent G1 arrest

    International Nuclear Information System (INIS)

    Kriegs, Malte; Gurtner, Kristin; Can, Yildiz; Brammer, Ingo; Rieckmann, Thorsten; Oertel, Reinhard; Wysocki, Marek; Dorniok, Franziska; Gal, Andreas; Grob, Tobias J.; Laban, Simon; Kasten-Pisula, Ulla; Petersen, Cordula; Baumann, Michael; Krause, Mechthild; Dikomey, Ekkehard

    2015-01-01

    Purpose: How EGF receptor (EGFR) inhibition induces cellular radiosensitization and with that increase in tumor control is still a matter of discussion. Since EGFR predominantly regulates cell cycle and proliferation, we studied whether a G1-arrest caused by EGFR inhibition may contribute to these effects. Materials and methods: We analyzed human non-small cell lung cancer (NSCLC) cell lines either wild type (wt) or mutated in p53 (A549, H460, vs. H1299, H3122) and HCT116 cells (p21 wt and negative). EGFR was inhibited by BIBX1382BS, erlotinib or cetuximab; p21 was knocked down by siRNA. Functional endpoints analyzed were cell signaling, proliferation, G1-arrest, cell survival as well as tumor control using an A549 tumor model. Results: When combined with IR, EGFR inhibition enhances the radiation-induced permanent G1 arrest, though solely in cells with intact p53/p21 signaling. This increase in G1-arrest was always associated with enhanced cellular radiosensitivity. Strikingly, this effect was abrogated when cells were re-stimulated, suggesting the initiation of dormancy. In line with this, only a small non-significant increase in tumor control was observed for A549 tumors treated with fractionated RT and EGFR inhibition. Conclusion: For NSCLC cells increase in radiosensitivity by EGFR inhibition results from enhanced G1-arrest. However, this effect does not lead to improved tumor control because cells can be released from this arrest by re-stimulation

  10. [Clinicopathological Study of Perforated Gastric Cancer Treated with Surgery].

    Science.gov (United States)

    Ishiguro, Toru; Fukuchi, Minoru; Kumagai, Youichi; Ishibashi, Keiichiro; Mochiki, Erito; Ishida, Hideyuki

    2018-02-01

    This retrospective study evaluated an appropriate surgical treatment in patients with perforated gastric cancer. The clinicopathological and survival data on 17 perforated gastric cancer patients treated with surgery were analyzed. The one-stage or two-stage gastrectomy was performed in 8 and 5 patients, respectively. The omental patch repair was performed in 4 patients. In univariate analysis, non-curative(R2)resection with gross residual tumor(p<0.01)and postoperative complications( p=0.01)were found to be significant unfavorable factors for overall survival(OS). In multivariate analysis, R2 resection was identified to be an only independent significant unfavorable factor for OS. Patients who underwent curative(R0) resection had long-term survival, while patients with R2 resection and postoperative complication had limited survival times. These results suggest that R0 resection may be optimal to improve survival in patients with perforated gastric cancer, regardless of whether patients underwent a one-stage or two-stage gastrectomy based on the patient's condition.

  11. The mechanisms of photodynamic action for treating of cancer patients

    Directory of Open Access Journals (Sweden)

    A. L. Akopov

    2015-01-01

    Full Text Available Current views on mechanisms of therapeutic effect of photodynamic therapy for treating of cancer patients are represented. The history of formation and development of the method is described. The main requirements for agents used as photosensitizers are listed. Detailed review of main photosensitizers used in clinical practice in Russia and in foreign countries with their chemical structure, main spectral characteristics was performed. Methods of its application, therapeutic dose ranges, indications, specifi c pharmacokinetic properties and side-effects are briefl y outlined. Advantages and disadvantages of the most popular modern photosensitizers, main mechanisms of entry of photosensitizers of different chemical structure into cancer cells are observed. Three main possible component of anti-tumor effect: direct damage of cancer cells, impairment of vascular stroma of tumor and elimination of tumor due to immune cells are shown and closely discussed. Necrosis and apotosis of neovascular net which are main development trends of anti-tumor action for photodynamic therapy are noticed. 

  12. SPATIAL DISTRUBITON OF CHILDREN TREATED BY CANCER IN ZONGULDAK, TURKEY

    Directory of Open Access Journals (Sweden)

    A. Topan

    2016-06-01

    Full Text Available This research is focused on the examination of child cancer cases in Zonguldak (Turkey descriptively in epidemiological aspect thanks to GIS. Universe of the study is composed of 60 children between 0-19 years old, treated in Children Oncology Clinic of Health Application and Research Center in BEU. Whole universe was reached without selecting a sample in the study. Data were collected by using a form prepared by obtaining expert advice and they were applied to children and their parents at study dates. Results were expressed as percentages. Chi-Square test was used in intergroup comparisons, results were assessed within 95% confidence interval and p<0.05 was considered as statistically significant. Variables that were used in the study were assessed, recorded in prepared data collection form and distribution maps were produced. When disease diagnosis of the children participated in the study were evaluated, it was observed that 33.3% (n=20 were being treated for ALL, 13.3% (n=8 for Medullablastoma and 11.7% (n=7 for Hodgkin-nonHodgkin Lymphoma. It was detected that 31.7% (n=19 were in Ereğli, 31.7% (n=19 were in Central district and 18.3% (n=11 were in Çaycuma, when the places where children were living were evaluated. Statistically significant difference was found (p=0.016 comparing disease diagnosis with living place, and overall distribution map of the number of cancer cases was produced in this context. This is the first research subjecting the distribution of cancer cases for Zonguldak province.

  13. Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib.

    Science.gov (United States)

    Caiola, Elisa; Frapolli, Roberta; Tomanelli, Michele; Valerio, Rossana; Iezzi, Alice; Garassino, Marina C; Broggini, Massimo; Marabese, Mirko

    2018-01-17

    Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive. Here we show that the NSCLC cells' response to sorafenib depends on the type of KRAS mutation. KRAS G12V cells respond less to sorafenib than the wild-type counterpart, in vitro and in vivo. To overcome this resistance, we used high-throughput screening with a siRNA library directed against 719 human kinases, and Wee1 was selected as a sorafenib response modulator. Inhibition of Wee1 by its specific inhibitor MK1775 in combination with sorafenib restored the KRAS mutated cells' response to the multi-target tyrosine kinase inhibitor. This combination of the Wee1 inhibitor with sorafenib, if confirmed in models with different genetic backgrounds, might be worth investigating further as a new strategy for KRAS mutated NSCLC.

  14. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  15. Economic impact of tissue testing and treatments of metastatic NSCLC in the era of personalized medicine.

    Directory of Open Access Journals (Sweden)

    Donna Marie Graham

    2014-09-01

    Full Text Available A paradigm-shift in the management of non-small cell lung cancer (NSCLC has resulted in many new therapies becoming available for patients with advanced disease. Stratification of treatment by histologic and molecular subtype is recommended in order to obtain the greatest clinical benefit for patients while minimizing adverse effects of treatment. However, these advances in diagnosis and treatment of NSCLC have come at a financial cost. This review highlights the economic impact of screening for molecular abnormalities and targeted treatment for advanced NSCLC. Major determinants of cost are drug acquisition and molecular testing. As technologies advance, molecular testing costs may reduce. However, we must collaborate with payers and manufacturers to ensure that high drug costs do not limit patient accessibility to potentially beneficial treatment.

  16. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application.

    Science.gov (United States)

    Maione, Paolo; Sacco, Paola Claudia; Sgambato, Assunta; Casaluce, Francesca; Rossi, Antonio; Gridelli, Cesare

    2015-09-01

    The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC.

  17. Treatment-related pneumonitis and acute esophagitis in non-small-cell lung cancer patients treated with chemotherapy and helical tomotherapy.

    Science.gov (United States)

    Song, Chang Hoon; Pyo, Hongryull; Moon, Sung Ho; Kim, Tae Hyun; Kim, Dae Woong; Cho, Kwan Ho

    2010-11-01

    To assess clinical outcomes and complications in patients with non-small-cell lung cancer (NSCLC) treated with helical tomotherapy (HT) with or without chemotherapy. Data from 37 NSCLC patients treated between January 2007 and August 2008 were analyzed retrospectively. Twenty-eight patients had Stage III disease. Concurrent and neoadjuvant chemotherapy was given to 24 and 14 patients, respectively. Radiotherapy was delivered to a total dose of 60-70.4 Gy at 2.0-2.4 Gy per fraction to the gross tumor volume and 50-64 Gy at 1.8-2.0 Gy per fraction to the planning target volume. With a median follow-up of 18 months (range, 6-27 months), 2-year local control and overall survival rates were 63% and 56% for all 37 patients, respectively, and were 78% and 75% for the patients with Stage III disease who received concurrent chemoradiotherapy alone. Acute esophagitis and treatment-related pneumonitis (TRP) ≥Grade 3 occurred in 5 and 7 patients, respectively. Four patients died of treatment-related death (TRD) after HT. In univariate analysis, poor performance status, total lung V(5), contralateral lung (CL) V(5), and V(10) were associated with TRD. Only CL V(5) remained significant in the multivariate analysis (p = 0.029). HT with chemotherapy has shown promising clinical outcomes, esophagitis, and TRPs. However, HT has produced a somewhat high rate of fatal pulmonary complications. Our data suggest that CL V(5) should be considered and kept as low as possible (<60%) in addition to the conventional dosimetric factors. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. AC-93253 iodide, a novel Src inhibitor, suppresses NSCLC progression by modulating multiple Src-related signaling pathways.

    Science.gov (United States)

    Lai, Yi-Hua; Lin, Sih-Yin; Wu, Yu-Shan; Chen, Huei-Wen; Chen, Jeremy J W

    2017-11-13

    The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment. Src and Src-related protein expression in AC-93253 iodide-treated PC9, PC9/gef, and A549 cells were assessed by western blotting. The effects of AC-93253 iodide on cancer cell colony formation, invasion, and migration were assessed in PC9 and PC9/gef cells. The synergistic effects of gefitinib and AC-93253 iodide were evaluated by combination index (CI)-isobologram analysis in gefitinib-resistant cell lines. The efficacy of AC-93253 iodide in vivo was determined using nude mice treated with either the compound or the vehicle. Among the compounds, AC-93253 iodide exhibited the most potent dose-independent inhibitory effects on the activity of Src as well as on that of the Src-related proteins EGFR, STAT3, and FAK. Furthermore, AC-93253 iodide significantly suppressed cancer cell proliferation, colony formation, invasion, and migration in vitro and tumor growth in vivo. AC-93253 iodide sensitized tumor cells to gefitinib treatment regardless of whether the cells were gefitinib-sensitive (PC9) or resistant (H1975 and PC9/gef), indicating that it may exert synergistic effects when used in combination with established therapeutic agents. Our findings also suggested that the inhibitory effects of AC-93253 iodide on lung cancer progression may be attributable to its ability to modulate multiple proteins

  19. Surgery in high-volume hospitals not commission on cancer accreditation leads to increased cancer-specific survival for early-stage lung cancer.

    Science.gov (United States)

    David, Elizabeth A; Cooke, David T; Chen, Yingjia; Perry, Andrew; Canter, Robert J; Cress, Rosemary

    2015-10-01

    Quality of oncologic outcomes is of paramount importance in the care of patients with non-small cell lung cancer (NSCLC). We sought to evaluate the relationship of hospital volume for lobectomy on cancer-specific survival in NSCLC patients treated in California, as well as the influence of Commission on Cancer (CoC) accreditation. The California Cancer Registry was queried from 2004 to 2011 for cases of Stage I NSCLC and 8,345 patients were identified. Statistical analysis was used to determine prognostic factors for cancer-specific survival. A total of 7,587 patients were treated surgically. CoC accreditation was not significant for cancer-specific survival, but treatment in high-volume centers was associated with longer survival when compared with low- and medium-volume centers (hazard ratio 1.77, 1.474 to 2.141 and hazard ratio 1.23, 1.058 to 1.438). These data suggest that surgical treatment in high-volume hospitals is associated with longer cancer-specific survival for early-stage NSCLC, but that CoC accreditation is not. Published by Elsevier Inc.

  20. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-08-30

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  1. Radiofrequency Tagged Surgery in Treating Patients With Breast Cancer

    Science.gov (United States)

    2018-01-19

    Positive Axillary Lymph Node; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

  2. N1-guanyl-1,7-diaminoheptane enhances the chemosensitivity of NSCLC cells to cetuximab through inhibition of eukaryotic translation initiation factor 5A2 activation.

    Science.gov (United States)

    Wang, X; Jiang, R; Cui, E-H; Feng, W-M; Guo, H-H; Gu, D-H; Tang, C-W; Xue, T; Bao, Y

    2016-04-01

    N1-guanyl-1, 7-diaminoheptane (GC7), an inhibitor of deoxyhypusine synthase has been shown to exhibit significant anti-cancer activity. However, the biological role of eukaryotic translation initiation factor 5A2 activation (EIF5A2) and GC7 on drug resistance in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we aimed to investigate the therapeutic effect of GC7 combined with cetuximab in NSCLC therapy. The current study used cell viability assays, EdU incorporation assays, and western blot to detect that the GC7 exhibited synergistic cytotoxicity with cetuximab in NSCLC. CCK-8 assays showed that combined treatment with GC7 and cetuximab significantly inhibited the viabilities in three NSCLC cell lines. In addition, EdU incorporation assays also indicated that GC7 co-treatment remarkably enhanced the cetuximab sensitivity in NSCLC cells. Nevertheless, down-regulation of EIF5A2 diminished the regulatory role of GC7 in cetuximab cytotoxicity. Western blot showed that transfection of EIF5A2 siRNA significantly suppressed the protein expression of EIF5A2 in NSCLC cells. These findings demonstrate that combined treatment with GC7 could enhance cetuximab sensitivity by inhibiting EIF5A2 in NSCLC cells, implying the potential clinical application of GC7 in cetuximab-based chemotherapy for NSCLC patients.

  3. Heterogeneous resistance mechanisms in an EGFR exon 19-mutated non-small cell lung cancer patient treated with erlotinib

    DEFF Research Database (Denmark)

    Santoni-Rugiu, Eric; Grauslund, Morten; Melchior, Linea C

    2017-01-01

    Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9-15 months during first-line...... an alternative pathway to EGFR-signaling. The patient received first-line erlotinib but after only 7 weeks showed metastatic pleural effusion, in which transformation to small cell lung cancer (SCLC) that retained the EGFR- and FGFR3-mutations was identified. Consequently, standard carboplatin-etoposide regimen...

  4. Clinical efficacy of percutaneous vertebroplasty combined with intensity-modulated radiotherapy for spinal metastases in patients with NSCLC

    Directory of Open Access Journals (Sweden)

    Li Y

    2015-08-01

    Full Text Available Yi Li,1,2 Yi Qing,1 Zhimin Zhang,3 Mengxia Li,1 Jiaying Xie,1 Ge Wang,1 Dong Wang1 1Department of Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 2Department of Oncology, Beibei Traditional Chinese Medical Hospital, Chongqing, 3Department of Oncology, Wuhan General Hospital of Guangzhou Command, People’s Liberation Army, Wuhan, Hubei, People’s Republic of China Objective: This study aimed to evaluate the safety and efficacy of percutaneous vertebroplasty (PVP combined with intensity-modulated radiotherapy (IMRT for metastatic lesions of patients with non-small-cell lung cancer (NSCLC at centrum vertebrae.Methods: A total of 39 patients with spinal metastatic NSCLC (stage IV were treated with PVP followed by IMRT (30 Gy/10F/2 W for metastatic lesion at centrum vertebrae under local anesthesia. Retrospective analysis was done with medical records and radiological data. The change of visual analog scale (VAS, activities of daily living, and kyphotic angle was measured preoperatively. The presence of complications was assessed preoperatively (baseline at 24 hours, 1 week, and 1, 3, 6, 12, and 24 months postoperatively, or until the patient died or was lost to follow-up. Survival was assessed in the group.Results: A total of 39 consecutive patients were successfully treated with PVP via a translateral approach and IMRT. Their mean VAS score decreased from 7.93±1.09 preoperatively to 4.14±1.15 by the 24-hour postoperative time point and was 3.92±1.23 at 1 week, 4.27±1.93 at 1 month, 3.24±1.35 at 3 months, 2.27±0.96 at 6 months, and 2.59±1.55 at 12 months after the procedure. The mean VAS score at all of the postoperative time points was decreased significantly from the preoperative baseline score (P<0.05. Activities of daily living evaluation showed that the patients had a significantly high life quality after the combined approach (50.9±11.7 vs 82.3±9.9, P<0.05. No severe complications

  5. 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

  6. Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

    Science.gov (United States)

    2017-10-16

    Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity

  7. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); Liang, Jian; Deng, Xin [Ruikang Hospital, Guangxi University of Traditional Chinese Medicine, Nanning 530003 (China); Chen, Yuxiang, E-mail: chenyx008@yahoo.cn [Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008 (China); School of Biological Science and Technology, Central South University, Changsha 410008 (China)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. Black-Right-Pointing-Pointer PTEN reexpression is mediated by miR-29b overexpression. Black-Right-Pointing-Pointer miR-29b regulates Dnmts expression in NSCLC tumor cells. Black-Right-Pointing-Pointer Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  9. The mechanism involved in the loss of PTEN expression in NSCLC tumor cells

    International Nuclear Information System (INIS)

    Li, Gang; Zhao, Jingfeng; Peng, Xianjing; Liang, Jian; Deng, Xin; Chen, Yuxiang

    2012-01-01

    Highlights: ► Radiation stimulates PTEN reexpression in NSCLC independent of p53 activation. ► PTEN reexpression is mediated by miR-29b overexpression. ► miR-29b regulates Dnmts expression in NSCLC tumor cells. ► Target therapy could be established by overexpressing miR-29b expression. -- Abstract: Loss of PTEN expression is observed in most non-small cell lung cancers (NSCLC). However, the mechanism by which PTEN expression is regulated in NSCLC has not been fully elucidated. In this study, we investigated the role of DNA methyltransferases (Dnmts), microRNA-29b (miR-29b), and anti-miR-29b inhibitor in PTEN promoter methylation and PTEN gene expression in H358 NSCLC cells in vitro and in vivo. PTEN mRNA was measured by RT-PCR. PTEN and Dnmts protein levels were measured by Western blot. miR-29b expression was detected by Northern blot. A xenograft H358 tumor mouse model was established by subcutaneously inoculating H358 cells into the right hind limbs of nude mice. We found that radiation induced cell apoptosis and hypomethylation in PTEN promoter, PTEN and miR-29b expression, and downregulation of Dnmt1, 3a and 3b expression in H358 tumor cells. The effect of radiation on gene expression and apoptosis was blocked by anti-miR-29b inhibitor. In the xenograft H358 tumor model, anti-miR-29b inhibitor reversed radiation-induced tumor growth delay, PTEN reexpression and downregulation of Dnmts expression. Our study suggested that miR-29b is an upstream molecule of PTEN. miR-29b regulates PTEN gene expression through downregulating Dnmts expression and subsequently induces hypomethylation in PTEN promoter. Targeting therapy could be established in NSCLC by upregulating miR-29b expression.

  10. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

    International Nuclear Information System (INIS)

    Jin, Hyeon-Ok; Hong, Sung-Eun; Kim, Chang Soon; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Lee, Jin Kyung

    2015-01-01

    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

  11. SU-F-R-53: CT-Based Radiomics Analysis of Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Huynh, E; Coroller, T; Narayan, V; Agrawal, V; Hou, Y; Romano, J; Franco, I; Mak, R; Aerts, H [Brigham Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (United States)

    2016-06-15

    Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable non-small cell lung cancer (NSCLC) patients and has demonstrated excellent local control and survival. However, some patients still develop distant metastases and local recurrence, and therefore, there is a clinical need to identify patients at high-risk of disease recurrence. The aim of the current study is to use a radiomics approach to identify imaging biomarkers, based on tumor phenotype, for clinical outcomes in SBRT patients. Methods: Radiomic features were extracted from free breathing computed tomography (CT) images of 113 Stage I-II NSCLC patients treated with SBRT. Their association to and prognostic performance for distant metastasis (DM), locoregional recurrence (LRR) and survival was assessed and compared with conventional features (tumor volume and diameter) and clinical parameters (e.g. performance status, overall stage). The prognostic performance was evaluated using the concordance index (CI). Multivariate model performance was evaluated using cross validation. All p-values were corrected for multiple testing using the false discovery rate. Results: Radiomic features were associated with DM (one feature), LRR (one feature) and survival (four features). Conventional features were only associated with survival and one clinical parameter was associated with LRR and survival. One radiomic feature was significantly prognostic for DM (CI=0.670, p<0.1 from random), while none of the conventional and clinical parameters were significant for DM. The multivariate radiomic model had a higher median CI (0.671) for DM than the conventional (0.618) and clinical models (0.617). Conclusion: Radiomic features have potential to be imaging biomarkers for clinical outcomes that conventional imaging metrics and clinical parameters cannot predict in SBRT patients, such as distant metastasis. Development of a radiomics biomarker that can identify patients at high-risk of

  12. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  13. Randomized, double-blind, placebo-controlled, phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small-cell lung cancer.

    Science.gov (United States)

    Spigel, David R; Burris, Howard A; Greco, F Anthony; Shipley, Dianna L; Friedman, Elke K; Waterhouse, David M; Whorf, Robert C; Mitchell, R Brian; Daniel, Davey B; Zangmeister, Jeffrey; Bass, J David; Hainsworth, John D

    2011-06-20

    Sorafenib, an oral multikinase inhibitor, has shown preliminary activity in non-small-cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial. Key eligibility criteria included the following: stage IIIB or IV NSCLC; one to two prior regimens; Eastern Cooperative Oncology Group performance status of 0 to 2; and measurable disease. Patients were randomly assigned 2:1 to sorafenib (400 mg orally twice a day) plus erlotinib (150 mg orally daily) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab. Treatment efficacy, measured by progression-free survival (PFS) and overall response rate (ORR), was compared. Treatment of 168 patients allowed detection of 40% improvement in the historical PFS of 2.2 months with single-agent erlotinib. One hundred sixty-eight patients enrolled from February 2008 to February 2009. Clinical characteristics of the two groups were similar. ORRs for sorafenib/erlotinib and placebo/erlotinib were 8% and 11%, respectively (P = .56); disease control rates were 54% and 38%, respectively (P = .056). Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib (hazard ratio, 0.86; 95% CI, 0.60 to 1.22; P = .196). Seventy-two patients consented to analyses of tumor epidermal growth factor receptor (EGFR). In 67 patients with EGFR wild-type (WT) tumors, median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib (P = .018); median overall survival (OS) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib (P = .019). An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization (FISH) EGFR-negative tumors (P = .064). Both regimens were tolerable, with modest toxicity increase with sorafenib. Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH

  14. Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives

    DEFF Research Database (Denmark)

    Vilmar, A C; Sorensen, J B

    2011-01-01

    of life. We conducted a literature search of tailored treatment already implemented in advanced NSCLC in order to highlight the information required to decide on the optimal oncological treatment for individual patients. 16 studies were identified by literature review. Significantly improved outcome......Treating patients with advanced nonsmall cell lung cancer (NSCLC) is a daunting task but during recent years new options have emerged. By tailoring treatment using either information on histological subtypes of NSCLC or biomarkers it is now possible to improve outcome and maintain stable quality......, respectively. In conclusion, tailoring treatment according to either histological subtype or EGFR mutation status in advanced NSCLC should today be part of daily practice based on current evidence. Future biomarkers need optimisation of methodology and prospective validation before clinical implementation....

