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  1. Cervical Cancer Stage IIIB

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    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IIIB Add to My Pictures View /Download : ... 1425x1326 View Download Large: 2850x2651 View Download Title: Cervical Cancer Stage IIIB Description: Stage IIIB cervical cancer; drawing ...

  2. HIGH-DOSE RATE BRACHYTHERAPY IN CARCINOMA CERVIX STAGE IIIB

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    Sathya Maruthavanan

    2016-07-01

    Full Text Available INTRODUCTION Radiotherapy is the standard treatment in locally advanced (IIB-IVA and early inoperable cases. The current standard of practice with curable intent is concurrent chemoradiation in which intracavitary brachytherapy is an integral component of radiotherapy. This study aims at assessing the efficacy of HDR ICBT (High-dose rate intracavitary brachytherapy in terms local response, normal tissue reactions, and feasibility. METHODS AND MATERIALS A total of 20 patients of stage IIIB cancer of the uterine cervix were enrolled in the study and were planned to receive concurrent chemotherapy weekly along with EBRT (external beam radiotherapy to a dose of 50 Gy/25 Fr. Suitability for ICBT was assessed at 40 Gy/20 Fr. 6/20 patients were suitable at 40 Gy and received HDR ICBT with a dose of 5.5 Gy to point A in 4 sessions (5.5 Gy/4 Fr. The remaining 14/20 patients completed 50 Gy and received HDR ICBT with a dose of 6 Gy to point A in 3 sessions (6 Gy/3 Fr. RESULTS A total of 66 intracavitary applications were done and only one application required dose modification due to high bladder dose, the pelvic control rate was 85% (17/20. 10% (2/20 had stable disease and 5% (1/20 had progressive disease at one year of follow up. When toxicity was considered only 15% developed grade I and grade II rectal complications. Patient compliance and acceptability was 100%. Patients were very comfortable with the short treatment time as compared with patients on LDR ICBT (low-dose rate intracavitary brachytherapy treatment interviewed during the same period. CONCLUSION This study proves that HDR brachytherapy is efficacious and feasible in carcinoma of cervix stage IIIB. It also proves that good dose distribution can be achieved with HDR intracavitary facility by the use of dose optimization. The short treatment time in HDR ICBT makes it possible to maintain this optimised dose distribution throughout the treatment providing a gain in the therapeutic ratio and

  3. Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer

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    Grutsch James F

    2009-01-01

    Full Text Available Abstract Background A frequent manifestation of advanced lung cancer is malnutrition, timely identification and treatment of which can lead to improved patient outcomes. Bioelectrical impedance analysis (BIA is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated the prognostic role of BIA-derived phase angle in advanced non-small cell lung cancer (NSCLC. Methods A case series of 165 stages IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle, independent of stage at diagnosis and prior treatment history. Results 93 were males and 72 females. 61 had stage IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3 degrees (range = 2.9 – 8. Patients with phase angle 5.3 had 12.4 months (95% CI: 10.5 to 18.7; n = 84; (p = 0.02. After adjusting for age, stage at diagnosis and prior treatment history we found that every one degree increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64 to 0.97, P = 0.02. Conclusion We found BIA-derived phase angle to be an independent prognostic indicator in patients with stage IIIB and IV NSCLC. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with advanced NSCLC.

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

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    Bang, Sun-Hwi; 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.

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

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

    1996-01-01

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

  6. Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-08-29

    ALK Gene Translocation; EGFR Activating Mutation; Recurrent Non-Small Cell Lung Carcinoma; ROS1 Gene Translocation; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

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

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    Bang Sun-Hwi

    2012-06-01

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

  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?

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    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

  9. Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

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    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.

  10. Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

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    2018-03-02

    Anal Basaloid Carcinoma; Anal Canal Cloacogenic Carcinoma; Anal Margin Squamous Cell Carcinoma; Stage II Anal Canal Cancer AJCC v6 and v7; Stage III Anal Canal Cancer AJCC v6 and v7; Stage IIIA Anal Canal Cancer AJCC v6 and v7; Stage IIIB Anal Canal Cancer AJCC v6 and v7

  11. Comparing treatment outcomes of stage IIIB cervical cancer patients between those with and without lower third of vaginal invasion.

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    Katanyoo, Kanyarat

    2017-11-01

    To evaluate treatment outcomes between stage IIIB cervical cancer with and without lower third of vaginal invasion (LTI) in terms of response to treatment and overall survival (OS). Matching one patient with LTI for 2 patients without LTI who had completed treatment between 1995 and 2012 were conducted by using treatment modalities (radiation therapy [RT] alone vs. concurrent chemoradiation therapy [CCRT]) and tumor histology (squamous cell carcinoma [SCC] vs. adenocarcinoma [ADC]). Treatment outcomes including complete response (CR) rate of RT/CCRT, patterns of treatment failure and survival outcomes were analyzed. Of 216 stage IIIB cervical cancer patients, 114 of them had no LTI and 72 had LTI. Most of the patients (83.8%) had tumor histology as SCC. The CR rates between stage IIIB without LTI and with LTI were 93.8% and 81.9% (p=0.009), and corresponding with disease progression at pelvis accounted for 18.2% and 34.4% (p=0.017), respectively. Distant metastasis was comparable between 2 groups of patients, 28.9% in patients without LTI and 29.5% in patients with LTI (p=0.988). The 2-year and 5-year OS of stage IIIB without LTI were 66.5% and 46.8% compared to stage IIIB with LTI which were 43.1% and 28.9% (p=0.004), respectively. For multivariable analysis, stage IIIB with LTI was only the influential factor on OS with hazard ratio (HR) of 1.63 (p=0.012). Stage IIIB cervical cancer patients with LTI have poorer treatment outcomes including response to treatment and survival outcomes than patients in the same stage without LTI. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  12. Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

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    2018-04-10

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7

  13. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

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    2017-05-23

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  14. Hyperfractionated external radiation therapy in stage IIIB carcinoma of uterine cervix: a prospective pilot study

    International Nuclear Information System (INIS)

    Faria, Sergio L.; Ferrigno, Robson

    1997-01-01

    Purpose: Brazil has one of the highest incidence of carcinoma of the cervix in the world. Half of the patients have advanced stages at the diagnosis. Due to this large number of patients we decided to conduct a prospective pilot study to investigate the tolerance to and survival rate with hyperfractionated external radiotherapy only in patients with Stage IIIB carcinoma of the uterine cervix. Methods and Materials: Between January 1991 and December 1993, 23 patients underwent hyperfractionated external beam radiotherapy without brachytherapy. All cases were biopsy proven squamous cell carcinoma of cervix clinically Staged as IIIB (FIGO). Hyperfractionation (HFX) was given with 1.2 Gy doses, twice daily at 6-h interval, 5 days/week, to the whole pelvis up to 72 Gy within 30 working days. Complications were evaluated by an adaptation of the RTOG Radiation Morbidity Scoring Table graded as 1 = none/mild; 2 = moderate, and 3 = severe. Results: Follow-up ranged from 27 to 50 months (median 40 months) on the 9 to 23 living patients at the time of the analysis in December 1995. There was no severe acute toxicity, but moderate acute reaction was high: 74%. The commonest site of complication was the intestine where severe late toxicity occurred in 2 of 23 (9%). Overall survival rate at 27 months was 48% and at 40 months was 43%. Discussion: There is little information in literature about HFX in carcinoma of the cervix. This is the third published study about it and the one that gave the highest total dose with external HFX of 60 x 1.2 Gy = 72 Gy. Theoretically, through the linear quadratic formula this schedule of HFX would be equivalent to 30 x 2 Gy = 60 Gy of standard fractionation, both treatments given in 30 working days. HFX schedules must be tested to establish their safety. Present results suggest being possible to further increase the total dose in the pelvis with hyperfractionated irradiation

  15. Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity

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    Zuliani, Antonio Carlos; Cunha, Maercio de Oliveira, E-mail: aczo.rt@gmail.co [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Esteves, Sergio C.B. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Secao de Radioterapia; Teixeira, Julio Cesar [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Tocoginecologia

    2010-07-01

    Objective: to compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR), high-dose-rate (HDR) brachytherapy and association of HDR and chemotherapy. Methods: between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. Results: the five-year progression-free survival (PFS) was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02). The five-year Overall Survival (OS) was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p 0.02). Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. Conclusion: patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups. (author)

  16. Non-small cell lung cancer in stages I-IIIB. Long-term results of definitive radiotherapy with doses {>=} 80 Gy in standard fractionation

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    Wurstbauer, Karl; Weise, Hannes; Deutschmann, Heinz; Kopp, Peter; Merz, Florian; Sedlmayer, Felix [Univ. Clinic of Radiotherapy and Radiation Oncology and radART - Inst. for research and development on Advanced Radiation Technologies, Paracelsus Medical Univ., Salzburg (Austria); Studnicka, Michael [Univ. Clinic of Pneumology, Paracelsus Medical Univ., Salzburg (Austria); Nairz, Olaf [Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany)

    2010-10-15

    Purpose: To investigate therapeutic outcome of dose escalation {>=} 80 Gy in nonresected non-small cell lung cancer (NSCLC). Patients and Methods: 124 consecutive patients with histologically/cytologically proven NSCLC were enrolled. Tumor stage I, II, IIIA, and IIIB was diagnosed in 30, eight, 39, and 47 patients, respectively. 38 patients (31%) had weight loss > 5% during the 3 months before diagnosis. A median dose of 88.2 Gy (range 80.0-96.0 Gy), 69.3 Gy (63.0-88.0 Gy) and 56.7 Gy was applied to primary lesions, involved lymph nodes, and elective nodes (within a region of about 6 cm cranial to macroscopically involved nodes), respectively. Daily fractional ICRU doses of 2.0-2.2 Gy were delivered by the conformal target-splitting technique. 58 patients (47%) received induction chemotherapy, in median two cycles prior to radiotherapy. Results: Median follow-up time of all patients was 19 months, of patients alive 72.4 months (69-121 months). The cumulative actual overall survival rate at 2 and 5 years amounts to 39% and 11.3%, respectively, resulting in a median overall survival time of 19.6 months. According to stages I, II, IIIA, and IIIB, the median overall survival times are 31.8, 31.4, 19.0, and 14.5 months, respectively. The locoregional tumor control rate at 2 years is 49%. Apart from one treatment-related death (pneumonitis), acute toxicity according to EORTC/RTOG scores was moderate: lung grade 2 (n = 7), grade 3 (n = 3); esophagus grade 1 (n = 11); heart grade 3 (n = 1, pericarditis). No late toxicity grade > 1 has been observed. Conclusion: Sequential, conventionally fractionated high-dose radiotherapy by conformal target splitting is well tolerated. The results for survival and locoregional tumor control seem to at least equalize the outcome of simultaneous chemoradiation approaches, which, at present, are considered ''state of the art'' for patients with nonresected NSCLC. A higher potential of radiation therapy might be reached

  17. Our Experiences with Erlotinib in Second and Third Line Treatment Patients with Advanced Stage Iiib/ Iv Non-Small Cell Lung Cancer

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    Bakir Mehić

    2008-11-01

    Full Text Available HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV openlabel, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H were selected from two Clinical centres (Sarajevo and Banja Luka. The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19. This population is defined as the Intent to Treat (ITT population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III. Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI disorders.

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

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

    2015-01-01

    pts with early stage NSCLC. However, it is unknown if all pts have same benefit of SBRT due to lack of randomized studies. This retrospective single-institution study reports survival and control rates for medical inoperable octogenarians vs. pts 80 and 80 and 137 were 80 and 0.05). No difference...

  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

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    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.

  20. [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.

  1. Treatment of stage IIIB cervical cancer with Californium-252 fast-neutron brachytherapy and external photon therapy.

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    Gallion, H H; Maruyama, Y; van Nagell, J R; Donaldson, E S; Rowley, K C; Yoneda, J; Beach, J L; Powell, D E; Kryscio, R J

    1987-05-15

    From January 1977 to July 1984, 32 patients with Stage IIIB cervical cancer were treated at the University of Kentucky Medical Center by a combination of outpatient neutron brachytherapy and external pelvic radiation. These patients received 4500 to 5000 rad external photon therapy and two or three outpatient Californium-252 (252Cf) implants, plus sidewall boost irradiation. Treatment results were compared retrospectively to those obtained in a historical control group of patients with Stage IIIB cervical cancer treated with external radiation and conventional photon brachytherapy from 1972 to 1976. Local or regional tumor recurrence developed in 53% of patients treated with neutron therapy and an additional 9% experienced distant metastases. Thirty-eight percent of patients remain free of disease 12 to 96 months (mean, 51 months) after therapy. The 2-year and 5-year survival rates of patients treated with neutron therapy were 53% and 36%, which were not significantly different than those obtained with photon brachytherapy (2-year survival, 61%; 5-year survival, 34%). Complications of neutron therapy were minimal and included proctitis (19%) and vaginal stenosis (9%). There were no cases of enteric fistulae. Outpatient neutron brachytherapy was cost effective and was well tolerated by patients.

  2. 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

  3. FIGO Stage IIIB squamous cell carcinoma of the uterine cervix: natural history, treatment results, and prognostic factors

    International Nuclear Information System (INIS)

    Eifel, Patricia J.; Logsdon, Mark D.

    1996-01-01

    Purpose: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix. Materials and Methods: The hospital and radiotherapy records of 1007 consecutive patients treated between 1960 and 1989 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. All patients were treated with radiation therapy (RT) either with curative intent (903 patients) or to palliate symptoms (104 patients). Patients who were selected for palliative treatment usually had a combination of adverse characteristics including massive tumor with bilateral pelvic wall fixation, hydronephrosis, bulky adenopathy, pathologic evidence of extrapelvic disease, and poor performance status. 64 (7%) of 903 patients failed to complete planned curative RT either because of progressive disease, complications, or poor compliance. Of 903 patients treated with curative intent, 319 (35%) were treated with external beam radiotherapy (EBRT) alone and 586 (65%) were treated with a combination of EBRT and intracavitary irradiation (ICRT). EBRT was usually delivered using 18-25 MV photons and ICRT was administered with Fletcher-Suit-Delclos applicators. Treatment philosophies evolved during the study period with greater emphasis placed on EBRT between 1966 and 1979 (52% treated with EBRT alone) compared with the other study years (15% treated with EBRT alone). 206 patients received investigational treatments including neutrons (69 pts), hyperbaric oxygen (66 pts), concurrent chemotherapy (29 pts), or neoadjuvant chemotherapy (42 pts). 875 patients have been followed until death. Median follow up for surviving patients is 171 months with only 9 surviving patients followed for 10%, or hgb < 10 gm% before treatment or at any time during radiotherapy. DSS was significantly better for patients whose treatment included ICRT (43% vs 21%; P< 0.0001). Also, patients who received

  4. 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

  5. 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

  6. 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

  7. Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens

    International Nuclear Information System (INIS)

    Mayer, A.; Nemeskeri, C.; Petnehazi, C.; Varga, S.; Naszaly, A.; Borgulya, G.

    2004-01-01

    Background: comprehensive literature on cervical cancer demonstrates, even today, the need for optimization of the timing of external-beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) in the treatment of stage IIA/B-IIIB cervical carcinoma. Patients and methods: 210 patients with carcinoma of the cervix were treated in the Municipal Center of Oncoradiology between January 1991 and December 1996 (FIGO IIA: n = 10, FIGO IIB: n = 113, and FIGO IIIB: n = 87). Two regimens were compared: sequential radiation therapy (SRT) with 4 x 8 Gy HDR-BT to point A followed by EBRT, and continuous radiation therapy (CRT) in which 5 x 6 Gy HDR-BT to point A, one session per week, was integrated into the EBRT. A total dose of 68-70 Gy to point A and 52-54 Gy to point B was given in EBRT with SRT, five fractions per week were applied. Four fractions per week were applied in CRT, i.e., no EBRT was performed on the day of HDR-BT. Total doses to points A and B were identical in both regimens. Overall treatment time (OTT) amounted to 56 days for SRT and 35 days for CRT. Median follow-up time was 3.4 (2.5-4.2) years. Results: progression-free 5-year-survival (PFS) was 71% in the CRT and 56% in the SRT group. Nevertheless, this difference was not statistically significant (p = 1.00), and the same was found in a subgroup analysis of the different tumor stages, showing, however, an unequivocal trend. Late bladder and rectal injuries occurred in 13% and 25%, respectively. Late rectal injuries were significantly more frequent with SRT than CRT (35 patients in the SRT and 18 patients in the CRT group; p = 0.037). This was due to the higher doses per fraction of HDR-BT in the SRT group. No difference was found regarding late bladder injuries (p = 0.837). Conclusion: for the patients included in this study, no advantage has been found so far in using CRT, i.e., shortening the OTT by weekly integration of HDR-BT into EBRT. Nevertheless, an obvious trend exists. The dose of 8 Gy per

  8. Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, A.; Nemeskeri, C.; Petnehazi, C.; Varga, S.; Naszaly, A. [Center of Oncoradiology, Uzsoki Hospital, Budapest (Hungary); Borgulya, G. [National Pediatric Cancer Registry of the Hungarian Pediatric Oncology Working Group, 2nd Dept. of Pediatrics, Semmelweis Univ. Budapest (Hungary)

    2004-04-01

    Background: comprehensive literature on cervical cancer demonstrates, even today, the need for optimization of the timing of external-beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) in the treatment of stage IIA/B-IIIB cervical carcinoma. Patients and methods: 210 patients with carcinoma of the cervix were treated in the Municipal Center of Oncoradiology between January 1991 and December 1996 (FIGO IIA: n = 10, FIGO IIB: n = 113, and FIGO IIIB: n = 87). Two regimens were compared: sequential radiation therapy (SRT) with 4 x 8 Gy HDR-BT to point A followed by EBRT, and continuous radiation therapy (CRT) in which 5 x 6 Gy HDR-BT to point A, one session per week, was integrated into the EBRT. A total dose of 68-70 Gy to point A and 52-54 Gy to point B was given in EBRT with SRT, five fractions per week were applied. Four fractions per week were applied in CRT, i.e., no EBRT was performed on the day of HDR-BT. Total doses to points A and B were identical in both regimens. Overall treatment time (OTT) amounted to 56 days for SRT and 35 days for CRT. Median follow-up time was 3.4 (2.5-4.2) years. Results: progression-free 5-year-survival (PFS) was 71% in the CRT and 56% in the SRT group. Nevertheless, this difference was not statistically significant (p = 1.00), and the same was found in a subgroup analysis of the different tumor stages, showing, however, an unequivocal trend. Late bladder and rectal injuries occurred in 13% and 25%, respectively. Late rectal injuries were significantly more frequent with SRT than CRT (35 patients in the SRT and 18 patients in the CRT group; p = 0.037). This was due to the higher doses per fraction of HDR-BT in the SRT group. No difference was found regarding late bladder injuries (p = 0.837). Conclusion: for the patients included in this study, no advantage has been found so far in using CRT, i.e., shortening the OTT by weekly integration of HDR-BT into EBRT. Nevertheless, an obvious trend exists. The dose of 8 Gy per

  9. Transition of historial tube flaps to free flap for 2-stage total knee arthroplasty in a patient with a history of Gustilo grade IIIB tibia fracture.

    Science.gov (United States)

    Spence, Sean A; Doren, Erin L; Dayicioglu, Deniz; Bernasek, Thomas

    2014-06-01

    We report the case of a 56-year-old patient who had posttraumatic bilateral knee arthritis and underwent sequential bilateral total knee arthroplasty (TKA). The left knee joint required 2-stage reconstruction: a free flap for enhanced soft-tissue coverage and then left knee TKA. Uniquely, at age 16 years this patient sustained a left tibia grade IIIB high-energy crush injury in a car crash and underwent reconstruction with multiple pedicle tube flaps and transfer of soft tissues. Most of that reconstruction was done between the ages of 16 and 19. At age 56 years, staged TKA was performed. To our knowledge, this is the first report of a knee reconstructed with pedicle tube flaps for a grade IIIB tibial fracture, followed years later by free-flap coverage before TKA. This report offers insights and treatment recommendations through long-term follow-up of a unique case and a historical perspective on how reconstructive options have evolved.

  10. Neoadjuvant chemoradiotherapy for cStage IIIA/IIIB locally advanced gastric cancer

    International Nuclear Information System (INIS)

    Inoue, Tatsushi; Suto, Hiromasa; Kashiwagi, Hirotaka

    2010-01-01

    We evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) with radio-enhancing S-1 for locally advanced gastric cancer. Patients who had a gastric cancer infiltrating into other organs (T4) or with bulky N2 were enrolled in this study. They received oral S-1 (65 mg/m 2 /day) administration and 50 Gy radiotherapy followed by radical surgery. In 12 subjects (male:female ratio, 7:5; mean age, 70.0 years), 10 (83.3%) completed NACRT and 12 (100%) underwent curative resection. Histopathological efficacy (≥Grade 1b) and down staging were observed 6 patients (75.0%) and 5 (62.5%), respectively, in 8 T4 patients. The efficacy was ≥Grade 2 in all 4 patients with bulky N2. No extra-nodal invasion was noted. In this series 1-and 3-year survival rates were 90.9% and 60.6%, respectively, during a mean observation period of 18.6 months. This procedure is applicable even to hemorrhaging patients. Outstanding antineoplastic effects are expected in locally advanced gastric cancer. (author)

  11. Intraoperative photodynamic therapy in patients with IIIb and IIIc stages of locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    D. D. Pak

    2013-01-01

    Full Text Available The study of efficiency of intraoperative photodynamic therapy (PDT with Photosens as the step of combined modality treatment in patients with IIIВ and IIIС stages of breast cancer was performed. The long-term outcomes were evaluated in two groups of patients: group 1 – after radical extended mastectomy combined with chemotherapy, radiotherapy and chemo- and hormonal therapy (138 patients, group 2 – the same treatment combined with intraoperative PDT (36 patients. For the patients with PDT photosens was administered i.v. in single dose 0.3 mg/kg for 2 h before surgery. The irradiation of operative field was performed single time (the light dose 30 J/cm2, with separate irradiation of subclavian, axillar and adjacent regions (the light dose 50 J/cm2. The results showed that intraoperative PDT was associated with better recurrence-free survival rates in patients with breast cancer: in the PDT group the average recurrence free survival was 44.9±3.4 months, in the group without PDT — 35.3±2.1 months. The obtained results confirm that intraoperative PDT for locally advanced breast cancer can be used successfully for devitalization of cancer cells on the wound superface and for prevention of intraoperative tumor dissemination and post-operative recurrence. 

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  13. Prognostic value of the standardized uptake value for {sup 18}F-fluorodeoxyglucose in patients with stage IIIB melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Bastiaannet, E.; Hoekstra, H.J. [University of Groningen, Department of Surgical Oncology, University Medical Centre Groningen, PO Box 30.001, Groningen (Netherlands); Hoekstra, O.S. [VU Amsterdam, Nuclear Medicine and PET Research, University Medical Centre, Amsterdam (Netherlands); Jong, J.R. de; Brouwers, A.H. [University of Groningen, Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen (Netherlands); Suurmeijer, A.J.H. [University of Groningen, Department of Pathology, University Medical Centre Groningen, Groningen (Netherlands)

    2012-10-15

    FDG PET/CT is an excellent tool to detect melanoma metastases and also allows quantification of FDG uptake using standardized uptake value (SUV). The aim of this study was to prospectively investigate the potential prognostic value of SUV for disease-free survival (DFS) and disease-specific survival (DSS) for patients with stage IIIB melanoma. From November 2003 to March 2008, all consecutive patients were included in the present study. Inclusion criteria were: palpable, histology- or cytology-proven lymph node metastases of melanoma, and referred to the University Medical Centre Groningen for FDG PET and CT examination. Patients without distant metastases were evaluated. Multivariable survival analysis was performed to determine whether SUV was associated with DFS and DSS (Cox proportional hazard analysis). In 80 patients (without distant metastases, 65 %) SUV could be measured. Overall 5-year DFS was 41 % (95% CI 26-56 %) and 24 % (95% CI 12-38 %) in patients with a low and high SUVmean (p = 0.02), respectively. Overall 5-year DSS was 48 % (95% CI 31-62 %) and 30 % (95% CI 17-45 %) in patients with a low and high SUVmean (p = 0.04), respectively. In the multivariable analysis, SUVmean was associated with DFS (hazard ratio 1.7; p = 0.048), but was not associated with DSS (hazard ratio 1.6; p = 0.1). The number of positive nodes, extranodal growth and gender were also associated with survival. FDG uptake in clinically overt nodal melanoma metastases is inversely associated with DFS. Univariate analysis showed an association with DSS. However, after adjustment for potential confounders this association was no longer significant. If these findings are confirmed in larger studies, SUVmean could potentially be used (in addition to the number of positive nodes, tumour size and extranodal growth) as a factor in deciding on adjuvant systemic treatment. (orig.)

  14. Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    Science.gov (United States)

    2018-03-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage II Vaginal Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vaginal Cancer AJCC v6 and v7; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified

  15. 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

  16. Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity Braquiterapia para carcinoma epidermóide do colo do útero estádio IIIB: sobrevida e toxicidade

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Zuliani

    2010-01-01

    Full Text Available OBJECTIVE: To compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR, high-dose-rate (HDR brachytherapy and association of HDR and chemotherapy. METHODS. Between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. RESULTS: The five-year progression-free survival (PFS was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02. The five-year Overall Survival (OS was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p = 0.02. Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. CONCLUSION: Patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups.OBJETIVO: Comparar três diferentes tratamentos para câncer de colo do útero, estádio IIIB: braquiterapia de baixa taxa de dose (LDR, alta taxa de dose (HDR e associação entre HDR e quimioterapia, quanto à sobrevida e toxicidade. MÉTODOS: Entre 1985 e 2005, 230 pacientes com carcinoma epidermoide de colo do útero estádio IIIB receberam teleterapia pélvica em quatro campos, doses entre 40 e 50.4 Gy, e três complementações diferentes. Grupo LDR, com 42 pacientes, recebeu uma ou duas inser

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

    International Nuclear Information System (INIS)

    Sanchez, Doris; Falquez, Roberto

    2002-01-01

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

  18. 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.

  19. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

    Directory of Open Access Journals (Sweden)

    Zhang Xin

    2009-07-01

    Full Text Available Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors. Patients and methods Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed. Results The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5% were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%. Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth. Conclusion The fact that a higher percentage CD133+ cells were strongly associated

  20. 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.

  1. Complete loss of PTEN protein expression correlates with shorter time to brain metastasis and survival in stage IIIB/C melanoma patients with BRAFV600 mutations.

    Science.gov (United States)

    Bucheit, Amanda D; Chen, Guo; Siroy, Alan; Tetzlaff, Michael; Broaddus, Russell; Milton, Denai; Fox, Patricia; Bassett, Roland; Hwu, Patrick; Gershenwald, Jeffrey E; Lazar, Alexander J; Davies, Michael A

    2014-11-01

    Loss of function of PTEN is a frequent event in melanoma, particularly in tumors with BRAF(V600) mutations. The prevalence, pathologic features, and clinical outcomes associated with PTEN loss in patients with stage IIIB/C melanoma were interrogated to improve our understanding of the clinical significance of this molecular event. Archival tissue from lymphadenectomy specimens among patients (n = 136) with stage IIIB or IIIC melanoma was assessed by DNA sequencing for activating BRAF and NRAS mutations, and by immunohistochemistry for the expression of PTEN protein. Associations of these molecular aberrations with demographics, tumor characteristics, and clinical outcomes were determined. The prevalence of BRAF(V600) mutations (40% overall), NRAS mutations (10%), and PTEN loss (25%) did not vary by pathologic substage. BRAF/NRAS mutation status did not correlate with distant disease-free survival (DDFS) or overall survival (OS). Complete loss of PTEN expression correlated with shorter OS but not DDFS. When stratified by specific sites of distant metastasis, PTEN loss was associated with significantly shorter time to melanoma brain metastasis (MBM), but not to liver, lung, or bone metastasis. Analysis of PTEN in mutationally defined subsets showed that PTEN loss was significantly associated with OS and time to MBM in patients with BRAF(V600) mutations. Loss of PTEN protein expression correlates significantly with decreased OS and time to MBM in stage IIIB/C melanoma patients with BRAF(V600) mutations. The findings add to evidence supporting a significant role for PTEN loss and the PI3K-AKT pathway in melanoma. ©2014 American Association for Cancer Research.

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

    International Nuclear Information System (INIS)

    Moustakis, Christos; Blanck, Oliver; Ebrahimi Tazehmahalleh, Fatemeh; Chan, Mark ka heng; Ernst, Iris; Haverkamp, Uwe; Eich, Hans Theodor; Krieger, Thomas; Duma, Marciana-Nona; Oechsner, Markus; Ganswindt, Ute; Heinz, Christian; Alheit, Horst; Blank, Hilbert; Nestle, Ursula; Wiehle, Rolf; Kornhuber, Christine; Ostheimer, Christian; Petersen, Cordula; Pollul, Gerhard; Baus, Wolfgang; Altenstein, Georg; Beckers, Eric; Jurianz, Katrin; Sterzing, Florian; Kretschmer, Matthias; Seegenschmiedt, Heinrich; Maass, Torsten; Droege, Stefan; Wolf, Ulrich; Schoeffler, Juergen; Guckenberger, Matthias

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-15

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

  4. A case report of successful intraoperative photo- dynamic therapy as the step of combined modality treatment in patient with stage IIIb breast cancer

    Directory of Open Access Journals (Sweden)

    E. К. Saribekyan

    2013-01-01

    Full Text Available The case of successful combined modality treatment in patient with stage IIIB T4bN1M0 breast cancer is reported. The first step included 2 courses of neoadjuvant polychemotherapy in CAF regimen with decrease of tumor size. The second step was irradiation (total dose of 45 Gy of breast and areas of regional metastasis. The third step was radical mastectomy by Madden with polypositional intraoperative photodynamic therapy with photosens (the output laser power 1500 mW, light dose 30 J/cm2, total time of irradiation – 25.6 min. The histological study of surgical specimen showed infiltrative ductal carcinoma with metastases in 3 nodes without fat invasion. In the post-operative period the patient had 3 courses of adjuvant chemotherapy in CAF regimen. Currently the duration of recurrence-free survival after treatment is 4 years. 

  5. Estadiamentos pré-operatório e patológico do CPNPC: análise retrospectiva de 291 casos Preoperative and pathological staging of NSCLC: retrospective analysis of 291 cases

    Directory of Open Access Journals (Sweden)

    Riad Naim Younes

    2010-01-01

    Full Text Available OBJETIVO: O objetivo do presente estudo foi avaliar a eficácia do estadiamento clínico pré-operatório com tomografia computadorizada com o estadiamento patológico. MÉTODOS: Entre 1990 e 2005, foram revisados retrospectivamente os prontuários dos pacientes com câncer de pulmão não-pequenas células (CPNPC. O estágio clínico foi baseado em exames pré-operatórios de imagem. Tomografia por emissão de pósitrons não foi incluída na rotina de exames pré-operatórios. Lesões suspeitas, que contra-indicassem a ressecção cirúrgica curativa, foram confirmadas patologicamente. O estágio patológico foi considerado aquele baseado na análise patológica pós-operatória ou em biópsia de lesão suspeita. Foi gerada uma tabela de correlação entre estágio clínico e patológico. Foram calculados o índice kappa de Cohen, a sensibilidade, a especificidade, o valor preditivo positivo e negativo, e a acurácia. RESULTADOS: 291 prontuários de pacientes foram revisados. Os estágios Ia, Ib, IIa, IIb, IIIa, IIIb e IV foram encontrados em 8,9%, 31,9%, 0,3%, 18,6%, 25,4%, 11% e 3,8%, respectivamente. Estágio patológico foi diferente do estágio clínico em 33% dos pacientes (15% foram sobre-estadiados e 18% sub-estadiados. Sensibilidade, especificidade, valor preditivo positivo e negativo, e acurácia foram 78%, 69%, 82%, 64% e 67%, respectivamente. O índice kappa de Cohen foi de 0,574 (P OBJECTIVE: The objective of this study was to evaluate the accuracy of preoperative clinical staging with computed tomography in predicting the correct pathological stage. METHODS: Medical records of non-small cell lung cancer (NSCLC patients treated, from 1990 to 2005 were reviewed. Clinical stage was based on routine preoperative clinical and imaging evaluation. Positron emission tomography was not routinely performed. Suspected lesions, that would preclude a surgical resection, were pathologically confirmed. The pathological stage was based on final

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

    Science.gov (United States)

    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.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-08-01

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

  9. High expression of CIP2A protein is associated with tumor aggressiveness in stage I–III NSCLC and correlates with poor prognosis

    Directory of Open Access Journals (Sweden)

    Cha GQ

    2017-12-01

    Full Text Available Geqi Cha,1 Jianyu Xu,1 Xiangying Xu,1 Bin Li,2 Shan Lu,1 Abiyasi Nanding,3 Songliu Hu,1 Shilong Liu1 1Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 2Department of Plastic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, 3Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China Abstract: The aim of this work was to examine the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A in non-small cell lung cancer (NSCLC and analyze its correlation with clinical outcomes. CIP2A protein levels were detected by immunohistochemistry (IHC. One hundred and eighty-four of 209 (88.3% primary stage I–III NSCLC specimens and 4 of 38 (10.5% adjacent normal lung tissue specimens expressed CIP2A protein. High expression of CIP2A was detected in 38.8% (81/209 of the NSCLC specimens. Patients diagnosed histologically with late-stage NSCLC (p<0.001 and malignant nodes (p=0.001 exhibited high CIP2A expression. Univariate analysis using the log-rank test identified CIP2A expression as a prognostic predictor for overall survival (p=0.005. In multivariate analyses using the Cox regression test, CIP2A expression, T stage, N stage, histological type, and chemotherapy were identified as independent prognostic factors (p=0.007, 0.001, 0.003, <0.001, and <0.001, respectively. Furthermore, Kaplan–Meier survival curves demonstrated that high CIP2A expression indicated poor prognosis in the subgroup of patients with squamous cell carcinoma (p=0.008. Similar results were noted in the subgroup of patients with adenocarcinoma, but the results did not reach statistical significance (p=0.084. We also used univariate analysis and multivariate analysis to assess the prognostic factors for overall survival in the subgroup of patients who received postoperative chemotherapy. CIP2A expression was also an independent prognostic factor in NSCLC

  10. Satellite pulmonary nodule in the same lobe (T4N0) should not be staged as IIIB non-small cell lung cancer.

    Science.gov (United States)

    Bryant, Ayesha S; Pereira, Sara J; Miller, Daniel L; Cerfolio, Robert James

    2006-11-01

    Treatment of non-small cell lung cancer depends on stage. Patients with T4 lesions represent a heterogeneous group. A case-control study of patients with pathologically proven, node-negative T4 lesions (T4 N0 M0) was conducted. Patients with T4 disease were stratified as T4 from a satellite nodule (T4-satellite) or T4 from local invasion (T4-invasion). T4-satellite patients were matched 1:4 for sex and histology with resected control patients with stage IA, IB, and IIA non-small cell lung cancer and matched 1:3 with stage II non-small cell lung cancer. Survival and the maximal standardized uptake value on F-18 fluorodeoxyglucose-positron emission tomography scans were compared. There were 337 patients, 26 patients with T4-satellite lesions, 25 with T4-invasion lesions, and 286 controls (104 patients with T1 N0 M0, 104 with T2 N0 M0, and 78 with T1 N1 M0 or T2 N1 M0 lesions). The two T4 groups were similar for age, race, sex, and neoadjuvant therapy rates. The 5-year survival was 80% for the T1 N0 M0 patients, 68% for T2 N0 M0, 57% for T4-satellite N0 M0, 45% for T1 N1 M0 or T2 N1 M0, and 30% for the T4-invasion N0 M0 patients (p = 0.016). Multivariate analysis showed that only the type of T4 impacted survival (p = 0.011). The median maximal standardized uptake values of the cancers were 4.2 for T1 N0 M0, 4.8 for T4-satellite, 5.4 for T2 N0 M0, 7.8 for T1 N1 M0 or T2 N1 M0, and 8.8 for the T4-invasion patients. Larger studies are needed; however, patients with T4-satellite non-small cell lung cancer who undergo complete resection have survival and maximal standardized uptake values similar to patients with stage IB and stage IIA lesions. Their survival is significantly better than those with T4-invasion. Patients with T4-satellite N0 M0 lesions should not be classified as stage IIIB and should not be grouped with patients with T4-invasion, and resection should be considered.

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-15

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

  13. Consolidative Involved-Node Proton Therapy for Stage IA-IIIB Mediastinal Hodgkin Lymphoma: Preliminary Dosimetric Outcomes From a Phase II Study

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Flampouri, Stella; Su Zhong; Morris, Christopher G. [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Latif, Naeem [University of Florida Hematology/Oncology, Jacksonville, FL (United States); Dang, Nam H.; Lynch, James [University of Florida Hematology/Oncology, Gainesville, FL (United States); Li Zuofeng; Mendenhall, Nancy P. [University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-05-01

    Purpose: To compare the dose reduction to organs at risk (OARs) with proton therapy (PT) versus three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with mediastinal Hodgkin lymphoma (HL) enrolled on a Phase II study of involved-node radiotherapy (INRT). Methods and Materials: Between June 2009 and October 2010, 10 patients were enrolled on a University of Florida institutional review board-approved protocol for de novo 'classical' Stage IA-IIIB HL with mediastinal (bulky or nonbulky) involvement after chemotherapy. INRT was planned per European Organization for Research and Treatment of Cancer guidelines. Three separate optimized plans were developed for each patient: 3D-CRT, IMRT, and PT. The primary end point was a 50% reduction in the body V4 with PT compared with 3D-CRT or IMRT. Results: The median relative reduction with PT in the primary end point, body V4, was 51% compared with 3D-CRT (p = 0.0098) and 59% compared with IMRT (p = 0.0020), thus all patients were offered treatment with PT. PT provided the lowest mean dose to the heart, lungs, and breasts for all 10 patients compared with either 3D-CRT or IMRT. The median difference in the OAR mean dose reduction with PT compared with 3D-CRT were 10.4 Gy/CGE for heart; 5.5 Gy/CGE for lung; 0.9 Gy/CGE for breast; 8.3 Gy/CGE for esophagus; and 4.1 Gy/CGE for thyroid. The median differences for mean OAR dose reduction for PT compared with IMRT were 4.3 Gy/CGE for heart, 3.1 Gy/CGE for lung, 1.4 Gy/CGE for breast, 2.8 Gy/CGE for esophagus, and 2.7 Gy/CGE for thyroid. Conclusions: All 10 patients benefitted from dose reductions to OARs with PT compared with either 3D-CRT or IMRT. It is anticipated that these reductions in dose to OAR will translate into lower rates of late complications, but long-term follow-up on this Phase II INRT study is needed.

  14. Consolidative Involved-Node Proton Therapy for Stage IA-IIIB Mediastinal Hodgkin Lymphoma: Preliminary Dosimetric Outcomes From a Phase II Study

    International Nuclear Information System (INIS)

    Hoppe, Bradford S.; Flampouri, Stella; Su Zhong; Morris, Christopher G.; Latif, Naeem; Dang, Nam H.; Lynch, James; Li Zuofeng; Mendenhall, Nancy P.

    2012-01-01

    Purpose: To compare the dose reduction to organs at risk (OARs) with proton therapy (PT) versus three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with mediastinal Hodgkin lymphoma (HL) enrolled on a Phase II study of involved-node radiotherapy (INRT). Methods and Materials: Between June 2009 and October 2010, 10 patients were enrolled on a University of Florida institutional review board–approved protocol for de novo “classical” Stage IA-IIIB HL with mediastinal (bulky or nonbulky) involvement after chemotherapy. INRT was planned per European Organization for Research and Treatment of Cancer guidelines. Three separate optimized plans were developed for each patient: 3D-CRT, IMRT, and PT. The primary end point was a 50% reduction in the body V4 with PT compared with 3D-CRT or IMRT. Results: The median relative reduction with PT in the primary end point, body V4, was 51% compared with 3D-CRT (p = 0.0098) and 59% compared with IMRT (p = 0.0020), thus all patients were offered treatment with PT. PT provided the lowest mean dose to the heart, lungs, and breasts for all 10 patients compared with either 3D-CRT or IMRT. The median difference in the OAR mean dose reduction with PT compared with 3D-CRT were 10.4 Gy/CGE for heart; 5.5 Gy/CGE for lung; 0.9 Gy/CGE for breast; 8.3 Gy/CGE for esophagus; and 4.1 Gy/CGE for thyroid. The median differences for mean OAR dose reduction for PT compared with IMRT were 4.3 Gy/CGE for heart, 3.1 Gy/CGE for lung, 1.4 Gy/CGE for breast, 2.8 Gy/CGE for esophagus, and 2.7 Gy/CGE for thyroid. Conclusions: All 10 patients benefitted from dose reductions to OARs with PT compared with either 3D-CRT or IMRT. It is anticipated that these reductions in dose to OAR will translate into lower rates of late complications, but long-term follow-up on this Phase II INRT study is needed.

  15. Preoperative staging of lung cancer with combined PET-CT

    DEFF Research Database (Denmark)

    Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann

    2009-01-01

    BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC....... METHODS: We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. 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.

  19. A volumetric analysis of GTVD and CTVHR as defined by the GEC ESTRO recommendations in FIGO stage IIB and IIIB cervical cancer patients treated with IGABT in a prospective multicentric trial (EMBRACE)

    DEFF Research Database (Denmark)

    Jastaniyah, Noha; Yoshida, Kenji; Tanderup, Kari

    2016-01-01

    PURPOSE: To quantify the gross tumor volume at diagnosis (GTVD) and high-risk clinical target volume (CTVHR) at brachytherapy (BT) and describe subgroups of patients with different patterns of response to chemoradiotherapy (CRT) in patients with FIGO stage IIB and IIIB cervical cancer treated...... regression in these groups through adaptation of the treatment technique including the use of needles. However, major variations remain at present with regard to dose to GTVBT and to CTVHR, which are most pronounced in G4 and G5. This new classification will be validated in future in regard to clinical...

  20. 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

  1. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Assessment of Parametrial Response by Growth Pattern in Patients With International Federation of Gynecology and Obstetrics Stage IIB and IIIB Cervical Cancer: Analysis of Patients From a Prospective, Multicenter Trial (EMBRACE)

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Kenji [Medical University of Vienna, Comprehensive Cancer Center, Vienna (Austria); Kobe University Graduate School of Medicine, Kobe (Japan); Jastaniyah, Noha [Medical University of Vienna, Comprehensive Cancer Center, Vienna (Austria); King Faisal Specialist Hospital and Research Center, Riyadh (Saudi Arabia); Sturdza, Alina, E-mail: alina.sturdza@akhwien.at [Medical University of Vienna, Comprehensive Cancer Center, Vienna (Austria); Lindegaard, Jacob [Aarhus University Hospital, Aarhus (Denmark); Segedin, Barbara [Institute of Oncology Ljubljana, Ljubljana (Slovenia); Mahantshetty, Umesh [Tata Memorial Hospital, Mumbai (India); Rai, Bhavana [Post Graduate Institute of Medical Education and Research, Chandigarh (India); Jürgenliemk-Schulz, Ina [University Medical Center, Utrecht (Netherlands); Haie-Meder, Christine [Institut Gustave Roussy, Paris (France); Sasaki, Ryohei [Kobe University Graduate School of Medicine, Kobe (Japan); Pötter, Richard [Medical University of Vienna, Comprehensive Cancer Center, Vienna (Austria)

    2015-11-15

    Purpose: To assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of image-guided adaptive brachytherapy. Methods and Materials: Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype on magnetic resonance imaging (expansive and infiltrative), and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at brachytherapy was evaluated, and the response to chemo-radiotherapy was classified as good, moderate, or poor. The response grade was compared between the 2 groups and analyzed with regard to tumor volumes, and dosimetric parameters. Results: A total of 452 patients were evaluated, of whom 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease, as indicated by a higher rate of FIGO stage IIIB disease, as well as radiologic evidence of extension into the distal parametrial space and to the pelvic side wall on magnetic resonance imaging. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%; P=.02), and poor response was more common in the infiltrative group (11% and 19%; P=.02). Mean gross tumor volume at diagnosis was equal in both groups (51.7 cm{sup 3}). The high-risk clinical target volume was larger in infiltrative tumors (37.9 cm{sup 3} vs 33.3 cm{sup 3}, P=.005). The mean high-risk clinical target volume D{sub 90} was slightly higher in expansive tumors (92.7 Gy and 89.4 Gy, P<.001). Conclusion: Infiltrative tumors are more advanced at presentation and respond less favorably to chemo-radiotherapy when compared with expansive tumors that are more or less equivalent in size. The use of image

  4. Alternating radiotherapy (RT) and chemotherapy (CT) for inoperable stage III non-small cell lung carcinoma (NSCLC): long-term results of two phase II cooperative trials

    International Nuclear Information System (INIS)

    Mirimanoff, R.O.; Alberto, P.; Bolla, M.; Mermillod, B.; Michel, G.; Mirabell, R.; Moro, D.