  15. The Predictive Value of Germline Polymorphisms in Patients with NSCLC

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund

    2010-01-01

    urgently needed. Single Nucleotide Polymorphisms (SNPs) are stable markers of potential clinical value and the study aimed at evaluating their use in lung cancer patients given standard chemotherapy. Genomic DNA was extracted from a pre-treatment blood sample drawn from patients with advanced Non....... Haplotypes were estimated and analyzed when relevant. There were no significant associations between SNPs in the EGF system or the DNA-repair system and RR, PFS or OS. In contrast, the VEGF+405, VEGF-460 and VEGF-2579, heterozygous patients had a higher response rate and longer PFS than homozygous patients....... Haplotype analysis of the VEGF+405 and VEGF- 460 supported our findings. These results were, however, not confirmed in the validation cohort. Although significant results regarding VEGF related SNPs, in the primary analysis, no predictive value of a broad panel of SNPs in NSCLC was found in the validation...

  16. Ultrasound elastography in patients with rectal cancer treated with chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Rafaelsen, S.R., E-mail: soeren.rafael.rafaelsen@slb.regionsyddanmark.dk [Department of Radiology, DCCG South, Vejle Hospital, 7100 Vejle (Denmark); Vagn-Hansen, C., E-mail: chris.aksel.vagn-hansen@slb.regionsyddanmark.dk [Department of Radiology, DCCG South, Vejle Hospital, 7100 Vejle (Denmark); Sørensen, T., E-mail: torben.soerensen@slb.regionsyddanmark.dk [Department of Radiology, DCCG South, Vejle Hospital, 7100 Vejle (Denmark); Lindebjerg, J., E-mail: jan.lindebjerg@slb.regionsyddanmark.dk [Department of Pathology, DCCG South, Vejle Hospital, 7100 Vejle (Denmark); Pløen, J., E-mail: john.ploeen@slb.regionsyddanmark.dk [Department of Oncology, DCCG South, Vejle Hospital, 7100 Vejle (Denmark); Jakobsen, A., E-mail: anders.jakobsen@slb.regionsyddanmark.dk [Department of Oncology, DCCG South, Vejle Hospital, 7100 Vejle (Denmark)

    2013-06-15

    Objective: The current literature has described several predictive markers in rectal cancer patients treated with chemoradiation, but so far none of them have been validated for clinical use. The purpose of the present study was to compare quantitative elastography based on ultrasound measurements in the course of chemoradiation with tumor response based on T stage classification and the Mandard tumor regression grading (TRG). Materials and methods: We prospectively examined 31 patients with rectal cancer planned for high dose radiochemotherapy. The tumor and the mesorectal fat elasticity were measured using the Acoustic Radiation Force Impulse to generate information on the mechanical properties of the tissue. The objective quantitative elastography shear wave velocity was compared to the T stage classification and TRG. Results: The baseline mean tumor elasticity was 3.13 m/s. Two and six weeks after the start of chemoradiation the velocities were 2.17 m/s and 2.11 m/s, respectively. The difference between baseline velocity and velocities during the treatment course was statistically significant, (p < 0.0001). Patients with tumor confined to the rectal wall at histopathology (ypT1-2) had a mean elasticity measurement after two weeks of treatment of 1.95 m/s, whereas tumors invading the mesorectal fat (ypT3-4) had a velocity of 2.47 m/s, (p < 0.05). The mean elasticity tended to be lower (1.99 m/s) after two weeks in patients with TRG 1–2 responses in contrast to 2.24 m/s in those with TRG 3–4. Conclusion: Ultrasound elastography after two weeks of chemoradiation seems to hold early predictive information to the pathological T stage.

  17. Peritumoural ground-glass opacity associated with tumour pseudoprogression in a patient with non-small cell lung cancer treated with nivolumab.

    Science.gov (United States)

    Kato, Ryoji; Hayashi, Hidetoshi; Tanizaki, Junko; Tanaka, Kaoru; Takeda, Masayuki; Nakagawa, Kazuhiko

    2017-01-01

    Nivolumab, a monoclonal antibody to programmed cell death protein-1 (PD-1), has revolutionised the management of patients with advanced non-small cell lung cancer (NSCLC). Treatment with nivolumab is associated with toxicities known as immune-related adverse events. Although pneumonitis is a potentially serious event, little is known of its clinical and radiographic features. We here report a case of NSCLC for which treatment with nivolumab resulted in the development of ground-glass opacity surrounding the primary lung tumour and an associated increase in tumour size. Administration of prednisone led to rapid resolution of both clinical symptoms and the abnormal shadow on the lung field as well as shrinkage of the tumour. However, retreatment with nivolumab induced clinical and radiographic manifestations similar to those triggered by the first challenge. Given the increasing use of PD-1 inhibitors in patients with NSCLC, further studies are warranted to provide a better understanding of this phenomenon.

  18. Association Between Endothelial Progenitor Cells and Treatment Response in Non-Squamous Non-small Cell Lung Cancer Treated with Bevacizumab.

    Science.gov (United States)

    Sudo, Kazuhisa; Sato, Kazuhiro; Sakamoto, Sho; Hasegawa, Yukiyasu; Asano, Mariko; Okuda, Yuji; Takeda, Masahide; Sano, Masaaki; Watanabe, Hiroyuki; Shioya, Takanobu; Ito, Hiroshi

    2017-10-01

    To investigate the association between the number of circulating endothelial progenitor cells (EPCs) in non-squamous non-small cell lung cancer (NSCLC) and disease outcome, in combination chemotherapy with and without bevacizumab. We retrospectively identified 25 non-squamous NSCLC cases, and divided them into high-EPC and low-EPC groups. Within each group, we compared disease outcomes, with or without the administration of bevacizumab. In the high-EPC group, chemotherapy with bevacizumab produced a significantly higher tumor reduction rate and objective response rate, with significantly longer progression-free survival, compared to chemotherapy without bevacizumab (pbevacizumab. The number of EPCs may be a useful biomarker to guide decision-making in the use of bevacizumab in non-squamous NSCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Association of CT perfusion imaging with plasma levels of TGF-β1 and VEGF in patients with NSCLC.

    Science.gov (United States)

    Li, Da-Wei; Wu, Bao-Zhong; Shi, Yu-Sen; Li, Zhi-Qun; Liu, Xu-Dong; Li, Xiao-Hua

    2016-02-01

    To study the association of CT perfusion imaging parameters with plasma level of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth (VEGF) in patients with non small cell lung cancer (NSCLC). A total of 67 patients with NSCLC (NSCLC group) and 64 patients with benign lesion (control group) were given with CT perfusion imaging to obtain blood flow, blood volume, mean transit time, time to peal and permeability surface through CT perfusion software. The plasma levels of TGF-β1 and VEGF were tested by ELISA. The relationship between plasma levels of TGF-β1, VEGF and CT perfusion imaging parameters were analyzed. CT perfusion imaging parameters and the plasma levels of TGF-β1 and VEGF of NSCLC group were significantly higher than the control group (P CT perfusion parameters and the levels of TGF-β1 and VEGF in NSCLC group showed significant difference in different tumor node metastasis stages (P CT perfusion imaging parameters in patients with NSCLC is closely associated with plasma TGF-β1, VEGF and its biological characteristics. CT perfusion imaging is a convenient method to detect tumor blood perfusion. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  20. Interventions for treating oral leukoplakia to prevent oral cancer.

    Science.gov (United States)

    Lodi, Giovanni; Franchini, Roberto; Warnakulasuriya, Saman; Varoni, Elena Maria; Sardella, Andrea; Kerr, Alexander R; Carrassi, Antonio; MacDonald, L C I; Worthington, Helen V

    2016-07-29

    participants because drop-out rates were similar between treatment and control groups. Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.

  1. Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer | Division of Cancer Prevention

    Science.gov (United States)

    This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer. |

  2. Targeting Androgen Receptor in Treating HER2 Positive Breast Cancer.

    Science.gov (United States)

    He, Licai; Du, Zhuanyun; Xiong, Xusheng; Ma, Hua; Zhu, Zhenfeng; Gao, Hongwei; Cao, Jiawei; Li, Tong; Li, Hongzhi; Yang, Kaiyan; Chen, Guorong; Richer, Jennifer K; Gu, Haihua

    2017-11-06

    Androgen receptor (AR) is widely expressed in different subtypes of breast cancer (BC). However, it is unclear how AR functions in HER2 positive (+) BC. Knockdown of AR with shRNAs and a new generation anti-androgen drug, Enzalutamide, were used to explore the involvement of AR on the growth of HER2 + BC cells (HCC1954 and SKBR3). AR shRNA or Enzalutamide inhibited the growth of SKBR3 cells at a similar extend compared to trastuzumab, an approved HER2 targeted drug. Combining Enzalutamide with trastuzumab further decreased the growth of HCC1954 and SKBR3 cells compared with single agent alone in vitro. Biochemical analysis revealed that inhibiting AR resulted in decreased HER2 phosphorylation and activation of Erk and Akt, without affecting the HER2 and HER3 expression. The in vivo efficacy of Enzalutamide was further tested using the HCC1954 xenograft model. Enzalutamide impaired the growth of HCC1954 tumor at a level comparable to that by trastuzumab. Enzalutamide decreased Ki67 staining and increased activated caspase3 staining compared with vehicle control in HCC1954 tumors. Our results indicate AR plays an important role in promoting the growth of HER2 + BC by cross-talking with the HER2 signaling. AR drug may be used as an alternative second line therapy for treating HER2 + BC.

  3. Emerging roles of RAC1 in treating lung cancer patients.

    Science.gov (United States)

    Zou, T; Mao, X; Yin, J; Li, X; Chen, J; Zhu, T; Li, Q; Zhou, H; Liu, Z

    2017-04-01

    The Ras-related C3 botulinum toxin substrate 1 (RAC1), a member of the Rho family of small guanosine triphosphatases, is critical for many cellular activities, such as phagocytosis, adhesion, migration, motility, cell proliferation, and axonal growth. In addition, RAC1 plays an important role in cancer angiogenesis, invasion, and migration, and it has been reported to be related to most cancers, such as breast cancer, gastric cancer, testicular germ cell cancer, and lung cancer. Recently, the therapeutic target of RAC1 in cancer has been investigated. In addition, some investigations have shown that inhibition of RAC1 can reverse drug-resistance in non-small cell lung cancer. In this review, we summarize the recent advances in understanding the role of RAC1 in lung cancer and the underlying mechanisms and discuss its value in clinical therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. [Combined-modality therapy for lung cancer].

    Science.gov (United States)

    Miura, Satoru; Yamamoto, Nobuyuki

    2010-06-01

    Lung cancer is treated with surgery, radiotherapy and chemotherapy according to histology and clinical stage. Advanced stage lung cancer patients cannot be cured, but early and locally-advanced stage patients can be cured by intensive combined-modality therapy. Combined-modality therapy with surgery plus adjuvant chemotherapy is standard for resectable IB-IIIA non-small cell lung cancer (NSCLC) and stage I small cell lung cancer (SCLC) patients. Chemoradiotherapy is standard for unresectable locally-advanced NSCLC and limited-stage SCLC patients. Recently, several new drugs, molecular targeted drugs, have become available for clinical use and trials. We reviewed standard and new strategy of combined-modality therapy for early and locally-advanced lung cancer patients.

  5. Volumetric response analysis during chemoradiation as predictive tool for optimizing treatment strategy in locally advanced unresectable NSCLC

    International Nuclear Information System (INIS)

    Bral, Samuel; Duchateau, Michael; De Ridder, Mark; Everaert, Hendrik; Tournel, Koen; Schallier, Denis; Verellen, Dirk; Storme, Guy

    2009-01-01

    Purpose: To study the feasibility of measuring volumetric changes in the primary tumor on megavoltage-computed tomography (MVCT) during chemoradiation and to examine the correlation with local response. Patients and methods: Fifteen consecutive patients with stage III, inoperable, locally advanced non-small cell lung cancer (NSCLC) were treated in a prospective dose escalation study protocol of concurrent chemoradiation. They were monitored for acute toxicity and evaluated with daily MVCT imaging. The volumetric changes were fitted to a negative exponential resulting in a regression coefficient (RC). Local response evaluation was done with positron emission tomography using the radio-labeled glucose analogue F18 fluorodeoxyglucose (FDG-PET). Results: The mean volume decrease (±standard deviation) was 73% (±18%). With a mean treatment time of 42 days this treatment schedule resulted in a mean decrease of 1.74%/day. Of the 13 evaluable patients seven developed a metabolic complete remission (MCR). The mean RC of the patients with MCR is 0.050 versus a mean RC of 0.023 in non-responders (p = 0.0074). Using a proposed cut-off value for the RC of 0.03 80% of the non-responders will be detected correctly while misclassifying 16.4% of patients who will eventually achieve an MCR. The total cumulative percentage of esophageal grade 3 or more toxicity was 46.7%. Conclusion: The RC derived from volumetric analysis of daily MVCT is prognostic and predictive for local response in patients treated with chemoradiation for a locally advanced NSCLC. Because this treatment schedule is toxic in nearly half of the patient population, MVCT is a tool in the implementation of patient-individualized treatment strategies.

  6. Detecting expression of 5T4 in CTCs and tumor samples from NSCLC patients.

    Directory of Open Access Journals (Sweden)

    Steven R Pirie-Shepherd

    Full Text Available The fetal oncogene 5T4 is a cell surface protein, with overexpression observed in a variety of cancers as compared to normal adult tissue. The ability to select patients with tumors that express high levels of 5T4 may enrich a clinical trial cohort with patients most likely to respond to 5T4 targeted therapy. To that end, we developed assays to measure 5T4 in both tumors and in circulating tumor cells (CTCs. We identified the presence of 5T4 in both adenocarcinoma and squamous cell carcinoma of lung, in all clinical stages and grades of disease. CTCs were identified in peripheral blood from the majority of patients with NSCLC, and 5T4 was detectable in most samples. Although 5T4 was present in both CTCs and tumors in most patients, there was no concordance between relative amount in either sample type. Clinical response rates of patients treated with the therapies directed against 5T4 in early stage clinical trials, as determined by these assays, may provide important insights into the biology of 5T4 in tumors and the mechanisms of action of 5T4-targeting therapy.

  7. Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar.

    NARCIS (Netherlands)

    Tang, S.C.; Nguyen, L.N.; Sparidans, R.W.; Wagenaar, E.; Beijnen, J.H.; Schinkel, A.H.

    2014-01-01

    Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase (ALK) rearrangement. We used knockout mice to study the roles of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in

  8. Research on Immunotherapy: Using the Immune System to Treat Cancer

    Science.gov (United States)

    ... Home Research Key Initiatives Immunotherapy NCI’s Role in Immunotherapy Research An oral squamous cancer cell (white) being ... immunotherapy to more patients with cancer. NCI-Supported Immunotherapy Research Immunotherapy research funded by or conducted at ...

  9. Transcriptionally targeted gene therapy to detect and treat cancer

    OpenAIRE

    Wu, Lily; Johnson, Mai; Sato, Makoto

    2003-01-01

    The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle t...

  10. Clinicopathological significance and potential drug target of T-cadherin in NSCLC

    Directory of Open Access Journals (Sweden)

    Wang Z

    2014-12-01

    Full Text Available Zhidong Wang,1 Bin Wang,1 Huanchen Guo,2 Guoyu Shi,2 Xiuqin Hong3 1Oncology Department, Eighth Hospital of Changsha, Changsha, People’s Republic of China; 2Department of Respiratory Medicine, Shouguang Hospital of Traditional Chinese Medicine, Shouguang, People’s Republic of China; 3Institute of Gerontology, Hunan Geriatric Hospital, Changsha, People’s Republic of China Background: Previous studies demonstrate that T-cadherin is a candidate tumor suppressor in several types of human tumors, including non-small cell lung cancer (NSCLC. Lack of protein expression of T-cadherin by hypermethylation has been found to play an important role in lung alveolar differentiation regulation and epithelial tumorigenesis. However, the correlation between T-cadherin hypermethylation and clinicopathological characteristics of NSCLC remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of T-cadherin hypermethylation on the incidence of NSCLC and clinicopathological characteristics.Methods: A detailed literature search was carried out for related research publications. Analyses of pooled data were performed. Odds ratio (OR and hazard ratio (HR were calculated and summarized, respectively.Results: Final analysis of 1,172 NSCLC patients from 15 eligible studies was performed. T-cadherin hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, based on the pooled OR from nine studies including 532 NSCLC and 372 normal lung tissue samples (OR=8.19, 95% confidence interval [CI]=5.41–12.39, P<0.00001. T-cadherin hypermethylation may also be associated with pathological types. The pooled OR was obtained from four studies including 111patients with squamous cell carcinoma and 106 with adenocarcinoma (OR=0.35, 95% CI=0.19–0.66, P=0.001, which indicated that T-cadherin hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. We did not find

  11. Special Section: Preventing, Detecting, and Treating Colorectal Cancer

    Science.gov (United States)

    ... a week-long series to promote colon and rectal (colorectal) cancer awareness and screening. Following that, research showed that ... niddk.nih.gov The American Cancer Society: www.cancer.org The American Society of Colon & Rectal Surgeons: www.fascrs.org Spring 2009 Issue: Volume ...

  12. Result of radiation therapy for non-resectable lung cancer

    International Nuclear Information System (INIS)

    Kataoka, Masaaki; Kawamura, Masashi; Kimura, Makoto; Mogami, Hiroshi; Kimura, Yoshiko; Hamamoto, Ken

    1988-01-01

    A total of 122 patients with non-resectable lung cancer, comprising 98 with non-small cell lung cancer (NSCLC) and 24 with small cell lung cancer (SCLC), who were treated from November 1976 through December 1985 with definitive radiation therapy (RT), were retrospectively analyzed for the outcome of RT. Overall, the 5-year survival rate was 6 %: it was 8 % for SCLC and 4 % for NSCLC. For NSCLC, survival was significantly better in stages I-III patients than stage IV patients (p < 0.01), although it was independent of histology, the combination of chemotherapy, and fractionation schedule. Local recurrence and distant metastasis were found to be the cause of death in 42 % and 13 %, respectively, in the stages I-II NSCLC group; and in 19 % and 52 %, respectively, in the SCLC group. The SCLC patients tended to have better survival when given chemotherapy before RT. Ten patients surviving for three years or more were characterized by having early stage of NSCLC, less than 100 cm of irradiated field, and a total dose of 60 Gy or more. Twelve patients (10 %) had severe radiation pneumonitis that resulted in death. Acute and fetal pneumonitis tended to be frequent when chemotherapy was combined with RT. (Namekawa, K.)

  13. Efficacy and safety of afatinib in Chinese patients with EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) previously responsive to first-generation tyrosine-kinase inhibitors (TKI) and chemotherapy: comparison with historical cohort using erlotinib

    International Nuclear Information System (INIS)

    Lee, Victor H. F.; Leung, Dennis K. C.; Choy, Tim-Shing; Lam, Ka-On; Lam, Pui-Mei; Leung, To-Wai; Kwong, Dora L. W.

    2016-01-01

    Afaitnib has shown anti-tumor activity against metastatic EGFR-mutated NSCLC after prior failure to first generation EGFR-TKI and chemotherapy. We prospectively evaluated the efficacy and safety of afatinib in Chinese patients who previously failed first-generation TKI and chemotherapy under a compassionate use program (CUP) and compared to the erlotinib cohort. Patients who suffered from metastatic EGFR-mutated NSCLC previously responsive to first-generation TKI and chemotherapy received afatinib until progression, loss of clinical benefits or intolerable toxicity. Treatment response, survival and safety were evaluated and compared to the erlotinib cohort. Twenty-five and 28 patients received afatinib and erlotinib respectively. More patients in the afatinib group had worse performance status (ECOG 2) than the erlotinib group (p = 0.008). After a median follow-up of 12.1 months, afatinib demonstrated comparable objective response rate (ORR) (20.0 % vs. 7.1 %, p = 0.17) but significantly higher disease control rate (DCR) (68.0 % vs. 39.3 %, p = 0.04) compared to erlotinib. Median progression-free survival (PFS) (4.1 months [95 % CI, 2.7–5.5 months] vs. 3.3 months [95 % CI, 2.2–4.3 months], p = 0.97) and overall survival (OS) were not different between the two groups (10.3 months [95 % CI, 7.5–13.0 months] vs. 10.8 months [95 % CI, 7.4–14.2 months], p = 0.51). Multivariate analyses revealed that age ≤70 years and time to progression (TTP) ≥18 months for the 1 st TKI therapy were prognostic of PFS (p = 0.006 and p = 0.008 respectively). Afatinib caused less rash (60.0 % vs. 67.9 %, p = 0.04) but more diarrhea (60.0 % vs. 10.7 %, p = 0.002) compared to erlotinib. Afatinib produced encouraging clinical efficacy as 2 nd TKI therapy with manageable safety profiles in our Chinese patients after failure to another TKI and systemic chemotherapy. This study was registered at ClinicalTrials.gov (NCT02625168) on 3 December 2015

  14. Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway

    Directory of Open Access Journals (Sweden)

    Xiaoying Hou

    2018-02-01

    Full Text Available Tumor metastasis is the most lethal and debilitating process that threatens cancer patients. Among the regulators involved in tumor metastasis, lysyl oxidase (LOX is an important contributor for tumor invasion, migration and the formation of the pre-metastatic niche. Although the relationship between LOX and poor prognosis of lung patients has been preliminary reported, the mechanism remains poorly understood. Here, we found that LOX overexpression is closely related to the survival of lung adenocarcinoma patients but not squamous cell carcinoma patients. Moreover, we confirmed that LOX expression is regulated by the activation of epidermal growth factor receptor (EGFR via the PI3K/AKT, MEK/ERK, and SAPK/JNK signaling pathways in non-small cell lung cancer (NSCLC. Meanwhile, the study also suggested that the traditional anti-fibrosis drug silibinin inhibited NSCLC cell migration in an EGFR/LOX dependent manner. In addition, an orthotopic implantation metastasis model also confirmed that the EGFR inhibitor WZ4002 and silibinin decreased tumor metastasis through the EGFR/LOX pathway. Altogether, this study revealed that LOX expression is regulated by the EGFR pathway and this may account for the anti-cancer metastasis effects of silibinin, indicating LOX as a potentially therapeutic target for NSCLC treatment.

  15. Breviscapine suppresses the growth of non-small cell lung cancer ...

    Indian Academy of Sciences (India)

    2017-02-10

    Feb 10, 2017 ... and safe drugs to treat NSCLC. A better understanding of the molecular pathogenesis in cancer progression is useful to discover therapeutic targets and develop novel anti-carcinoma medicines. MicroRNA. (miRNA) is a class of endogenous small non-coding RNA molecules with lengths of ~21–25 bases, ...

  16. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

    NARCIS (Netherlands)

    Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; Heuvel, M. van den; Ciuleanu, T.E.; Badin, F.; Ready, N.; Hiltermann, T.J.N.; Nair, S.; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J.M.; Rodriguez-Abreu, D.; Borghaei, H.; umenschein GR, J.r. Bl; Villaruz, L.C.; Havel, L.; Krejci, J.; rral Jaime, J. Co; Chang, H.; Geese, W.J.; Bhagavatheeswaran, P.; Chen, A.C.; Socinski, M.A.