    1996-01-01

    Purpose/Objective: The treatment of inoperable Stage III NSCLC with conventional RT alone results in a high incidence of local and distant failures and in very limited long-term survival rates. In two consecutive phase II cooperative trials, we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy. Materials and Methods: A total of one hundred and thirty two patients were enrolled. Between 2/86 and 9/89, 65 patients were entered in the first trial (G.I) and between 12/89 and 10/92 67 were enrolled in the second trial (G.II). In both protocols, RT was administered twice daily, with 6 hours interval, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3 and 6, 7, over an elapsed time of 6 weeks. In G.I, 3 cycles of cisplatin, 60 mg/m2 d.1, mitomycin, 8 mg/m2 d.1 and vindesin 3 mg/m2 d.1 and 8, were given during weeks 1, 5 and 9, whereas in G.II, cisplatin 70 mg/m2 d.1 and vinblastin 5 mg/m2 d.1 and 8 were given during weeks 1, 5, 9, 13, 17 and 21. Patients' characteristics included the following : median age was 55.5 years (28-70), male to female ratio was 7.3 : 1, tumor Stage were III A in 44% and III B in 56%, performance status (P.S.) were 0 in 36%, 1 in 52% and 2 in 12%. Histologic type consisted in squamous cell carcinoma in 60%, adenocarcinoma in 22%, large cell carcinoma in 14% and undifferentiated NSCLC in 4%. Results: With a minimum follow-up of 3 years, the 1, 2, 5 and 8 year overall survival probability was 56% (95% C.I. 47% - 64%), 27% (20% - 35%), 12% (7% - 18%) and 9% (3% - 16%) respectively, with a median survival of 13.6 months (11.4 - 16.8). Median follow-up for survivors was 6 years (3.3 - 9.9). There were no survival differences between Stage III A and III B (p = .84), PS 0, ,, 2 (p = .87), sex (p = .45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died : 102 from NSCLC, 4 from acute toxicity, 2

  5. Long-term results for Stage IIIB cervical cancer patients receiving external beam radiotherapy combined with either HDR (252)Cf or HDR (60)Co intracavitary brachytherapy.

    Science.gov (United States)

    Ulinskas, K; Janulionis, E; Valuckas, K P; Samerdokiene, V; Atkocius, V; Rivard, M J

    2016-01-01

    The aim of this work was to compare the long-term curative effects and complications of patients diagnosed with cervical cancer International Federation of Gynecology and Obstetrics IIIB (n = 430) as treated with Californium-252 ((252)Cf) or cobalt-60 ((60)Co) intracavitary brachytherapy (ICBT) combined with external beam radiotherapy (EBRT). Cervical cancer cases with a history of treatment with (252)Cf or (60)Co ICBT combined with EBRT were selected from the Lithuanian National Cancer Institute database. Complications and second primary malignancies were compared in both patients groups. Estimates of the 5-, 10-, and 15-year overall survival and disease-free survival rates were computed with the Kaplan-Meier method and a Cox proportional hazards model applied using STATA software. At 5, 10, and 15 years, the overall survival rates were 46.9%, 39.3%, and 34.6% for the (252)Cf group and 35.4%, 26.9%, and 22.5% for the (60)Co group (p = 0.004), respectively. The disease-free survival rates were 42.1%, 35.0%, and 31.0% for the (252)Cf group and 32.0%, 25.1%, and 21.4% for the (60)Co group (p = 0.009), respectively. Histopathologic type of adenocarcinoma increased the risk of death for the (252)Cf group (hazard ratio 3.62). Histopathologic tumor type (hazard ratio 7.48) and recurrence (hazard ratio 2.83) were factors that statistically and significantly influenced the patient prognosis for the (60)Co group. Applying (252)Cf ICBT with EBRT was effective for International Federation of Gynecology and Obstetrics IIIB cervical cancer patients. Moreover, long-term followup data demonstrated higher survival rates in patients treated with (252)Cf ICBT than (60)Co ICBT. Complications in patients treated with neutron ICBT were not more frequent or severe than those treated with (60)Co ICBT. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  6. Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer

    International Nuclear Information System (INIS)

    Peng, Rui-Qing; Zeng, Yi-Xin; Zhang, Xiao-Shi; Wu, Xiao-Jun; Ding, Ya; Li, Chun-Yan; Yu, Xing-Juan; Zhang, Xing; Pan, Zhi-Zhong; Wan, De-Sen; Zheng, Li-Ming

    2010-01-01

    The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer. Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed. The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates. This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response

  7. 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.

  8. 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...

  9. Cutaneous head and neck melanoma in OPTiM, a randomized phase 3 trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor for the treatment of unresected stage IIIB/IIIC/IV melanoma.

    Science.gov (United States)

    Andtbacka, Robert H I; Agarwala, Sanjiv S; Ollila, David W; Hallmeyer, Sigrun; Milhem, Mohammed; Amatruda, Thomas; Nemunaitis, John J; Harrington, Kevin J; Chen, Lisa; Shilkrut, Mark; Ross, Merrick; Kaufman, Howard L

    2016-12-01

    Cutaneous head and neck melanoma has poor outcomes and limited treatment options. In OPTiM, a phase 3 study in patients with unresectable stage IIIB/IIIC/IV melanoma, intralesional administration of the oncolytic virus talimogene laherparepvec improved durable response rate (DRR; continuous response ≥6 months) compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Retrospective review of OPTiM identified patients with cutaneous head and neck melanoma given talimogene laherparepvec (n = 61) or GM-CSF (n = 26). Outcomes were compared between talimogene laherparepvec and GM-CSF treated patients with cutaneous head and neck melanoma. DRR was higher for talimogene laherparepvec-treated patients than for GM-CSF treated patients (36.1% vs 3.8%; p = .001). A total of 29.5% of patients had a complete response with talimogene laherparepvec versus 0% with GM-CSF. Among talimogene laherparepvec-treated patients with a response, the probability of still being in response after 12 months was 73%. Median overall survival (OS) was 25.2 months for GM-CSF and had not been reached with talimogene laherparepvec. Treatment with talimogene laherparepvec was associated with improved response and survival compared with GM-CSF in patients with cutaneous head and neck melanoma. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1752-1758, 2016. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc.

  10. Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study.

    Directory of Open Access Journals (Sweden)

    Wolfgang Hilbe

    Full Text Available Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles.Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2 and docetaxel (75 mg/m2 d1 q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly. The primary endpoint was radiological response according to RECIST.40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95% underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months.Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected.EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

  11. 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.

  12. A randomized phase II trial of concurrent chemoradiation with two doses of radiotherapy, 60Gy and 66Gy, concomitant with a fixed dose of oral vinorelbine in locally advanced NSCLC

    DEFF Research Database (Denmark)

    Hansen, Olfred; Knap, Marianne; Khalil, Azza A

    2017-01-01

    Introduction: In order to test the best performing radiation dose with a convenient chemotherapy schedule of an oral formulation of radio-sensitizing vinorelbine in inoperable locally advanced non-small cell lung cancer (NSCLC), we performed a randomized phase II trial based on a "pick the winner......" design. Methods: After 2 cycles of neoadjuvant chemotherapy, 117 patients with NSCLC stage IIB-IIIB in performance status 0-1 were randomized to radiotherapy 60. Gy/30 fractions or 66. Gy/33 fractions concurrent with a fixed dose of oral vinorelbine 50. mg administered 3 times weekly. The primary...... endpoint was local progression free interval. A scheduled FDG-PET-CT-scan was performed 9. months after randomization. The study was registered at ClinicalTrials.gov (NCT 00887783). Results: Both arms were well tolerated. The local progression free interval at 9. months was 54% in the 60. Gy arm and 59...

  13. Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Finkle, Joshua H.; Jo, Stephanie Y.; Yuan, Cindy; Pu, Yonglin [University of Chicago, Department of Radiology, Chicago, IL (United States); Ferguson, Mark K. [University of Chicago, Department of Surgery, Chicago, IL (United States); Liu, Hai-Yan [First Hospital of Shanxi Medical University, Department of Nuclear Medicine, Taiyuan, Shanxi (China); Zhang, Chenpeng [Shanghai Jiao Tong University, Department of Nuclear Medicine, RenJi Hospital, School of Medicine, Shanghai (China); Zhu, Xuee [Nanjing Medical University, Department of Radiology, BenQ Medical Center, Nanjing, Jiangsu Province (China)

    2017-08-15

    Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTV{sub WB}) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTV{sub WB} to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTV{sub WB}, MTV{sub WB} may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTV{sub WB} in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTV{sub WB}, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTV{sub WB}. The optimal MTV{sub WB} cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. The optimal MTV{sub WB} cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTV{sub WB} (below 29.2 mL) and the stage IIIA patients with high MTV{sub WB} (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTV{sub WB} stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTV{sub WB} stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTV{sub WB} was observed in a large range of cutoff values from 15 to 55 mL in

  14. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.

    Science.gov (United States)

    Zhong, Wen-Zhao; Wang, Qun; Mao, Wei-Min; Xu, Song-Tao; Wu, Lin; Shen, Yi; Liu, Yong-Yu; Chen, Chun; Cheng, Ying; Xu, Lin; Wang, Jun; Fei, Ke; Li, Xiao-Fei; Li, Jian; Huang, Cheng; Liu, Zhi-Dong; Xu, Shun; Chen, Ke-Neng; Xu, Shi-Dong; Liu, Lun-Xu; Yu, Ping; Wang, Bu-Hai; Ma, Hai-Tao; Yan, Hong-Hong; Yang, Xue-Ning; Zhou, Qing; Wu, Yi-Long

    2018-01-01

    Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m 2 on days 1 and 8) plus intravenous cisplatin (75 mg/m 2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate

  15. High-dose-rate intracavitary brachytherapy combined with external beam radiotherapy for stage IIIb adenocarcinoma of the uterine cervix in Japan. A multi-institutional study of Japanese Society of Therapeutic Radiology and Oncology 2006-2007 (Study of JASTRO 2006-2007)

    International Nuclear Information System (INIS)

    Niibe, Yuzuru; Kenjo, Masahiro; Onishi, Hiroshi

    2010-01-01

    The current study was a retrospective questionnaire survey of stage IIIb adenocarcinoma of the uterine cervix treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in Japan aimed to investigate the optimal dose on the basis of the biological effective dose and prognostic factors. Between 1990 and 2000, 61 patients with stage IIIb adenocarcinoma of the uterine cervix underwent high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in 19 major hospitals in Japan. This retrospective questionnaire survey was performed by mail including survey charts to be fulfilled by radiation oncologists in these 19 major hospital. Fifty had only adenocarcinoma components and 11 had adenosquamous cell carcinoma components. All patients were treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy. Total biological effective dose (T-BED 10 ) was calculated from the sum of the biological effective doses of the external beam radiation therapy and the intracavitary brachytherapy. Thirty-two patients underwent chemotherapy. The 5-year overall survival rate of all patients was 20.2%. Stratified by total biological effective dose, the 5-year overall survival rate was 0% for T-BED 10 10 between 75 and 100 Gy and 0% for T-BED 10 >110 Gy (P=0.15). Stratified by histopathology, the 5-year overall survival rate was 22.1% for adenocarcinoma and 13.6% for adenosquamous cell carcinoma (P=0.43). Stratified by chemotherapy, the 5-year overall survival rate was 20.3% in patients who received chemotherapy and 20.4% in patients who did not receive chemotherapy (P=0.96). The 5-year overall survival rate of stage IIIb adenocarcinoma of the uterine cervix in this retrospective questionnaire survey was 20.2%. The optimal T-BED 10 and evident prognostic factors were not clear from this questionnaire survey. (author)

  16. 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.

  17. 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)

  18. The Quality of Staging Non-Small Cell Lung Cancer in the Netherlands: Data From the Dutch Lung Surgery Audit.

    Science.gov (United States)

    Heineman, David Jonathan; Ten Berge, Martijn Geert; Daniels, Johannes Marlene; Versteegh, Michaël Ignatius; Marang-van de Mheen, Perla Jacqueline; Wouters, Michael Wilhelmus; Schreurs, Wilhelmina Hendrika

    2016-11-01

    Clinical staging of non-small cell lung cancer (NSCLC) determines the initial treatment offered to a patient. The similarity between clinical and pathologic staging in some studies is as low as 50%, and others publish results as high as 91%. The Dutch Lung Surgery Audit is a clinical database that registers the clinical and pathologic TNM of almost all NSCLC patients who undergo operations in the Netherlands. The objective of this study was to determine the accuracy of clinical staging of NSCLC. Prospective data were derived from the Dutch Lung Surgery Audit in 2013 and 2014. Patients were included if they had undergone a surgical resection for stage IA to IIIB NSCLC without neoadjuvant treatment and had a positron emission tomography-computed tomography scan as part of the clinical workup. Clinical (c)TNM and pathologic (p)TNM were compared, and whether discrepancy was based on tumor or nodal staging was determined. From 2,834 patients identified, 2,336 (82.4%) fulfilled the inclusion criteria and had complete data. Of these 2,336, 1,276 (54.6%) were staged accurately, 707 (30.3%) were clinically understaged, and 353 (15.1%) were clinically overstaged. In the understaged group, 346 patients had a higher pN stage (14.8%), of which 148 patients had unforeseen N2 disease (6.3%). In the overstaged group, 133 patients had a cN that was higher than the pN (5.7%). Accuracy of NSCLC staging in the Netherlands is low (54.6%), even in the era of positron emission tomography-computed tomography. Especially accurate nodal staging remains challenging. Future efforts should include the identification of specific pitfalls in NSCLC staging. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Textural features in pre-treatment [F18]-FDG-PET/CT are correlated with risk of local recurrence and disease-specific survival in early stage NSCLC patients receiving primary stereotactic radiation therapy

    International Nuclear Information System (INIS)

    Pyka, Thomas; Bundschuh, Ralph A; Andratschke, Nicolaus; Mayer, Benedikt; Specht, Hanno M; Papp, Laszló; Zsótér, Norbert; Essler, Markus

    2015-01-01

    Textural features in FDG-PET have been shown to provide prognostic information in a variety of tumor entities. Here we evaluate their predictive value for recurrence and prognosis in NSCLC patients receiving primary stereotactic radiation therapy (SBRT). 45 patients with early stage NSCLC (T1 or T2 tumor, no lymph node or distant metastases) were included in this retrospective study and followed over a median of 21.4 months (range 3.1–71.1). All patients were considered non-operable due to concomitant disease and referred to SBRT as the primary treatment modality. Pre-treatment FDG-PET/CT scans were obtained from all patients. SUV and volume-based analysis as well as extraction of textural features based on neighborhood gray-tone difference matrices (NGTDM) and gray-level co-occurence matrices (GLCM) were performed using InterView Fusion™ (Mediso Inc., Budapest). The ability to predict local recurrence (LR), lymph node (LN) and distant metastases (DM) was measured using the receiver operating characteristic (ROC). Univariate and multivariate analysis of overall and disease-specific survival were executed. 7 out of 45 patients (16%) experienced LR, 11 (24%) LN and 11 (24%) DM. ROC revealed a significant correlation of several textural parameters with LR with an AUC value for entropy of 0.872. While there was also a significant correlation of LR with tumor size in the overall cohort, only texture was predictive when examining T1 (tumor diameter < = 3 cm) and T2 (>3 cm) subgroups. No correlation of the examined PET parameters with LN or DM was shown. In univariate survival analysis, both heterogeneity and tumor size were predictive for disease-specific survival, but only texture determined by entropy was determined as an independent factor in multivariate analysis (hazard ratio 7.48, p = .016). Overall survival was not significantly correlated to any examined parameter, most likely due to the high comorbidity in our cohort. Our study adds to the growing evidence

  20. Acceptance and Commitment Therapy in Improving Well-Being in Patients With Stage III-IV Cancer and Their Partners

    Science.gov (United States)

    2018-02-06

    Malignant Female Reproductive System Neoplasm; Malignant Hepatobiliary Neoplasm; Partner; Stage III Breast Cancer; Stage III Cervical Cancer; Stage III Colorectal Cancer; Stage III Lung Cancer; Stage III Prostate Cancer; Stage III Skin Melanoma; Stage III Uterine Corpus Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Lung Carcinoma; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Breast Cancer; Stage IV Cervical Cancer; Stage IV Colorectal Cancer; Stage IV Lung Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVA Colorectal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Cervical Cancer; Stage IVB Colorectal Cancer; Stage IVB Uterine Corpus Cancer

  1. 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

  2. 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)

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. Chemical vapor deposition of group IIIB metals

    Science.gov (United States)

    Erbil, A.

    1989-11-21

    Coatings of Group IIIB metals and compounds thereof are formed by chemical vapor deposition, in which a heat decomposable organometallic compound of the formula given in the patent where M is a Group IIIB metal, such as lanthanum or yttrium and R is a lower alkyl or alkenyl radical containing from 2 to about 6 carbon atoms, with a heated substrate which is above the decomposition temperature of the organometallic compound. The pure metal is obtained when the compound of the formula 1 is the sole heat decomposable compound present and deposition is carried out under nonoxidizing conditions. Intermetallic compounds such as lanthanum telluride can be deposited from a lanthanum compound of formula 1 and a heat decomposable tellurium compound under nonoxidizing conditions.

  4. 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

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

    Science.gov (United States)

    2014-12-18

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

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

    Science.gov (United States)

    2017-06-05

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

  7. Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

    Science.gov (United States)

    2018-02-15

    Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. MELT-IIIB: an updated version of the melt code

    International Nuclear Information System (INIS)

    Tabb, K.K.; Lewis, C.H.; O'Dell, L.D.; Padilla, A. Jr.; Smith, D.E.; Wilburn, N.P.

    1979-04-01

    The MELT series is a reactor modeling code designed to investigate a wide variety of hypothetical accident conditions, particularly the transient overpower sequence. MELT-IIIB is the latest in the series

  9. 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.

  10. Natural history of SMA IIIb: muscle strength decreases in a predictable sequence and magnitude.

    Science.gov (United States)

    Deymeer, Feza; Serdaroglu, Piraye; Parman, Yesim; Poda, Mehves

    2008-08-26

    To assess the natural progression of muscle weakness in spinal muscular atrophy (SMA) IIIb. Ten patients with SMA IIIb were followed for at least 10 years. Age at disease onset varied between 9 and 18 years. Patients were initially seen 2 to 10 years after disease onset. They were evaluated at approximately 2, 5, 10, 15, and 20 years of disease duration depending on the timing of their initial visit after onset. Medical Research Council (MRC) scale was used with particular attention to proximal muscles. The MRC grade declined with years in all of the muscles. The decline was usually not more than by one MRC grade for each 5-year period. There were 5-10 year periods when some muscles appeared to remain stationary. The succession of weakness was first triceps, then biceps and deltoid for upper extremity muscles and first thigh adductors, then iliopsoas, then quadriceps femoris, then hamstrings, thigh abductors, and gluteus maximus for lower extremity muscles. There was a remarkable uniformity between patients in the MRC grade for each muscle at each stage: in the first 5 years of the disease, triceps, iliopsoas, thigh adductors, and quadriceps femoris were the muscles which had noticeable weakness. These findings show that strength in spinal muscular atrophy IIIb decreases over time, explaining the progressive functional loss. The sequence of weakness in the lower extremities suggests that the disease starts segmentally involving the upper lumbar segments of the medulla spinalis initially. The slowness of the deterioration may have implications for clinical trials.

  11. 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.

  12. [Application of the 2007 lung cancer staging system by International Association for the Study of Lung Cancer].

    Science.gov (United States)

    Wang, Jia; Wu, Nan; Zheng, Qing-feng; Feng, Yuan; Yan, Shi; Yang, Yue

    2009-08-18

    To compare the prognoses of non-small cell lung cancer patients based respectively on the 6th-Edition Staging System for NSCLC (the 6th-Edition Staging System) and the new staging system by the International Association for the Study of Lung Cancer (IASLC) (new staging system). Data were collected from 136 operated NSCLC patients from Sep. 2003 through Oct. 2007. Those data were staged based respectively on the 6th-Edition Staging System and the new staging system. The 2-year no-recurrence survival rate was calculated, and life span was analyzed using the Kaplan-Meier method of SPSS 13.0 software. (1) In this series, using the 6th-Edition Staging System, there were 56, 23, 53 and 4 patients in stage I, stage II, stage III and stage IV respectively; using the new staging system, there were 50, 31, 54 and 1 patients in stage I, stage II, stage III and stage IV respectively. There were 6 patients in stage I according to the 6th-Edition Staging System who had become 6 patients in stage II according to the new staging system, 1 patient in stage II 1 in stage III, 3 patients in stage III 3 in stage II, 1 patient in stage III 1 in stage IV, and 4 patients in stage IV 4 in stage III. (2) According to the 6th-Edition Staging System, the 2-year no-recurrence survival rates for Ia, Ib, IIa, IIb,IIIa, IIIb and IV were 95.0%, 83.3%, 100.0%, 63.6%, 52.1%, 80.0% and 50.0% respectively, and according to the new staging system, the 2-year cumulative survival rates for I a, Ib, IIa, IIb, IIIa, IIIb and IV were 95.5%, 89.3%, 68.4%, 63.6%, 52.8%, 50.0% and 0.0% respectively. After Chi square analysis, there was no distinguished difference between the 2 staging systems for the 2-year cumulative survival rate. (3) According to the 6th-Edition Staging System, the difference between the no-recurrence rate of stage I and stage II was not statistically significant (P = 0.232), and the difference between the no-recurrence rates of stage II and III was statistically significant(P = 0

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

    2017-05-03

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

  15. TREATMENT OF THE CHRONIC WAR TIBIAL OSTEOMYELITIS, GUSTILIO TYPE IIIB AND CIERNY MADER IIIB, USING VARIOUS METHODS. A RETROSPECTIVE STUDY

    OpenAIRE

    Pedrag Grubor

    2014-01-01

    Introduction: War osteomyelitis is an inflammation of all the bone elements at the place of bone fracture resulting from a war wound. Method of work: During the Bosnian (1992-1995), 2,195 wounded people underwent primary surgical treatment for their wounded extremities. Tibia wounds were dominant in 695 (31.66%) of the cases, and 59 (8.48%) of which developed chronic osteomyelitis. The Gustilo’s Classification score was IIIB and the Cierny-Mader’s Classification score was IIIB. The average...

  16. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097, Paclitaxel, and Carboplatin Before Surgery in Treating Patients With Stage II or Stage III Triple-Negative Breast Cancer

    Science.gov (United States)

    2015-09-03

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  17. 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

  18. Endodontic management of dens invaginatus Type IIIb: Case series.

    Science.gov (United States)

    Martins, Jorge N R; da Costa, Rui Pereira; Anderson, Craig; Quaresma, Sérgio André; Corte-Real, Luís S M; Monroe, Adam D

    2016-01-01

    Dens invaginatus may be seen as a developmental malformation. It is characterized by an invagination of the enamel and dentin, creating a lumen inside the affected tooth, which may extend as deep as the apical foramen. Oehlers Type IIIb is considered the most challenging clinical conditions. The purpose of this study is to discuss the nonsurgical endodontic management of vital and necrotic dens invaginatus Type IIIb cases. Due to the complex anatomical consideration of dens invaginatus Type IIIb, endodontic treatment is extremely technique sensitive. A conservative approach was used in a vital case to treat the invaginated lumen only, to preserve the vitality of the pulp, and a more invasive approach was used in a necrotic case to debride the lumen and necrotic pulp for proper disinfection of the root canal system. Although different, all the approaches were successful. The clinical signs and symptoms were resolved. The vital case remains vital after 19 months, and the recall radiographs were able to show satisfactory periapical healing both in vital and necrotic cases. Due to the highly complex anatomy of dens invaginatus Type IIIb, the decision of preserving the pulp vitality may not be related only to pulpal diagnosis but also to the technical requirements of the treatment. Although very technically sensitive, it may be possible to treat the invaginated lumen exclusively, while preserving the vitality of the pulp. Necrotic cases may require a more aggressive approach to achieve a favorable prognosis.

  19. The neurobehavioral phenotype in mucopolysaccharidosis Type IIIB: An exploratory study

    Directory of Open Access Journals (Sweden)

    E. Shapiro

    2016-03-01

    Conclusions: On most behavioral measures, MPS IIIB patients did not differ substantially from MPS IIIA patients over age six, demonstrating autistic features and a Klüver Bucy-like syndrome including lack of fear and poor attention. Delay in onset of behavioral symptoms was associated with later diagnosis in two patients. Lack of fear, poor attention, and autistic-like symptomatology are as characteristic of MPS IIIB as they are of MPS IIIA. A possible difference is that the some behavioral abnormalities develop more quickly in MPS IIIB. If this is so, these patients may become at risk for harm and present a challenge for parenting even earlier than do those with MPS IIIA. In future clinical trials of new treatments, especially with respect to quality of life and patient management, improvement of these behaviors will be an essential goal. Because very young patients were not studied, prospective natural history documentation of the early development of abnormal behaviors in MPS IIIB is needed.

  20. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    Science.gov (United States)

    2017-05-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

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

    Science.gov (United States)

    2017-08-07

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

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

    Science.gov (United States)

    2017-06-14

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

  3. 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

  4. 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.

  5. Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

    Science.gov (United States)

    2017-04-12

    Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

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

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Yoshinao [Hirosaki Univ., Aomori (Japan). School of Medicine; Takahashi, Jutaro; Fukuda, Hiroshi [and others

    1998-12-01

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

  7. 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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-01

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

  10. 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

  11. 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

  12. Two panels of plasma microRNAs as non-invasive biomarkers for prediction of recurrence in resectable NSCLC.

    Directory of Open Access Journals (Sweden)

    Céline Sanfiorenzo

    Full Text Available The diagnosis of non-small cell lung carcinoma (NSCLC at an early stage, as well as better prediction of outcome remains clinically challenging due to the lack of specific and robust non-invasive markers. The discovery of microRNAs (miRNAs, particularly those found in the bloodstream, has opened up new perspectives for tumor diagnosis and prognosis. The aim of our study was to determine whether expression profiles of specific miRNAs in plasma could accurately discriminate between NSCLC patients and controls, and whether they are able to predict the prognosis of resectable NSCLC patients. We therefore evaluated a series of seventeen NSCLC-related miRNAs by quantitative real-time (qRT-PCR in plasma from 52 patients with I-IIIA stages NSCLC, 10 patients with chronic obstructive pulmonary disease (COPD and 20-age, sex and smoking status-matched healthy individuals. We identified an eleven-plasma miRNA panel that could distinguish NSCLC patients from healthy subjects (AUC = 0.879. A six-plasma miRNA panel was able to discriminate between NSCLC patients and COPD patients (AUC = 0.944. Furthermore, we identified a three-miRNA plasma signature (high miR-155-5p, high miR-223-3p, and low miR-126-3p that significantly associated with a higher risk for progression in adenocarcinoma patients. In addition, a three-miRNA plasma panel (high miR-20a-5p, low miR-152-3p, and low miR-199a-5p significantly predicted survival of squamous cell carcinoma patients. In conclusion, we identified two plasma miRNA expression profiles that may be useful for predicting the outcome of patients with resectable NSCLC.

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

    Science.gov (United States)

    2018-02-01

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

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

    Science.gov (United States)

    2018-04-06

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

  15. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2018-02-06

    Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

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

    Science.gov (United States)

    2017-12-28

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

  17. 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

  18. Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response

    Directory of Open Access Journals (Sweden)

    Popovich Phillip G

    2010-07-01

    Full Text Available Abstract Background Recently, using a mouse model of mucopolysaccharidosis (MPS IIIB, a lysosomal storage disease with severe neurological deterioration, we showed that MPS IIIB neuropathology is accompanied by a robust neuroinflammatory response of unknown consequence. This study was to assess whether MPS IIIB lymphocytes are pathogenic. Methods Lymphocytes from MPS IIIB mice were adoptively transferred to naïve wild-type mice. The recipient animals were then evaluated for signs of disease and inflammation in the central nervous system. Results Our results show for the first time, that lymphocytes isolated from MPS IIIB mice caused a mild paralytic disease when they were injected systemically into naïve wild-type mice. This disease is characterized by mild tail and lower trunk weakness with delayed weight gain. The MPS IIIB lymphocytes also trigger neuroinflammation within the CNS of recipient mice characterized by an increase in transcripts of IL2, IL4, IL5, IL17, TNFα, IFNα and Ifi30, and intraparenchymal lymphocyte infiltration. Conclusions Our data suggest that an autoimmune response directed at CNS components contributes to MPS IIIB neuropathology independent of lysosomal storage pathology. Adoptive transfer of purified T-cells will be needed in future studies to identify specific effector T-cells in MPS IIIB neuroimmune pathogenesis.

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

    Science.gov (United States)

    2017-11-15

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

  1. Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

    Science.gov (United States)

    2017-09-12

    Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  2. DART-bid (Dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily)–a novel approach for non-resected NSCLC: final results of a prospective study, correlating radiation dose to tumor volume

    International Nuclear Information System (INIS)

    Wurstbauer, Karl; Sedlmayer, Felix; Deutschmann, Heinz; Dagn, Karin; Kopp, Peter; Zehentmayr, Franz; Lamprecht, Bernd; Porsch, Peter; Wegleitner, Birgit; Studnicka, Michael

    2013-01-01

    Sequential chemo-radiotherapies with intensive radiation components deliver promising results in non-resected non-small cell lung cancer (NSCLC). In general, radiation doses are determined by dose constraints for normal tissues, not by features relevant for tumor control. DART-bid targets directly the doses required for tumor control, correlating doses to tumor volume in a differentiated mode. Radiation doses to primary tumors were aligned along increasing tumor size within 4 groups (<2.5 cm/2.5–4.5 cm/4.5–6.0 cm/>6.0 cm; mean number of three perpendicular diameters). ICRU-doses of 73.8 Gy/79.2 Gy/84.6 Gy/90.0 Gy, respectively, were applied. Macroscopically involved nodes were treated with a median dose of 59.4 Gy, nodal sites about 6 cm cranial to involved nodes electively with 45 Gy. Fractional doses were 1.8 Gy twice daily (bid). 2 cycles chemotherapy were given before radiotherapy. Between 2004 and 2009, 160 not selected patients with 164 histologically/cytologically proven NSCLC were enrolled; Stage I: 38 patients; II: 6 pts.; IIIA: 69 pts.; IIIB: 47 pts. Weight loss >5%/3 months: 38 patients (24%). Primary endpoints are local and regional tumor control rates at 2 years (as >90% of locoregional failures occur within 2 years). Secondary endpoints are survival and toxicity. With a minimum follow-up time of 2 years for patients alive, the final results are presented. 32 local and 10 regional recurrences occurred. The local and regional tumor control rates at 2 years are 77% and 93%, respectively. The median overall survival (OS) time is 28.0 months, the 2- and 5-year OS rates are 57% and 19%, respectively. For stage III patients, median OS amounts to 24.3 months, 2- /5-year OS rates to 51% and 18%, respectively. 2 treatment-related deaths (progressive pulmonary fibrosis) occurred in patients with pre-existing pulmonary fibrosis. Further acute and late toxicity was mild. This novel approach yields a high level of locoregional tumor control and survival times

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

    NARCIS (Netherlands)

    J. Hou (Jun)

    2010-01-01

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

  4. TREATMENT OF THE CHRONIC WAR TIBIAL OSTEOMYELITIS, GUSTILIO TYPE IIIB AND CIERNY MADER IIIB, USING VARIOUS METHODS. A RETROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Pedrag Grubor

    2014-04-01

    Full Text Available Introduction: War osteomyelitis is an inflammation of all the bone elements at the place of bone fracture resulting from a war wound. Method of work: During the Bosnian (1992-1995, 2,195 wounded people underwent primary surgical treatment for their wounded extremities. Tibia wounds were dominant in 695 (31.66% of the cases, and 59 (8.48% of which developed chronic osteomyelitis. The Gustilo’s Classification score was IIIB and the Cierny-Mader’s Classification score was IIIB. The average age of the patients was 38.2 years, sex representation: 57 (97% males and 2 (3% females. Cause of fracture: bullets 18 (31%, shell pieces 39 (66%, and combined 2 (3%, with polytrauma in 31 (52.54%. The most dominant infective agent was Staphylo-coccus aureus 31 (52%. We used Papineau’s method in 5 (8.50%, sequestration in 28 (47.45%, fenestration and sequestration in 17 (29%, only Forage of the tibia in 3 (5%, and decortication and resection in 6 (10%. We used the instantaneous vacuum for 36 (61% patients. The aim of this work is to evaluate some perceptions in the therapy of the chronic fistulous war osteomyelitis tibia in a decade-long work. The study is retrospective and analyzes the use of surgical methods in the treatment of chronic osteomyelitis tibia caused by the high kinetic energy projectiles. Results: Each of the 59 patients had an average of three surgical treatments. In spite of the above-mentioned treatments, 9 (15.25% out of the 59 patients had chronic fistulous osteomyelitis. The average length of treatment was 36 days, and the duration of the ex-acerbation was 7 months. Transfusion was used for 23 (40% patients. In the group of patients, the microbiological finding after operation was negative in 44 (75%. In 13 (22% patients, infection manifested very early (i.e. during the first hospitalization. Conclusion: Primary treatment of the war wound with sterilization is a crucial factor of acute (i.e. chronic osteomyelitis prevention and

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

    Directory of Open Access Journals (Sweden)

    Wang Z

    2014-12-01

    that T-cadherin hypermethylation was correlated with the sex or smoking status, clinical stages, or epidermal growth factor receptor (EGFR mutation status. However, T-cadherin hypermethylation was found to be significantly higher in poorly differentiated NSCLC than in moderately and highly differentiated NSCLC, and NSCLC patients with T-cadherin hypermethylation had a lower survival rate than those without T-cadherin hypermethylation.Conclusion: The results of this meta-analysis suggest that T-cadherin hypermethylation is associated with an increased risk and worse survival in NSCLC. T-cadherin hypermethylation, which induces the inactivation of T-cadherin gene, plays an important role in the carcinogenesis, cancer progression, as well as clinical outcome. Keywords: methylation, lung cancer, meta-analysis, EGFR, odds ratio, hazard ratio

  6. Induction chemotherapy followed by concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Tan, E.H.; Ang, P.T.; Leong, S.S.; Khoo, K.S.; Wee, J.; Fong, K.W.; Tan, T.; Lee, K.S.; Chua, E.J.; Eng, P.; Hsu, A.; Tan, Y.K.; Ong, Y.Y.

    1999-01-01

    che favourable experience with the combination regimen of vinorelbine, ifosfamide and cisplatin (NIP) in patients with metastatic non-small cell lung cancer (NSCLC) has led to a protocol assessing this regimen as an induction treatment in patients with stage III unresectable NSCLC, followed by thoracic radiotherapy with concurrent daily cisplatin as a radiosensitizer. Two cycles of NIP were administered 21 days apart; each cycle comprised i.v. vinorelbine 25 mg/m 2 on days 1 and 8, i.v. ifosfamide 3 g/m 2 on day 1 with MESNA as uroprotection, and i.v. cisplatin 50 mg/m 2 on day 1. Radical thoracic radiotherapy commenced on day 43 to a total dose of 64 Gy and i.v. cisplatin 6 mg/m 2 was given concurrently prior to each fraction of radiation as a sensitiser. Two more cycles of NIP were given to patients who responded favourably to the induction treatment about 2 weeks after completion of radiation. Between July 1995 and July 1997, 44 patients were treated with this protocol. This treatment schedule was generally well tolerated. Grade 3-4 neutropenia occurred in 50% of the patients and neutropenic sepsis was seen in 8. Grade 3-4 oesophagitis was uncommon. Most of the patients were able to complete the induction and concurrent chemoradiotherapy phase. Major response occurred in 75% of the patients with 2 (4.5%) complete responses (CR). A total of 6 patients achieved CR after chemoradiotherapy. At a median follow-up of 35 months, the median overall survival for all patients was 15 months with a 3-year survival rate of 24%. The median overall survival for stage IIIA patients was 19 months with a 3-year survival rate of 39% in contrast to 13 months' median overall survival and only 15% 3-year survival rate for stage IIIB. The NIP regimen results in a high response rate in NSCLC and this treatment programme seems to benefit selected patients with stage III disease. (orig.)

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

    Science.gov (United States)

    2018-02-12

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

  8. Survival of primary irradiated patients with NSCLC in dependence of the pretherapeutical haemoglobin level; Ueberlebenszeiten ausschliesslich bestrahlter NSCLC-Patienten. Die Bedeutung des praetherapeutischen Haemoglobinwerts

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, R.; Kovacs, G.; Heinrichsohn, D.; Galalae, R.; Kimmig, B. [Kiel Univ. (Germany). Klinik fuer Strahlentherapie (Radioonkologie)

    1998-03-01

    We have analysed the files of 96 primary radiated patients to evaluate the pre-therapeutic haemoglobin level as well as sex, age, histopathology, total dose and fractionation. The analysis of Karnofsky-status or patient condition was not performed as there was a lack of sufficient data in the patient files. Histopathology, sex, age as well as total dose and fractionation of the radiation treatment were similar in the cohort building 3 groups: Hb<11 g/dl, Hb between 11 to 15 g/dl and Hb>15 g/dl. The investigation resulted in the observation, that lower levels of initial serum haemoglobin concentration compared to levels over 15 g/dl are negative prognostic factors. Higher initial haemoglobin concentration is a high significant positive prognostic factor (p=0,0001). The applied total dose (>30 Gy, >50 Gy, >55 Gy) was not a significant prognostic factor in this patient material, where two thirds of the patients had an advanced cancer (stage IIIB or Stage IV). (orig./MG) [Deutsch] Wir werteten retrospektiv fuer 96 Patienten den Serum-Hb-Wert, der vor einer primaeren perkutanen Strahlentherapie bestimmt wurde, anhand der Krankenunterlagen aus. Tumorhistologie, Geschlecht und Altersverteilung sowie Dosis und Fraktionierung der Strahlentherapie wurden fuer die Gruppen Hb<11 g/dl, Hb von 11 bis 15 g/dl und Hb>15 g/dl ueberprueft und in allen Gruppen als annaehernd homogen festgestellt. Eine Rekonstruktion von Daten zum Allgemeinzustand der Patienten oder eine Klassifizierung nach dem Karnofsky-Index konnte aufgrund fehlender oder unvollstaendiger Dokumentation nicht durchgefuehrt werden. Hoehere praetherapeutische Haemoglobinkonzentrationen (>15 g/dl) korrelierten mit hochsignifikant laengeren Ueberlebenszeiten (p=0,0001). Unterschiedlich hohe Gesamtdosen (>30 Gy, >50 Gy, 55 bis 60 Gy) hatten keinen signifikanten Einfluss auf das Ueberleben in einem Patientengut, von dem zwei Drittel unter Stadium IIIB- oder Stadium-VI-Tumoren litten. (orig./MG)

  9. DART-bid for loco-regionally advanced NSCLC. Summary of acute and late toxicity with long-term follow-up; experiences with pulmonary dose constraints

    International Nuclear Information System (INIS)

    Wurstbauer, Karl; Zehentmayr, Franz; Deutschmann, Heinz; Sedlmayer, Felix; Dagn, Karin; Exeli, Ann-Katrin; Kopp, Peter; Porsch, Peter; Maurer, Birgit; Studnicka, Michael

    2017-01-01

    To report acute and late toxicity with long-term follow-up, and to describe our experiences with pulmonary dose constraints. Between 2002 and 2009, 150 patients with 155 histologically/cytologically proven non-small cell lung cancer (NSCLC; tumor stages II, IIIA, IIIB in 6, 55 and 39%, respectively) received the following median doses: primary tumors 79.2 Gy (range 72.0-90.0 Gy), lymph node metastases 59.4 Gy (54.0-73.8 Gy), nodes electively 45 Gy; with fractional doses of 1.8 Gy twice daily (bid). In all, 86% of patients received 2 cycles of chemotherapy previously. Five treatment-related deaths occurred: pneumonitis, n = 1; progressive pulmonary fibrosis in patients with pre-existing pulmonary fibrosis, n = 2; haemorrhage, n = 2. In all, 8% of patients experienced grade 3 and 1.3% grade 4 pneumonitis; 11% showed late fibrotic alterations grade 2 in lung parenchyma. Clinically relevant acute esophagitis (grade 2 and 3) was seen in 33.3% of patients, 2 patients developed late esophageal stenosis (G3). Patients with upper lobe, middle lobe and central lower lobe tumours (n = 130) were treated with V20 (total lung) up to 50% and patients with peripheral lower lobe tumours (n = 14, basal lateral tumours excluded) up to 42%, without observing acute or late pulmonary toxicity >grade 3. Only patients with basal lateral lower lobe tumours (n = 5) experienced grade 4/5 pulmonary toxicity; V20 for this latter group ranged between 30 and 53%. The mean lung dose was below the QUANTEC recommendation of 20-23 Gy in all patients. The median follow-up time of all patients is 26.3 months (range 2.9-149.4) and of patients alive 80.2 months (range 63.9-149.4.). The median overall survival time of all patients is 26.3 months; the 2-, 5- and 8-year survival rates of 54, 21 and 15%, respectively. The local tumour control rate at 2 and 5 years is 70 and 64%, the regional control rate 90 and 88%, respectively. Grade 4 or 5 toxicity occurred in 7/150 patients (4.7%), which can be

  10. Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Shaw, Edward G.; Deming, Richard L.; Creagan, Edward T.; Nair, Suresh; Su, John Q.; Levitt, Ralph; Steen, Preston D.; Wiesenfeld, Martin; Mailliard, James A.

    1995-01-01

    Purpose: Gamma interferon has a wide range of properties, including the ability to sensitize solid tumor cells to the effects of ionizing radiation. The North Central Cancer Treatment Group has previously completed pilot studies of accelerated hyperfractionated thoracic radiation therapy (AHTRT) in patients with unresectable Stage IIIA/B nonsmall cell lung cancer (NSCLC). This Phase I study was designed to assess the toxicity of concomitant gamma interferon and AHTRT in a similar patient population. Methods and Materials: Between December 1991 and May 1992, 18 patients with unresectable Stage IIIA/B NSCLC were treated with daily gamma interferon (0.2 mg subcutaneously) concomitant with AHTRT (60 Gy given in 1.5 Gy twice daily fractions). All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 with weight loss < 5%. Eight patients had Stage IIIA and 10 had Stage IIIB disease. Results: Nine patients (50%) experienced severe, life-threatening, or fatal toxicities. Eight of the patients (44%) developed significant radiation pneumonitis, which was severe in six patients and fatal in two patients (11% treatment-related mortality). Two patients (11%) developed severe radiation esophagitis. With follow-up of 15-21 months, 2 patients are alive, and 16 have died. The median survival time and 1-year survival rate is 7.8 months and 38%, respectively. Conclusion: Gamma interferon appeared to sensitize normal lung tissue to the effects of radiation, as demonstrated by the high incidence of severe or fatal radiation pneumonitis. We do not recommend pursuing gamma interferon as a radiosensitizer in this setting

  11. 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...

  12. 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.

  13. Real-time pcr (qpcr) assay for rhizoctonia solani anastomoses group ag2-2 iiib

    International Nuclear Information System (INIS)

    Abbas, S.J.; Ahmad, B.