    2017-01-01

    BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  17. Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

    International Nuclear Information System (INIS)

    Jorge, S.E.D.C.; Kobayashi, S.S.; Costa, D.B.

    2014-01-01

    Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC

  18. Proteomic analysis of cervical cancer cells treated with ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    medical care, especially in the field of clinical oncology. As SAHA has shown good results in human cancer therapy, we used HeLa cells as a model to identify whether SAHA would be effective in cervical cancer. We took the proteomics approach, particularly 2-DE and MS, to identify the altered proteins in HeLa cells before ...

  19. Influenza vaccination in children being treated with chemotherapy for cancer

    NARCIS (Netherlands)

    Goossen, Ginette M.; Kremer, Leontien C. M.; van de Wetering, Marianne D.

    2009-01-01

    Influenza infection is a potential cause of severe morbidity in children with cancer, therefore vaccination against influenza is recommended. However, there are conflicting data concerning the immune response to influenza vaccination in children with cancer and the value of vaccination remains

  20. Influenza vaccination in children being treated with chemotherapy for cancer

    NARCIS (Netherlands)

    Goossen, Ginette M.; Kremer, Leontien C. M.; van de Wetering, Marianne D.

    2013-01-01

    Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear. 1.

  1. Proteomic analysis of cervical cancer cells treated with ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Cervical cancer is one of the most common cancers and a leading cause of death among women worldwide. It is characterized by a well-defined premalignant phase that can be suspected on cytological examination of exfoliated cervical cells and confirmed on histological examination of cervical material. However, this is ...

  2. Drug repositioning for non-small cell lung cancer by using machine learning algorithms and topological graph theory.

    Science.gov (United States)

    Huang, Chien-Hung; Chang, Peter Mu-Hsin; Hsu, Chia-Wei; Huang, Chi-Ying F; Ng, Ka-Lok

    2016-01-11

    Non-small cell lung cancer (NSCLC) is one of the leading causes of death globally, and research into NSCLC has been accumulating steadily over several years. Drug repositioning is the current trend in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development process of drugs, as well as reducing side effects. This work integrates two approaches--machine learning algorithms and topological parameter-based classification--to develop a novel pipeline of drug repositioning to analyze four lung cancer microarray datasets, enriched biological processes, potential therapeutic drugs and targeted genes for NSCLC treatments. A total of 7 (8) and 11 (12) promising drugs (targeted genes) were discovered for treating early- and late-stage NSCLC, respectively. The effectiveness of these drugs is supported by the literature, experimentally determined in-vitro IC50 and clinical trials. This work provides better drug prediction accuracy than competitive research according to IC50 measurements. With the novel pipeline of drug repositioning, the discovery of enriched pathways and potential drugs related to NSCLC can provide insight into the key regulators of tumorigenesis and the treatment of NSCLC. Based on the verified effectiveness of the targeted drugs predicted by this pipeline, we suggest that our drug-finding pipeline is effective for repositioning drugs.

  3. Proposing Essential Medicines to Treat Cancer: Methodologies, Processes, and Outcomes.

    Science.gov (United States)

    Shulman, Lawrence N; Wagner, Claire M; Barr, Ronald; Lopes, Gilberto; Longo, Giuseppe; Robertson, Jane; Forte, Gilles; Torode, Julie; Magrini, Nicola

    2016-01-01

    A great proportion of the world's cancer burden resides in low- and middle-income countries where cancer care infrastructure is often weak or absent. Although treatment of cancer is multidisciplinary, involving surgery, radiation, systemic therapies, pathology, radiology, and other specialties, selection of medicines that have impact and are affordable has been particularly challenging in resource-constrained settings. In 2014, at the invitation of the WHO, the Union for International Cancer Control convened experts to develop an approach to propose essential cancer medicines to be included in the WHO Model Essential Medicines Lists (EML) for Adults and for Children, as well as a resulting new list of cancer medicines. Experts identified 29 cancer types with potential for maximal treatment impact, on the basis of incidence and benefit of systemic therapies. More than 90 oncology experts from all continents drafted and reviewed disease-based documents outlining epidemiology, diagnostic needs, treatment options, and benefits and toxicities. Briefing documents were created for each disease, along with associated standard treatment regimens, resulting in a list of 52 cancer medicines. A comprehensive application was submitted as a revision to the existing cancer medicines on the WHO Model Lists. In May 2015, the WHO announced the addition of 16 medicines to the Adult EML and nine medicines to the Children's EML. The list of medications proposed, and the ability to link each recommended medicine to specific diseases, should allow public officials to apply resources most effectively in developing and supporting nascent or growing cancer treatment programs. © 2015 by American Society of Clinical Oncology.

  4. Analysis of cervical cancer cells treated with radiotherapy or arterial infusion chemotherapy

    International Nuclear Information System (INIS)

    Izutu, Toshihiko; Nishiya, Iwao

    1995-01-01

    The present study was designed to analyze cervical cancer cells treated with radiotherapy or intraarterial infusion of CDDP using image analysis. Total nuclear extinction (TE), 5 N-exceeding rate (5 NER) and nuclear area (NA) gradually increased following irradiation, in cervical cancer cases. TE and 5 NER increased markedly following radiotherapy in good response cases. TE, 5 NER and NA were not-changed following irradiation in poor response cases. 5 NER, in good prognostic cases was higher than in poor prognostic cases, significantly among cervical cancer cases treated with radiotherapy. 5 NER and NA increased dramatically in good response cases treated with intraarterial infusion of CDDP. (author)

  5. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

    International Nuclear Information System (INIS)

    Roato, Ilaria; Mussa, Antonio; Ferracini, Riccardo; Caldo, Davide; Godio, Laura; D'Amico, Lucia; Giannoni, Paolo; Morello, Emanuela; Quarto, Rodolfo; Molfetta, Luigi; Buracco, Paolo

    2010-01-01

    Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process

  6. Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies

    NARCIS (Netherlands)

    Stegeman, H.; Span, P.N.; Peeters, W.J.M.; Verheijen, M.M.; Grenman, R.; Meijer, T.W.H.; Kaanders, J.H.A.M.; Bussink, J.

    2016-01-01

    BACKGROUND: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). RESULTS/METHODOLOGY: pAKT was induced by

  7. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3...

  8. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III ß-tubulin (TUBB3...

  9. Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC

    DEFF Research Database (Denmark)

    Chaib, Imane; Karachaliou, Niki; Pilotto, Sara

    2017-01-01

    Background: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) ...

  10. Pharmaceutically treated anxiety but not depression prior to cancer diagnosis predicts the onset of cardiovascular disease among breast cancer survivors

    NARCIS (Netherlands)

    Schoormans, Dounya; Van De Poll-franse, Lonneke; Vissers, Pauline; Van Herk-sukel, Myrthe P. P.; Pedersen, Susanne S.; Rottmann, Nina; Horsbøl, Trine; Dalton, Susanne; Denollet, Johan

    2017-01-01

    PURPOSE: To examine the associations between pharmaceutically treated anxiety and depression present in the year prior to breast cancer diagnosis and the risk of incident cardiovascular disease (CVD), while controlling for traditional cardiovascular risk factors and clinical characteristics in a

  11. Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

    Directory of Open Access Journals (Sweden)

    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.

  12. Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL.

    Science.gov (United States)

    Iaboni, Margherita; Russo, Valentina; Fontanella, Raffaela; Roscigno, Giuseppina; Fiore, Danilo; Donnarumma, Elvira; Esposito, Carla Lucia; Quintavalle, Cristina; Giangrande, Paloma H; de Franciscis, Vittorio; Condorelli, Gerolama

    2016-03-08

    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.

  13. The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Fei Zhou

    Full Text Available BACKGROUND AND OBJECTIVE: Overexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Two hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP methods. RESULTS: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (-1195G/A polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26-4.84 and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28-6.20. No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39-0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39-0.94, respectively while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14-2.56 and P value = 0.025; OR = 1.65; 95%CI  = 1.06-2.57, respectively. CONCLUSION: This investigation for the first time

  14. Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Wang, Tai-Jing; Chang, Po-Yuan; Syu, Jhan-Jhang; Chen, Jyh-Cheng; Chen, Chien-Yu; Jian, Yun-Ting; Jian, Yi-Jun; Zheng, Hao-Yu; Chen, Wen-Ching; Lin, Yun-Wei

    2015-10-01

    Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Preventing Fatigue in Patients With Breast Cancer Treated with Chemotherapy

    National Research Council Canada - National Science Library

    Marrow, Gary

    2001-01-01

    ... or alleviate the development of treatment-induced fatigue. We conducted a randomized, double-blind, placebo-controlled clinical trial with 124 breast cancer patients who were studied for up to four successive chemotherapy treatments...

  16. Cannabinoid Receptors: A Novel Target for Treating Prostate Cancer

    National Research Council Canada - National Science Library

    Mukhtar, Hasan; Afaq, Farrukh; Sarfaraz, Sami

    2006-01-01

    .... Based on these data we suggested that WlN-55,212-2 or other non-habit forming cannabinoid receptor agonists could be developed as novel therapeutic agents for the treatment of prostate cancer (Sarfaraz et al., 2005...

  17. Immunotherapy for Non-small-cell Lung Cancer: Current Status and Future Obstacles.

    Science.gov (United States)

    Cho, Ju Hwan

    2017-12-01

    Lung cancer is one of the leading causes of death worldwide. There are 2 major subtypes of lung cancer, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Studies show that NSCLC is the more prevalent type of lung cancer that accounts for approximately 80%-85% of cases. Although, various treatment methods, such as chemotherapy, surgery, and radiation therapy have been used to treat lung cancer patients, there is an emergent need to develop more effective approaches to deal with advanced stages of tumors. Recently, immunotherapy has emerged as a new approach to combat with such tumors. The development and success of programmed cell death 1 (PD-1)/program death-ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockades in treating metastatic cancers opens a new pavement for the future research. The current mini review discusses the significance of immune checkpoint inhibitors in promoting the death of tumor cells. Additionally, this review also addresses the importance of tumor-specific antigens (neoantigens) in the development of cancer vaccines and major challenges associated with this therapy. Immunotherapy can be a promising approach to treat NSCLC because it stimulates host's own immune system to recognize cancer cells. Therefore, future research should focus on the development of new methodologies to identify novel checkpoint inhibitors and potential neoantigens.

  18. Chronic fatigue in cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Rucinska, M.; Wojtukiewicz, M.Z.; Tokajuk, P.

    2004-01-01

    Fatigue is one of the most prevalent and profound symptoms related to both malignancy and anti-neoplastic treatment. It is being reported in 60% to 80% of cancer patients. We review the correlation between the cancer-related fatigue syndrome and radiotherapy. In patients undergoing radiotherapy, fatigue is often cumulative and may reach its peak during the last weeks of treatment. The presence of fatigue prior to therapy initiation is the most important predictive factor of the occurrence of radiotherapy-related cancer fatigue syndrome. Occasionally, fatigue persists for a prolonged period of months and even years beyond radiotherapy. Anemia may be one of major causative factors responsible for the development of the cancer-related fatigue syndrome. Fatigue has an enormous physical, mental, emotional, and economic impact on cancer patients, their families and care-providers. The treatment of radiation-related fatigue remains unknown. The initial approach should cover efforts aimed at the correction of potential etiologies, especially anemia. Education concerning fatigue greatly benefits some patients. It seems that exercise may be beneficial in relieving fatigue, bearing in mind that the exercise program for cancer patients should be initiated gradually and significantly individualized. (author)

  19. Characteristics of Mycobacterium avium complex (MAC pulmonary disease in previously treated lung cancer patients

    Directory of Open Access Journals (Sweden)

    Erin Meier

    2017-01-01

    Conclusion: MAC pulmonary disease in previously treated lung cancer can occur without apparent risk factors for this NTM infection. Symptomatic improvement with MAC antimicrobial therapy appears to be lower than expected but comorbidities might influence outcomes in this patient population.

  20. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju

    2017-01-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refra...

  1. Treating the incurables: Cancer asylums in 18th and 19th century.

    Science.gov (United States)

    Karamanou, Marianna; Psaltopoulou, Theodora; Markatos, Kostas; Karaoglanis, Georgios; Androutsos, George

    2017-01-01

    For centuries several hypotheses were formulated on cancer's pathogenesis such as contagiousness, melancholy, heredity and sexuality. In the 18th and 19th century, despite the advent of medical thought and practice, cancer was considered an incurable and contagious disease. Hospitals were refusing to treat cancer patients while the social stigma which followed the disease made primordial the need for the establishment of special institutions. In our article we will present the cancer asylums which counterbalanced the prejudices of the time and contributed to the establishment of modern cancer hospitals.

  2. Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

    International Nuclear Information System (INIS)

    Bernchou, Uffe; Schytte, Tine; Bertelsen, Anders; Bentzen, Søren M.; Hansen, Olfred; Brink, Carsten

    2013-01-01

    Purpose: This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC). Methods: A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component. Results: The CT density of healthy lung tissue was observed to increase significantly (p 12 months. Conclusions: The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil

    DEFF Research Database (Denmark)

    Ording, Anne Gulbech; Cronin Fenton, Deirdre; Christensen, Mariann

    2013-01-01

    Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil......Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil...

  5. Robotic Radiosurgery. Treating prostata cancer and related genitourinary applications

    Energy Technology Data Exchange (ETDEWEB)

    Ponsky, Lee E. (ed.) [Case Western Reserve University School of Medicine, Cleveland, OH (United States). University Hospitals Case Medical Center

    2012-07-01

    Prostate cancer is the most common cancer among North American and European men, but its treatment continues to be problematic owing to serious side-effects, including erectile dysfunction, urinary incontinence, and potential lower GI complications. Robotic radiosurgery offers a novel, rapid, non-invasive outpatient treatment option for prostate cancer that combines robotics, advanced image-guided motion detection, and automated real-time corrective spatial positioning with submillimeter precision. This book examines all aspects of the treatment of prostate cancer with robotic radiosurgery. After introductory sections on radiosurgery as a multidisciplinary practice and specific issues relating to prostate cancer, the important challenge posed by prostate motion when administering radiation therapy is examined in depth, with detailed discussion as to how image-guided robotic radiosurgery overcomes this problem by continously identifying the precise location of the prostate throughout the course of treatment. A further major section is devoted to a discussion of techniques and potential radiobiological and clinical advantages of hypofractionated radiation delivery by means of robotic radiosurgery systems. The book closes by discussing other emerging genitourinary applications of robotic radiosurgery. All of the authors are experts in their field who present a persuasive case for this fascinating technique. (orig.)

  6. Offspring of patients treated for cancer in childhood

    International Nuclear Information System (INIS)

    Li, F.P.; Fine, W.; Jaffe, N.; Holmes, G.E.; Holmes, F.F.

    1979-01-01

    Genetic effects of cancer in childhood were examined among offspring of patients enrolled in the tumor registries of the Sidney Farber Cancer Institute and the Kansas University Medical Center. For 146 patients, 84 women and 62 men, 293 pregnancies were reported after cessation of treatment of diverse neoplasms. The outcomes of 286 completed pregnancies were as follows: 242 live births (1 set of twins), 1 stillbirth, 25 spontaneous abortions, and 19 therapeutic abortions. Seven live-born infants died during the first 2 years of life, a frequency in accord with expectation. Two offspring have developed cancer. One girl and her father had bilateral hereditary retinoblastoma. A second girl developed acute myelocytic leukemia; her mother had received radiotherapy during childhood for a brain tumor. Compared with their cousins and with published figures for the general population, the study progeny had no excess of congenital anomalles or other diseases. Chromosome and immunoglobulin studies of a few offspring did not reveal damage from preconception exposure to cancer chemotherapy and radiotherapy. Findings indicated that large collaborative studies are needed to monitor the offspring of childhood cancer survivors for inherited traits associated with the parental tumors and for mutagenic effects of therapy, particularly intense multimodality treatments

  7. Robotic Radiosurgery. Treating prostata cancer and related genitourinary applications

    International Nuclear Information System (INIS)

    Ponsky, Lee E.

    2012-01-01

    Prostate cancer is the most common cancer among North American and European men, but its treatment continues to be problematic owing to serious side-effects, including erectile dysfunction, urinary incontinence, and potential lower GI complications. Robotic radiosurgery offers a novel, rapid, non-invasive outpatient treatment option for prostate cancer that combines robotics, advanced image-guided motion detection, and automated real-time corrective spatial positioning with submillimeter precision. This book examines all aspects of the treatment of prostate cancer with robotic radiosurgery. After introductory sections on radiosurgery as a multidisciplinary practice and specific issues relating to prostate cancer, the important challenge posed by prostate motion when administering radiation therapy is examined in depth, with detailed discussion as to how image-guided robotic radiosurgery overcomes this problem by continously identifying the precise location of the prostate throughout the course of treatment. A further major section is devoted to a discussion of techniques and potential radiobiological and clinical advantages of hypofractionated radiation delivery by means of robotic radiosurgery systems. The book closes by discussing other emerging genitourinary applications of robotic radiosurgery. All of the authors are experts in their field who present a persuasive case for this fascinating technique. (orig.)

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

    Science.gov (United States)

    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.

  9. Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

    2018-01-01

    BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherap...

  10. Cardiovascular Toxicity of Common Chemotherapy Drugs Used to Treat Breast Cancer: An Overview

    Directory of Open Access Journals (Sweden)

    Charles A. Bomzer

    2014-08-01

    Full Text Available Treatment of breast cancer often exposes patients to many different drugs. Some of these drugs have toxic effects involving the cardiovascular system. This review provides an overview of the drugs most commonly used to treat breast cancer and their potential adverse impact on the cardiovascular system.

  11. Cardiovascular Toxicity of Common Chemotherapy Drugs Used to Treat Breast Cancer: An Overview

    OpenAIRE

    Charles A. Bomzer

    2014-01-01

    Treatment of breast cancer often exposes patients to many different drugs. Some of these drugs have toxic effects involving the cardiovascular system. This review provides an overview of the drugs most commonly used to treat breast cancer and their potential adverse impact on the cardiovascular system.

  12. Triphala, Ayurvedic formulation for treating and preventing cancer: a review.

    Science.gov (United States)

    Baliga, Manjeshwar Shrinath

    2010-12-01

    Triphala (Sanskrit tri = three and phala = fruits), composed of the three medicinal fruits Phyllanthus emblica L. or Emblica officinalis Gaertn., Terminalia chebula Retz., and Terminalia belerica Retz. is an important herbal preparation in the traditional Indian system of medicine, Ayurveda. Triphala is an antioxidant-rich herbal formulation and possesses diverse beneficial properties. It is a widely prescribed Ayurvedic drug and is used as a colon cleanser, digestive, diuretic, and laxative. Cancer is a major cause of death, and globally studies are being conducted to prevent cancer or to develop effective nontoxic therapeutic agents. Experimental studies in the past decade have shown that Triphala is useful in the prevention of cancer and that it also possesses antineoplastic, radioprotective and chemoprotective effects. This review for the first time summarizes these results, with emphasis on published observations. Furthermore, the possible mechanisms responsible for the beneficial effects and lacunas in the existing knowledge that need to be bridged are also discussed.

  13. Maximum standardized uptake value from staging FDG-PET/CT does not predict treatment outcome for early-stage non-small-cell lung cancer treated with stereotactic body radiotherapy.

    Science.gov (United States)

    Burdick, Michael J; Stephans, Kevin L; Reddy, Chandana A; Djemil, Toufik; Srinivas, Shyam M; Videtic, Gregory M M

    2010-11-15

    To perform a retrospective review to determine whether maximum standardized uptake values (SUV(max)) from staging 2-deoxy-2- [(18)F] fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) studies are associated with outcomes for early-stage non-small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-two medically inoperable patients were treated between October 17, 2003 and August 17, 2007 with SBRT for T1-2N0M0 NSCLC. SBRT was administered as 60 Gy in 3 fractions, 50 Gy in 5 fractions, or 50 Gy in 10 fractions using abdominal compression and image-guided SBRT. Cox proportional hazards regression was performed to determine whether PET SUV(max) and other variables influenced outcomes: mediastinal failure (MF), distant metastases (DM), and overall survival (OS). Biopsy was feasible in 49 patients (68.1%). Forty-nine patients had T1N0 disease, and 23 had T2N0 disease. Median SUV(max) was 6.55 (range, 1.5-21). Median follow-up was 16.9 months (range, 0.1-37.9 months). There were 3 local failures, 8 MF, 19 DM, and 30 deaths. Two-year local control, MF, DM, and OS rates were 94.0%, 10.4%, 30.1%, and 61.3%, respectively. In univariate analysis, PET/CT SUV(max), defined either as a continuous or dichotomous variable, did not predict for MF, DM, or OS. On multivariable analysis, the only predictors for overall survival were T1 stage (hazard ratio = 0.331 [95% confidence interval, 0.156-0.701], p = 0.0039) and smoking pack-year history (hazard ratio = 1.015 [95% confidence interval, 1.004-1.026], p = 0.0084). Pretreatment PET SUV(max) did not predict for MF, DM, or OS in patients treated with SBRT for early-stage NSCLC. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. PKIB promotes cell proliferation and the invasion-metastasis cascade through the PI3K/Akt pathway in NSCLC cells.

    Science.gov (United States)

    Dou, Penghui; Zhang, Danfeng; Cheng, Zhuoxin; Zhou, Gang; Zhang, Linyou

    2016-11-01

    Lung cancer is one of the most common malignancies in the world, and non-small cell lung cancer (NSCLC) is a major subtype of lung cancer. Overgrowth of tumor cells usually results from the intensive proliferation of cancer cells, but the mechanisms by which the proliferation of cancer cells are promoted are currently unclear. Thus, it is necessary to determine the vital factors involved in regulating the growth of NSCLC. The MTT assay, BrdU assay, western blots, and migration and invasion assays were used in our study. Here, we found that PKIB (cAMP-dependent protein kinase inhibitor-β), a novel molecular target, was up-regulated in NSCLC tissues compared with the normal tissues adjacent to the tumors. Moreover, overexpression of PKIB promoted cell proliferation and potentiated the invasion and migration in A549 cells, whereas knocking down PKIB gene expression inhibited the proliferation and attenuated the invasive behavior and metastasis in H1299 cells. However, all of these effects of PKIB on cell proliferation and metastasis were reduced by inhibiting the PI3K/Akt pathway. Our results indicate that PKIB promotes cell proliferation and tumorigenesis by activating the PI3K/Akt pathway in NSCLC, implying that this is an important underlying mechanism that affects the progression of NSCLC. © 2016 by the Society for Experimental Biology and Medicine.

  15. Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC

    DEFF Research Database (Denmark)

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

    2010-01-01

    report the heart toxicities in locally-regionally advanced NSCLC (LA-NSCLC) patients (pts) treated with RT in our centre.   Methods and material: From 01.01.1995-30.11.2007, 287 pts with LA-NSCLC (stage IIB-IIIB) were treated with RT at our centre with planned dose 60-66 Gy. All RT was applied as 3D RT...... year was 64%, 35% and 14%, respectively. In a Cox regression analyses of time to CE, age > 65 year, + induction chemotherapy, smoking, high mean dose to left + right ventricles or whole heart was not a statistically significant factor, whereas low FEV-1, large GTV, low Hb, poor PS, high V20 to lunge......, and gender did.   Discussion: We did not find a correlation between high mean dose to left + right ventricles or whole heart and having a CE. Having a CE was not related to worsen survival.   Factors in model Relative Hazard Ratio (95% CI) p-value   FEV-1 (150 ml) 2.02 (1...