    2014-01-01

    Rhizoctonia solani anastomosis group AG2-2 IIIB is a severe sugar beet and maize pathogen. It causes crown and root rot disease which leads to yield losses world-wide. The soil-borne pathogen is difficult to detect and quantify by conventional methods. We developed a real-time PCR (qPCR) assay for the quantification of genomic DNA of Rhizoctonia solani AG2-2 IIIB based on the ITS region of rDNA genes. The limit of quantification of the assay is 1.8 pg genomic DNA. The amplification efficiency was 96.4. The assay will be helpful in the diagnoses of Rhizoctonia solani infection of sugar beet and maize roots and in the quantification of R. solani AG2-2 IIIB inoculum in plant debris and soil. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-01

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

  15. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Osti, Mattia Falchetto [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy); Agolli, Linda, E-mail: lindaagolli@yahoo.it [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy); Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi [Institute of Radiation Oncology, La Sapienza University, Sant' Andrea Hospital, Rome (Italy)

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  16. FIGO IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy

    International Nuclear Information System (INIS)

    Logsdon, Mark D.; Eifel, Patricia J.

    1999-01-01

    Purpose: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix. Methods and Materials: The records of 1,096 patients treated with radiation therapy between 1960 and 1993 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. Of these, 983 (90%) were treated with curative intent and 113 were treated only to achieve palliation of symptoms. Of 907 patients who completed the intended curative treatment, 641 (71%) were treated with a combination of external beam irradiation (EBRT) and intracavitary irradiation (ICRT) and 266 (29%) were treated with EBRT only. The median duration of treatment for these 907 patients was 51 days. Between 1966 and 1980, only 52% of patients who completed treatment with curative intent received ICRT, compared with 92% of patients treated during 1981-1993, an increase that reflects an evolution in the philosophy of treatment for advanced tumors. In general, the intensity of ICRT correlated inversely with the dose of EBRT to the central pelvis. Median follow-up of surviving patients was 134 months. Results: For 983 patients treated with initial curative intent, disease-specific survival (DSS) was significantly worse for those who were 52 Gy of EBRT to the central pelvis had DSS rates of 27-34%, compared with 53% for patients treated with lower doses of EBRT to the central pelvis and more intensive ICRT (p 52 Gy of EBRT to the central pelvis (57-68%), compared with those who had 48-52 Gy (28%) and those who had ≤ 47 Gy of EBRT to the central pelvis (15%) (p < 0.0001). Outcome was also compared for four time periods during which different treatment policies were in place for patients with Stage IIIB disease. The highest DSS (51%) and lowest actuarial complication rate (17%) were achieved during the most recent period (1981-1993) when modest doses of EBRT were combined with relatively

  17. 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...

  18. 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.

  19. Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma.

    Science.gov (United States)

    Puzanov, Igor; Milhem, Mohammed M; Minor, David; Hamid, Omid; Li, Ai; Chen, Lisa; Chastain, Michael; Gorski, Kevin S; Anderson, Abraham; Chou, Jeffrey; Kaufman, Howard L; Andtbacka, Robert H I

    2016-08-01

    Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma. In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (10(6) plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (10(8) plaque-forming units/mL). Ipilimumab (3 mg/kg) was administered intravenously every 3 weeks for four infusions, beginning in week 6. The primary end point was incidence of dose-limiting toxicities. Secondary end points were objective response rate by immune-related response criteria and safety. Median duration of treatment with T-VEC was 13.3 weeks (range, 2.0 to 95.4 weeks). Median follow-up time for survival analysis was 20.0 months (1.0 to 25.4 months). Nineteen patients were included in the safety analysis. No dose-limiting toxicities occurred, and no new safety signals were detected. Grade 3/4 treatment-related adverse events (AEs) were seen in 26.3% of patients; 15.8% had AEs attributed to T-VEC, and 21.1% had AEs attributed to ipilimumab. The objective response rate was 50%, and 44% of patients had a durable response lasting ≥ 6 months. Eighteen-month progression-free survival was 50%; 18-month overall survival was 67%. T-VEC with ipilimumab had a tolerable safety profile, and the combination appeared to have greater efficacy than either T-VEC or ipilimumab monotherapy. © 2016 by American Society of Clinical Oncology.

  20. 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

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

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E

    2013-01-01

    NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC....

  2. 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...

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  4. DART-bid for loco-regionally advanced NSCLC. Summary of acute and late toxicity with long-term follow-up; experiences with pulmonary dose constraints

    Energy Technology Data Exchange (ETDEWEB)

    Wurstbauer, Karl [Paracelsus Medical University, Institute for Research and Development on Advanced Radiation Technologies (radART), Salzburg (Austria); Zehentmayr, Franz; Deutschmann, Heinz; Sedlmayer, Felix [Paracelsus Medical University, Institute for Research and Development on Advanced Radiation Technologies (radART), Salzburg (Austria); Paracelsus Medical University Clinics, Department of Radiotherapy and Radiation Oncology, Landeskrankenhaus, Salzburg (Austria); Dagn, Karin; Exeli, Ann-Katrin; Kopp, Peter [Paracelsus Medical University Clinics, Department of Radiotherapy and Radiation Oncology, Landeskrankenhaus, Salzburg (Austria); Porsch, Peter; Maurer, Birgit; Studnicka, Michael [Paracelsus Medical University Clinics, Departement of Pneumology, Salzburg (Austria)

    2017-04-15

    To report acute and late toxicity with long-term follow-up, and to describe our experiences with pulmonary dose constraints. Between 2002 and 2009, 150 patients with 155 histologically/cytologically proven non-small cell lung cancer (NSCLC; tumor stages II, IIIA, IIIB in 6, 55 and 39%, respectively) received the following median doses: primary tumors 79.2 Gy (range 72.0-90.0 Gy), lymph node metastases 59.4 Gy (54.0-73.8 Gy), nodes electively 45 Gy; with fractional doses of 1.8 Gy twice daily (bid). In all, 86% of patients received 2 cycles of chemotherapy previously. Five treatment-related deaths occurred: pneumonitis, n = 1; progressive pulmonary fibrosis in patients with pre-existing pulmonary fibrosis, n = 2; haemorrhage, n = 2. In all, 8% of patients experienced grade 3 and 1.3% grade 4 pneumonitis; 11% showed late fibrotic alterations grade 2 in lung parenchyma. Clinically relevant acute esophagitis (grade 2 and 3) was seen in 33.3% of patients, 2 patients developed late esophageal stenosis (G3). Patients with upper lobe, middle lobe and central lower lobe tumours (n = 130) were treated with V20 (total lung) up to 50% and patients with peripheral lower lobe tumours (n = 14, basal lateral tumours excluded) up to 42%, without observing acute or late pulmonary toxicity >grade 3. Only patients with basal lateral lower lobe tumours (n = 5) experienced grade 4/5 pulmonary toxicity; V20 for this latter group ranged between 30 and 53%. The mean lung dose was below the QUANTEC recommendation of 20-23 Gy in all patients. The median follow-up time of all patients is 26.3 months (range 2.9-149.4) and of patients alive 80.2 months (range 63.9-149.4.). The median overall survival time of all patients is 26.3 months; the 2-, 5- and 8-year survival rates of 54, 21 and 15%, respectively. The local tumour control rate at 2 and 5 years is 70 and 64%, the regional control rate 90 and 88%, respectively. Grade 4 or 5 toxicity occurred in 7/150 patients (4.7%), which can be

  5. 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

  6. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    Science.gov (United States)

    2017-06-29

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  7. 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.

  8. 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

  9. Prediction of residual metabolic activity after treatment in NSCLC patients

    International Nuclear Information System (INIS)

    Rios Velazquez, Emmanuel; Aerts, Hugo J.W.L.; Oberije, Cary; Ruysscher, Dirk De; Lambin, Philippe

    2010-01-01

    Purpose. Metabolic response assessment is often used as a surrogate of local failure and survival. Early identification of patients with residual metabolic activity is essential as this enables selection of patients who could potentially benefit from additional therapy. We report on the development of a pre-treatment prediction model for metabolic response using patient, tumor and treatment factors. Methods. One hundred and one patients with inoperable NSCLC (stage I-IV), treated with 3D conformal radical (chemo)-radiotherapy were retrospectively included in this study. All patients received a pre and post-radiotherapy fluorodeoxyglucose positron emission tomography-computed tomography FDG-PET-CT scan. The electronic medical record system and the medical patient charts were reviewed to obtain demographic, clinical, tumor and treatment data. Primary outcome measure was examined using a metabolic response assessment on a post-radiotherapy FDG-PET-CT scan. Radiotherapy was delivered in fractions of 1.8 Gy, twice a day, with a median prescribed dose of 60 Gy. Results. Overall survival was worse in patients with residual metabolic active areas compared with the patients with a complete metabolic response (p=0.0001). In univariate analysis, three variables were significantly associated with residual disease: larger primary gross tumor volume (GTVprimary, p=0.002), higher pre-treatment maximum standardized uptake value (SUV max , p=0.0005) in the primary tumor and shorter overall treatment time (OTT, p=0.046). A multivariate model including GTVprimary, SUV max , equivalent radiation dose at 2 Gy corrected for time (EQD2, T) and OTT yielded an area under the curve assessed by the leave-one-out cross validation of 0.71 (95% CI, 0.65-0.76). Conclusion. Our results confirmed the validity of metabolic response assessment as a surrogate of survival. We developed a multivariate model that is able to identify patients at risk of residual disease. These patients may benefit from

  10. Inhomogeneous dose escalation increases expected local control for NSCLC patients with lymph node involvement without increased mean lung dose

    DEFF Research Database (Denmark)

    Nielsen, Tine B; Hansen, Olfred; Schytte, Tine

    2014-01-01

    but also for patients with involved lymph nodes. MATERIAL AND METHODS: Highly modulated IMRT plans with homogeneous dose distributions with a prescribed dose of 66Gy/33F were created for 20 NSCLC patients, staged T1b-T4 N0-N3, using standard PTV dose coverage of 95-107%. For each patient, an inhomogeneous......BACKGROUND: Higher doses to NSCLC tumours are required to increase the low control rates obtained with conventional dose prescriptions. This study presents the concept of inhomogeneous dose distributions as a general way to increase local control probability, not only for isolated lung tumours...... dose distribution was created with dose constraints of: PTV-coverage ≥ 95%, same mean lung dose as obtained in the homogeneous dose plan, maximum doses of 45 and 66 Gy to spinal canal and oesophagus, respectively, and V74Gy

  11. 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

  12. Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy.

    Science.gov (United States)

    Holley, Rebecca J; Ellison, Stuart M; Fil, Daniel; O'Leary, Claire; McDermott, John; Senthivel, Nishanthi; Langford-Smith, Alexander W W; Wilkinson, Fiona L; D'Souza, Zelpha; Parker, Helen; Liao, Aiyin; Rowlston, Samuel; Gleitz, Hélène F E; Kan, Shih-Hsin; Dickson, Patricia I; Bigger, Brian W

    2018-01-01

    Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in the degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to accumulation of partially degraded heparan sulphate within lysosomes and the extracellular matrix, giving rise to severe CNS degeneration with progressive cognitive impairment and behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy in the related disease mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the brain following bone marrow engraftment, secrete the missing enzyme and cross-correct neighbouring cells. However, little neurological correction is achieved in patients with mucopolysaccharidosis IIIB. We have therefore developed an ex vivo haematopoietic stem cell gene therapy approach in a mouse model of mucopolysaccharidosis IIIB, using a high-titre lentiviral vector and the myeloid-specific CD11b promoter, driving the expression of NAGLU (LV.NAGLU). To understand the mechanism of correction we also compared this with a poorly secreted version of NAGLU containing a C-terminal fusion to IGFII (LV.NAGLU-IGFII). Mucopolysaccharidosis IIIB haematopoietic stem cells were transduced with vector, transplanted into myeloablated mucopolysaccharidosis IIIB mice and compared at 8 months of age with mice receiving a wild-type transplant. As the disease is characterized by increased inflammation, we also tested the anti-inflammatory steroidal agent prednisolone alone, or in combination with LV.NAGLU, to understand the importance of inflammation on behaviour. NAGLU enzyme was substantially increased in the brain of LV.NAGLU and LV.NAGLU-IGFII-treated mice, with little expression in wild-type bone marrow transplanted mice. LV.NAGLU treatment led to behavioural correction, normalization of heparan sulphate and sulphation patterning, reduced inflammatory cytokine

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

    Science.gov (United States)

    2017-11-15

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

  14. Expressions of c-Cbl, Cbl-b and EGFR and Its Role of Prognosis in NSCLC

    Directory of Open Access Journals (Sweden)

    Xin JIAO

    2011-06-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR is closely correlated with the progression of lung cancer. Its activity is modulated by Casitas B-lineage lymphoma (Cbl family. The aim of this study is to investigate the expression and clinical relevance of c-Cbl, Cbl-b and EGFR in non-small cell lung cancer (NSCLC. Methods Expressions of c-Cbl, Cbl-b and EGFR protein were detected with tissue microarrays and immunohistochemistry technique in 94 cases of NSCLC. The correlations between the expression of the three proteins and clinicopathological parameters were analyzed. Results The positive expression rates of EGFR, c-Cbl and Cbl-b were 60.6% (57/94, 30.9% (29/94 and 84.0% (79/94, respectively. The expression of EGFR, c-Cbl and Cbl-b was not associated with age, pathological type, TNM stage, lymph node metastasis, and smoking history. c-Cbl and Cbl-b status was not significantly correlated with overall survival. Subgroup analyses showed that c-Cbl-positive patients had longer survival than c-Cbl-negative patients in EGFR-positive group (P=0.014. Conclusion Detection of c-Cbl protein levels might contribute to the prognosis evaluation of EGFR-positive NSCLC.

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

    Science.gov (United States)

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

    2012-02-01

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

  16. DART-bid for loco-regionally advanced NSCLC : Summary of acute and late toxicity with long-term follow-up; experiences with pulmonary dose constraints.

    Science.gov (United States)

    Wurstbauer, Karl; Zehentmayr, Franz; Deutschmann, Heinz; Dagn, Karin; Exeli, Ann-Katrin; Kopp, Peter; Porsch, Peter; Maurer, Birgit; Studnicka, Michael; Sedlmayer, Felix

    2017-04-01

    To report acute and late toxicity with long-term follow-up, and to describe our experiences with pulmonary dose constraints. Between 2002 and 2009, 150 patients with 155 histologically/cytologically proven non-small cell lung cancer (NSCLC; tumor stages II, IIIA, IIIB in 6, 55 and 39%, respectively) received the following median doses: primary tumors 79.2 Gy (range 72.0-90.0 Gy), lymph node metastases 59.4 Gy (54.0-73.8 Gy), nodes electively 45 Gy; with fractional doses of 1.8 Gy twice daily (bid). In all, 86% of patients received 2 cycles of chemotherapy previously. Five treatment-related deaths occurred: pneumonitis, n = 1; progressive pulmonary fibrosis in patients with pre-existing pulmonary fibrosis, n = 2; haemorrhage, n = 2. In all, 8% of patients experienced grade 3 and 1.3% grade 4 pneumonitis; 11% showed late fibrotic alterations grade 2 in lung parenchyma. Clinically relevant acute esophagitis (grade 2 and 3) was seen in 33.3% of patients, 2 patients developed late esophageal stenosis (G3). Patients with upper lobe, middle lobe and central lower lobe tumours (n = 130) were treated with V20 (total lung) up to 50% and patients with peripheral lower lobe tumours (n = 14, basal lateral tumours excluded) up to 42%, without observing acute or late pulmonary toxicity >grade 3. Only patients with basal lateral lower lobe tumours (n = 5) experienced grade 4/5 pulmonary toxicity; V20 for this latter group ranged between 30 and 53%. The mean lung dose was below the QUANTEC recommendation of 20-23 Gy in all patients. The median follow-up time of all patients is 26.3 months (range 2.9-149.4) and of patients alive 80.2 months (range 63.9-149.4.). The median overall survival time of all patients is 26.3 months; the 2-, 5- and 8‑year survival rates of 54, 21 and 15%, respectively. The local tumour control rate at 2 and 5 years is 70 and 64%, the regional control rate 90 and 88%, respectively. Grade 4 or 5 toxicity occurred in 7/150 patients

  17. Calculation of Atmospheric Transmittance by IBM 3033 Computer Code LOWTRAN IIIB.

    Science.gov (United States)

    1983-06-01

    empir- ical expression was obtained by Roberts et al [Ref. 6] for the temperature dependence which is given in 2qn 2.9 belcw. It was fcund that the...vapor continuum described in Roberts et al £Bef. 6] have been used in LOWTRAN IIIB with the appropriate conversion of units as follows. The...XX ». « HOUZ ^SCS » » »-MM »-»- #*" S* *_» •.>—«PS •N*-^^T«JC

  18. A novel interference mechanism by a type IIIB CRISPR-Cmr module in Sulfolobus

    DEFF Research Database (Denmark)

    Deng, Ling; Garrett, Roger Antony; Shah, Shiraz Ali

    2013-01-01

    Recent studies on CRISPR-based adaptive immune systems have revealed extensive structural and functional diversity of the interference complexes which often coexist intracellularly. The archaeon Sulfolobus islandicus REY15A encodes three interference modules, one of type IA and two of type IIIB...... targeting. A rationale is provided for the intracellular coexistence of the different interference systems in S.¿islandicus REY15A which cooperate functionally by sharing a single Cas6 protein for crRNA processing and utilize crRNA products from identical CRISPR spacers....

  19. 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.

  20. Focus on Nintedanib in NSCLC and other tumors

    Directory of Open Access Journals (Sweden)

    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.

  1. Changes in pulmonary function after definitive radiotherapy for NSCLC

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H

    2009-01-01

    INTRODUCTION: Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life......, the development of HRQOL during the first nine weeks were compared between PS 2 and PS 0/1 patients. We used the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Standardized area under the curve for all HRQOL items, and HRQOL responses classified as better, stable or worse, were compared between the groups. RESULTS...

  3. 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....

  4. Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.

    Science.gov (United States)

    Kerr, K M; Dafni, U; Schulze, K; Thunnissen, E; Bubendorf, L; Hager, H; Finn, S; Biernat, W; Vliegen, L; Losa, J H; Marchetti, A; Cheney, R; Warth, A; Speel, E-J; Blackhall, F; Monkhorst, K; Jantus Lewintre, E; Tischler, V; Clark, C; Bertran-Alamillo, J; Meldgaard, P; Gately, K; Wrona, A; Vandenberghe, P; Felip, E; De Luca, G; Savic, S; Muley, T; Smit, E F; Dingemans, A-M C; Priest, L; Baas, P; Camps, C; Weder, W; Polydoropoulou, V; Geiger, T R; Kammler, R; Sumiyoshi, T; Molina, M A; Shames, D S; Stahel, R A; Peters, S

    2018-01-01

    Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

  5. Combined type IIIB with bilateral type I thyroplasty for pitch lowering with maintenance of vocal fold tension.

    Science.gov (United States)

    Hoffman, Matthew R; Devine, Erin E; Remacle, Marc; Ford, Charles N; Wadium, Elizabeth; Jiang, Jack J

    2014-06-01

    To evaluate type IIIB thyroplasty using the excised larynx bench apparatus and determine how altering vocal fold contour by performing bilateral medialization of the inferior vocal fold affects phonation. This procedure could be performed in patients for whom pitch lowering is desirable, such as female-to-male transsexuals or male patients with mutational falsetto in whom intensive voice therapy was insufficient. Aerodynamic, acoustic, and high-speed videokymographic data were collected for nine larynges at three subglottal pressure inputs for each of three conditions: normal; type IIIB thyroplasty; and combined type IIIB with modified bilateral type I thyroplasty intended to create a more rectangular glottal configuration. Each larynx served as its own control. Phonation threshold flow (p = 0.005), phonation threshold power (p = 0.031), and airflow varied across conditions with highest values for type IIIB thyroplasty and lowest for the combined procedure. Fundamental frequency was significantly different (p thyroplasty provided some further decrease in frequency, but mostly served to increase tension, reduce airflow, and produce a vibratory pattern which more closely mirrored control trials. Exploration of this combined procedure in patients may be warranted if not completely satisfied with the results from type IIIB thyroplasty alone.

  6. 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.

  7. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2018-03-22

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  8. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2017-10-16

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  9. A type III-B CRISPR-Cas effector complex mediating massive target DNA destruction.

    Science.gov (United States)

    Han, Wenyuan; Li, Yingjun; Deng, Ling; Feng, Mingxia; Peng, Wenfang; Hallstrøm, Søren; Zhang, Jing; Peng, Nan; Liang, Yun Xiang; White, Malcolm F; She, Qunxin

    2017-02-28

    The CRISPR (clustered regularly interspaced short palindromic repeats) system protects archaea and bacteria by eliminating nucleic acid invaders in a crRNA-guided manner. The Sulfolobus islandicus type III-B Cmr-α system targets invading nucleic acid at both RNA and DNA levels and DNA targeting relies on the directional transcription of the protospacer in vivo. To gain further insight into the involved mechanism, we purified a native effector complex of III-B Cmr-α from S. islandicus and characterized it in vitro. Cmr-α cleaved RNAs complementary to crRNA present in the complex and its ssDNA destruction activity was activated by target RNA. The ssDNA cleavage required mismatches between the 5΄-tag of crRNA and the 3΄-flanking region of target RNA. An invader plasmid assay showed that mutation either in the histidine-aspartate acid (HD) domain (a quadruple mutation) or in the GGDD motif of the Cmr-2α protein resulted in attenuation of the DNA interference in vivo. However, double mutation of the HD motif only abolished the DNase activity in vitro. Furthermore, the activated Cmr-α binary complex functioned as a highly active DNase to destroy a large excess DNA substrate, which could provide a powerful means to rapidly degrade replicating viral DNA. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Preoperative staging of lung cancer with PET/CT

    DEFF Research Database (Denmark)

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

    2011-01-01

    PURPOSE: Positron emission tomography (PET)/CT has become a widely used technology for preoperative staging of non-small cell lung cancer (NSCLC). Two recent randomized controlled trials (RCT) have established its efficacy over conventional staging, but no studies have assessed its cost......-effectiveness. The objective of this study was to assess the cost-effectiveness of PET/CT as an adjunct to conventional workup for preoperative staging of NSCLC. METHODS: The study was conducted alongside an RCT in which 189 patients were allocated to conventional staging (n = 91) or conventional staging + PET/CT (n = 98...... perspective, the cost-effectiveness of PET/CT for staging NSCLC seems to depend on the willingness to pay in order to avoid a futile thoracotomy. However, given that four outliers in terms of extreme comorbidity were all randomized to the PET/CT arm, there is uncertainty about the conclusion. When hospital...

  11. Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what?