  16. Sexual dysfunction in premenopausal women treated for breast cancer

    African Journals Online (AJOL)

    A diagnosis of breast cancer may affect the woman's self-esteem, sexuality and intimate relationships. Surgical alteration or loss of the breast, a symbol of femininity and sexuality, may negatively impact her body-image. Chemotherapy may cause ovarian damage leading to premature menopause. The psychological effects ...

  17. Cancer risk in patients with spondyloarthritis treated with TNF inhibitors

    DEFF Research Database (Denmark)

    Hellgren, Karin; Dreyer, Lene; Arkema, Elizabeth V.

    2017-01-01

    Background Safety data on cancer risks following tumour necrosis factor a inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks...

  18. Evaluation of Three Small Molecular Drugs for Targeted Therapy to Treat Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jun Ni

    2016-01-01

    Conclusions: Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC.

  19. Redox-Responsive Manganese Dioxide Nanoparticles for Enhanced MR Imaging and Radiotherapy of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mi Hyeon Cho

    2017-12-01

    Full Text Available In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid and analyzed their effect on non-small cell lung cancer (NSCLC cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH-responsive dissolution and subsequent enhancement in magnetic resonance (MR imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.

  20. Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab

    DEFF Research Database (Denmark)

    Rohrberg, Kristoffer Staal; Pappot, Helle; Lassen, Ulrik

    2011-01-01

    Malignancies in the upper gastrointestinal (UGI) tract are amongst the most aggressive cancers and only few treatment options exist. We have recently analysed data from a phase II trial where patients with UGI cancers were treated with erlotinib and bevacizumab. The combination therapy could......: 1.0-1.9). EGFR expression and KRAS mutation status were not correlated to response or survival. We conclude that VEGF-A and VEGFR-2 could potentially be predictive markers in patients with UGI cancers treated with erlotinib and bevacizumab....

  1. Survival after early-stage breast cancer of women previously treated for depression

    DEFF Research Database (Denmark)

    Suppli, Nis Frederik Palm; Johansen, Christoffer; Kessing, Lars Vedel

    2017-01-01

    Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material...... and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous...... treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before...

  2. XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC.

    Science.gov (United States)

    Qin, Sida; Yang, Chengcheng; Zhang, Boxiang; Li, Xiang; Sun, Xin; Li, Gang; Zhang, Jing; Xiao, Guodong; Gao, Xiao; Huang, Guanghong; Wang, Peili; Ren, Hong

    2016-10-01

    X-linked inhibitor of apoptosis protein (XIAP) and second mitochondrial-derived activator of caspase (Smac) are two important prognostic biomarkers for cancer. They are negatively correlated in many types of cancer. However, their relationship is still unknown in lung cancer. In the present study, we found that there was a negative correlation between Smac and XIAP at the level of protein but not mRNA in NSCLC patients. However, XIAP overexpression had no effect on degrading endogenous Smac in lung cancer cell lines. Therefore, we constructed plasmids with full length of Smac (fSmac) and mature Smac (mSmac) which located in cytoplasm instead of original mitochondrial location, and was confirmed by immunofluorescence. Subsequently, we found that mSmac rather than fSmac was degraded by XIAP and inhibited cell viability. CHX chase assay and ubiquitin assay were performed to illustrate XIAP degraded mSmac through ubiquitin pathway. Overexpression of XIAP partially reverted apoptotic induction and cell viability inhibition by mSmac, which was due to inhibiting caspase-3 activation. In nude mouse xenograft experiments, mSmac inhibited Ki-67 expression and slowed down lung cancer growth, while XIAP partially reversed the effect of mSmac by degrading it. In conclusion, XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC.

  3. Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum

    International Nuclear Information System (INIS)

    Melichar, Bohuslav; Hyšpler, Radomír; Dragounová, Emanuela; Dvořák, Josef; Kalábová, Hana; Tichá, Alena

    2007-01-01

    Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum. Intestinal permeability was assessed in 36 breast and ovarian cancer patients treated with paclitaxel/platinum combination by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose and mannitol after oral challenge. The significance of differences during the therapy compared to pre-treatment values was studied by Wilcoxon paired test. The differences between groups of patient were studied by Mann-Whitney U test. Fisher exact test was used to compare the frequency in different subgroups. After administration of the first dose, a significant (p < 0.05) decrease in xylose absorption and increased lactulose/mannitol, sucrose/mannitol, lactulose/xylose and sucrose/xylose ratios were observed, but these parameters returned subsequently to pre-treatment levels. Patients who experienced serious (grade 3 or 4) toxicity had at baseline significantly lower percentages of xylose, mannitol and sucrose, and higher lactulose/mannitol ratio. Nine of 13 (69%) patients with baseline lactulose/mannitol ratio 0.070 or above experienced serious toxicity compared to 4 out of 23 patients (17%) with the ratio below 0.070 (p = 0.002). Post-treatment lactulose, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were significantly increased in patients with serious toxicity. A transient significant increase in lactulose/monosaccharide and sucrose/monosaccharide ratios was observed in ovarian and breast cancer patients treated with paclitaxel

  4. Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.

    Science.gov (United States)

    Sadhukha, Tanmoy; Wiedmann, Timothy S; Panyam, Jayanth

    2013-07-01

    Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Long-lasting Disease Stabilization in the Absence of Toxicity in Metastatic Lung Cancer Patients Vaccinated with an Epitope Derived from Indoleamine 2,3 Dioxygenase

    DEFF Research Database (Denmark)

    Iversen, Trine Zeeberg; Engell-Noerregaard, Lotte; Ellebaek, Eva

    2014-01-01

    PURPOSE: To investigate targeting of indoleamine 2,3 dioxygenase (IDO) enzyme using a synthetic peptide vaccine administered to patients with metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: In a clinical phase I study, we treated 15 HLA-A2-positive patients with stage III-IV N...

  6. [Effect on late-stage mammary cancer treated by endocrinotherapy or chemotherapy combined with pingxiao capsule].

    Science.gov (United States)

    Zhang, Qing-yuan; Zhao, Wen-hui; Lai, Yu-juan

    2005-12-01

    To explore the action of pingxiao capsules (PXC) and its significance in the treatment of late stage mammary cancer (LSMC). One hundred and forty-two LSMC patients were randomized into four groups: the two single treated groups treated by endocrinotherapy (ET) alone (n = 27) and by chemotherapy alone (n=44) respectively, and the two PXC combined treated groups treated with PXC plus endocrinotherapy (n=27) or chemotherapy (n=44). The remission rate and progression time (TTP) of disease, the survival time and quality of life (QOL) of patients, and the adverse reaction were compared between the single treated groups and the combined treated groups. The median progression time was obviously prolonged, and QOL improved in the combined treated groups than those in the single treated groups (P endocrino-therapy in clinical application for treatment of LSMC patients.

  7. Prevalence and predictors of cognitive dysfunction in opioid-treated patients with cancer: a multinational study

    DEFF Research Database (Denmark)

    Kurita, Geana P; Sjøgren, Per; Ekholm, Ola

    2011-01-01

    PURPOSE To identify prevalence and associated factors of cognitive dysfunction in opioid-treated patients with cancer. PATIENTS AND METHODS EPOS (European Pharmacogenetic Opioid Study) is a prospective cross-sectional multicenter study in which adult patients with cancer who received treatment...... with opioids for moderate or severe pain for at least 3 days were included. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). MMSE scores were categorized into definite cognitive dysfunction (scores ...-treated patients with cancer had possible or definite cognitive dysfunction. Lung cancer, daily opioid doses of 400 mg or more (oral morphine equivalents), older age, low KPS, shorter time since cancer diagnosis, and absence of BTP were predictors for cognitive dysfunction....

  8. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Jabbour, Salma K.; Kim, Sinae; Haider, Syed A.; Xu, Xiaoting; Wu, Alson; Surakanti, Sujani; Aisner, Joseph; Langenfeld, John; Yue, Ning J.; Haffty, Bruce G.; Zou, Wei

    2015-01-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

  9. Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warner, Andrew [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada); Dahele, Max [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Hu, Bo; Palma, David A. [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology, MAASTRO Clinic, Maastricht (Netherlands); Tsujino, Kayoko [Department of Radiation Oncology, Hyogo Cancer Center, Akashi (Japan); Moreno-Jimenez, Marta [Department of Oncology, Clínica Universidad, Universidad de Navarra, Pamplona (Spain); Kim, Tae Hyun [Department of Radiation Oncology, National Cancer Center, Goyang-si, Gyeonggi (Korea, Republic of); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina (United States); Rengan, Ramesh [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); De Petris, Luigi [Department of Oncology and Pathology, Karolinska University Hospital, Stockholm (Sweden); Ramella, Sara [Department of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); De Dios, Núria Rodriguez [Department of Radiation Oncology, Hospital de la Esperanza, Parc de Salut Mar, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Rodrigues, George, E-mail: George.Rodrigues@lhsc.on.ca [Department of Radiation Oncology, London Health Sciences Centre, London, Ontario (Canada)

    2016-03-01

    Purpose: Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. Methods and Materials: Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA. Results: Median follow-up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] ≥100 cm{sup 3}: 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV{sub 1}], defined as the ratio of FEV{sub 1} to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm{sup 3} or GTV ≥100 cm{sup 3} and FEV{sub 1} ≥80%) and high-risk (GTV ≥100 cm{sup 3} and FEV{sub 1} <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV{sub 1}, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R{sup 2} = 0

  10. Vorinostat and metformin sensitize EGFR-TKI resistant NSCLC cells via BIM-dependent apoptosis induction.

    Science.gov (United States)

    Chen, Hengyi; Wang, Yubo; Lin, Caiyu; Lu, Conghua; Han, Rui; Jiao, Lin; Li, Li; He, Yong

    2017-11-07

    There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in various types of tumor cells, however, this effect is attenuated by the high expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance. This study aimed to investigate the cooperative effect and evaluate possible molecular mechanisms. The results showed that vorinostat combined with gefitinib augmented BIM expression and increased the sensitivity of EGFR-TKI resistant NSCLC cells to gefitinib, adding metformin simultaneously could obviously inhibit the expression of anti-apoptotic proteins, and further increased expression levels of BIM and BAX, and as a result, further improved the sensitivity of gefitinib both on the NSCLC cells with intrinsic and acquired resistance to EGFR-TKI. In addition, autophagy induced by gefitinib and vorinostat could be significantly suppressed by metformin, which might also contribute to enhance apoptosis and improve sensitivity of gefitinib. These results suggested that the combination of vorinostat and metformin might represent a novel strategy to overcome EGFR-TKI resistance associated with BIM-dependent apoptosis in larger heterogeneous populations.

  11. Malignant Cardiac Tamponade from Non-Small Cell Lung Cancer: Case Series from the Era of Molecular Targeted Therapy

    Directory of Open Access Journals (Sweden)

    Bob T. Li

    2014-12-01

    Full Text Available Cardiac tamponade complicating malignant pericardial effusion from non-small cell lung cancer (NSCLC is generally associated with extremely poor prognosis. With improved systemic chemotherapy and molecular targeted therapy for NSCLC in recent years, the prognosis of such patients and the value of invasive cardiothoracic surgery in this setting have not been adequately examined. We report outcomes from a contemporary case series of eight patients who presented with malignant cardiac tamponade due to NSCLC to an Australian academic medical institution over an 18 months period. Two cases of cardiac tamponade were de novo presentations of NSCLC and six cases were presentations following previous therapy for NSCLC. The median survival was 4.5 months with a range between 9 days to alive beyond 17 months. The two longest survivors are still receiving active therapy at 17 and 15 months after invasive surgical pericardial window respectively. One survivor had a histological subtype of large cell neuroendocrine carcinoma and the other received targeted therapy for epidermal growth factor receptor mutation. These results support the consideration of active surgical palliation to treating this oncological emergency complicating NSCLC, including the use of urgent drainage, surgical creation of pericardial window followed by appropriate systemic therapy in suitably fit patients.

  12. Treatment outcomes in stage IIIA non-small-cell lung cancer in a community cancer center.

    Science.gov (United States)

    Hanson, Shaun; Persad, Kamleish; Qiao, Xian; Guarino, Michael; Petrelli, Nicholas

    2015-08-01

    Treatment outcomes for non-small-cell lung cancer (NSCLC) patients diagnosed at stage IIIA have been analyzed in many studies, which generally involve patients younger and healthier than the average patient with this disease. To analyze demographics and treatment outcomes in patients with stage IIIA NSCLC at a community cancer center. We reviewed charts of 226 patients diagnosed with stage IIIA NSCLC from January 2003 to December 2008 treated at our community cancer center. Results Median overall survival for all patients and sequentially and concurrently treated chemoradiation patients were 18 months, and 18 months, and 20 months, respectively. Median overall survival for women and men was 24 months and 16 months, respectively. Median overall survival for all patients and sequentially and concurrently treated chemoradiation patients were 18 months, and 18 months, and 20 months, respectively. Median overall survival for women and men was 24 months and 16 months, respectively. Study design was retrospective and some medical records were not available. However, this population is likely representative of patients treated in similar settings. In our population, advanced age and male gender were associated with lower median survival. Responses to concurrent and sequential chemoradiation seemed to differ based on age group, which may be useful as a prognostic guideline for similar populations. ©2015 Frontline Medical Communications.

  13. Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells

    OpenAIRE

    Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Kanterewicz, Beatriz; Balius, Trent; Belani, Chandra P.; Hershberger, Pamela A.

    2010-01-01

    We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel le...

  14. Bevacizumab Plus Radiosurgery for Nonsquamous Non-Small Cell Lung Cancer Patients with Brain Metastases: Safe Combination?

    Science.gov (United States)

    Guinde, Julien; Carron, Romain; Tomasini, Pascale; Greillier, Laurent; Régis, Jean; Barlesi, Fabrice

    2017-11-01

    In the context of bronchial cancers, the brain is one of the most frequent sites for metastases. Local treatments of these metastases have evolved and are often combined to obtain greater efficiency, while the main objective remains to reduce the symptoms. Radiosurgery is currently used as a primary option for patients harboring few numbers of small to middle-sized brain metastases. In nonsquamous non-small cell lung cancer (NSCLC), chemotherapy is often associated with bevacizumab. Our goal was to assess the safety of this early combination. Six patients with advanced nonsquamous NSCLC were treated with radiosurgery for the management of their brain metastases (n = 40), followed within bevacizumab. No systemic or cerebral adverse event of grade 3 (intratumoral or parenchymal hemorrhage) or unexpected toxicity secondary to bevacizumab has been indexed. Radiosurgery may be safely combined with bevacizumab quite early on for patients with nonsquamous NSCLC with brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy

    Science.gov (United States)

    Santarpia, Mariacarmela; Daffinà, Maria Grazia; D’Aveni, Alessandro; Marabello, Grazia; Liguori, Alessia; Giovannetti, Elisa; Karachaliou, Niki; Gonzalez Cao, Maria; Rosell, Rafael; Altavilla, Giuseppe

    2017-01-01

    The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib’s efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse. Different mechanisms of acquired resistance have been identified, including secondary ALK mutations, ALK copy number alterations and activation of bypass tracks. Different highly potent and brain-penetrant next-generation ALK inhibitors have been developed and tested in NSCLC patients with ALK rearrangements. Ceritinib, a structurally distinct and selective ALK inhibitor, showed 20 times higher potency than crizotinib in inhibiting ALK and had activity against the most common crizotinib-resistant mutations, including L1196M and G1269A, in preclinical models. In Phase I and II studies, ceritinib demonstrated pronounced activity in both crizotinib-naïve and crizotinib-refractory patients, with responses observed regardless of the presence of ALK resistance mutations. Ceritinib was the first ALK inhibitor to be approved for the treatment of crizotinib-refractory, ALK-rearranged NSCLC, and recent results from a Phase III study have demonstrated superior efficacy compared to standard chemotherapy in the first- and second-line setting. We provide an extensive overview of ceritinib from the design of the compound through preclinical data until efficacy and toxicity results from Phase I–III clinical studies. We review the molecular alterations associated with resistance to ceritinib and highlight the importance of obtaining tumor biopsy at progression to tailor therapy based upon the

  16. Pharmaceutically treated anxiety but not depression prior to cancer diagnosis predicts the onset of cardiovascular disease among breast cancer survivors

    DEFF Research Database (Denmark)

    Schoormans, Dounya; van de Poll-Franse, Lonneke; Vissers, Pauline

    2017-01-01

    PURPOSE: To examine the associations between pharmaceutically treated anxiety and depression present in the year prior to breast cancer diagnosis and the risk of incident cardiovascular disease (CVD), while controlling for traditional cardiovascular risk factors and clinical characteristics......, anxiety, and depression. By multivariable Cox regression analysis, we examined the risk associated with pharmaceutically treated anxiety and depression for developing CVD after cancer diagnosis, adjusting for age, pharmaceutically treated hypertension, hypercholesterolemia, and diabetes mellitus.......05-1.08] after full adjustment. This association was restricted to breast cancer survivors who were 65 years or younger. Depression was not associated with CVD risk [HR = 0.89; 95% CI 0.52-1.53]. Older age [HR = 1.06; 95% CI 1.05-1.08], hypertension [HR = 1.80; 95% CI 1.32-2.46], and hypercholesterolemia [HR = 1...

  17. In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model

    Science.gov (United States)

    Kolokotroni, Eleni; Dionysiou, Dimitra; Veith, Christian; Kim, Yoo-Jin; Franz, Astrid; Grgic, Aleksandar; Bohle, Rainer M.; Stamatakos, Georgios

    2016-01-01

    The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. In silico experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs’ cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the in-vivo cell-killing ability of various chemotherapies. Correlation studies of such estimates with

  18. Exploration of Postoperative Follow-up Strategies for Early Staged NSCLC Patients on the Basis of Follow-up Result of 416 Stage I NSCLC Patients after Lobectomy

    Directory of Open Access Journals (Sweden)

    Liang DAI

    2018-03-01

    Full Text Available Background and objective Currently, there is no consensus on the follow-up strategy (follow-up time interval and content of non-small cell lung cancer (NSCLC in the world, and the relevant clinical evidence is also very limited. In this study, we aimed to summarize the recurrence/metastasis sites and timings of stage I NSCLC patients based on their follow-up data, aiming to provide a basis of follow-up time interval and content for this group of patients. Methods We retrospectively analyzed the 416 stage I NSCLC patients that underwent continuous anatomic lobectomy between Jan. 2000 to Oct. 2013 in our prospective lung cancer database. According to the recurrence/metastasis sites and timings, the long term follow-up time interval and content were explored. Results The 5-yr disease free survival (DFS and overall survival (OS in the whole group were 82.4% and 85.4%, respectively. There were 76 cases (18.3% had recurrence/metastasis during follow-up, among which the most frequent site was pulmonary metastasis (21 cases, 5.0%, followed by brain metastasis (20 cases, 4.8%, bone metastasis (12 cases, 2.9%, and mediastinal lymph node metastasis (12 cases, 2.9%. Among the factors that could influence recurrence/metastasis, patients with pT2a suffered from a higher recurrence/metastasis rate compared to patients with pT1 (P=0.006, with 5-yr DFS being 73.8% and 87.3%, respectively (P=0.002, and the 5-yr OS being 77.7% and 90.3%, respectively (P=0.011. Conclusion The commonest recurrence/metastasis sites of stage I NSCLC after anatomic lobectomy are lung, brain and mediastinal lymph nodes, the risk of recurrence/metastasis within 2 years were equal to that between 3 years and 5 years. The follow-up frequencies and content within 2 years could be adjusted according to T stages.

  19. [Exploration of Postoperative Follow-up Strategies for Early Staged NSCLC Patients on the Basis of Follow-up Result of 416 Stage I NSCLC Patients after Lobectomy].

    Science.gov (United States)

    Dai, Liang; Yan, Wanpu; Kang, Xiaozheng; Fu, Hao; Yang, Yongbo; Zhou, Haitao; Liang, Zhen; Xiong, Hongchao; Lin, Yao; Chen, Keneng

    2018-03-20

    Currently, there is no consensus on the follow-up strategy (follow-up time interval and content) of non-small cell lung cancer (NSCLC) in the world, and the relevant clinical evidence is also very limited. In this study, we aimed to summarize the recurrence/metastasis sites and timings of stage I NSCLC patients based on their follow-up data, aiming to provide a basis of follow-up time interval and content for this group of patients. We retrospectively analyzed the 416 stage I NSCLC patients that underwent continuous anatomic lobectomy between Jan. 2000 to Oct. 2013 in our prospective lung cancer database. According to the recurrence/metastasis sites and timings, the long term follow-up time interval and content were explored. The 5-yr disease free survival (DFS) and overall survival (OS) in the whole group were 82.4% and 85.4%, respectively. There were 76 cases (18.3%) had recurrence/metastasis during follow-up, among which the most frequent site was pulmonary metastasis (21 cases, 5.0%), followed by brain metastasis (20 cases, 4.8%), bone metastasis (12 cases, 2.9%), and mediastinal lymph node metastasis (12 cases, 2.9%). Among the factors that could influence recurrence/metastasis, patients with pT2a suffered from a higher recurrence/metastasis rate compared to patients with pT1 (P=0.006), with 5-yr DFS being 73.8% and 87.3%, respectively (P=0.002), and the 5-yr OS being 77.7% and 90.3%, respectively (P=0.011). The commonest recurrence/metastasis sites of stage I NSCLC after anatomic lobectomy are lung, brain and mediastinal lymph nodes, the risk of recurrence/metastasis within 2 years were equal to that between 3 years and 5 years. The follow-up frequencies and content within 2 years could be adjusted according to T stages.

  20. Outcomes of Sinonasal Cancer Treated With Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dagan, Roi, E-mail: rdagan@floridaproton.org [Department of Radiation Oncology, University of Florida, Gainesville, Florida (United States); Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States); Bryant, Curtis; Li, Zuofeng; Yeung, Daniel [Department of Radiation Oncology, University of Florida, Gainesville, Florida (United States); Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States); Justice, Jeb; Dzieglewiski, Peter; Werning, John [Department of Otolaryngology, University of Florida, Gainesville, Florida (United States); Fernandes, Rui; Pirgousis, Phil [Department of Oral and Maxillofacial Surgery, University of Florida, Jacksonville, Florida (United States); Lanza, Donald C. [Sinus & Nasal Institute of Florida, St. Petersburg, Florida (United States); Morris, Christopher G.; Mendenhall, William M. [Department of Radiation Oncology, University of Florida, Gainesville, Florida (United States); Department of Radiation Oncology, University of Florida, Jacksonville, Florida (United States)

    2016-05-01

    Purpose: To report disease outcomes after proton therapy (PT) for sinonasal cancer. Methods and Materials: Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. Results: The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with

  1. Does concurrent chemotherapy improve local control and survival over radiotherapy alone or induction chemotherapy in stage III non-small cell lung cancer (NSCLC)? Results at 3 years in 140 patients (pts) with a minimum follow-up of 24 months

    International Nuclear Information System (INIS)

    Reboul, F.; Brewer, Y.; Vincent, P.; Chauvet, B.; Faure, C. Felix; Taulelle, M.

    1996-01-01

    Purpose/Objective: Recent Phase III trials have demonstrated a significant but limited survival benefit of induction chemotherapy over standard radiotherapy alone in Stage III NSCLC. Induction chemotherapy does not significantly improve local control and substantially prolongs overall treatment time in this poor prognosis population. Concurrent chemotherapy has the potential for improving local control through drug-radiation interactions. This study was designed to determine the overall survival after standard fractionation radiotherapy with concurrent cisplatin or cisplatin-etoposide, as well as the feasibility and toxicity of this approach. Material and Methods: From July 1989 to February 1994, 140 favorable pts according to CALGB criteria with histologically proven medically or technically inoperable stage III NSCLC were treated with radiotherapy and concurrent chemotherapy. Median age was 64 years with a majority of males (93%), WHO status 1 (66.4%), and squamous cell histology (72%). Clinical stage was IIIA (65.7%), IIIB (34.3%), N0-1 (20.8%), N2 (57.8%) or N3 (21.4%). Median tumor size was 6 cm. Using once-daily fractionation, pts received thoracic radiotherapy (TRT) up to a median dose of 60 Gy (n=116), or 45 Gy preceding surgery (n=24). No pts received induction chemotherapy before TRT. During TRT, all pts received two cycles of cisplatin (20 mg/sqm/d over 5 days). In addition to cisplatin, the last 67 pts received etoposide (50 mg/sqm/d over 5 days). After TRT, 48 of these pts received two additional cycles of cisplatin-etoposide. Results: With a minimum follow-up of 24 months (median 58 months), overall survival was 34.3% and 24.9% at 2 and 3 years respectively. Age, sex, performance status, histologic type or grade, tumor size, and T stage, had no significant predictive value for survival. Three-year survival according to clinical stage (IIIA : 26%, IIIB : 22.7%) was not statistically different. Univariate analysis identified 3 significant factors for

  2. 18F-Fluorodeoxyglucose Positron Emission Tomography-Based Assessment of Local Failure Patterns in Non-Small-Cell Lung Cancer Treated With Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Sura, Sonal; Greco, Carlo; Gelblum, Daphna; Yorke, Ellen D.; Jackson, Andrew; Rosenzweig, Kenneth E.

    2008-01-01

    Purpose: To assess the pattern of local failure using 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans after radiotherapy (RT) in non-small-cell lung cancer (NSCLC) patients treated with definitive RT whose gross tumor volumes (GTVs) were defined with the aid of pre-RT PET data. Method and Materials: The data from 26 patients treated with involved-field RT who had local failure and a post-RT PET scan were analyzed. The patterns of failure were visually scored and defined as follows: (1) within the GTV/planning target volume (PTV); (2) within the GTV, PTV, and outward; (3) within the PTV and outward; and (4) outside the PTV. Local failure was also evaluated as originating from nodal areas vs. the primary tumor. Results: We analyzed 34 lesions. All 26 patients had recurrence originating from their primary tumor. Of the 34 lesions, 8 (24%) were in nodal areas, 5 of which (63%) were marginal or geographic misses compared with only 1 (4%) of the 26 primary recurrences (p = 0.001). Of the eight primary tumors that had received a dose of <60 Gy, six (75%) had failure within the GTV and two (25%) at the GTV margin. At doses of ≥60 Gy, 6 (33%) of 18 had failure within the GTV and 11 (61%) at the GTV margin, and 1 (6%) was a marginal miss (p < 0.05). Conclusion: At lower doses, the pattern of recurrences was mostly within the GTV, suggesting that the dose might have been a factor for tumor control. At greater doses, the treatment failures were mostly at the margin of the GTV. This suggests that visual incorporation of PET data for GTV delineation might be inadequate, and more sophisticated approaches of PET registration should be evaluated

  3. Dysphagia in head and neck cancer patients treated with chemoradiotherapy.

    Science.gov (United States)

    Platteaux, Nele; Dirix, Piet; Dejaeger, Eddy; Nuyts, Sandra

    2010-06-01

    Dysphagia is a very common complaint of head and neck cancer patients and can exist before, during, and after chemoradiotherapy. It leads to nutritional deficiency, weight loss, and prolonged unnatural feeding and also has a major potential risk for aspiration. This has a significant negative impact on the patient's entire quality of life. Because treatment of dysphagia in this setting is rarely effective, prevention is paramount. Several strategies have been developed to reduce dysphagia. These include swallowing exercises, treatment modification techniques such as intensity-modulated radiotherapy, selective delineation of elective nodes, reducing xerostomia by parotid-sparing radiotherapy, and adding of radioprotectors. However, more research is needed to further decrease the incidence of dysphagia and improve quality of life.

  4. Autopsy findings in 40 cases of esophageal cancer treated with radiation therapy

    International Nuclear Information System (INIS)

    Yamakawa, Michitaka; Shiojima, Kazumi; Hasegawa, Masatoshi

    1995-01-01

    We analyzed local control, lymph node metastases and distant metastases for autopsy cases of esophageal cancer treated with radiation therapy alone. Thirty-eight patients had squamous cell carcinoma, one had adenosquamous carcinoma and one had undifferentiated carcinoma. Sixteen patients received a total dose less than 60 Gy and 24 received 60 Gy or more. The 1-year, 3-year, 5-year overall survival rates by Kaplan-Meier method were 45.8%, 16.7%, 8.3%, respectively. Four patients (10%) were free of tumors, and another six (15%) had no primary tumor but metastases. Thirty patients had persistent or recurrent primary tumors. Local tumor control rates were 25% for all patients and 34% for patients who survived more than 3 months and 33% for patients irradiated with 60 Gy or more. Tumor type, tumor length and survival times were significantly related with tumor control rates. Perforations into neighboring organs were observed in eighteen patients (45%); 12 were perforated into respiratory systems, 4 into vascular systems, 1 into the mediastinum and 1 into the pleural cavity. Thirty-two patients (80%) had lymph node metastases. Twenty-seven patients (68%) had distant metastases; 20 in the lung, 19 in the liver, 10 in the stomach, 8 in the pancreas and the adrenal gland, 7 in the pleura, 6 in the bone and the heart and the diaphragm. Concurrent double cancer was observed at autopsy in six patients; 2 early gastric cancers, 2 latent hepatomas, 1 lung cancer, 1 latent thyroid cancer. Three patients had a history of resection of other cancer before radiation therapy to esophageal cancer; 2 had gastric cancer and 1 had submandibular cancer. One patient who had another esophageal cancer apart from the first esophageal cancer received radiation therapy 12 years ago. In conclusion, the local control rate was 33% for autopsy cases of esophageal cancer treated with radiation therapy of 60 Gy or more. (J.P.N.)

  5. Autopsy findings in 40 cases of esophageal cancer treated with radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamakawa, Michitaka; Shiojima, Kazumi; Hasegawa, Masatoshi [Gunma Univ., Maebashi (Japan). School of Medicine] [and others

    1995-09-01

    We analyzed local control, lymph node metastases and distant metastases for autopsy cases of esophageal cancer treated with radiation therapy alone. Thirty-eight patients had squamous cell carcinoma, one had adenosquamous carcinoma and one had undifferentiated carcinoma. Sixteen patients received a total dose less than 60 Gy and 24 received 60 Gy or more. The 1-year, 3-year, 5-year overall survival rates by Kaplan-Meier method were 45.8%, 16.7%, 8.3%, respectively. Four patients (10%) were free of tumors, and another six (15%) had no primary tumor but metastases. Thirty patients had persistent or recurrent primary tumors. Local tumor control rates were 25% for all patients and 34% for patients who survived more than 3 months and 33% for patients irradiated with 60 Gy or more. Tumor type, tumor length and survival times were significantly related with tumor control rates. Perforations into neighboring organs were observed in eighteen patients (45%); 12 were perforated into respiratory systems, 4 into vascular systems, 1 into the mediastinum and 1 into the pleural cavity. Thirty-two patients (80%) had lymph node metastases. Twenty-seven patients (68%) had distant metastases; 20 in the lung, 19 in the liver, 10 in the stomach, 8 in the pancreas and the adrenal gland, 7 in the pleura, 6 in the bone and the heart and the diaphragm. Concurrent double cancer was observed at autopsy in six patients; 2 early gastric cancers, 2 latent hepatomas, 1 lung cancer, 1 latent thyroid cancer. Three patients had a history of resection of other cancer before radiation therapy to esophageal cancer; 2 had gastric cancer and 1 had submandibular cancer. One patient who had another esophageal cancer apart from the first esophageal cancer received radiation therapy 12 years ago. In conclusion, the local control rate was 33% for autopsy cases of esophageal cancer treated with radiation therapy of 60 Gy or more. (J.P.N.).

  6. Report of two cases of pseudoprogression in patients with non-small cell lung cancer treated with nivolumab-including histological analysis of one case after tumor regression.

    Science.gov (United States)

    Tanizaki, Junko; Hayashi, Hidetoshi; Kimura, Masatomo; Tanaka, Kaoru; Takeda, Masayuki; Shimizu, Shigeki; Ito, Akihiko; Nakagawa, Kazuhiko

    2016-12-01

    The recent approval of nivolumab and other immune-checkpoint inhibitors for the treatment of certain solid tumors including non-small cell lung cancer (NSCLC) has transformed cancer therapy. However, it will be important to characterize effects of such agents not seen with classical cytotoxic drugs or other targeted therapeutics. We here report two cases of NSCLC showing so-called pseudoprogression during nivolumab treatment. In both cases, imaging assessment revealed that liver metastatic lesions initially progressed but subsequently shrank during continuous nivolumab administration, with treatment also resulting in a decline in serum levels of carcinoembryonic antigen. Histological evaluation of the liver metastatic lesion of one case after regression revealed fibrotic tissue containing infiltrated lymphocytes positive for CD3, CD4, or CD8 but no viable tumor cells, suggestive of a durable immune reaction even after a pathological complete response. Given the increasing use of immune-checkpoint inhibitors in patients with NSCLC or other solid tumors, further clinical evaluation and pathological assessment are warranted to provide a better understanding of such pseudoprogression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Science.gov (United States)

    Clements, Karen M.; Peltz, Gerson; Faries, Douglas E.; Lang, Kathleen; Nyambose, Joshua; Earle, Craig C.; Sugarman, Katherine P.; Taylor, Douglas C. A.; Thompson, David; Marciniak, Martin D.

    2010-01-01

    Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC. PMID:22482053

  8. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Karen M. Clements

    2010-01-01

    Full Text Available Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC. We examined the impact of histology on survival of patients (N=2,644 with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G and cisplatin/carboplatin plus a taxane (C/C+T identified retrospectively in the SEER cancer registry (1997–2002. Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P=.018. No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction =.257. There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC.

  9. Advanced cancer cases treated with cultivated wild ginseng phamacopuncture.

    Science.gov (United States)

    Lee, Jong-Hoon; Kwon, Ki-Rok; Cho, Chong-Kwan; Han, Sung Soo R; Yoo, Hwa-Seung

    2010-06-01

    After administering cultivated wild ginseng pharmacopuncture (CWGP) to advanced cancer patients, the response and survival rate were evaluated. This prospective observational pilot study of CWGP was conducted at the East-West Cancer Center of Daejeon University, Dunsan Oriental Hospital from August 2007 to June 2008. Seven patients were recruited for this study. One cycle of treatment consisted of intravenous infusion of CWGP (20 mL/day) for 2 weeks with an expected treatment duration of four cycles (60 days, 2 months). Blood tests were conducted every cycle and computed tomography was performed every second cycle as follow-up. Overall survival was measured from initial administration of CWGP to death. We used the international standards provided by the Response Evaluation Criteria in Solid Tumors for measuring response rate and Kaplan-Meier analysis to determine statistical significance. Seven patients received a total of 55 cycles (1 with 1 cycle, 2 with 2 cycles, 1 with 3 cycles, 2 with 13 cycles, 1 with 20 cycles). One-year survival rate was 57.1%, and the median survival time was 544 days. Among these patients, two non-small cell lung carcinoma patients and one advanced gastric adenocarcinoma patient showed stable disease. Two patients dropped out after the first and second cycles of treatment without receiving a new computed tomography scan. Two patients showed progressive disease. Although a further large scale study is necessary, CWGP showed potential as an effective treatment for two non-small cell lung carcinoma patients and one advanced gastric carcinoma patient. Copyright 2010 Korean Pharmacopuncture Institute. Published by .. All rights reserved.

  10. Superselective intra-arterial chemoradiotherapy for laryngeal cancer. Is it reasonable to treat glottic cancer in a similar way to supraglottic cancer?

    International Nuclear Information System (INIS)

    Yoshizaki, Tomokazu; Murono, Shigeyuki; Wakisaka, Naohiro; Kondo, Satoru; Furukawa, Mitsuru

    2006-01-01

    The standard treatment for advanced laryngeal cancer has been shifting from total laryngectomy to various organ preservation therapies such as subtotal laryngectomy and chemoradiotherapy. Robbins showed remarkable results with RADPLAT, the superselective intra-arterial infusion of supradose cisplatin (150 mg/m 2 ), against advanced head and neck cancer. However, the volume of laryngeal cancer is smaller than those of the other sites of head and neck cancers, and so a swaller less dose of cisplatin could save advanced laryngeal cancer patients. It may be reasonable to treat these subtypes of laryngeal cancer with a different modality. Thirty-five patients with laryngeal cancer were treated with tri-weekly intra-arterial infusion of cisplatin (100 mg/body). A 200 times molar excessive amount of sodium thiosulfate was intravenously infused to reduce the toxicity of cisplatin. Ten of 16 patients with glottic cancer and 10 of 19 patients with supraglottic cancer were followed for more than 2 years. Larynx preservation rate of glottic and supraglottic cancer was 80% and 70%, and progression-free survival rate was 80% and 50%, respectively. Grade III and IV toxic events were less frequent than with RADPLAT or systemic administration of a similar dose of cisplatin. Glottic and supraglottic cancers show different clinical behaviors. Our protocol with less cisplatin than RADPLAT is especially effective for glottic cancer. (author)

  11. Risk of virus-associated cancer in female arthritis patients treated with biologigal DMARDs

    DEFF Research Database (Denmark)

    Cordtz, René; Mellemkjær, Lene; Glintborg, Bente

    2016-01-01

    and standardized incidence ratios (SIRs) were calculated. RESULTS: In total, 24 and 32 virus-associated cancers were identified among ever and never bDMARD users, respectively (hazard ratio = 0.9, 95% CI: 0.7, 1.2). Oropharyngeal (n = 3, SIR = 4.0, 95% CI: 1.3, 12.4) and anal (n = 2, SIR = 2.5, 95% CI: 0.6, 10.......0) cancer only occurred among bDMARD-treated patients. SIR was not increased for cervical cancer, either in ever or never bDMARD-treated patients. SIRs for Hodgkin's and non-Hodgkin's lymphomas were increased in never bDMARD-treated patients (SIR = 2.5, 95% CI: 1.5, 4.0). CONCLUSION: bDMARD therapy...

  12. SU-F-R-54: CT-Texture Based Early Tumor Treatment Response Assessment During Radiation Therapy Delivery: Small Cell Versus Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Paul, J; Gore, E; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2016-06-15

    Purpose: Tumor treatment response may potentially be assessed during radiation therapy (RT) by analyzing changes in CT-textures. We investigated the different early RT-responses between small cell (SCLC) and non-small cell lung cancer (NSCLC) as assessed by CT-texture. Methods: Daily diagnostic-quality CT acquired during routine CT-guided RT using a CT-on-Rails for 13-NSCLC and 5-SCLC patients were analyzed. These patient had ages ranging from 45–78 and 38–63 years, respectively, for NSCLC and SCLC groups, and tumor-stages ranging from T2-T4, and were treated with either RT or chemotherapy and RT with 45–66Gy/ 20–34 fractions. Gross-tumor volume (GTV) contour was generated on each daily CT by populating GTV contour from simulation to daily CTs with manual editing if necessary. CT-texture parameters, such as Hounsfield Unit (HU) histogram, mean HU, skewness, kurtosis, entropy, and short-run high-gray level emphasis (SRHGLE), were calculated in GTV from each daily CT-set using an in house software tool. Difference in changes of these texture parameters during RT between NSCLC and SCLC was analyzed and compared with GTV volume changes. Results: Radiation-induced changes in CT-texture were different between SCLC and NSCLC. Average changes from first to the last fractions for NSCLC and SCLC in GTV were 28±10(12–44) and 30±15(11–47) HU (mean HU reduction), 12.7% and 18.3% (entropy), 50% and 55% (SRHGLE), 19% and 22% (kurtosis), and 5.2% and 22% (skewness), respectively. Good correlation in kurtosis changes and GTV was seen (R{sup 2}=0.8923) for SCLC, but not for NSCLC (R{sup 2}=0.4748). SCLC had better correlations between GTV volume reduction and entropy (SCLC R{sup 2}=0.847; NSCLC R{sup 2}=0.6485), skewness (SCLC R{sup 2}=0.935; NSCLC R{sup 2}=0.7666), or SRHGLE (SCLC R{sup 2}=0.9619; NSCLC R{sup 2}=0.787). Conclusion: NSCLC and SCLC exhibited different early RT-responses as assessed by CT-texture changes during RT-delivery. The observed larger changes in

  13. [Erectile dysfunction in patients treated for bladder and prostate cancer].

    Science.gov (United States)

    Tkocz, Michał T; Kupajski, Maciej T

    2009-01-01

    The disorders of the erectile dysfunction are well-known complication connected with the operating interventions of abdominal and pelvic surgery. Radical treatment of the malignancy, vascular operations and transurethral resection can lead to the rise of these disorders. The majority of these interventions is carried out at patients in the old age at which the disorders of the erection already existed about the various degree of intensification before treating operating how also the presence of the illnesses of the leaders to their rise or intensification after finishing the treatment (diabetes, arterial hypertension, arteriosclerosis). Patients in the young aged wait not only curing from the malignancy from second side, but also the behaviour of the quality of the life (QOL - quality of life), which the correct erection enabling is one of elements satisfying living together.

  14. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC

    Science.gov (United States)

    Besse, Benjamin; Charrier, Mélinda; Lapierre, Valérie; Dansin, Eric; Lantz, Olivier; Planchard, David; Le Chevalier, Thierry; Livartoski, Alain; Barlesi, Fabrice; Laplanche, Agnès; Ploix, Stéphanie; Vimond, Nadège; Peguillet, Isabelle; Théry, Clotilde; Lacroix, Ludovic; Zoernig, Inka; Dhodapkar, Kavita; Dhodapkar, Madhav; Viaud, Sophie; Soria, Jean-Charles; Reiners, Katrin S.; Pogge von Strandmann, Elke; Vély, Frédéric; Rusakiewicz, Sylvie; Eggermont, Alexander; Pitt, Jonathan M.; Zitvogel, Laurence; Chaput, Nathalie

    2016-01-01

    ABSTRACT Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN-γ-free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN-γ-Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN-γ-Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN-γ-Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN-γ-Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC. PMID:27141373

  15. Bilateral breast cancer treated with breast-conserving surgery and definitive irradiation

    International Nuclear Information System (INIS)

    Man, C. Fung; Schultz, Delray; Solin, Lawrence J.

    1996-01-01

    Objective: To assess whether patients with early stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complication rates, and cosmetic outcomes. Material and Methods: We reviewed 55 cases of patients with synchronous or sequential bilateral breast cancer treated with definitive irradiation following breast-conserving surgery at our institution from 1977 to 1992. Analysis of cases was limited to women who were AJCC clinical Stage 0, I, and II. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, AJCC stage, pathologic axillary lymph nodes status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Analysis regarding matching technique, cosmetic outcome, and complication rate was also performed. The 5- and 10-year overall survival (OS), no evidence of disease (NED) survival, relapse-free survival (RFS), and local control rates were evaluated. Twelve women (22%) presented with synchronous bilateral carcinoma, and 43 women (78%) had sequential bilateral carcinoma. Of the 12 patients with synchronous cancer, 5 received adjuvant chemotherapy, 2 received Tamoxifen, and 1 received both adjuvant therapies. Of the 43 patients with sequential cancer, 6 received chemotherapy, 1 received Tamoxifen, and 1 received both adjuvant therapies for the first cancer treatment; seven received chemotherapy and 6 received Tamoxifen for the second cancer treatment. Results: The median age at the time of treatment of the first cancer was 56 years (range 26-86 years). For the 12 patients with synchronous cancer, the median follow-up was 48 months (range 9-164). For the 43 patients with sequential cancer, the median follow-up was 112 months (range 52-188 months) after the first cancer, and 59 months (range 11-153 months) after the second. The median dose delivered was 64 Gy (range 42-72 Gy) using a combination of

  16. Dabrafenib plus trametinib in patients with previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer : An open-label, phase 2 trial

    NARCIS (Netherlands)

    Planchard, David; Smit, Egbert F.; Groen, Harry J. M.; Mazieres, Julien; Besse, Benjamin; Helland, Aslaug; Giannone, Vanessa; D'Amelio, Anthony M.; Zhang, Pingkuan; Mookerjee, Bijoyesh; Johnson, Bruce E.

    2017-01-01

    Background: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We

  17. Clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital

    OpenAIRE

    Qureshi, Fawad; Shafi, Azhar; Ali, Sheeraz; Siddiqui, Neelam

    2016-01-01

    Objective: To determine the clinical predictors of anticipatory emesis in patients treated with chemotherapy at a tertiary care cancer hospital. Methods: This was a cross-sectional study conducted on 200 patients undergoing first line chemotherapy with minimum of two cycles at inpatient department and chemotherapy bay of Shaukat Khanum Memorial Cancer Hospital and Research Centre Pakistan. Anticipatory nausea and vomiting develops before administration of chemotherapy. Clinical signs and symp...

  18. Novel Listeria Vectors Secreting Gut Flora Altering Agents to Prevent Colon Cancer and Treat Colitis

    Science.gov (United States)

    2016-09-01

    84 years of age. The significant age risk for colorectal cancer is extensively validated in the USA and worldwide in industrial countries (reviewed...mitigate age-related colitis and related colon cancer risk. Effects will be tested in both young and aged mice in well-established models of colitis and...wild type versus B7-H1 KO mice (which represent mice treated with recombinant scFv vectors). Epithelial damage was significantly more severe in B7-H1

  19. Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non-Small Cell Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ann T. Bell

    2017-02-01

    Full Text Available Introduction: While epidermal growth factor receptor (EGFR inhibitors have improved progression-free survival in patients with non-small cell lung cancer (NSCLC, one of the most common adverse effects is papulopustular skin eruption, which is frequently severe enough to be treated with oral minocycline or doxycycline. Case: We present a case of an 87-year-old man who developed a severe papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of the eruption with 100 mg of minocycline twice daily for 8 months eventually led to blue-gray skin hyperpigmentation. After 30 months, this side effect was recognized as minocycline drug deposition, which was confirmed with skin biopsy. Discussion: Compliance with EGFR inhibitor therapy in NSCLC is often challenging due to common side effects, most notably cutaneous skin eruptions. Treatment of cutaneous toxicities is important to preserve patient compliance with targeted cancer therapy. Use of minocycline to treat the most common cutaneous side effect (papulopustular eruption can in turn cause blue-black skin, eye, or tooth discoloration that can nullify its benefits, resulting in suboptimal patient adherence to cancer therapy. Although this adverse effect is well known in dermatology literature as a risk when using minocycline to treat acne, rosacea, or blistering disorders, it is less well documented in oncology literature. We present this case to highlight the need for greater consideration of unique patient characteristics in selecting an oral antibiotic as a treatment modality for EGFR inhibitor skin toxicities.