    OpenAIRE

    Sroufe, Rameses; Kong, Feng-Ming (Spring)

    2015-01-01

    More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternativ...

  12. The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers

    International Nuclear Information System (INIS)

    Apostolova, Ivayla; Ego, Kilian; Steffen, Ingo G.; Buchert, Ralph; Wertzel, Heinz; Achenbach, H.J.; Riedel, Sandra; Schreiber, Jens; Schultz, Meinald; Furth, Christian; Amthauer, Holger; Derlin, Thorsten; Hofheinz, Frank; Kalinski, Thomas

    2016-01-01

    Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC). The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with 18 F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures. SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with

  13. The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers

    Energy Technology Data Exchange (ETDEWEB)

    Apostolova, Ivayla; Ego, Kilian; Steffen, Ingo G. [University Hospital, Otto-von-Guericke University Magdeburg, Clinic of Radiology and Nuclear Medicine, Magdeburg (Germany); Buchert, Ralph [University Medicine Charite, Clinic of Nuclear Medicine, Berlin (Germany); Wertzel, Heinz; Achenbach, H.J. [Lung Clinic Lostau GmbH, Lostau (Germany); Riedel, Sandra; Schreiber, Jens [University Hospital, Otto-von-Guericke University Magdeburg, Clinic of Pneumology, Magdeburg (Germany); Schultz, Meinald [Institute of Pathology Stendal, Stendal (Germany); Furth, Christian; Amthauer, Holger [University Hospital, Otto-von-Guericke University Magdeburg, Clinic of Radiology and Nuclear Medicine, Magdeburg (Germany); University Medicine Charite, Clinic of Nuclear Medicine, Berlin (Germany); Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Hofheinz, Frank [Helmholtz-Center Dresden-Rossendorf, Dresden (Germany); Kalinski, Thomas [University Hospital Magdeburg, Otto-von-Guericke University Magdeburg, Institute for Pathology, Magdeburg (Germany); Institute for Pathology Lademannbogen, Hamburg (Germany)

    2016-12-15

    Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC). The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with {sup 18}F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures. SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with

  14. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees

    NARCIS (Netherlands)

    Nara, P. L.; Smit, L.; Dunlop, N.; Hatch, W.; Merges, M.; Waters, D.; Kelliher, J.; Gallo, R. C.; Fischinger, P. J.; Goudsmit, J.

    1990-01-01

    Emergence in two chimpanzees of human immunodeficiency virus type 1 (HIV-1) IIIB variants resistant to neutralization by the preexisting antibody is described. Viruses isolated from the HIV-1 IIIB gp120-vaccinated and -challenged animal were more resistant to neutralization by the chimpanzee's own

  15. 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...

  16. 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...

  17. Solar Type IIIb Radio Bursts as Tracers for Electron Density Fluctuations in the Corona

    Science.gov (United States)

    Mugundhan, V.; Hariharan, K.; Ramesh, R.

    2017-11-01

    We present an estimation of the electron density modulation index (δ{Ne}/Ne) for the first time using solar type IIIb radio burst observations. The mean value of δ{Ne}/Ne is calculated to be ≈ 0.006±0.002 over the heliocentric distance range r ≈1.6 - 2.2 R_{⊙}. The estimated {δ{Ne}}/{Ne} shows a power law dependence on r with a power law index ≈ 0.31±0.10. The wavenumber (k) spectrum for the electron density fluctuation ({δ{Ne}/Ne})2 values shows a Kolmogorov-like behavior. Using δ{Ne}/Ne and the Kolmogorov turbulence index, we estimated the amplitude of density turbulence [Cn2{(r)}] in the aforementioned range of r.

  18. 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.

  19. Delayed flap reconstruction with vacuum-assisted closure management of the open IIIB tibial fracture.

    Science.gov (United States)

    Hou, Zhiyong; Irgit, Kaan; Strohecker, Kent A; Matzko, Michelle E; Wingert, Nathaniel C; DeSantis, Joseph G; Smith, Wade R

    2011-12-01

    Vacuum-assisted closure (VAC) therapy has been shown to be effective at reducing bacterial counts in wounds until definitive bony coverage. However, there is continued debate over timing and type of definitive wound coverage even with VAC therapy application. From 2004 to 2009, 32 patients with Gustilo type IIIB open tibia fractures were initially treated with VAC therapy were included. The number of debridements, length of treatment with VAC dressing, definitive wound coverage management, and length of hospital stay, flap-related complications, and time to radiographic fracture healing were recorded. The mean Injury Severity Score was 17.3 ± 2.0. All wounds closed after being treated with the primary VAC closure. The mean interval between the initial injury and definitive intervention was 10.9 days ± 0.3 days. Twenty of 27 patients (74%) underwent rotational muscle flaps; four received free muscle flaps and three only with split-thickness skin grafts for definitive wound coverage. Nine of 32 patients (28%) underwent below knee amputation, five without flap coverage after several VAC sessions and four after definitive flap coverage. The average time to union was 10.0 months ± 2.0 months. Eight patients developed nonunion and 11 patients developed infections. The average follow-up time is 2.4 years ± 0.2 years. Patients were divided into two groups for analysis according to the interval time. The rate of infection was significantly increased in patients who had an interval of more than 7 days from the time of injury to flap coverage. The VAC therapy may help to reduce the flap size and need for a flap transfer for type IIIB open tibial fractures. However, prolonged periods of VAC usage, greater than 7 days, should be avoided to reduce higher infection and amputation risks.

  20. A phase I study of gemcitabine with concurrent radiotherapy in stage III, locally advanced non-small cell lung cancer

    NARCIS (Netherlands)

    van Putten, JWG; Price, A; van der Leest, AHD; Gregor, A; Little, FA; Groen, HJM

    Purpose: Our goal was to find the maximum tolerated dose of gemcitabine administered concurrently with thoracic radiotherapy in locally advanced non-small cell lung cancer (NSCLC). Patients and Methods: Patients with stage III NSCLC and a radiation planning volume less than 2000 cm(3) were included.

  1. Antibody response to a synthetic peptide covering a LAV-1/HTLV-IIIB neutralization epitope and disease progression

    NARCIS (Netherlands)

    Boucher, C. A.; de Wolf, F.; Houweling, J. T.; Bakker, M.; Dekker, J.; Roos, M. T.; Coutinho, R. A.; van der Noordaa, J.; Goudsmit, J.

    1989-01-01

    Sequential sera of homosexual men participating in a prospective study on the incidence of HIV-1 infection and risk factors for AIDS were tested for the presence of antibodies to a synthetic 17-mer (Neu21; KSIRIQRGPGRAFVTIG) representing a neutralization epitope as present on the LAV-1/HTLV-IIIB

  2. Pathway Targeted Immunotherapy: Rationale and Evidence of Durable Clinical Responses with a Novel, EGF-directed Agent for Advanced NSCLC.

    Science.gov (United States)

    Rosell, Rafael; Neninger, Elia; Nicolson, Marianne; Huber, Rudolf M; Thongprasert, Sumitra; Parikh, Purvish M; D'Hondt, Erik

    2016-11-01

    Abnormalities in the epidermal growth factor (EGF) and EGFR pathway promote progression of NSCLC. Immunization with EGF vaccine induces specific, neutralizing anti-EGF antibodies that prevent binding of the ligand to its receptor. This concept of pathway targeted immunotherapy (PTI) was validated in vitro by dose-related suppression of EGFR, Akt, and Erk1/2 phosphorylation in cell lines with different mutations. A randomized phase II trial showed improved overall survival (OS) in subgroups with advanced NSCLC showing a clear immunologic response. By per-protocol analysis of the ensuing phase IIb trial, patients receiving EGF PTI survived 3 months longer than controls (12.43 versus 9.43 months; hazard ratio = 0.77 [95% confidence interval, 0.61-0.98]). These data were confirmed in a larger trial showing an OS benefit over control of >3 months. The variable most strongly correlated with efficacy was circulating EGF at enrolment. Patients with serum EGF levels >250 pg/mL benefited most from treatment with EGF PTI. Of 188 patients tested, 94 were above this biomarker threshold. The OS benefit from active versus control treatment was 6.7 months. More than 15% of patients had responses for >5 years. Long-term survivors are seen in all EGF PTI trials. Treatment is well-tolerated, induces high anti-EGF antibody titers, reduces levels of circulating serum EGF, achieves durable responses, and significantly prolongs OS. A threshold of 250 pg/mL has been set to enrich the study population in the ongoing pivotal trial. This biomarker-guided study in an enriched population of patients with both squamous and nonsquamous stage IV NSCLC aims to replicate the favorable efficacy/tolerability balance of earlier studies. Copyright © 2016 International Association for the Study of Lung Cancer. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  4. Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB.

    Science.gov (United States)

    Kan, Shih-Hsin; Aoyagi-Scharber, Mika; Le, Steven Q; Vincelette, Jon; Ohmi, Kazuhiro; Bullens, Sherry; Wendt, Daniel J; Christianson, Terri M; Tiger, Pascale M N; Brown, Jillian R; Lawrence, Roger; Yip, Bryan K; Holtzinger, John; Bagri, Anil; Crippen-Harmon, Danielle; Vondrak, Kristen N; Chen, Zhi; Hague, Chuck M; Woloszynek, Josh C; Cheung, Diana S; Webster, Katherine A; Adintori, Evan G; Lo, Melanie J; Wong, Wesley; Fitzpatrick, Paul A; LeBowitz, Jonathan H; Crawford, Brett E; Bunting, Stuart; Dickson, Patricia I; Neufeld, Elizabeth F

    2014-10-14

    Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disease characterized by profound intellectual disability, dementia, and a lifespan of about two decades. The cause is mutation in the gene encoding α-N-acetylglucosaminidase (NAGLU), deficiency of NAGLU, and accumulation of heparan sulfate. Impediments to enzyme replacement therapy are the absence of mannose 6-phosphate on recombinant human NAGLU and the blood-brain barrier. To overcome the first impediment, a fusion protein of recombinant NAGLU and a fragment of insulin-like growth factor II (IGFII) was prepared for endocytosis by the mannose 6-phosphate/IGFII receptor. To bypass the blood-brain barrier, the fusion protein ("enzyme") in artificial cerebrospinal fluid ("vehicle") was administered intracerebroventricularly to the brain of adult MPS IIIB mice, four times over 2 wk. The brains were analyzed 1-28 d later and compared with brains of MPS IIIB mice that received vehicle alone or control (heterozygous) mice that received vehicle. There was marked uptake of the administered enzyme in many parts of the brain, where it persisted with a half-life of approximately 10 d. Heparan sulfate, and especially disease-specific heparan sulfate, was reduced to control level. A number of secondary accumulations in neurons [β-hexosaminidase, LAMP1(lysosome-associated membrane protein 1), SCMAS (subunit c of mitochondrial ATP synthase), glypican 5, β-amyloid, P-tau] were reduced almost to control level. CD68, a microglial protein, was reduced halfway. A large amount of enzyme also appeared in liver cells, where it reduced heparan sulfate and β-hexosaminidase accumulation to control levels. These results suggest the feasibility of enzyme replacement therapy for MPS IIIB.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-15

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

  6. 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.

  7. 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

  8. Noninvasive image texture analysis differentiates K-ras mutation from pan-wildtype NSCLC and is prognostic.

    Directory of Open Access Journals (Sweden)

    Glen J Weiss

    Full Text Available Non-invasive characterization of a tumor's molecular features could enhance treatment management. Quantitative computed tomography (CT based texture analysis (QTA has been used to derive tumor heterogeneity information, and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer (NSCLC and other cancers. In this study, we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC.Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel. Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA. QTA was applied to regions of interest in the primary tumor. Non-parametric Mann Whitney test assessed the ability of the QTA, clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype. A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters. Kaplan-Meier survival analysis assessed the ability of these markers to predict survival.QTA was applied to 48 cases identified, 27 had a K-ras mutation and 21 cases were pan-wildtype. Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation. A five node decision tree had sensitivity, specificity, and accuracy values (95% CI of 96.3% (78.1-100, 81.0% (50.5-97.4, and 89.6% (72.9-97.0; respectively. Kurtosis was a significant predictor of OS and DFS, with a lower kurtosis value linked with poorer survival.Lower kurtosis and positive skewness are significantly associated with K-ras mutations. A QTA feature such as kurtosis is prognostic for OS and DFS. Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with

  9. 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

  10. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

    OpenAIRE

    Li, Chun-Yan; Li, Bao-Xiu; Liang, Yi; Peng, Rui-Qing; Ding, Ya; Xu, Da-Zhi; Zhang, Xin; Pan, Zhi-Zhong; Wan, De-Sen; Zeng, Yi-Xin; Zhu, Xiao-Feng; Zhang, Xiao-Shi

    2009-01-01

    Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was inves...

  11. 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

  12. 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 ...

  13. RIP Input Tables From Wapdeg For LA Design Selection: Enhanced Design Alternative IIIb

    International Nuclear Information System (INIS)

    K.G. Mon; K.G. Mast; J.H. Lee

    1999-01-01

    The purpose of this calculation is to document the Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b. 'Software Routine Report for WAPDEG' (Version 3.09)) simulations used to analyze degradation and failure of 2-cm thick titanium grade 7 corrosion resistant material (CRM) drip shields as well as degradation and failure of the waste packages over which they are placed. The waste packages are composed of two corrosion resistant materials (CRM) barriers. The outer barrier is composed of 2 cm of Alloy 22 and the inner barrier is composed of 1.5 cm of titanium grade 7. The WAPDEG simulation results are post-processed into tables of drip shield/waste package degradation time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer code. This calculation supports Performance Assessment analysis of the License Application Design Selection (LADS) Enhanced Design Alternative IIIb

  14. ON THE RATES OF TYPE Ia SUPERNOVAE IN DWARF AND GIANT HOSTS WITH ROTSE-IIIb

    International Nuclear Information System (INIS)

    Quimby, Robert M.; Yuan Fang; Akerlof, Carl; Wheeler, J. Craig; Warren, Michael S.

    2012-01-01

    We present a sample of 23 spectroscopically confirmed Type Ia supernovae (SNe Ia) that were discovered in the background of galaxy clusters targeted by ROTSE-IIIb and use up to 18 of these to determine the local (z-bar 0.05) volumetric rate. Since our survey is flux limited and thus biased against fainter objects, the pseudo-absolute magnitude distribution (pAMD) of SNe Ia in a given volume is an important concern, especially the relative frequency of high- to low-luminosity SNe Ia. We find that the pAMD derived from the volume-limited Lick Observatory Supernova Search (LOSS) sample is incompatible with the distribution of SNe Ia in a volume-limited (z B > –16) galaxies, whereas only 1 out of 79 nearby SDSS-II SNe Ia have such faint hosts. It is possible that previous works have undercounted either low-luminosity SNe Ia, SNe Ia in low-luminosity hosts, or peculiar SNe Ia (sometimes explicitly), and the total SNe Ia rate may be higher than the canonical value.

  15. 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.

  16. 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.

  17. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2017-06-12

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  18. Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma

    Science.gov (United States)

    2017-12-20

    ALK Fusion Protein Expression; BRAF wt Allele; Invasive Skin Melanoma; MET Fusion Gene Positive; NRAS wt Allele; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; RET Fusion Positive; ROS1 Fusion Positive; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

  19. 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

  20. ON THE RATES OF TYPE Ia SUPERNOVAE IN DWARF AND GIANT HOSTS WITH ROTSE-IIIb

    Energy Technology Data Exchange (ETDEWEB)

    Quimby, Robert M. [Kavli IPMU, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8583 (Japan); Yuan Fang [Research School of Astronomy and Astrophysics, Australian National University, Weston Creek, ACT 2611 (Australia); Akerlof, Carl [Physics Department, University of Michigan, Ann Arbor, MI 48109 (United States); Wheeler, J. Craig [Department of Astronomy, McDonald Observatory, University of Texas, Austin, TX 78712 (United States); Warren, Michael S. [Theoretical Division, Mail Stop B227, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2012-12-01

    We present a sample of 23 spectroscopically confirmed Type Ia supernovae (SNe Ia) that were discovered in the background of galaxy clusters targeted by ROTSE-IIIb and use up to 18 of these to determine the local (z-bar 0.05) volumetric rate. Since our survey is flux limited and thus biased against fainter objects, the pseudo-absolute magnitude distribution (pAMD) of SNe Ia in a given volume is an important concern, especially the relative frequency of high- to low-luminosity SNe Ia. We find that the pAMD derived from the volume-limited Lick Observatory Supernova Search (LOSS) sample is incompatible with the distribution of SNe Ia in a volume-limited (z < 0.12) sub-sample of the Sloan Digital Sky Survey II (SDSS-II). The LOSS sample requires far more low-luminosity SNe Ia than the SDSS-II can accommodate. Even though LOSS and SDSS-II have sampled different SNe Ia populations, their volumetric rates are surprisingly similar. Using the same model pAMD adopted in the SDSS-II SNe Ia rate calculation and excluding two high-luminosity SNe Ia from our sample, we derive a rate that is marginally higher than previous low-redshift determinations. With our full sample and the LOSS pAMD, our rate is more than double the canonical value. We also find that 5 of our 18 SNe Ia are hosted by very low luminosity (M{sub B} > -16) galaxies, whereas only 1 out of 79 nearby SDSS-II SNe Ia have such faint hosts. It is possible that previous works have undercounted either low-luminosity SNe Ia, SNe Ia in low-luminosity hosts, or peculiar SNe Ia (sometimes explicitly), and the total SNe Ia rate may be higher than the canonical value.

  1. Factors Affecting Optimal Aortic Remodeling After Thoracic Endovascular Aortic Repair of Type B (IIIb) Aortic Dissection

    Energy Technology Data Exchange (ETDEWEB)

    Chen, I-Ming [National Yang Ming University, Institute of Clinical Medicine, School of Medicine (China); Chen, Po-Lin; Huang, Chun-Yang [National Yang Ming University, Department of Medicine, School of Medicine (China); Weng, Shih-Hsien; Chen, Wei-Yuan; Shih, Chun-Che, E-mail: ccshih@vghtpe.gov.tw [National Yang Ming University, Institute of Clinical Medicine, School of Medicine (China)

    2017-05-15

    PurposeThe purpose of this study was to determine factors associated with entire aortic remodeling after thoracic endovascular aortic repair (TEVAR) in patients with type B dissection.Materials and MethodsThe patients with type B (IIIb) dissections who underwent TEVAR from 2006 to 2013 with minimum of 2 years of follow-up computed tomography data were retrospectively reviewed. Based on the status of false lumen remodeling of entire aorta, patients were divided into three groups: complete regression, total thrombosis, and inadequate regression with patent abdominal false lumen.ResultsA total of 90 patients (72 males, 18 females; mean age 56.6 ± 16.4 years) were included and divided into the complete regression (n = 22), total thrombosis (n = 18), and inadequate regression (n = 50) groups. Multivariate logistic regression analysis indicated that dissection extension to iliac arteries, increased preoperative number of dissection tear over abdominal aorta, and decreased preoperative abdominal aorta bifurcation true lumen ratio, as compared between the inadequate and complete regression groups, were associated with a persistent false lumen (odds ratio = 33.33, 2.304, and 0.021; all, p ≤ 0.012). Comparison of 6, 12, and 24 months postoperative data revealed no significant differences at any level, suggesting that the true lumen area ratio might not change after 6 months postoperatively.ConclusionsIncreased preoperative numbers of dissection tear around the abdominal visceral branches, dissection extension to the iliac arteries, and decreased preoperative true lumen area ratio of abdominal aorta are predictive of entire aortic remodeling after TEVAR in patients with type B dissection.Level of EvidenceIII.

  2. A prognostic DNA methylation signature for stage I non-small-cell lung cancer.

    Science.gov (United States)

    Sandoval, Juan; Mendez-Gonzalez, Jesus; Nadal, Ernest; Chen, Guoan; Carmona, F Javier; Sayols, Sergi; Moran, Sebastian; Heyn, Holger; Vizoso, Miguel; Gomez, Antonio; Sanchez-Cespedes, Montse; Assenov, Yassen; Müller, Fabian; Bock, Christoph; Taron, Miquel; Mora, Josefina; Muscarella, Lucia A; Liloglou, Triantafillos; Davies, Michael; Pollan, Marina; Pajares, Maria J; Torre, Wenceslao; Montuenga, Luis M; Brambilla, Elisabeth; Field, John K; Roz, Luca; Lo Iacono, Marco; Scagliotti, Giorgio V; Rosell, Rafael; Beer, David G; Esteller, Manel

    2013-11-10

    Non-small-cell lung cancer (NSCLC) is a tumor in which only small improvements in clinical outcome have been achieved. The issue is critical for stage I patients for whom there are no available biomarkers that indicate which high-risk patients should receive adjuvant chemotherapy. We aimed to find DNA methylation markers that could be helpful in this regard. A DNA methylation microarray that analyzes 450,000 CpG sites was used to study tumoral DNA obtained from 444 patients with NSCLC that included 237 stage I tumors. The prognostic DNA methylation markers were validated by a single-methylation pyrosequencing assay in an independent cohort of 143 patients with stage I NSCLC. Unsupervised clustering of the 10,000 most variable DNA methylation sites in the discovery cohort identified patients with high-risk stage I NSCLC who had shorter relapse-free survival (RFS; hazard ratio [HR], 2.35; 95% CI, 1.29 to 4.28; P = .004). The study in the validation cohort of the significant methylated sites from the discovery cohort found that hypermethylation of five genes was significantly associated with shorter RFS in stage I NSCLC: HIST1H4F, PCDHGB6, NPBWR1, ALX1, and HOXA9. A signature based on the number of hypermethylated events distinguished patients with high- and low-risk stage I NSCLC (HR, 3.24; 95% CI, 1.61 to 6.54; P = .001). The DNA methylation signature of NSCLC affects the outcome of stage I patients, and it can be practically determined by user-friendly polymerase chain reaction assays. The analysis of the best DNA methylation biomarkers improved prognostic accuracy beyond standard staging.

  3. Glutathione S-transferase PI (GST-PI) mRNA expression and DNA methylation is involved in the pathogenesis and prognosis of NSCLC.