  20. Fingerprint changes among cancer patients treated with paclitaxel.

    Science.gov (United States)

    Azadeh, Payam; Dashti-Khavidaki, Simin; Joybari, Ali Yaghobi; Sarbaz, Samaneh; Jafari, Atefeh; Yaseri, Mehdi; Amini, Afshin; Farasatinasab, Maryam

    2017-04-01

    Fingerprints have long been used for personal identification; however, some case reports suggested that some chemotherapy agents such as paclitaxel lead to fingerprints loss due to hand-and-foot syndrome (HFS). This case-control study was performed on 65 patients who received chemotherapy regimens with/without paclitaxel. Patients with the history of receiving any drugs with significant HFS adverse effect or patients with any conditions that affect fingerprints were excluded. Baseline and post-chemotherapy images of fingerprint examples were referred to the Iranian Society of Legal Medicine to compare changes in the fingerprints. Thirty-one patients entered in the paclitaxel and 34 subjects in the control groups. Seventeen patients (54.8%) in the paclitaxel group experienced fingerprint changes, whereas no patient had fingerprint changes in the control group. By physical examination, no patients in the two groups experienced HFS. After adjusting for age, sex, occupation, and cancer type, there was a significant difference between the two groups regarding fingerprint changes (P = 0.002, OR 13.69, 95% CI 2.05 to infinite). Considering that fingerprint recognition has been utilized in both government and civilian investigation, patients taking paclitaxel and centers necessitating fingerprint identification should be informed about possible fingerprint changes by paclitaxel.

  1. OncoTREAT: a software assistant for cancer therapy monitoring

    International Nuclear Information System (INIS)

    Bornemann, Lars; Dicken, Volker; Kuhnigk, Jan-Martin; Krass, Stefan; Peitgen, Heinz-Otto; Wormanns, Dag; Shin, Hoen-Oh; Bauknecht, Hans-Christian; Diehl, Volker; Fabel, Michael; Meier, Stefan; Kress, Oliver

    2007-01-01

    ObjectCancer is one of the leading causes of death worldwide and therapy options are often associated with severe stress for the patient and high costs. Therefore, precise evaluation of therapy success is essential. Material and Methods In the framework of the VICORA research project (Virtual Institute for Computer Assistance in Clinical Radiology), a software application was developed to support the radiologist in evaluating the response to tumor therapy. The application provides follow-up support for oncological therapy monitoring by volumetric quantification of lung, liver and brain metastases as well as enlarged lymph nodes and assists the user by temporal registration of lesion positions. Results With close cooperation between computer scientists and radiologists the application was tested and optimized to achieve a high degree of usability. Several clinical studies were carried out to evaluate the robustness and reproducibility of the volumetry methods. Conclusion Automatic volumetry and segmentation allows reliable detection of tumor growth and has the potential to increase reliability and significance of monitoring tumor growth in follow-up examinations. (orig.)

  2. Swallowing assessment in early laryngeal cancer patients treated either with surgery or radiotherapy

    International Nuclear Information System (INIS)

    Celedon L, Carlos; Gambi A, Galo; Royer F, Michel; Esquivel C, Patricia; Arteaga J, Patricia; Valdes P, Constanza

    2008-01-01

    Swallowing is a complex neuromuscular process that requires anatomical indemnity and an adequate coordination of several organs. Laryngeal cancer treatment may cause swallowing disorders. Traditionally, a high frequency of this type of disorder after surgery has been reported, but no actual data concerning its incidence in patients undergoing radiotherapy for early laryngeal cancer has been published. Aim. To compare swallowing disorders frequency posterior to treatment in early laryngeal cancer patients. Material and Method. Two groups of early laryngeal cancer patients were transversally studied, one treated with vertical partial surgery (CP), and the other treated exclusively with radiotherapy. Each patient had otorhinolaryngological, nasofibroscopic and video fluoroscopic evaluations after treatment. Differences between groups were compared using the - square test. Results. Twenty patients per group were entered in this study, predominantly males of similar age. Both groups presented a high incidence of aspiration symptoms (55% in RT and 35% in CP). There were no significant differences between both groups. Discussion and Conclusion. A high incidence of swallowing disorders in patients treated for early laryngeal cancer was found. It should then be considered as a frequent alteration in this group of patients, either treated with RT or CP

  3. Incidence of cancer in adolescent idiopathic scoliosis patients treated 25 years previously

    DEFF Research Database (Denmark)

    Simony, Ane; Hansen, Emil Jesper; Christensen, Steen Bach

    2016-01-01

    PURPOSE: To report the incidence of cancer in a cohort of adolescent idiopathic scoliosis (AIS) patients treated 25 years previously. METHODS: 215 consecutive AIS patients treated between 1983 and 1990 were identified and requested to return for clinical and radiographic examination. The incidence...... of cancer was determined through chart review and follow-up interviews. Using the original radiographic log file that included patient position, mAs, kV and the total number of X-rays taken, a radiation physicist calculated the total radiation dose during treatment and follow-up adjusted for BMI and sex...

  4. Other primary malignancies in breast cancer patients treated with breast conserving surgery and radiation therapy.

    Science.gov (United States)

    Yi, Min; Cormier, Janice N; Xing, Yan; Giordano, Sharon Hermes; Chai, Christy; Meric-Bernstam, Funda; Vlastos, Georges; Kuerer, Henry M; Mirza, Nadeem Q; Buchholz, Thomas A; Hunt, Kelly K

    2013-05-01

    Our purpose was to examine the incidence and impact on survival of other primary malignancies (OPM) outside of the breast in breast cancer patients and to identify risk factors associated with OPM. Patients with stage 0-III breast cancer treated with breast conserving therapy at our center from 1979 to 2007 were included. Risk factors were compared between patients with/without OPM. Logistic regression was used to identify factors that were associated with OPM. Standardized incidence ratios (SIRs) were calculated. Among 4,198 patients in this study, 276 (6.6 %) developed an OPM after breast cancer treatment. Patients with OPM were older and had a higher proportion of stage 0/I disease and contralateral breast cancer compared with those without OPM. In a multivariate analysis, older patients, those with contralateral breast cancer, and those who did not receive chemotherapy or hormone therapy were more likely to develop OPM after breast cancer. Patients without OPM had better overall survival. The SIR for all OPM sites combined after a first primary breast cancer was 2.91 (95 % confidence interval: 2.57-3.24). Significantly elevated risks were seen for numerous cancer sites, with SIRs ranging from 1.84 for lung cancer to 5.69 for ovarian cancer. Our study shows that breast cancer patients have an increased risk of developing OPM over the general population. The use of systemic therapy was not associated with increased risk of OPM. In addition to screening for a contralateral breast cancer and recurrences, breast cancer survivors should undergo screening for other malignancies.

  5. The combination of anti-KIR monoclonal antibodies with anti-PD-1/PD-L1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in NSCLC

    Directory of Open Access Journals (Sweden)

    He YY

    2018-04-01

    Full Text Available Yayi He,1,2,* Sangtian Liu,1,* Jane Mattei,3 Paul A Bunn Jr,2 Caicun Zhou,1 Daniel Chan2 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China; 2Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 3Oncology Department, Moinhos de Vento Hospital, Porto Alegre, Brazil *These authors contributed equally to this work Background: The anti-programmed death-1 (PD-1/programmed death ligand-1 (PD-L1 monoclonal antibody has a good effect in the treatment of non-small cell lung cancer (NSCLC, but not all PD-1/PD-L1 positive patients can get benefit from it. Compensatory expression of other immune checkpoints may be correlated with the poor efficacy of anti-PD-1/PD-L1 monoclonal antibodies. The inhibitory human leukocyte antigen (HLA/killer cell Ig-like receptor (KIR can effectively block the killing effect of natural killer (NK cells on tumors. Our previous studies have confirmed that high expression of KIR was correlated with poor prognosis of NSCLC. Inhibitory KIR expression was positively correlated with the expression of PD-1. Methods: The expressions of KIR 2D (L1, L3, L4, S4 (BC032422/ADQ31987/NP_002246/NP_036446, Abcam and PD-1 (NAT 105, Cell marque proteins was assessed by immunohis­tochemistry. Results: The expression of inhibitory KIR in tumor cells or tumor infiltrating lymphocytes (TILs is associated with PD-1 expression. Among PD-1 positive patients, 76.3% were KIR 2D (L1, L3, L4, S4 positive on tumor cells, and 74.6% were KIR 2D (L1, L3, L4, S4 positive on TILs. We compared the expression of inhibitory KIR before and after treatment with nivolumab in 11 patients with NSCLC. We found that five (45.5% patients had positive expression of inhibitory KIR in tumor tissue after being treated with anti-PD-1 monoclonal antibodies, two of whom exhibited a significant

  6. Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer

    Science.gov (United States)

    2015-10-01

    AD_________________ (Leave blank) Award Number: W81XWH-13-1-0211 TITLE: Development of Antidepressants as Novel Agents to Treat Small Cell Lung...DATES COVERED 1 Aug 2013 - 31 Jul 2015 4. TITLE AND SUBTITLE Development of Antidepressants as Novel Agents to Treat Small Cell Lung Cancer 5a... antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells. The candidate drugs activate stress pathways

  7. Acupuncture in Treating Dry Mouth Caused By Radiation Therapy in Patients With Head and Neck Cancer | Division of Cancer Prevention

    Science.gov (United States)

    RATIONALE: Acupuncture may help relieve dry mouth caused by radiation therapy. PURPOSE: This randomized phase III trial is studying to see how well one set of acupuncture points work in comparison to a different set of acupuncture points or standard therapy in treating dry mouth caused by radiation therapy in patients with head and neck cancer. |

  8. Polymer nanoparticles for drug and small silencing RNA delivery to treat cancers of different phenotypes

    Science.gov (United States)

    Devulapally, Rammohan; Paulmurugan, Ramasamy

    2013-01-01

    Advances in nanotechnology have provided powerful and efficient tools in development of cancer diagnosis and therapy. There are numerous nanocarriers that are currently approved for clinical use in cancer therapy. In recent years, biodegradable polymer nanoparticles (NPs) have attracted a considerable attention for their ability to function as a possible carrier for target-specific delivery of various drugs, genes, proteins, peptides, vaccines, and other biomolecules in humans without much toxicity. This review will specifically focus on the recent advances in polymer-based nanocarriers for various drugs and small silencing RNA’s loading and delivery to treat different types of cancer. PMID:23996830

  9. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M

    2010-01-01

    the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor......Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...

  10. Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy.

    Science.gov (United States)

    Shi, Anhui; Zhu, Guangying; Wu, Hao; Yu, Rong; Li, Fuhai; Xu, Bo

    2010-05-12

    To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP. Median follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p 4.2% and NTCP 50% were 5.7% and 29.2%, respectively (p < 0.01). NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

  11. Yttrium-90 used to treat colon cancer: Awaiting investigational new drug approval

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    A new radiation treatment takes just 14 to 21 days to shrink colorectal tumors in laboratory mice, is under review for clinical trials with human cancer patients. The treatment has succeeded in reducing the size of tumors by up to 95%. Colon cancer, the second leading cause of cancer deaths in the US, is extremely difficult to treat unless it is detected early enough for surgical procedures. In laboratory tests over the last 5 years, a team of researchers has developed the treatment using yttrium-90. The yttrium-90 is transported to the tumors by attaching it to monoclonal antibodies that seek out the cancer cells. Once the radioisotope has been targeted to the tumor, the radiation destroys many of the cells, dramatically reducing the size of the tumor. Since this treatment usually does not completely eliminate all the cancer cells, it cannot be called a cure, but it does seem to be an effective method of shrinking colorectal tumors

  12. Effect of ABCG2/BCRP Expression on Efflux and Uptake of Gefitinib in NSCLC Cell Lines.

    Directory of Open Access Journals (Sweden)

    Maricla Galetti

    Full Text Available BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers resistance to several classes of cancer chemotherapeutic agents and to a number of novel molecularly-targeted therapeutics such as tyrosine kinase inhibitors. Gefitinib is an orally active, selective EGFR tyrosine kinase inhibitor used in the treatment of patients with advanced non small cell lung cancer (NSCLC carrying activating EGFR mutations. Membrane transporters may affect the distribution and accumulation of gefitinib in tumour cells; in particular a reduced intracellular level of the drug may result from poor uptake, enhanced efflux or increased metabolism.The present study, performed in a panel of NSCLC cell lines expressing different ABCG2 plasma membrane levels, was designed to investigate the effect of the efflux transporter ABCG2 on intracellular gefitinib accumulation, by dissecting the contribution of uptake and efflux processes.Our findings indicate that gefitinib, in lung cancer cells, inhibits ABCG2 activity, as previously reported. In addition, we suggest that ABCG2 silencing or overexpression affects intracellular gefitinib content by modulating the uptake rather than the efflux. Similarly, overexpression of ABCG2 affected the expression of a number of drug transporters, altering the functional activities of nutrient and drug transport systems, in particular inhibiting MPP, glucose and glutamine uptake.Therefore, we conclude that gefitinib is an inhibitor but not a substrate for ABCG2 and that ABCG2 overexpression may modulate the expression and activity of other transporters involved in the uptake of different substrates into the cells.

  13. Neuropathic pain in cancer patients treated with bortezomib.

    Science.gov (United States)

    Expósito Vizcaíno, S; Casanova-Mollà, J; Escoda, L; Galán, S; Miró, J

    The neuropathic pain is the most habitual problem in the neuropathy induced by chemotherapy (NIQ) and the one that more interferes in the quality of life of the patients. His precocious detection turns out to be fundamental to reduce or to eliminate the problems that from this one stem. The aims of this study were: 1) determine the incident and NIQ's characteristics and neuropathic pain in patients with mieloma multiple (MM) treated with bortezomib, and 2) to evaluate the impact of the neuropathic pain in the activities of the daily life (AVD). All the patients diagnosed of MM candidates for treatment with bortezomib attended in the Hospital Joan XXIII during 2013, took part. The participants were interviewed individually and were reporting on the presence, the characteristics and the impact of the pain, as well as of the adverse effects of the bortezomib. There took part 22 persons, of which NIQ presented the half, being the degree 2 the predominant one. The most habitual location of the neuropathic pain was hands and feet; it was appearing in a spontaneous and progressive way deteriorating in rest and during the night, with predominance of positive symptoms. The impact of the pain was reflected in all the AVD. The principal limitation was the disability to enjoy the life. The peripheral neuropathy occupied the first place in order of subjective importance for the patient followed by the fatigue and the constipation. A proper assessment and early detection of neuropathic pain is critical to minimizing its impact on the quality of life of patients. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Lung cancer mortality risk among breast cancer patients treated with anti-estrogens.

    Science.gov (United States)

    Bouchardy, Christine; Benhamou, Simone; Schaffar, Robin; Verkooijen, Helena M; Fioretta, Gerald; Schubert, Hyma; Vinh-Hung, Vincent; Soria, Jean-Charles; Vlastos, Georges; Rapiti, Elisabetta

    2011-03-15

    The Women's Health Initiative randomized clinical trial reported that menopausal hormone therapy increases lung cancer mortality risk. If this is true, use of anti-estrogens should be associated with decreased lung cancer mortality risk. The authors compared lung cancer incidence and mortality among breast cancer patients with and without anti-estrogen therapy. Our study included all 6655 women diagnosed with breast cancer between 1980 and 2003 and registered at the Geneva Cancer Registry. Among these women, 46% (3066) received anti-estrogens. All women were followed for occurrence and death from lung cancer until December 2007. The authors compared incidence and mortality rates among patients with and without anti-estrogens with those expected in the general population by Standardized Incidence Ratios (SIRs) and Standardized Mortality Ratios (SMRs). After a total of 57,257 person-years, 40 women developed lung cancer. SIRs for lung cancer were not significantly decreased among breast cancer patients with and without anti-estrogens (0.63, 95% confidence intervals [CI], 0.33-1.10; and 1.12, 95% CI, 0.74-1.62, respectively) while SMR was decreased among women with anti-estrogens (0.13, 95% CI, 0.02-0.47, P<.001) but not for women without anti-estrogens (0.76, 95% CI, 0.43-1.23). Compared with expected outcomes in the general population, breast cancer patients receiving anti-estrogen treatment for breast cancer had lower lung cancer mortality. This study further supports the hypothesis that estrogen therapy modifies lung cancer prognosis. Copyright © 2011 American Cancer Society.

  15. Anti-cancer capacity of plasma-treated PBS: effect of chemical composition on cancer cell cytotoxicity.

    Science.gov (United States)

    Van Boxem, Wilma; Van der Paal, Jonas; Gorbanev, Yury; Vanuytsel, Steven; Smits, Evelien; Dewilde, Sylvia; Bogaerts, Annemie

    2017-11-28

    We evaluate the anti-cancer capacity of plasma-treated PBS (pPBS), by measuring the concentrations of NO 2 - and H 2 O 2 in pPBS, treated with a plasma jet, for different values of gas flow rate, gap and plasma treatment time, as well as the effect of pPBS on cancer cell cytotoxicity, for three different glioblastoma cancer cell lines, at exactly the same plasma treatment conditions. Our experiments reveal that pPBS is cytotoxic for all conditions investigated. A small variation in gap between plasma jet and liquid surface (10 mm vs 15 mm) significantly affects the chemical composition of pPBS and its anti-cancer capacity, attributed to the occurrence of discharges onto the liquid. By correlating the effect of gap, gas flow rate and plasma treatment time on the chemical composition and anti-cancer capacity of pPBS, we may conclude that H 2 O 2 is a more important species for the anti-cancer capacity of pPBS than NO 2 - . We also used a 0D model, developed for plasma-liquid interactions, to elucidate the most important mechanisms for the generation of H 2 O 2 and NO 2 - . Finally, we found that pPBS might be more suitable for practical applications in a clinical setting than (commonly used) plasma-activated media (PAM), because of its higher stability.

  16. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, John M. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Ross, Rudi [21st Century Oncology, Fort Myers, Florida (United States); Harder, Eileen M.; Mancini, Brandon R. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Soulos, Pamela R. [Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut (United States); Finkelstein, Steven E.; Shafman, Timothy D.; Dosoretz, Arie P. [21st Century Oncology, Fort Myers, Florida (United States); Evans, Suzanne B.; Husain, Zain A.; Yu, James B. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Gross, Cary P. [Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut (United States); Decker, Roy H., E-mail: roy.decker@yale.edu [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)

    2016-12-01

    Purpose: To determine the effect of biologically effective dose (BED{sub 10}) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED{sub 10} and radiation treatment schedule. The linear-quadratic equation was used to calculate BED{sub 10} and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED{sub 10}. The primary outcome was OS. We used the Kaplan-Meier method, the log–rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED{sub 10} was associated with OS. Results: We identified 747 patients who met inclusion criteria. The median BED{sub 10} was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED{sub 10} had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED{sub 10} had a median survival of 22 months (log–rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED{sub 10} ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. Conclusions: We found that dose escalation to 105 Gy BED

  18. Surgical Results of Non-small Cell Lung Cancer in Nepal

    Directory of Open Access Journals (Sweden)

    Binay Thakur

    2014-12-01

    Conclusions: Earlier stage (pI-II, R0 resection and pathological pNo-1 has the best five year overall survival in Nepalese patients with NSCLC as well. Keywords: lung cancer; NSCLC; pulmonary resection.

  19. cMET in NSCLC: Can We Cut off the Head of the Hydra? From the Pathway to the Resistance

    Directory of Open Access Journals (Sweden)

    Nele Van Der Steen

    2015-03-01

    Full Text Available In the last decade, the tyrosine kinase receptor cMET, together with its ligand hepatocyte growth factor (HGF, has become a target in non-small cell lung cancer (NSCLC. Signalization via cMET stimulates several oncological processes amongst which are cell motility, invasion and metastasis. It also confers resistance against several currently used targeted therapies, e.g., epidermal growth factor receptor (EGFR inhibitors. In this review, we will discuss the basic structure of cMET and the most important signaling pathways. We will also look into aberrations in the signaling and the effects thereof in cancer growth, with the focus on NSCLC. Finally, we will discuss the role of cMET as resistance mechanism.

  20. 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......%. At 2       years, 54% were without local or distant progression, and overall survival       was 47%. Within 6 months after treatment, one or more Grade >/=2 reactions       were observed in 48% of the patients. Conclusions: Stereotactic body       radiotherapy in patients with limited-stage NSCLC...

  1. Carvacrol Targets AXL to Inhibit Cell Proliferation and Migration in Non-small Cell Lung Cancer Cells.

    Science.gov (United States)

    Jung, Chi Young; Kim, So-Young; Lee, Chuhee

    2018-01-01

    AXL has been reported to be overexpressed and highly activated in various cancer types. In this study, we demonstrated the effect of carvacrol on cell proliferation and migration in non-small cell lung cancer (NSCLC) cells by impeding the expression and activation of AXL. The levels of AXL protein, mRNA and promoter activity were evaluated by western blot, reverse transcription polymerase chain reaction (RT-PCR) and luciferase assay, respectively. AXL-overexpressing cells were established by ectopic expression of AXL cDNA. Cell viability, clonogenicity, and migration were measured in carvacrol-treated NSCLC cells. Carvacrol treatment of NSCLC cells caused down-regulation of AXL expression at the transcriptional level and also inhibited phosphorylation of AXL upon ligand stimulation. Carvacrol suppressed cell proliferation and migration and its inhibitory effect was attenuated in AXL-overexpressing NSCLC cells. Our data demonstrate that AXL is a crucial therapeutic target of carvacrol-induced inhibition of NSCLC cell proliferation and migration. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  2. TheraBite exercises to treat trismus secondary to head and neck cancer

    NARCIS (Netherlands)

    Kamstra, Jolanda I.; Roodenburg, Jan L. N.; Beurskens, Carien H. G.; Reintsema, Harry; Dijkstra, Pieter U.

    The aim of this study was to evaluate the effect of TheraBite exercises on mouth opening and to analyze factors influencing this effect in a patient record evaluation. Effect of exercises with a TheraBite to treat trismus was evaluated in 69 head and neck cancer patients of two university medical

  3. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M

    2010-01-01

    the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor...

  4. Capecitabine and bevacizumab in heavily pre-treated patients with advanced colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Boisen, Mogens Karsbøl; Fromm, Anne-Lene Gunge

    2012-01-01

    No standard treatment exists for patients with metastatic colorectal cancer who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin, irinotecan and an anti-EGFR antibody. The efficacy and safety of bevacizumab and capecitabine in heavily pre-treated patients with metastatic...

  5. Artificial neural network analysis to assess hypernasality in patients treated for oral or oropharyngeal cancer

    NARCIS (Netherlands)

    de Bruijn, Marieke; ten Bosch, Louis; Kuik, Dirk J.; Langendijk, Johannes A.; Leemans, C. Rene; Verdonck-de Leeuw, Irma

    2011-01-01

    Objective. Investigation of applicability of neural network feature analysis of nasalance in speech to assess hypernasality in speech of patients treated for oral or oropharyngeal cancer. Patients and methods. Speech recordings of 51 patients and of 18 control speakers were evaluated regarding

  6. Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

    Directory of Open Access Journals (Sweden)

    Cavazzoni Andrea

    2012-12-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

  7. Effect of a See and Treat clinic on skin cancer treatment time.

    Science.gov (United States)

    McLaughlin, Scott J P; Kenealy, John; Locke, Michelle B

    2017-10-11

    Many plastic surgery departments in Australasia have experienced increasing referrals for management of skin lesions. This has driven a demand for new strategies to decrease patient waiting time and administrative costs. The aim of this study was to determine if a purpose-built See and Treat skin cancer clinic could provide a faster skin cancer treatment pathway with comparable clinical outcomes and acceptability to patients. This was a prospective observational study of patients treated through the See and Treat clinic with a retrospective control cohort. The prospective 'See and Treat' cohort included a consecutive series of 106 patients, while the retrospective cohort included a consecutive series of 200 patients. Patient demographics, time from referral to surgery and operative measures were analysed. One hundred patients in the prospective cohort completed an anonymous satisfaction survey regarding their treatment. The average time from referral to surgery was reduced from 121 days in the retrospective cohort to 60 days in the See and Treat cohort (P See and Treat experience overall. We show that a considerable reduction in the time between referral and surgery can be achieved through a See and Treat clinic without compromise of the success of surgical treatment. Moreover, such a treatment pathway has been shown to be acceptable, and largely preferable, to patients. © 2017 Royal Australasian College of Surgeons.

  8. Exercise echocardiography in asymptomatic survivors of childhood cancer treated with anthracyclines

    DEFF Research Database (Denmark)

    Sieswerda, Elske; Kremer, Leontien C M; Vidmar, Suzanna

    2010-01-01

    BACKGROUND: Exercise echocardiography reveals abnormalities in asymptomatic childhood cancer survivors who previously have been treated with anthracyclines. We determined the added value of monitoring childhood cancer survivors with exercise echocardiography compared to monitoring with resting...... echocardiography alone to predict anthracycline-induced cardiotoxicity. Secondary aims were to evaluate change in resting cardiac function over 10 years and to determine risk factors for late cardiotoxicity. PROCEDURE: We invited a cohort of 110 originally asymptomatic anthracycline-treated childhood cancer...... survivors, who had undergone cardiac tests including exercise echocardiography 10.5 years earlier, for new cardiac evaluation. Each subject underwent a resting echocardiogram at both evaluations. At first evaluation a repeat echocardiogram was performed following peak exercise. Resting echocardiographic...

  9. Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non-small cell lung cancer.

    Science.gov (United States)

    Zhang, Limin; Jiang, Tao; Li, Xuefei; Wang, Yan; Zhao, Chao; Zhao, Sha; Xi, Lei; Zhang, Shijia; Liu, Xiaozhen; Jia, Yijun; Yang, Hui; Shi, Jinpeng; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun

    2017-08-01

    The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib. A total of 55 patients with ALK-positive NSCLC and 14 patients with ROS1-positive NSCLC who were treated with crizotinib were enrolled into the current study. The Bim deletion polymorphism was analyzed by polymerase chain reaction. The clinical features of the Bim deletion polymorphism and its impact on the effect of crizotinib were investigated. The Bim deletion polymorphism was present in 9 of 69 patients with ALK-positive or ROS1-positive NSCLC (13.0%). There were no differences noted with regard to clinicopathological features between patients with and without the Bim deletion polymorphism. Patients with the Bim deletion polymorphism had a significantly shorter progression-free survival (PFS) and lower objective response rate compared with those without (median PFS, 182 days vs 377 days [P = .008]) (objective response rate, 44.4% vs 81.7% [P =.041]) in all populations. The significant difference in PFS was observed in patients with ALK-positive NSCLC (83 days vs 305 days [P =.0304]) compared with those with ROS1-positive NSCLC (218 days vs not reached [P =.082]). Multivariate analysis indicated that the Bim deletion polymorphism was an independent predictive factor for patients with ALK-positive NSCLC who were treated with crizotinib (hazard ratio, 4.786 [P =.006]). The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in

  10. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors.

    Science.gov (United States)

    Patnaik, Amita; Rosen, Lee S; Tolaney, Sara M; Tolcher, Anthony W; Goldman, Jonathan W; Gandhi, Leena; Papadopoulos, Kyriakos P; Beeram, Muralidhar; Rasco, Drew W; Hilton, John F; Nasir, Aejaz; Beckmann, Richard P; Schade, Andrew E; Fulford, Angie D; Nguyen, Tuan S; Martinez, Ricardo; Kulanthaivel, Palaniappan; Li, Lily Q; Frenzel, Martin; Cronier, Damien M; Chan, Edward M; Flaherty, Keith T; Wen, Patrick Y; Shapiro, Geoffrey I

    2016-07-01

    We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumor-specific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Dose-limiting toxicity was grade 3 fatigue. The maximum tolerated dose was 200 mg every 12 hours. The most common possibly related treatment-emergent adverse events involved fatigue and the gastrointestinal, renal, or hematopoietic systems. Plasma concentrations increased with dose, and pharmacodynamic effects were observed in proliferating keratinocytes and tumors. Radiographic responses were achieved in previously treated patients with breast cancer, NSCLC, and melanoma. For hormone receptor-positive breast cancer, the overall response rate was 31%; moreover, 61% of patients achieved either response or stable disease lasting ≥6 months. Abemaciclib represents the first selective inhibitor of CDK4 and CDK6 with a safety profile allowing continuous dosing to achieve sustained target inhibition. This first-in-human experience demonstrates single-agent activity for patients with advanced breast cancer, NSCLC, and other solid tumors. Cancer Discov; 6(7); 740-53. ©2016 AACR.See related commentary by Lim et al., p. 697This article is highlighted in the In This Issue feature, p. 681. ©2016 American Association for Cancer Research.

  11. Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and miRNA expression profiles

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V. Bharath; Yuan, Ta-Chun [Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan (China); Liou, Je-Wen [Department of Biochemistry, School of Medicine, Tzu-Chi University, Hualien, Taiwan (China); Yang, Chih-Jen [Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan (China); Sung, Ping-Jyun [Graduate Institute of Marine Biotechnology, Department of Life Science, National Dong Hwa University, Pingtung, Taiwan (China); Weng, Ching-Feng, E-mail: cfweng@mail.ndhu.edu.tw [Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan (China)

    2011-02-10

    Antroquinonol a derivative of Antrodia camphorata has been reported to have antitumor effects against various cancer cells. However, the effect of antroquinonol on cell signalling and survival pathways in non-small cell lung cancer (NSCLC) cells has not been fully demarcated. Here we report that antroquinonol treatment significantly reduced the proliferation of three NSCLC cells. Treatment of A549 cells with antroquinonol increased cell shrinkage, apoptotic vacuoles, pore formation, TUNEL positive cells and increased Sub-G1 cell population with respect to time and dose dependent manner. Antroquinonol treatment not only increased the Sub-G1 accumulation but also reduced the protein levels of cdc2 without altering the expression of cyclin B1, cdc25C, pcdc2, and pcdc25C. Antroquinonol induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of Caspase 3 and PARP cleavage in A549 cells. Moreover, antroquinonol treatment down regulated the expression of Bcl2 proteins, which was correlated with the decreased PI3K and mTOR protein levels without altering pro apoptotic and anti apoptotic proteins. Results from the microarray analysis demonstrated that antroquinonol altered the expression level of miRNAs compared with untreated control in A549 cells. The data collectively suggested the antiproliferative effect of antroquinonol on NSCLC A549 cells, which provides useful information for understanding the anticancer mechanism influenced by antroquinonol and is the first report to suggest that antroquinonol may be a promising chemotherapeutic agent for lung cancer.

  12. Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and miRNA expression profiles

    International Nuclear Information System (INIS)

    Kumar, V. Bharath; Yuan, Ta-Chun; Liou, Je-Wen; Yang, Chih-Jen; Sung, Ping-Jyun; Weng, Ching-Feng

    2011-01-01

    Antroquinonol a derivative of Antrodia camphorata has been reported to have antitumor effects against various cancer cells. However, the effect of antroquinonol on cell signalling and survival pathways in non-small cell lung cancer (NSCLC) cells has not been fully demarcated. Here we report that antroquinonol treatment significantly reduced the proliferation of three NSCLC cells. Treatment of A549 cells with antroquinonol increased cell shrinkage, apoptotic vacuoles, pore formation, TUNEL positive cells and increased Sub-G1 cell population with respect to time and dose dependent manner. Antroquinonol treatment not only increased the Sub-G1 accumulation but also reduced the protein levels of cdc2 without altering the expression of cyclin B1, cdc25C, pcdc2, and pcdc25C. Antroquinonol induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of Caspase 3 and PARP cleavage in A549 cells. Moreover, antroquinonol treatment down regulated the expression of Bcl2 proteins, which was correlated with the decreased PI3K and mTOR protein levels without altering pro apoptotic and anti apoptotic proteins. Results from the microarray analysis demonstrated that antroquinonol altered the expression level of miRNAs compared with untreated control in A549 cells. The data collectively suggested the antiproliferative effect of antroquinonol on NSCLC A549 cells, which provides useful information for understanding the anticancer mechanism influenced by antroquinonol and is the first report to suggest that antroquinonol may be a promising chemotherapeutic agent for lung cancer.

  13. The Risk of Neutropenia and Leukopenia in Advanced Non-Small Cell Lung Cancer Patients Treated With Erlotinib

    Science.gov (United States)

    Zhou, Jian-Guo; Tian, Xu; Cheng, Long; Zhou, Quan; Liu, Yuan; Zhang, Yu; Bai, Yu-ju; Ma, Hu

    2015-01-01

    Abstract Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a critical member of systemic therapy for advanced non-small-cell lung cancer (NSCLC). Erlotinib is the first-generation EGFR-TKIs, the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations. However, the safety of erlotinib plus chemotherapy (CT) or erlotinib alone for advanced NSCLC remains controversial. We carried out a systematic meta-analysis to determine the overall risk of neutropenia and leukopenia associated with erlotinib. PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. RR with 95% CIs for neutropenia and leukopenia were all extracted. The random-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were conducted. We identified 12 eligible studies involving 3932 patients. Erlotinib plus CT or alone relative to CT is associated with significantly decreased risks of neutropenia and leukopenia in patients with advanced NSCLC (RR, 0.38; 95% CI, 0.21–0.71; P = 0.00; incidence: 9.9 vs. 35.2%) and (RR, 0.32; 95% CI, 0.11–0.93; P = 0.04; incidence: 3.5 vs. 11.6%), respectively. The subgroup analysis by erlotinb with or without CT showed that erlotinib combine with CT have no significance decrease the relative risks of neutropenia or leukopenia (RR, 0.98; 95% CI, 0.78–1.23; P = 0.87; incidence: 26.2 vs. 30.5%) and (RR, 0.81; 95% CI, 0.34–1.95; P = 0.64; incidence: 6.5 vs. 9.3%), respectively. However, erlotinib alone could decrease incidence of neutropenia (RR, 0.14; 95% CI, 0.07–0.27; P = 0.00; incidence: 3.7 vs. 40.8%) or leukopenia (RR, 0.07; 95% CI, 0.01–0.45; P = 0.01; incidence: 0.8 vs. 15.7%). The power analysis

  14. Recombinant nematode anticoagulant protein c2 inhibits cell invasion by decreasing uPA expression in NSCLC cells.

    Science.gov (United States)

    Tong, Yu; Yue, Jun; Mao, Meng; Liu, Qingqing; Zhou, Jing; Yang, Jiyun

    2015-04-01

    Nematode anticoagulant protein c2 (NAPc2) is an 85-residue polypeptide originally isolated from the hematophagous hookworm, Ancylostoma caninum. Several studies have shown that rNAPc2 inhibits the growth of primary and metastatic tumors in mice independently of its ability to initiate coagulation. We obtained bioactive recombinant rNAPc2 by splicing of the rNAPc2-intein-CBD fusion proteins expressed in E. coli ER2566. In the in vitro assay, rNAPc2 obviously inhibited the invasive ability of non-small cell lung cancer (NSCLC) cells in a dose-dependent manner. Furthermore, rNAPc2 suppressed tumor growth in vivo by daily intraperitoneal injection of rNAPc2 in an NSCLC cell xenograft model of nude mice. Respectively, rNAPc2 downregulated the production of urokinase plasminogen activator (uPA) (P<0.05) and suppressed nuclear factor-κB (NF-κB) activity. We also identified that inhibition of NF-κB activity impaired cell invasion and reduced the uPA production in NSCLC cells. Meanwhile, NF-κB was found to directly bind to the uPA promoter in vitro. These results demonstrated that rNAPc2 inhibits cell invasion at least in part through the downregulation of the NF-κB-dependent metastasis-related gene expression in NSCLC. Our results also suggest that uPA, a known metastasis-promoting gene, is indirectly regulated by rNAPc2 through NF-κB activation. These results indicate that rNAPc2 may be a potent agent for the prevention of NSCLC progression.

  15. Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in patients with non-small cell lung cancer pre-treated with a non-platinum-based regimen in the first-line setting: a randomized phase II study of the Hellenic Oncology Research Group (HORG).

    Science.gov (United States)

    Kentepozidis, N; Economopoulou, P; Christofyllakis, Ch; Chelis, L; Polyzos, A; Vardakis, N; Koinis, F; Vamvakas, L; Katsaounis, P; Kalbakis, K; Nikolaou, Ch; Georgoulias, V; Kotsakis, A

    2017-03-01

    Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine. A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m 2 on day 1 and 100 mg/m 2 on day 8 plus cisplatin 80 mg/m 2 on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m 2 plus cisplatin 80 mg/m 2 on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR). The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018). In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients. CLINICALTRIALS. NCT00614965.

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

    Science.gov (United States)

    Fung, Simon Fung Fee; Warren, Graham W; Singh, Anurag K

    2012-01-01

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

  17. Stage and tissue-specific prognostic impact of miR-182 in NSCLC

    International Nuclear Information System (INIS)

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

    2014-01-01

    MicroRNA (miR)-182 is frequently upregulated in cancers, has generally been viewed as an oncogene and is possibly connected to angiogenesis. We aimed to explore what impact miR-182 has in non-small cell lung cancer (NSCLC), and more explicitly its correlation with angiogenic markers. From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarray blocks (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-182 in tumor cells, and immunohistochemistry (IHC) was used to detect the expression of angiogenesis related protein markers. In univariate analyses, high tumor cell expression of miR-182 was a positive prognostic factor for patients with squamous cell carcinoma (SCC, P = 0.042) and stage II patients (P = 0.003). Also in the multivariate analysis, high tumor cell miR-182 expression was associated with a good prognosis in the same groups (SCC: HR 0.57, CI 95% 0.33-0.99, P = 0.048; stage II: HR 0.50, CI 95% 0.28-0.90, P = 0.020). We found significant correlations between miR-182 and the angiogenesis related markers FGF2, HIF2α and MMP-7. In patients with SCC and in stage II patients, high tumor cell miR-182 expression is an independent positive prognostic factor

  18. 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.

    Science.gov (United States)

    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.

  19. Alkali-treated titanium selectively regulating biological behaviors of bacteria, cancer cells and mesenchymal stem cells.

    Science.gov (United States)

    Li, Jinhua; Wang, Guifang; Wang, Donghui; Wu, Qianju; Jiang, Xinquan; Liu, Xuanyong

    2014-12-15

    Many attentions have been paid to the beneficial effect of alkali-treated titanium to bioactivity and osteogenic activity, but few to the other biological effect. In this work, hierarchical micro/nanopore films were prepared on titanium surface by acid etching and alkali treatment and their biological effects on bacteria, cancer cells and mesenchymal stem cells were investigated. Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and human cholangiocarcinoma cell line RBE were used to investigate whether alkali-treated titanium can influence behaviors of bacteria and cancer cells. Responses of bone marrow mesenchymal stem cells (BMMSCs) to alkali-treated titanium were also subsequently investigated. The alkali-treated titanium can potently reduce bacterial adhesion, inhibit RBE and BMMSCs proliferation, while can better promote BMMSCs osteogenesis and angiogenesis than acid-etched titanium. The bacteriostatic ability of the alkali-treated titanium is proposed to result from the joint effect of micro/nanotopography and local pH increase at bacterium/material interface due to the hydrolysis of alkali (earth) metal titanate salts. The inhibitory action of cell proliferation is thought to be the effect of local pH increase at cell/material interface which causes the alkalosis of cells. This alkalosis model reported in this work will help to understand the biologic behaviors of various cells on alkali-treated titanium surface and design the intended biomedical applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The economic burden of cancer in the UK: a study of survivors treated with curative intent.

    Science.gov (United States)

    Marti, Joachim; Hall, Peter S; Hamilton, Patrick; Hulme, Claire T; Jones, Helen; Velikova, Galina; Ashley, Laura; Wright, Penny

    2016-01-01

    We aim to describe the economic burden of UK cancer survivorship for breast, colorectal and prostate cancer patients treated with curative intent, 1 year post-diagnosis. Patient-level data were collected over a 3-month period 12-15 months post-diagnosis to estimate the monthly societal costs incurred by cancer survivors. Self-reported resource utilisation data were obtained via the electronic Patient-reported Outcomes from Cancer Survivors system and included community-based health and social care, medications, travel costs and informal care. Hospital costs were retrieved through data linkage. Multivariate regression analysis was used to examine cost predictors. Overall, 298 patients were included in the analysis, including 136 breast cancer, 83 colorectal cancer and 79 prostate cancer patients. The average monthly societal cost was $ US 409 (95%CI: $ US 316-$ US 502) [mean: £ 260, 95%CI: £ 198-£ 322] and was incurred by 92% of patients. This was divided into costs to the National Health Service (mean: $ US 279, 95%CI: $ US 207-$ US 351) [mean: £ 177, 95%CI: £ 131-£ 224], patients' out-of-pocket (OOP) expenses (mean: $ US 40, 95%CI: $ US 15-$ US 65) [mean: £ 25, 95%CI: £ 9-£ 42] and the cost of informal care (mean: $ US 110, 95%CI: $ US 57-$ US 162) [mean: £ 70, 95%CI: £ 38-£ 102]. The distribution of costs was skewed with a small number of patients incurring very high costs. Multivariate analyses showed higher societal costs for breast cancer patients. Significant predictors of OOP costs included age and socioeconomic deprivation. This study found the economic burden of cancer survivorship is unevenly distributed in the population and that cancer survivors may still incur substantial costs over 1 year post-diagnosis. In addition, this study illustrates the feasibility of using an innovative online data collection platform to collect patient-reported resource utilisation information. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Reporting Late Rectal Toxicity in Prostate Cancer Patients Treated With Curative Radiation Treatment

    International Nuclear Information System (INIS)

    Faria, Sergio L.; Souhami, Luis; Joshua, Bosede; Vuong, Te; Freeman, Carolyn R.

    2008-01-01

    Purpose: Long-term rectal toxicity is a concern for patients with prostate cancer treated with curative radiation. However, comparing results of late toxicity may not be straightforward. This article reviews the complexity of reporting long-term side effects by using data for patients treated in our institution with hypofractionated irradiation. Methods and Materials: Seventy-two patients with localized prostate cancer treated with hypofractionated radiotherapy alone to a dose of 66 Gy in 22 fractions were prospectively assessed for late rectal toxicity according to the Common Toxicity Criteria, Version 3, scoring system. Ninety percent of patients had more than 24 months of follow-up. Results are compared with data published in the literature. Results: We found an actuarial incidence of Grade 2 or higher late rectal toxicity of 27% at 30 months and a crude incidence of Grade 2 or higher late rectal toxicity of 18%. This was mostly severe toxicity documented during follow-up. The incidence of Grade 3 rectal toxicity at the last visit was 3% compared with 13% documented at any time during follow-up. Conclusion: Comparison of late toxicity after radiotherapy in patients with prostate cancer must be undertaken with caution because many factors need to be taken into consideration. Because accurate assessment of late toxicity in the evaluation of long-term outcome after radiotherapy in patients with localized prostate cancer is essential, there is a need to develop by consensus guidelines for assessing and reporting late toxicity in this group of patients

  2. Evaluation of quality of life and psychological response in cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Takahashi, Takeo; Hondo, Mikito; Nishimura, Keiichiro; Kitani, Akira; Yamano, Takafumi; Yanagita, Hisami; Osada, Hisato; Shinbo, Munefumi; Honda, Norinari

    2008-01-01

    The importance of the quality of life (QOL) and mental condition of patients being treated for cancer is now recognized. In this study, we evaluated QOL and mental condition in patients with cancer before and after radiotherapy. The subjects were 170 patients who had undergone radiotherapy. The examination of QOL was performed using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), and mental condition (anxiety and depression) was examined using the hospital anxiety and depression scale (HADS). These examinations were performed at the start of radiotherapy and immediately after radiotherapy. The QOL score was slightly higher in all patients after the completion of radiotherapy than before the start of radiotherapy. In the palliative radiotherapy group, QOL score was significantly improved by treatment. Anxiety and depression were improved after radiotherapy. There was a correlation between the degrees of improvement of the HADS and QOL score. We could treat cancer patients by radiotherapy without reducing their QOL, and improvement in QOL was significant in the palliative radiotherapy group. Mental condition was also improved after radiotherapy. (author)

  3. DNA damage response (DDR) pathway engagement in cisplatin radiosensitization of non-small cell lung cancer.

    Science.gov (United States)

    Sears, Catherine R; Cooney, Sean A; Chin-Sinex, Helen; Mendonca, Marc S; Turchi, John J

    2016-04-01

    Non-small cell lung cancers (NSCLC) are commonly treated with a platinum-based chemotherapy such as cisplatin (CDDP) in combination with ionizing radiation (IR). Although clinical trials have demonstrated that the combination of CDDP and IR appear to be synergistic in terms of therapeutic efficacy, the mechanism of synergism remains largely uncharacterized. We investigated the role of the DNA damage response (DDR) in CDDP radiosensitization using two NSCLC cell lines. Using clonogenic survival assays, we determined that the cooperative cytotoxicity of CDDP and IR treatment is sequence dependent, requiring administration of CDDP prior to IR (CDDP-IR). We identified and interrogated the unique time and agent-dependent activation of the DDR in NSCLC cells treated with cisplatin-IR combination therapy. Compared to treatment with CDDP or IR alone, CDDP-IR combination treatment led to persistence of γH2Ax foci, a marker of DNA double-strand breaks (DSB), for up to 24h after treatment. Interestingly, pharmacologic inhibition of DDR sensor kinases revealed the persistence of γ-H2Ax foci in CDDP-IR treated cells is independent of kinase activation. Taken together, our data suggest that delayed repair of DSBs in NSCLC cells treated with CDDP-IR contributes to CDDP radiosensitization and that alterations of the DDR pathways by inhibition of specific DDR kinases can augment CDDP-IR cytotoxicity by a complementary mechanism. Published by Elsevier B.V.