    Science.gov (United States)

    Grimminger, Peter P; Maus, Martin K H; Schneider, Paul M; Metzger, Ralf; Hölscher, Arnulf H; Sugita, Hirofumi; Danenberg, Peter V; Alakus, Hakan; Brabender, Jan

    2012-10-01

    The aim of this study was to investigate the relevance of mRNA expression and DNA methylation of GST-PI in tumor and non-tumor lung tissue from NSCLC patients in terms of prognostic and pathogenetic value of this biomarker. Quantitative real-time PCR was used to measure mRNA expression and DNA methylation of GST-PI in paired tumor (T) and non-tumor (N) lung tissue of 91 NSCLC patients. Of all 91 patients 49% were stage I, 21% stage II and 30% stage IIIA. Forty-seven percent of the patients had squamous cell carcinoma, 36% adenocarcinoma and 17% large cell carcinoma. All patients were R0 resected. GST-PI mRNA expression could be measured in 100% in both (T and N) tissues; GST-PI DNA methylation was detected in 14% (N) and 14% (T). The median GST-PI mRNA expression in N was 7.83 (range: 0.01-19.43) and in T 13.15 (range: 0.01-116.8; p≤0.001). The median GST-PI methylation was not significantly different between T and N. No associations were seen between the mRNA expression or DNA methylation levels and clinical or histopathologic parameters such as gender, age, TNM stage, tumor histology and grading. The median survival of the investigated patients was 59.7 years (the median follow-up was 85.9 months). High GST-PI DNA methylation was significantly associated with a worse prognosis (p=0.041, log rank test). No correlation was found between the GST-PI DNA methylation levels and the correlating mRNA expression levels. GST-PI mRNA expression seems to be involved in the pathogenesis of NSCLC. High levels of GST-PI DNA methylation in tumor tissue of NSCLC patients have a potential as a biomarker identifying subpopulations with a more aggressive tumor biology. Quantitation of GST-PI DNA methylation may be a useful method to identify patients with a poor prognosis after curative resection and who will benefit from intensive adjuvant therapy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2018-03-02

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

  9. 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.

  10. 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.

  11. MiR-186 Inhibited Migration of NSCLC via Targeting cdc42 and Effecting EMT Process.

    Science.gov (United States)

    Dong, Ying; Jin, Xintian; Sun, Zhiqiang; Zhao, Yueming; Song, Xianjing

    2017-03-01

    In this study, qRT-PCR was employed to identify that miR-186 expression level in NSCLC tissues are highly associated with lymph node metastasis. In addition, through the application of western blotting, luciferase assay and qRT-PCR, it was found that miR-186 targeted 3'UTR of cdc42 mRNA and down-regulated cdc42 protein level in a post-transcriptional manner. Transwell assay indicated that cdc42 partially reversed the effect of miR-186 mimics. Besides, miR-186 was proved to regulate EMT by influencing biomarkers of this process and cell adhesion ability. Thus, miR-186 is a potential target for NSCLC therapy. miR-186 is proposed to be one of tumor-suppressors and may serve as a therapeutic target in NSCLC treatment.

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy and factors influencing consideration for surgery in stage III non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Melissa A.L. Vyfhuis, MD PhD

    2017-07-01

    Conclusions: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

  1. [The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

    Science.gov (United States)

    Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

    2017-12-01

    This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

  2. Alternating radiotherapy and chemotherapy for inoperable stage III non-small-cell lung cancer: long-term results of two phase II GOTHA trials

    International Nuclear Information System (INIS)

    Mirimanoff, Rene-Olivier; Moro, Denis; Bolla, Michel; Michel, Genevieve; Brambilla, Christian; Mermillod, Bernadette; Miralbell, Raymond; Alberto, Pierre

    1998-01-01

    Purpose/Objective: To report on two consecutive Phase II cooperative trials in which we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy in inoperable Stage III non-small cell lung cancer (NSCLC). Patients and Methods: Between February 1986 and September 1989, 65 patients were entered in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocols, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m 2 day 1, mitomycin, 8 mg/m 2 day 1, and vindesin 3 mg/m 2 day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisplatin 70 mg/m 2 day 1 and vinblastin 5 mg/m 2 day 1 and the first day of the following week were given during weeks 1, 5, 9, 13, 17, and 21. Results: With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8-year overall survival probability was 56% (95% CI 47-64%), 27% (20-35%), 12% (7-18%) and 9% (3-16%), respectively, with a median survival of 13.6 months (11.4-16.8). Median follow-up for survivors was 6 years (3.3-9.9). There were no survival differences between Stages IIIA and IIIB (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown causes. Correlation between response and long-term survival was poor, since of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25%), or 'progressive disease' (1, 4%). First site of relapse was

  3. Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive" mediastinal nodes in the staging of non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Moloney, F

    2014-05-01

    The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC).

  4. 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...

  5. Mediastinal staging for lung cancer: the influence of biopsy volume

    DEFF Research Database (Denmark)

    Nelson, Elof; Pape, Christian; Jørgensen, Ole Dan

    2010-01-01

    OBJECTIVE: Mediastinal staging is of paramount importance prior to surgery for non-small-cell lung cancer (NSCLC) to identify patients with N2-disease. Mediastinoscopy remains the gold standard, and sampling from at least three lymph node stations is generally recommended. It is unknown whether...

  6. 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

  7. Evaluation of NGS and RT-PCR methods for ALK rearrangement in European NSCLC patients

    DEFF Research Database (Denmark)

    Letovanec, Igor; Finn, Stephen; Zygoura, Panagiota

    2018-01-01

    INTRODUCTION: The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase-poly...

  8. 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...

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

    Science.gov (United States)

    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.

  10. 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

  11. Genome analysis of the sugar beet pathogen Rhizoctonia solani AG2-2IIIB revealed high numbers in secreted proteins and cell wall degrading enzymes.

    Science.gov (United States)

    Wibberg, Daniel; Andersson, Louise; Tzelepis, Georgios; Rupp, Oliver; Blom, Jochen; Jelonek, Lukas; Pühler, Alfred; Fogelqvist, Johan; Varrelmann, Mark; Schlüter, Andreas; Dixelius, Christina

    2016-03-17

    Sugar beet (Beta vulgaris) is a crop cultivated for its high content in sugar, but it is vulnerable to many soil-borne pathogens. One of them is the basidiomycete Rhizoctonia solani. This fungal species has a compatibility system regulating hyphal fusions (anastomosis). Consequently, R. solani species are categorized in anastomosis groups (AGs). AG2-2IIIB isolates are most aggressive on sugar beet. In the present study, we report on the draft genome of R. solani AG2-2IIIB using the Illumina technology. Genome analysis, interpretation and comparative genomics of five sequenced R. solani isolates were carried out. The draft genome of R. solani AG2-2IIIB has an estimated size of 56.02 Mb. In addition, two normalized EST libraries were sequenced. In total 20,790 of 21,980 AG2-2IIIB isotigs (transcript isoforms) were mapped on the genome with more than 95 % sequence identity. The genome of R. solani AG2-2IIIB was predicted to harbor 11,897 genes and 4908 were found to be isolate-specific. R. solani AG2-2IIIB was predicted to contain 1142 putatively secreted proteins and 473 of them were found to be unique for this isolate. The R. solani AG2-2IIIB genome encodes a high number of carbohydrate active enzymes. The highest numbers were observed for the polysaccharide lyases family 1 (PL-1), glycoside hydrolase family 43 (GH-43) and carbohydrate estarase family 12 (CE-12). Transcription analysis of selected genes representing different enzyme clades revealed a mixed pattern of up- and down-regulation six days after infection on sugar beets featuring variable levels of resistance compared to mycelia of the fungus grown in vitro. The established R. solani AG2-2IIIB genome and EST sequences provide important information on the gene content, gene structure and transcriptional activity for this sugar beet pathogen. The enriched genomic platform provides an important platform to enhance our understanding of R. solani biology.

  12. Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project.

    Science.gov (United States)

    Bubendorf, Lukas; Dafni, Urania; Schöbel, Martin; Finn, Stephen P; Tischler, Verena; Sejda, Aleksandra; Marchetti, Antonio; Thunnissen, Erik; Verbeken, Eric K; Warth, Arne; Sansano, Irene; Cheney, Richard; Speel, Ernst Jan M; Nonaka, Daisuke; Monkhorst, Kim; Hager, Henrik; Martorell, Miguel; Savic, Spasenija; Kerr, Keith M; Tan, Qiang; Tsourti, Zoi; Geiger, Thomas R; Kammler, Roswitha; Schulze, Katja; Das-Gupta, Ashis; Shames, David; Peters, Solange; Stahel, Rolf A

    2017-09-01

    In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome. Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells. A total of 182 MET IHC+ and EGFR/KRAS WT tumors were analyzed for METex14 skipping mutation. MET IHC+ was found in 23.8% of 2432 patients, significantly associated with female gender, small tumor size, and adenocarcinoma histology. We observed a high inter-laboratory variability in IHC and SISH analysis. MET amplification prevailed in 4.6% and MET GCN≥5 in 4.1% of 1572 patients. MET amplification and MET GCN≥5 were not significantly associated with any tumor characteristics or stage. Both were significantly associated with IHC MET positivity (poverexpression, SISH MET amplification or high MET GCN was found with OS, RFS or TTR. MET overexpression is found in 23.8% of surgically resected NSCLC. MET amplification prevails in 4.6% and is associated with MET overexpression. Both have no influence on prognosis. The large inter-laboratory variability in IHC highlights the challenge of MET IHC analysis in routine practice. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    2018-02-14

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

  14. Radiation therapy alone in the treatment of cervix cancer stages IIB and IIB. Results from Hospital Mario Gatti, Pontificia Universidade Catolica de Campinas

    International Nuclear Information System (INIS)

    Ferrigno, Robson; Oliveira Faria, Sergio Luis Campos de

    1995-01-01

    From September 1989 to December 1992, 178 patients with cervix cancer were treated with radiation therapy alone, being 81 stage IIIB patients were randomized according to the number of intracavitary brachytherapy insertion realized after external irradiation. Of these, 34 were treated with two intracavitary insertion (group A) and 47 with one insertion (group B). Among stage IIIB patients, 54 were treated with one intracavitary insertion after external irradiation (group C) and 47 with external irradiation alone as they had no geometrical condition for intracavitary insertion (group D). There were no statistical difference in 50 months disease free survival among patients stage IIB treated with one or two intracavitary insertion, 72,3% and 70.6% respectively (P=0,711). The 50 months disease free survival were better in patients stage IIIB treated with external irradiation followed by one intracavitary insertion, compared with those treated with external irradiation alone, 51,8% and 30,2% respectively (P=0,007). This series suggests that there is no difference in the treatment of stage IIB cervix cancer with one or two intracavitary insertion. Among stage IIIB patients, the worse result of those treated with external irradiation alone was probably due to the unfavorable prognostic factors, as they were excluded for brachytherapy because they showed no geometrical condition for intracavitary insertion and larger tumor volume. (author)

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

    Directory of Open Access Journals (Sweden)

    Au David H

    2011-06-01

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

  16. First-line systemic treatment of advanced stage non-small-cell lung cancer in Asia: consensus statement from the Asian Oncology Summit 2009.

    Science.gov (United States)

    Soo, Ross A; Anderson, Benjamin O; Cho, Byoung Chul; Yang, Chih-Hsin; Liao, Meilin; Lim, Wan-Teck; Goldstraw, Peter; Mok, Tony S

    2009-11-01

    Non-small-cell lung cancer (NSCLC) is an increasing global challenge, especially in low-income countries. Most guidelines for the management of advanced-stage NSCLC have limited effect in countries with resource constraints. Following a systematic literature search, we present an overview of the management of advanced-stage NSCLC in the first-line setting, discuss resources required for systemic therapy, and provide treatment recommendations stratified to four resources levels. Treatment guidelines appropriate for different resource levels offer a realistic approach to management of advanced-stage NSCLC, by recognising the limitations of a particular health-care system. Although there are many barriers to cancer control in low-resource countries, these can be overcome by using measures that are culturally appropriate, economically feasible, and evidence-based. Initiatives include strategic planning, tobacco control, training of health-care workers, access to therapeutic agents, acquisition of information, public education, and alliances with established institutions and international organisations.

  17. 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

  18. An archaeal CRISPR type III-B system exhibiting distinctive RNA targeting features and mediating dual RNA and DNA interference

    DEFF Research Database (Denmark)

    Peng, Wenfang; Feng, Mingxia; Feng, Xu

    2015-01-01

    CRISPR-Cas systems provide a small RNA-based mechanism to defend against invasive genetic elements in archaea and bacteria. To investigate the in vivo mechanism of RNA interference by two type III-B systems (Cmr-α and Cmr-β) in Sulfolobus islandicus, a genetic assay was developed using plasmids...... carrying an artificial mini-CRISPR (AC) locus with a single spacer. After pAC plasmids were introduced into different strains, Northern analyses confirmed that mature crRNAs were produced from the plasmid-borne CRISPR loci, which then guided gene silencing to target gene expression. Spacer mutagenesis....... islandicus Cmr-α mediated transcription-dependent DNA interference, the Cmr-α constitutes the first CRISPR system exhibiting dual targeting of RNA and DNA....

  19. 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...

  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. 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

  2. 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...

  3. 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.

  4. The significance of serum leptin level in patients with early stage nonsmall cell lung cancer.

    Science.gov (United States)

    Karatas, Fatih; Yalcin, Bulent; Sahin, Suleyman; Akbulut, Hakan; Utkan, Gungor; Demirkazik, Ahmet; Icli, Fikri

    2017-01-01

    The serum leptin level (SLL) has been shown to increase in patients with nonsmall cell lung cancer (NSCLC). However, available data regarding the relation between SLL and tumor subtypes, survival, cachexia, and tumor respectability in NSCLC are still under debate. The aim of this study is to evaluate SLL in NSCLC patients with and without cachexia. A total of 71 patients with early stage NSCLC were enrolled in this prospective study. SLL was measured by enzyme-linked immunosorbent assay. The relationship between SLL and clinicopathological factors including histopathological subtypes, weight loss, overall survival, and tumor resectability were evaluated. Of the 71 patients, 57 (81%) were male with a mean age of 63.3 ± 8.2 years. The rates of histological subtypes of NSCLC were as follows: Squamous cell carcinoma 60.5%, adenocarcinoma 32%, and others 7.2%. Mean SLL was 12.9 ± 38.4 pmol/mL. There was no distinctive difference between SLL, weight loss, and survival. However, when stratifying the groups according to the lung cancer histological subtypes, mean SLL was significantly higher in patients with adenocarcinoma than those with squamous cell subtype (26.9 ± 6.2 pmol/mL vs. 5.1 ± 9.1 pmol/mL, P = 0.004). SLL might be beneficial as a useful biomarker in preclinical setting of NSCLC to guide detecting the lung cancer subtypes as well as monitoring the patients.

  5. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. In vivo 3-dimensional analysis of stage III Kienböck disease: pattern of carpal deformity and radioscaphoid joint congruity.

    Science.gov (United States)

    Kawanishi, Yohei; Moritomo, Hisao; Omokawa, Shohei; Murase, Tsuyoshi; Sugamoto, Kazuomi; Yoshikawa, Hideki

    2015-01-01

    To examine 3-dimensional carpal alignment and radioscaphoid joint (RSJ) congruity among normal wrists and those with Lichtman stage III Kienböck disease or scapholunate dislocation (SLD). We conducted 3-dimensional analysis based on computed tomographic data to compare 10 wrists of stage III Kienböck disease (5 IIIa and 5 IIIb) with 5 normal wrists and 3 wrists with SLD. A markerless bone registration technique was used to investigate the 3-dimensional position of the scaphoid relative to the radius. To evaluate RSJ congruency, the inferred contact area between the scaphoid proximal pole and the distal radius was calculated from 3-dimensional bone models. The scaphoid position was not significantly different from normal wrists in stage IIIa Kienböck disease. Stage IIIb Kienböck disease was meaningfully associated with a flexed scaphoid and proximal translation of the centroid, but not dorsal translation of the scaphoid proximal pole, where RSJ congruity was preserved. With SLD, the scaphoid flexed to the same extent as that in stage IIIb Kienböck disease, and the proximal pole translated dorsally together with the capitate, producing RSJ incongruity. The patterns of carpal collapse differed between stage IIIb Kienböck disease and SLD in terms of RSJ congruity. Our study showed that stage IIIb Kienböck disease did not involve dorsal subluxation of the scaphoid proximal pole and that RSJ congruity was retained, unlike SLD. Our results suggest that carpal collapse in Kienböck disease is not associated with RSJ incongruity, which may explain why there are asymptomatic patients with Kienböck disease and carpal collapse. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  14. 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...

  15. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2018-01-12

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  16. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    Science.gov (United States)

    2018-01-12

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; WT1 Positive

  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. 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.

  19. 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.

  20. Target RNA capture and cleavage by the Cmr type III-B CRISPR–Cas effector complex

    Science.gov (United States)

    Hale, Caryn R.; Cocozaki, Alexis; Li, Hong

    2014-01-01

    The effector complex of the Cmr/type III-B CRISPR (clustered regularly interspaced short palindromic repeat)–Cas (CRISPR-associated) system cleaves RNAs recognized by the CRISPR RNA (crRNA) of the complex and includes six protein subunits of unknown functions. Using reconstituted Pyrococcus furiosus Cmr complexes, we found that each of the six Cmr proteins plays a critical role in either crRNA interaction or target RNA capture. Cmr2, Cmr3, Cmr4, and Cmr5 are all required for formation of a crRNA-containing complex detected by native gel electrophoresis, and the conserved 5′ repeat sequence tag and 5′-OH group of the crRNA are essential for the interaction. Interestingly, capture of the complementary target RNA additionally requires both Cmr1 and Cmr6. In detailed functional studies, we determined that P. furiosus Cmr complexes cleave target RNAs at 6-nucleotide (nt) intervals in the region of complementarity, beginning 5 nt downstream from the crRNA tag and continuing to within ∼14 nt of the 3′ end of the crRNA. Our findings indicate that Cmr3 recognizes the signature crRNA tag sequence (and depends on protein–protein interactions with Cmr2, Cmr4, and Cmr5), each Cmr4 subunit mediates a target RNA cleavage, and Cmr1 and Cmr6 mediate an essential interaction between the 3′ region of the crRNA and the target RNA. PMID:25367038

  1. OECD/NEA burnup credit criticality benchmarks phase IIIB. Burnup calculations of BWR fuel assemblies for storage and transport

    Energy Technology Data Exchange (ETDEWEB)

    Okuno, Hiroshi; Naito, Yoshitaka; Suyama, Kenya [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-02-01

    The report describes the final results of the Phase IIIB Benchmark conducted by the Expert Group on Burnup Credit Criticality Safety under the auspices of the Nuclear Energy Agency (NEA) of the Organization for Economic Cooperation and Development (OECD). The Benchmark was intended to compare the predictability of current computer code and data library combinations for the atomic number densities of an irradiated PWR fuel assembly model. The fuel assembly was irradiated under specific power of 25.6 MW/tHM up to 40 GWd/tHM and cooled for five years. The void fraction was assumed to be uniform throughout the channel box and constant, at 0, 40 and 70%, during burnup. In total, 16 results were submitted from 13 institutes of 7 countries. The calculated atomic number densities of 12 actinides and 20 fission product nuclides were found to be for the most part within a range of {+-}10% relative to the average, although some results, esp. {sup 155}Eu and gadolinium isotopes, exceeded the band, which will require further investigation. Pin-wise burnup results agreed well among the participants. The results in the infinite neutron multiplication factor k{sub {infinity}} also accorded well with each other for void fractions of 0 and 40%; however some results deviated from the averaged value noticeably for the void fraction of 70%. (author)

  2. OECD/NEA burnup credit criticality benchmarks phase IIIB: Burnup calculations of BWR fuel assemblies for storage and transport

    International Nuclear Information System (INIS)

    Okuno, Hiroshi; Naito, Yoshitaka; Suyama, Kenya

    2002-02-01

    The report describes the final results of the Phase IIIB Benchmark conducted by the Expert Group on Burnup Credit Criticality Safety under the auspices of the Nuclear Energy Agency (NEA) of the Organization for Economic Cooperation and Development (OECD). The Benchmark was intended to compare the predictability of current computer code and data library combinations for the atomic number densities of an irradiated PWR fuel assembly model. The fuel assembly was irradiated under specific power of 25.6 MW/tHM up to 40 GWd/tHM and cooled for five years. The void fraction was assumed to be uniform throughout the channel box and constant, at 0, 40 and 70%, during burnup. In total, 16 results were submitted from 13 institutes of 7 countries. The calculated atomic number densities of 12 actinides and 20 fission product nuclides were found to be for the most part within a range of ±10% relative to the average, although some results, esp. 155 Eu and gadolinium isotopes, exceeded the band, which will require further investigation. Pin-wise burnup results agreed well among the participants. The results in the infinite neutron multiplication factor k ∞ also accorded well with each other for void fractions of 0 and 40%; however some results deviated from the averaged value noticeably for the void fraction of 70%. (author)

  3. CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.

    Science.gov (United States)

    Martínez-Muñoz, Laura; Barroso, Rubén; Dyrhaug, Sunniva Y; Navarro, Gemma; Lucas, Pilar; Soriano, Silvia F; Vega, Beatriz; Costas, Coloma; Muñoz-Fernández, M Ángeles; Santiago, César; Rodríguez Frade, José Miguel; Franco, Rafael; Mellado, Mario

    2014-05-13

    CCR5 and CXCR4, the respective cell surface coreceptors of R5 and X4 HIV-1 strains, both form heterodimers with CD4, the principal HIV-1 receptor. Using several resonance energy transfer techniques, we determined that CD4, CXCR4, and CCR5 formed heterotrimers, and that CCR5 coexpression altered the conformation of both CXCR4/CXCR4 homodimers and CD4/CXCR4 heterodimers. As a result, binding of the HIV-1 envelope protein gp120IIIB to the CD4/CXCR4/CCR5 heterooligomer was negligible, and the gp120-induced cytoskeletal rearrangements necessary for HIV-1 entry were prevented. CCR5 reduced HIV-1 envelope-induced CD4/CXCR4-mediated cell-cell fusion. In nucleofected Jurkat CD4 cells and primary human CD4(+) T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can help to understand why X4 HIV-1 strains infection affect T-cell types differently during AIDS development and indicate that receptor oligomerization might be a target for previously unidentified therapeutic approaches for AIDS intervention.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall...... was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain...... the association with income or living alone for early-stage NSCLC patients. CONCLUSION: Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors. Thus, even...