  4. Risk of thromboembolism in cisplatin versus carboplatin-treated patients with lung cancer.

    Science.gov (United States)

    Kim, Eric S; Baran, Andrea M; Mondo, Esther L; Rodgers, Thomas D; Nielsen, Gradon C; Dougherty, David W; Pandya, Kishan J; Rich, David Q; van Wijngaarden, Edwin

    2017-01-01

    Carboplatin is widely used to treat lung cancer in the United States as an alternative to cisplatin. Several studies have demonstrated that cisplatin-based regimen is associated with a high frequency of thromboembolic complications. However, there has been limited investigation directly comparing the risk of thromboembolic events (TEEs) between cisplatin- and carboplatin-treated patients with lung cancer. All lung cancer patients treated with cisplatin or carboplatin at Wilmot Cancer Center, University of Rochester between 2011 and 2014 were included. Patient characteristics including exposure (cisplatin vs. carboplatin) and outcome (TEEs between the time of the first dose of cisplatin or carboplatin and 4 weeks after the last dose) were collected by reviewing electronic medical records. A Fisher's exact test was used to compare the proportion of incident TEEs between cisplatin and carboplatin groups. The risk of TEE associated with carboplatin compared to cisplatin was assessed using multiple logistic regression. Among 415 subjects, 317 patients (76.4%) received carboplatin and 98 (23.6%) patients received cisplatin. In the carboplatin group, 10.9% (33/302) of evaluable patients developed treatment-related TEEs vs. 14.7% (14/95) in the cisplatin group. There was no significant difference in the risk of developing TEEs between the two groups (P = 0.32). However, 15.2% of carboplatin-related TEEs were arterial thromboses compared to none in the cisplatin group. The incidence of carboplatin-related TEEs was high in lung cancer patients without significant difference in the risk of developing TEEs between cisplatin and carboplatin groups. Potential use of prophylactic anticoagulation in all platinum-treated patients should be further investigated.

  5. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lisa Helene Toft; Østerlind, Kell Erik; Rytter, C.

    2008-01-01

    treatment of non-small cell lung cancer (NSCLC). Secondary aims were to evaluate toxicity, efficacy, and subjective reasons the preference. PATIENTS AND METHODS: Sixty-one patients were randomized in a cross-over trial to two cycles of carboplatin day 1 and vinorelbine day 1 and day 8 iv followed by two...

  6. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  7. The role of Gefitinib in patients with non-small-cell lung cancer in India

    Directory of Open Access Journals (Sweden)

    Asmita Anilkumar Mehta

    2013-01-01

    Full Text Available Background: Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, represents a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC. We analyzed the data of patients who received Gefitinib for NSCLC in a tertiary care center in South India. Materials and Methods: Sixty-three patients with advanced NSCLC who had received Gefitinib either after failure of conventional chemotherapy or were previously not treated as they were unfit or unwilling for conventional treatment were included in the analysis. Results: The median follow-up for the cohort was 311 days (range 11-1544 days. Median time to progression was 161 (range 9-883 days. Complete and partial remission was seen in 1 (2% and 6 (9% patients, respectively, with overall response rate of 11%. Twenty-four (38% patients had stable disease. Gefitinib was well tolerated with no significant side effects. Conclusion: Gefitinib shows anti-tumor activity in pretreated or previously untreated patients with advanced NSCLC. It has a favorable toxicity profile and is well tolerated. Gefitinib should be considered as a viable therapy in patients with NSCLC.

  8. Thymidylate synthase protein expression levels remain stable during paclitaxel and carboplatin treatment in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    BACKGROUND: Thymidylate synthase (TS) is a potential predictive marker for efficacy of treatment with pemetrexed. The current study aimed at investigating whether TS expression changes during non-pemetrexed chemotherapy of non-small cell lung cancer (NSCLC), thus making rebiopsy necessary...... for deciding on pemetrexed second-line treatment. MATERIALS AND METHODS: TS immunohistochemístry was performed on biopsies and available resection specimens from 65 NSCLC patients stage T1-3N0-2 treated with preoperative carboplatin and paclitaxel [neoadjuvant chemotherapy (NAC)-group] and from 53 NSCLC...... in primary tumors remained unchanged, and new biopsies for deciding on second-line pemetrexed does not seem warranted based on the current results....

  9. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

    NARCIS (Netherlands)

    Breugom, A. J.; van Gijn, W.; Muller, E. W.; Berglund, Å; van den Broek, C. B. M.; Fokstuen, T.; Gelderblom, H.; Kapiteijn, E.; Leer, J. W. H.; Marijnen, C. A. M.; Martijn, H.; Meershoek-Klein Kranenbarg, E.; Nagtegaal, I. D.; Påhlman, L.; Punt, C. J. A.; Putter, H.; Roodvoets, A. G. H.; Rutten, H. J. T.; Steup, W. H.; Glimelius, B.; van de Velde, C. J. H.

    2015-01-01

    The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with

  10. Renal function and symptoms/adverse effects in opioid-treated patients with cancer

    DEFF Research Database (Denmark)

    Kurita, G P; Lundström, S; Sjøgren, P

    2015-01-01

    BACKGROUND: Renal impairment and the risk of toxicity caused by accumulation of opioids and/or active metabolites is an under-investigated issue. This study aimed at analysing if symptoms/adverse effects in opioid-treated patients with cancer were associated with renal function. METHODS: Cross...... and cognitive dysfunction were assessed (EORTC QLQ-C30). Glomerular filtration rate (GFR) was estimated using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Creatinine) equations. RESULTS: Mild to severe low GFR was observed...... in routine cancer pain care....

  11. Targeting Redox Homeostasis in LKB1-deficient NSCLC

    Science.gov (United States)

    2014-09-01

    profiling to identify critical nodes that regulate energy metabolism and antioxidant functions in LKB1-deficient NSCLC cells. LKB1 is a tumor suppressive...of exogenous EGF (Fig. 5B). EGF treatment stimulated phosphorylation of EGFR and Akt in both control and shLKB1 cells. EGFR phosphorylation was

  12. Breast cancer patients treated with chemotherapy reports more unmet supportive care needs in the early treatment phase, than patients treated only with radiotherapy

    DEFF Research Database (Denmark)

    Jensen-Johansen, Mikael Birkelund; Meldgaard, Anette; Henriksen, Jette

    2016-01-01

    treatment period. Eighty-five percent agreed to participate and 100 women filled out the baseline questionnaire. Forty-five women were under treatment with radiation-therapy, forty-nine with chemo-therapy and four women were treated with both radiation- and chemotherapy. Design and methods: As part......Breast Cancer Patients Treated with Chemo-therapy Reports More Unmet Supportive Care Needs in the Early Treatment Phase, than Patients Treated Only with Radio-therapy Jensen-Johansen, Mikael Birkelund, Meldgaard, Anette, Henriksen, Jette, Villadsen, Ingrid VIA University College, Holstebro, Denmark...... Aims: The purpose was to identify unmet supportive care needs in the early treatment phase of women treated for breast cancer and to investigate differences in needs between groups treated with chemo-therapy and radiationtherapy. If it is possible to identify early unmet needs, it may be possible...

  13. Sublobar resection versus lobectomy in patients aged ≤35 years with stage IA non-small cell lung cancer: a SEER database analysis.

    Science.gov (United States)

    Gu, Chang; Wang, Rui; Pan, Xufeng; Huang, Qingyuan; Zhang, Yangyang; Yang, Jun; Shi, Jianxin

    2017-11-01

    Sublobar resection has been increasingly adopted in elderly patients with stage IA non-small cell lung cancer (NSCLC), but the equivalency of sublobar resection versus lobectomy among young patients with stage IA NSCLC is unknown. Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified patients aged ≤35 years who were diagnosed between 2004 and 2013 with pathological stage IA NSCLC and treated with sublobar resection or lobectomy. We used propensity-score matching to minimize the effect of potential confounders that existed in the baseline characteristics of patients in different treatment groups. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of patients who underwent sublobar resection or lobectomy were compared in stratification analysis. Overall, we identified 188 patients who had stage IA disease, 32 (17%) of whom underwent sublobar resection. We did not identify any difference in OS/LCSS between patients who received sublobar resection versus lobectomy before (log-rank p = 0.6354) or after (log-rank p = 0.5305) adjusting for propensity scores. Similarly, we still could not recognize different OS/LCSS rates among stratified T stage groups or stratified lymph node-removed groups before or after adjusting for propensity scores. Sublobar resection is not inferior to lobectomy for young patients with stage IA NSCLC. Considering sublobar resection better preserves lung function and has reduced overall morbidity, sublobar resection may be preferable for the treatment of young patients with stage IA NSCLC.

  14. CT-guided 125I seeds implantation combined with NP chemotherapy for the treatment of intractable central airway stenosis caused by NSCLC

    International Nuclear Information System (INIS)

    Hu Yongjin; Du Xueming; Xu Jianhui; Wu Chunwa

    2012-01-01

    Objective: To explore the clinical value of radioactive 125 I seeds implantation combined with NP in treating intractable central airway stenosis caused by non-small cell cancer (NSCLC). Methods: A prospective cohort study of 80 patients, who were admitted to Beichen hospital (Tianjin, China) during the period from January 2004 to March 2010, were enrolled in this study. The patients were randomly divided into study group (n=42) and control group (n=38). Percutaneous CT-guided intratumoral implantation of 125 I seeds was carried out in the patients of the study group. Treatment plan system (TPS) was used to design the distribution and the number of 125 I seeds with PD=80-100 CY, and the source intensity was 0.8 mCi. Three days after operation the NP chemotherapy started and it was performed for 2 cycles. Only two cycles of NP chemotherapy was used for the patients in the control group. After the treatment, the cross area of the airway at its narrowest level was measured and the dyspnea index was evaluated. Results: All the patients were followed up for two months. The preoperative and postoperative stenosis rate of the airway in study group was 47.82%±17.55% and 15.76%±4.65%, respectively. The trachea was unobstructed and the dyspnea was markedly improved. The postoperative cross area of the airway at its narrowest level was significantly bigger than the preoperative one (P 0.05). Conclusion: Radioactive 125 I seeds implantation combined with NP chemotherapy is a safe and effective treatment for NSCLC. (authors)

  15. Screening for thyroid cancer in survivors of childhood and young adult cancer treated with neck radiation.

    Science.gov (United States)

    Tonorezos, Emily S; Barnea, Dana; Moskowitz, Chaya S; Chou, Joanne F; Sklar, Charles A; Elkin, Elena B; Wong, Richard J; Li, Duan; Tuttle, R Michael; Korenstein, Deborah; Wolden, Suzanne L; Oeffinger, Kevin C

    2017-06-01

    The optimal method of screening for thyroid cancer in survivors of childhood and young adult cancer exposed to neck radiation remains controversial. Outcome data for a physical exam-based screening approach are lacking. We conducted a retrospective review of adult survivors of childhood and young adult cancer with a history of neck radiation followed in the Adult Long-Term Follow-Up Clinic at Memorial Sloan Kettering between November 2005 and August 2014. Eligible patients underwent a physical exam of the thyroid and were followed for at least 1 year afterwards. Ineligible patients were those with prior diagnosis of benign or malignant thyroid nodules. During a median follow-up of 3.1 years (range 0-9.4 years), 106 ultrasounds and 2277 physical exams were performed among 585 patients. Forty survivors had an abnormal thyroid physical exam median of 21 years from radiotherapy; 50% of those with an abnormal exam were survivors of Hodgkin lymphoma, 60% had radiation at ages 10-19, and 53% were female. Ultimately, 24 underwent fine needle aspiration (FNA). Surgery revealed papillary carcinoma in seven survivors; six are currently free of disease and one with active disease is undergoing watchful waiting. Among those with one or more annual visits, representing 1732 person-years of follow-up, no cases of thyroid cancer were diagnosed within a year of normal physical exam. These findings support the application of annual physical exam without routine ultrasound for thyroid cancer screening among survivors with a history of neck radiation. Survivors with a history of neck radiation may not require routine thyroid ultrasound for thyroid cancer screening. Among adult survivors of childhood and young adult cancer with a history of radiation therapy to the neck, annual physical exam is an acceptable thyroid cancer screening strategy.

  16. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma.

    Science.gov (United States)

    Raissouni, Soundouss; Raissouni, Ferdaous; Rais, Ghizlane; Aitelhaj, Meryem; Lkhoyaali, Siham; Latib, Rachida; Mohtaram, Amina; Rais, Fadoua; Mrabti, Hind; Kabbaj, Nawal; Amrani, Naima; Errihani, Hassan

    2012-08-09

    Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  17. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Raissouni Soundouss

    2012-08-01

    Full Text Available Abstract Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders.

  18. Second cancer risk and mortality in men treated with radiotherapy for stage I seminoma

    Science.gov (United States)

    Horwich, A; Fossa, S D; Huddart, R; Dearnaley, D P; Stenning, S; Aresu, M; Bliss, J M; Hall, E

    2014-01-01

    Background: Patients with stage I testicular seminoma are typically diagnosed at a young age and treatment is associated with low relapse and mortality rates. The long-term risks of adjuvant radiotherapy in this patient group are therefore particularly relevant. Methods: We identified patients and obtained treatment details from 12 cancer centres (11 United Kingdom, 1 Norway) and ascertained second cancers and mortality through national registries. Data from 2629 seminoma patients treated with radiotherapy between 1960 and 1992 were available, contributing 51 151 person-years of follow-up. Results: Four hundred and sixty-eight second cancers (excluding non-melanoma skin cancers) were identified. The standardised incidence ratio (SIR) was 1.61 (95% confidence interval (CI): 1.47–1.76, P<0.0001). The SIR was 1.53 (95% CI: 1.39–1.68, P<0.0001) when the 32 second testicular cancers were also excluded. This increase was largely due to an excess risk to organs in the radiation field; for pelvic–abdominal sites the SIR was 1.62 (95% CI: 1.43–1.83), with no significant elevated risk of cancers in organs elsewhere. There was no overall increase in mortality with a standardised mortality ratio (SMR) of 1.06 (95% CI: 0.98–1.14), despite an increase in the cancer-specific mortality (excluding testicular cancer deaths) SMR of 1.46 (95% CI: 1.30–1.65, P<0.0001). Conclusion: The prognosis of stage I seminoma is excellent and it is important to avoid conferring long-term increased risk of iatrogenic disease such as radiation-associated second cancers. PMID:24263066

  19. Is IMRT Superior or Inferior to 3DCRT in Radiotherapy for NSCLC? A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Xingsheng Hu

    Full Text Available There are no adequate data to determine whether intensity-modulated radiotherapy (IMRT is superior to three-dimensional conformal radiotherapy (3DCRT in the treatment of non-small cell lung cancer (NSCLC. This meta-analysis was conducted to compare the clinical outcomes of IMRT and 3DCRT in the treatment of NSCLC.No exclusions were made based on types of study design. We performed a literature search in PubMed, EMBASE and the Cochrane library databases from their inceptions to April 30, 2015. The overall survival (OS and relative risk (RR of radiation pneumonitis and radiation oesophagitis were evaluated. Two authors independently assessed the methodological quality and extracted data. Publication bias was evaluated by funnel plot using Egger's test results.From the literature search, 10 retrospective studies were collected, and of those, 5 (12,896 patients were selected for OS analysis, 4 (981 patients were selected for radiation pneumonitis analysis, and 4 (1339 patients were selected for radiation oesophagitis analysis. Cox multivariate proportional hazards models revealed that 3DCRT and IMRT had similar OS (HR = 0.96, P = 0.477 but that IMRT reduced the incidence of grade 2 radiation pneumonitis (RR = 0.74, P = 0.009 and increased the incidence of grade 3 radiation oesophagitis (RR = 2.47, P = 0.000.OS of IMRT for NSCLC is not inferior to that of 3DCRT, but IMRT significantly reduces the risk of radiation pneumonitis and increases the risk of radiation oesophagitis compared to 3DCRT.

  20. Pharmacological management of relapsed/refractory NSCLC with chemical drugs.

    Science.gov (United States)

    Karachaliou, Niki; Sosa, Aaron E; Barron, Feliciano Barron; Gonzalez Cao, Maria; Santarpia, Mariacarmela; Rosell, Rafael

    2017-02-01

    Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach. Areas covered: In this review we are discussing the current treatment of relapsed or refractory lung cancer. We have thoroughly searched the literature (Pubmed) the last five years for studies or reviews published on the issue of second-line therapy in lung cancer using as key words, lung cancer, relapse, EGFR mutations, ALK rearrangements, chemotherapy and immunotherapy Expert opinion: The prognosis of lung cancer has been radically improved. Due to the recent development of checkpoint inhibitors, this also occurs for patients whose tumor's are not driven by a genetic alteration and who, until recently, derived only minimal benefit from chemotherapy.

  1. Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer

    Science.gov (United States)

    2018-03-02

    Recurrent Colon Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Rectal Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Rectal Cancer AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal

  2. SU-E-T-289: Dose-Volume-Effect Relationships for Lung Cancer Patients Treated with SBRT On a Prospective Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Mayyas, E; Brown, S; Liu, J; Kim, J; Sun, Z; Devpura, S; Ajlouni, M; Siddiqui, F; Movsas, B; Chetty, I [Henry Ford Hospital, Detroit, MI (United States)

    2015-06-15

    Purpose: Stereotactic body radiotherapy (SBRT) is commonly used to treat early stage lung tumors. This study was designed to evaluate associations between dose, volume and clinical outcomes including analysis of both clinical toxicity scores and quality of life (QOL) data for non-small cell lung cancer patients treated with SBRT. Preliminary results are presented. Methods: Sixty-seven NSCLC patients, 46 primarily with early stage, and 21 with recurrent disease were treated with dose regimens consisting mainly of 12 Gy x 4 fractions, and 3 or 5 fractions at lower dose, for patients with recurrent disease (Table 1). Follow-up data is being collected at baseline, after treatment and at 3, 6, 12, 18 and 24 months post-treatment. Clinical follow-up data acquired to date was assessed using the Charlson Comorbidity Clinical and Toxicity Scoring forms. QOL data was evaluated using the EQ-5D, and FACT-TOI validated surveys. All outcomes surveys are collected within an “in-house” developed outcomes database. Results: The median follow-up was 3.5±0.8 months. Mean lung doses (MLD) were converted to BED-2 Gy using the linear-quadratic model with an alpha/beta=3.0. Average MLD was 3.7+3.1 Gy (range: 0.4–20.9 Gy). The percentages of patients with > grade 2 cough, dyspnea and fatigue were 13.3, 17.0, 6.3%, respectively. Preliminary analyses (at 3 months after SBRT) show a mild correlation between MLD > 2 Gy and > grade 2 cough (borderline significant) and dyspnea (significant, p<0.05). One patient was observed with a grade 3 cough. Given the short follow-up, tumor control is not yet assessable. Conclusion: The SBRT dose fractionation regimen of 12 Gy x 4 was well tolerated at early time points. Additional follow-up is required to assess the long-term clinical outcome efficacy and toxicity profiles of the dose regimen.

  3. SU-E-T-289: Dose-Volume-Effect Relationships for Lung Cancer Patients Treated with SBRT On a Prospective Protocol

    International Nuclear Information System (INIS)

    Mayyas, E; Brown, S; Liu, J; Kim, J; Sun, Z; Devpura, S; Ajlouni, M; Siddiqui, F; Movsas, B; Chetty, I

    2015-01-01

    Purpose: Stereotactic body radiotherapy (SBRT) is commonly used to treat early stage lung tumors. This study was designed to evaluate associations between dose, volume and clinical outcomes including analysis of both clinical toxicity scores and quality of life (QOL) data for non-small cell lung cancer patients treated with SBRT. Preliminary results are presented. Methods: Sixty-seven NSCLC patients, 46 primarily with early stage, and 21 with recurrent disease were treated with dose regimens consisting mainly of 12 Gy x 4 fractions, and 3 or 5 fractions at lower dose, for patients with recurrent disease (Table 1). Follow-up data is being collected at baseline, after treatment and at 3, 6, 12, 18 and 24 months post-treatment. Clinical follow-up data acquired to date was assessed using the Charlson Comorbidity Clinical and Toxicity Scoring forms. QOL data was evaluated using the EQ-5D, and FACT-TOI validated surveys. All outcomes surveys are collected within an “in-house” developed outcomes database. Results: The median follow-up was 3.5±0.8 months. Mean lung doses (MLD) were converted to BED-2 Gy using the linear-quadratic model with an alpha/beta=3.0. Average MLD was 3.7+3.1 Gy (range: 0.4–20.9 Gy). The percentages of patients with > grade 2 cough, dyspnea and fatigue were 13.3, 17.0, 6.3%, respectively. Preliminary analyses (at 3 months after SBRT) show a mild correlation between MLD > 2 Gy and > grade 2 cough (borderline significant) and dyspnea (significant, p<0.05). One patient was observed with a grade 3 cough. Given the short follow-up, tumor control is not yet assessable. Conclusion: The SBRT dose fractionation regimen of 12 Gy x 4 was well tolerated at early time points. Additional follow-up is required to assess the long-term clinical outcome efficacy and toxicity profiles of the dose regimen

  4. Pain management of opioid-treated cancer patients in hospital settings in Denmark

    DEFF Research Database (Denmark)

    Lundorff, L.; Peuckmann, V.; Sjøgren, Per

    2008-01-01

    AIM: To evaluate the performance and quality of cancer pain management in hospital settings. METHODS: Anaesthesiologists specialised in pain and palliative medicine studied pain management in departments of oncology and surgery. Study days were randomly chosen and patients treated with oral opioids......-treated patients in hospital settings: however, focussing on average pain intensity, the outcome seems favourable compared with other countries. Pain mechanisms were seldom examined and adjuvant drugs were not specifically used for neuropathic pain. Opioid dosing intervals and supplemental opioid doses were most...

  5. The pitfalls of treating anorectal conditions after radiotherapy for prostate cancer.

    LENUS (Irish Health Repository)

    Thornhill, J A

    2012-03-01

    We present a salutary lesson learned from three cases with significant complications that followed anorectal intervention in the presence of radiation proctitis due to prior radiotherapy for adenocarcinoma of the prostate. After apparent routine rubber band ligation for painful haemorrhoids, one patient developed a colo-cutaneous fistula. Following laser coagulation for radiation proctitis, one patient required a pelvic exenteration for a fistula, while another developed a rectal stenosis. Those diagnosing and treating colonic conditions should be mindful of the increased prevalence of patients who have had radiotherapy for prostate cancer and the potential for complications in treating these patients.

  6. Exercise bra discomfort is associated with insufficient exercise levels among Australian women treated for breast cancer.

    Science.gov (United States)

    Gho, Sheridan A; Munro, Bridget J; Jones, Sandra C; Steele, Julie R

    2014-03-01

    Although participating in exercise is beneficial for breast cancer survivors, not being able to find a comfortable exercise bra can be a barrier to exercise. It is likely that side effects specific to breast cancer treatment exacerbate exercise bra discomfort. This study aimed to determine the relationship between patient characteristics, physical side effects, exercise bra discomfort and exercise behaviours. Four hundred thirty-two breast cancer survivors completed an online survey related to their treatment and demographic background, current exercise levels, reported exercise bra discomfort and breast cancer treatment side effects. Patient characteristics and exercise levels were considered in a binary logistic regression against reporting bra discomfort to ascertain significant relationships (p bra discomfort. Eight out of nine physical side effects were significantly related to reporting exercise bra discomfort. Reporting exercise bra discomfort was significantly related to not achieving a minimal recommended level of exercise. This is the first study in the scientific literature that systematically links the reporting of exercise bra discomfort to not achieving recommended levels of exercise. This effect of bra discomfort on exercise was found after controlling for age, surgery type and current treatment among a large cohort of women treated for breast cancer. Furthermore, results from this study suggest that physical side effects, as a result of surgery and treatment associated with breast cancer, are linked to experiencing bra discomfort during ex