  5. 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.

  6. 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.

  7. 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...

  8. Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

    Directory of Open Access Journals (Sweden)

    Kyla Walworth

    Full Text Available Elevated valosin containing protein (VCP/p97 levels promote the progression of non-small cell lung carcinoma (NSCLC. Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC progression. The VCP inhibitor(s (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface were tested for their in vitro efficacy in modulating H1299 (NSCLC cells proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay and migration (p<0.05; scratch-assay, and increased apoptosis (p<0.05; caspase-3/7-assay as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion as compared to the control-DDN treatment (p<0.05. Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay and increased caspase-3/7 mediated apoptotic cell death (p<0.05 as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001 by DDNDBeQ treatment as compared to control

  9. Clinical Staging of Stage I Non-Small Cell Lung Cancer in the Netherlands-Need for Improvement in an Era With Expanding Nonsurgical Treatment Options: Data From the Dutch Lung Surgery Audit.

    Science.gov (United States)

    Heineman, David Jonathan; Ten Berge, Martijn Geert; Daniels, Johannes Marlene; Versteegh, Michaël Ignatius; Marang-van de Mheen, Perla Jacqueline; Wouters, Michael Wilhelmus; Schreurs, Wilhelmina Hendrika

    2016-11-01

    The clinical stage of non-small cell lung cancer (NSCLC) determines the initial treatment, whereas the pathologic stage best determines prognosis and the need for adjuvant treatment. In an era in which stereotactic ablative radiotherapy (SABR) has become an alternative modality to surgical intervention, clinical staging is even more important, because pathologic staging is omitted in the case of SABR. The objective of this study was to determine the concordance between clinical and pathologic stage in routine clinical practice for patients with early-stage NSCLC. Prospective data were derived from the Dutch Lung Surgery Audit (DLSA) in 2013 and 2014. Patients with clinical stage I NSCLC who underwent surgical resection and had a positron emission tomography-computed tomography (PET-CT) scan in their clinical workup were selected. Clinical and pathologic TNM (cTNM and pTNM) stages were compared. From a total of 1,790 patients with clinical stage I, 1,555 (87%) patients were included in this analysis. Concordance between cTNM and pTNM was 59.9%. Of the patients with clinical stage I, 22.6% were upstaged to pathologic stage II or higher. In total, 14.9% of all patients with clinical stage I had nodal metastases, and 5.5% of all patients had unforeseen N2 disease. In patients with clinical stage T2a tumors, 21.3% had nodal metastases, 14.5% being N1 and 6.7% being N2 disease. Concordance between clinical and pathologic stage is 59.9%. In patients with clinical stage I NSCLC, 22.6% were upstaged to pathologic stage II or higher, which is an indication for adjuvant chemotherapy. Improvement in accuracy of staging is thus needed, particularly for these patients. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. Laser Capture Microdissection Assisted Identification of Epithelial MicroRNA Expression Signatures for Prognosis of Stage I NSCLC

    Science.gov (United States)

    2011-10-01

    proteina RNA and from thr old slide respectiv dissectat at room buffer (b circles) a miR‐16 ( treated i 3 or 20 h Log2‐tran determin obtained RNA...yield f day‐old slides RT), or at ‐80 day. C. Total NU6‐2 (black ircles) from i ith proteinase heir standard U6‐2 and m antification...columns, and overnight digestion of dissected samples with proteinase K. Storage of slides carrying stained tissue sections at room temperature for up to a

  12. 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.

  13. 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.

  14. 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.

  15. Inter- and intrafractional movement of the tumour in extracranial stereotactic radiotherapy of NSCLC

    DEFF Research Database (Denmark)

    Jensen, Henrik R; Hansen, Olfred; Hjelm-Hansen, Mogens

    2008-01-01

    PURPOSE: The purpose of this study is to determine the inter- and intra-fractional respiration induced tumour movements as well as setup accuracy in a stereotactic body frame for stereotactic treatments of NSCLC patients. PATIENTS AND METHODS: From August 2005 to March 2008, 26 patients with NSCLC....... These coordinate constitute the data of this study. RESULTS: The standard deviations of the respiration induced intra-fractional movements were: LR: 0.9 mm, AP: 1.6 mm and CC: 2.0 mm (1 SD). The inter-fractional movements were: LR: 1.1 mm, AP: 1.3 mm and CC: 1.7 mm (1 SD). Finally the set up accuracies in the body...... frame were LR: 1.5 mm, AP: 1.1 mm and CC: 1.7 mm (1 SD). DISCUSSION AND CONCLUSIONS: Consecutive CT scans can be used to evaluate the respiration induced tumour movement. For patients immobilized in a stereotactic body frame, large movements of the tumour are rarely seen within the lung...

  16. 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.

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    BACKGROUND: Up to 45% of operations with curative intent for non-small-cell lung cancer (NSCLC) can be regarded as futile, apparently because the stage of the disease is more advanced than expected preoperatively. During the past decade several studies have evaluated the usefulness of endoscopic ...

  19. [Guideline on 'non-small cell lung carcinoma; staging and treatment'

    NARCIS (Netherlands)

    Meerbeeck, J.P. van; Koning, C.C.; Tjan-Heijnen, V.C.; Boekema, A.G.; Kaandorp, C.J.; Burgers, J.S.

    2005-01-01

    A national, evidence-based guideline on the staging and treatment of patients with non-small cell lung carcinoma (NSCLC) has been compiled by the various disciplines involved. The initial diagnostic measures in patients with suspected lung cancer include history taking, physical examination and

  20. Target RNA capture and cleavage by the Cmr type III-B CRISPR-Cas effector complex.

    Science.gov (United States)

    Hale, Caryn R; Cocozaki, Alexis; Li, Hong; Terns, Rebecca M; Terns, Michael P

    2014-11-01

    The effector complex of the Cmr/type III-B CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated) system cleaves RNAs recognized by the CRISPR RNA (crRNA) of the complex and includes six protein subunits of unknown functions. Using reconstituted Pyrococcus furiosus Cmr complexes, we found that each of the six Cmr proteins plays a critical role in either crRNA interaction or target RNA capture. Cmr2, Cmr3, Cmr4, and Cmr5 are all required for formation of a crRNA-containing complex detected by native gel electrophoresis, and the conserved 5' repeat sequence tag and 5'-OH group of the crRNA are essential for the interaction. Interestingly, capture of the complementary target RNA additionally requires both Cmr1 and Cmr6. In detailed functional studies, we determined that P. furiosus Cmr complexes cleave target RNAs at 6-nucleotide (nt) intervals in the region of complementarity, beginning 5 nt downstream from the crRNA tag and continuing to within ∼14 nt of the 3' end of the crRNA. Our findings indicate that Cmr3 recognizes the signature crRNA tag sequence (and depends on protein-protein interactions with Cmr2, Cmr4, and Cmr5), each Cmr4 subunit mediates a target RNA cleavage, and Cmr1 and Cmr6 mediate an essential interaction between the 3' region of the crRNA and the target RNA. © 2014 Hale et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

    Science.gov (United States)

    Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

    2018-04-15

    To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

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

    Science.gov (United States)

    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.

  3. Endobronchial ultrasound-guided transbronchial needle aspiration for nodal staging in non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    D. Coutinho

    2017-03-01

    Full Text Available Introduction: Lung cancer staging has recently evolved to include endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA for nodal assessment. Aim: Evaluate the performance and safety of EBUS-TBNA as a key component of a staging algorithm for non-small cell lung carcinoma (NSCLC and as a single investigation technique for diagnosis and staging of NSCLC. Methods: Patients undergoing EBUS-TBNA for NSCLC staging at our institution between April 1, 2010 and December 31, 2014 were consecutively included with prospective data collection. EBUS-TBNA was performed under general anesthesia through a rigid scope. Results: A total of 122 patients, 84.4% males, mean age 64.2 years. Histological type: 78 (63.9% adenocarcinoma, 33 (27.0% squamous cell carcinoma, 11 (8.9% undifferentiated/other NSCLC. A total of 435 lymph node stations were punctured. Median number of nodes per patient was 4. EBUS-TBNA nodal staging: 63 (51.6% N0; 8 (6.5% N1; 34 (27.9% N2, and 17 (13.9% N3. EBUS-TBNA was the primary diagnostic procedure in 27 (22.1% patients. EBUS-TBNA NSCLC staging had a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy rate of 83.3, 100, 100, 86.1, and 91.8%, respectively. No complications were attributable to the procedure. Conclusion: A comprehensive lung cancer staging strategy that includes EBUS-TBNA seems to be safe and effective. Our EBUS-TBNA performance and safety in this particular setting was in line with previously published reports. Additionally, our study showed that, in selected patients, lung cancer diagnosis and staging are achievable with a single endoscopic technique. Keywords: EBUS-TBNA, Non-small cell lung carcinoma, Nodal staging

  4. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC.......The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...

  5. Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data

    Science.gov (United States)

    Müller, Margareta; Vignon-Clementel, Irene E.; Drasdo, Dirk

    2016-01-01

    We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids (MCTS) of SK-MES-1 cells, a non-small cell lung cancer (NSCLC) cell line, growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spatial labeling patterns for cell proliferation, extracellular matrix (ECM), cell distribution and cell death. We start with a simple model capturing part of the experimental observations. We then show, by performing a sensitivity analysis at each development stage of the model that its complexity needs to be stepwise increased to account for further experimental growth conditions. We thus ultimately arrive at a model that mimics the MCTS growth under multiple conditions to a great extent. Interestingly, the final model, is a minimal model capable of explaining all data simultaneously in the sense, that the number of mechanisms it contains is sufficient to explain the data and missing out any of its mechanisms did not permit fit between all data and the model within physiological parameter ranges. Nevertheless, compared to earlier models it is quite complex i.e., it includes a wide range of mechanisms discussed in biological literature. In this model, the cells lacking oxygen switch from aerobe to anaerobe glycolysis and produce lactate. Too high concentrations of lactate or too low concentrations of ATP promote cell death. Only if the extracellular matrix density overcomes a certain threshold, cells are able to enter the cell cycle. Dying cells produce a diffusive growth inhibitor. Missing out the spatial information would not permit to infer the mechanisms at work. Our findings suggest that this iterative data integration together with intermediate model sensitivity analysis at each model development stage, provide a promising strategy to infer predictive yet minimal (in the above sense) quantitative models of tumor growth, as prospectively of other tissue

  6. Efficiency of Staging Work-Ups in the Evaluation of Carcinoma of the Uterine Cervix

    International Nuclear Information System (INIS)

    Kim, Jae Sung; Ha, Sung Whan

    1991-01-01

    A series of 510 patients with carcinoma of the uterine cervix given the curative radiation therapy from March 1979 through December 1986 was evaluated to determine the value of intravenous pyelography(IVP), cystoscopy, sigmoidoscopy, and abdomino-pelvic CT as staging work-up prior to treatment. On IVP and cystoscopy, 10.7%(49/456) and 5/3%(24/452) showed abnormality, respectively, but only 0.7% (3/413) did on signoidoscopy. As a result of these work-ups prerequisite to FIGO staging, twenty six (5.1%) out of 510 patients were upstaged from the stage determined by the findings of physical examination alone. The proportions of upstaging in each stage were as follows none in stage IB(35), IIA (89) and IIIA(8), 7.9%(20/252) in stage IIB(14 patients to FIGO Stage IIIB, 6 patients to FIGO stage IVA), and 4.8% (6/126) in stage IIIB (all to FIGO stage IVA). Positive findings of staging work-ups were found only in patients with advanced stages of stage IIB or over determined by physical examination alone but not in those with earlier stages. CT was performed in 337 patients. CT detected pelvic lymph node (LN) enlargement in 25.2% (85/337) and paraaortic LN enlargement in 7.4% (25/337). Pelvic LN positivity was well correlated with increasing stage but paraaortic LN positivity was not. In the evaluation of parametrial involvement, CT findings were in accordance with those of physical examination only in 65.6%(442/674). When compared with endoscopic studies, CT had much lower positive predictive value than negative predictive value in the evaluation of adjacent organ invasion. The staging work-ups should be individualized by the disease extent of each patient, and then the efficiency of work-ups may be increased without compromising the appropriate FIGO staging and treatment

  7. 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 ...

  8. 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.

  9. Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung.

    Science.gov (United States)

    Spigel, David R; Edelman, Martin J; O'Byrne, Kenneth; Paz-Ares, Luis; Mocci, Simonetta; Phan, See; Shames, David S; Smith, Dustin; Yu, Wei; Paton, Virginia E; Mok, Tony

    2017-02-01

    Purpose The phase III OAM4971g study (METLung) examined the efficacy and safety of onartuzumab plus erlotinib in patients with locally advanced or metastatic non-small-cell lung cancer selected by MET immunohistochemistry whose disease had progressed after treatment with a platinum-based chemotherapy regimen. Patients and Methods Patients were randomly assigned at a one-to-one ratio to receive onartuzumab (15 mg/kg intravenously on day 1 of each 21-day cycle) plus daily oral erlotinib 150 mg or intravenous placebo plus daily oral erlotinib 150 mg. The primary end point was overall survival (OS) in the intent-to-treat population. Secondary end points included median progression-free survival, overall response rate, biomarker analysis, and safety. Results A total of 499 patients were enrolled (onartuzumab, n = 250; placebo, n = 249). Median OS was 6.8 versus 9.1 months for onartuzumab versus placebo (stratified hazard ratio [HR], 1.27; 95% CI, 0.98 to 1.65; P = .067), with a greater number of deaths in the onartuzumab arm (130 [52%] v 114 [46%]). Median progression-free survival was 2.7 versus 2.6 months (stratified HR, 0.99; 95% CI, 0.81 to 1.20; P = .92), and overall response rate was 8.4% and 9.6% for onartuzumab versus placebo, respectively. Exploratory analyses using MET fluorescence in situ hybridization status and gene expression showed no benefit for onartuzumab; patients with EGFR mutations showed a trend toward shorter OS with onartuzumab treatment (HR, 4.68; 95% CI, 0.97 to 22.63). Grade 3 to 5 adverse events were reported by 56.0% and 51.2% of patients, with serious AEs in 33.9% and 30.7%, for experimental versus control arms, respectively. Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non-small-cell lung cancer.

  10. small Cell Lung Cancer

    African Journals Online (AJOL)

    Hospital of Qiqihar Medical University Hospital. Inclusion criteria for the current study was histologically and cytologically confirmed NSCLC patients, patients with either lung cancer stage. IIIA, IIIB or IV, chemotherapy naïve, patients having evaluable and measureable disease,. WHO performance status (PS): 0 – 2, no active.

  11. Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Aasebø, Ulf; Sundstrøm, Stein H

    2008-01-01

    BACKGROUND: There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients....... PATIENTS AND METHODS: The 123 PS 2 patients were compared to 309 PS 0/1 patients regarding survival, quality of life (QOL) and treatment toxicity. RESULTS: PS 2 patients had lower haemoglobin, lower global QOL and more pain, nausea/vomiting and dyspnea at inclusion. 68% of PS 2 patients received three...... chemotherapy courses vs. 85% in the PS 0/1 group (PPS 2 group, 4.5 vs. 8.9 months and 10% vs. 37% (PPS 2 patients needed blood transfusions (P=0.03) and hospitalization (PPS 2 patients had better relief of pain and dyspnea...

  12. Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC

    DEFF Research Database (Denmark)

    Hansen, Olfred; Schytte, Tine; Nielsen, Morten

    2015-01-01

    . Material and methods. Altogether, 478 patients completed radical radiotherapy in doses of 60-66 Gy/30-33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups ... specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups ..., the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy...

  13. Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy

    Directory of Open Access Journals (Sweden)

    Santarpia M

    2017-07-01

    Full Text Available Mariacarmela Santarpia,1 Maria Grazia Daffinà,1 Alessandro D’Aveni,1 Grazia Marabello,1 Alessia Liguori,1 Elisa Giovannetti,2–4 Niki Karachaliou,5 Maria Gonzalez Cao,6 Rafael Rosell,7,8 Giuseppe Altavilla1 1Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, Messina, Italy; 2Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; 3Department of Nanoscience and Nanotechnologies, CNR-Nano, Institute of Nanoscience and Nanotechnology, 4Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy; 5Institute of Oncology Rosell (IOR, University Hospital Sagrat Cor, 6Oncology Department, Institute of Oncology Rosell (IOR, Quirón-Dexeus University Institute, Barcelona, 7Cancer Biology and Precision Medicine Program, Germans Trias i Pujol Research Institute, 8Catalan Institute of Oncology, Germans Trias i Pujol University Hospital, Badalona, Spain Abstract: 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

  14. 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...

  15. 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.

  16. Next-generation sequencing in NSCLC and melanoma patients: a cost and budget impact analysis

    Science.gov (United States)

    van Amerongen, Rosa A; Retèl, Valesca P; Coupé, Veerle MH; Nederlof, Petra M; Vogel, Maartje J; van Harten, Wim H

    2016-01-01

    Next-generation sequencing (NGS) has reached the molecular diagnostic laboratories. Although the NGS technology aims to improve the effectiveness of therapies by selecting the most promising therapy, concerns are that NGS testing is expensive and that the ‘benefits’ are not yet in relation to these costs. In this study, we give an estimation of the costs and an institutional and national budget impact of various types of NGS tests in non-small-cell lung cancer (NSCLC) and melanoma patients within The Netherlands. First, an activity-based costing (ABC) analysis has been conducted on the costs of two examples of NGS panels (small- and medium-targeted gene panel (TGP)) based on data of The Netherlands Cancer Institute (NKI). Second, we performed a budget impact analysis (BIA) to estimate the current (2015) and future (2020) budget impact of NGS on molecular diagnostics for NSCLC and melanoma patients in The Netherlands. Literature, expert opinions, and a data set of patients within the NKI (n = 172) have been included in the BIA. Based on our analysis, we expect that the NGS test cost concerns will be limited. In the current situation, NGS can indeed result in higher diagnostic test costs, which is mainly related to required additional tests besides the small TGP. However, in the future, we expect that the use of whole-genome sequencing (WGS) will increase, for which it is expected that additional tests can be (partly) avoided. Although the current clinical benefits are expected to be limited, the research potentials of NGS are already an important advantage. PMID:27899957

  17. Effect of ABCG2/BCRP Expression on Efflux and Uptake of Gefitinib in NSCLC Cell Lines

    Science.gov (United States)

    Galetti, Maricla; Petronini, Pier Giorgio; Fumarola, Claudia; Cretella, Daniele; La Monica, Silvia; Bonelli, Mara; Cavazzoni, Andrea; Saccani, Francesca; Caffarra, Cristina; Andreoli, Roberta; Mutti, Antonio; Tiseo, Marcello; Ardizzoni, Andrea; Alfieri, Roberta R.

    2015-01-01

    Background 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. Aim 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. Methods and Results 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. Conclusions 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. PMID:26536031

  18. Meta-analysis of adjuvant chemotherapy versus surgery alone in T2aN0 stage IB non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Tianxiang Zhang

    2018-01-01

    Conclusion: Adjuvant chemotherapy after surgery was beneficial to the patients with Stage IB disease in terms of OS and progression-free survival. Therefore, we recommend clinicians to take this treatment strategy into account for the patients with Stage IB NSCLC.

  19. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial.

    Science.gov (United States)

    Tardieu, Marc; Zérah, Michel; Gougeon, Marie-Lise; Ausseil, Jérome; de Bournonville, Stéphanie; Husson, Béatrice; Zafeiriou, Dimitrios; Parenti, Giancarlo; Bourget, Philippe; Poirier, Béatrice; Furlan, Valérie; Artaud, Cécile; Baugnon, Thomas; Roujeau, Thomas; Crystal, Ronald G; Meyer, Christian; Deiva, Kumaran; Heard, Jean-Michel

    2017-09-01

    Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy. Local regulatory authorities in France allowed inclusion of up to four children in this phase 1/2 study. Treatment was 16 intraparenchymal deposits (four in the cerebellum) of a recombinant adenoassociated viral vector serotype 2/5 (rAAV2/5) encoding human α-N-acetylglucosaminidase (NAGLU) plus immunosuppressive therapy. We assessed tolerance, neurocognitive progression, brain growth, NAGLU enzymatic activity in CSF, and specific anti-NAGLU immune response for 30 months after surgery. This trial is registered with EudraCT, number 2012-000856-33, and the International Standard Clinical Trial Registry, number ISRCTN19853672. Of seven eligible children, the four youngest, from France (n=2), Italy (n=1), and Greece (n=1), aged 20, 26, 30, and 53 months, were included between February, 2012, and February, 2014. 125 adverse events were recorded, of which 117 were treatment emergent and included six classified as severe, but no suspected unexpected serious adverse drug reactions were seen. Vector genomes were detected in blood for 2 days after surgery. Compared with the natural history of mucopolysaccharidosis type III syndromes, neurocognitive progression was improved in all patients, with the youngest patient having function close to that in healthy children. Decrease in developmental quotient was -11·0 points in patient one, -23·0 in patient two, -29·0 in patient three, and -17·0 in patient four, compared with -37·7 in the natural history of the disease. NAGLU activity was detected in lumbar CSF and was 15-20% of that in unaffected children. Circulating T lymphocytes that proliferated and produced tumour

  20. 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

  1. 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...

  2. 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...

  3. 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) ...

  4. 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

  5. Treatment of carcinoma of uterine cervix stage III by adriamycin, bleomycin and cisplatinum, neoadjuvant, modified radical hysterectomy and adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Valle, J.C. do; Ribeiro, C.W.; Rezende, Magda C.; Figueiredo, E.; Chu, C.

    1987-01-01

    Forty-eight patients with untreated carcinoma of the cervix stage III A and IIIB, were submitted to 3 to 5 cycles of a combination of adriamycin (ADR), bleomycin (BLEO) and cisplatinum (CDDP), followed by modified radical hysterectomy and adjuvant chemotherapy, 6 cycles, of the same association. The surgical aspect is emphasized and the operative sequence is described. A comparative evaluation between the treatment presented and the radiotherapy is done. The survical rate is studied. (M.A.C.) [pt

  6. 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.)

  7. 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.

  8. 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.

  9. Patient outcomes of monotherapy with hypofractionated three-dimensional conformal radiation therapy for stage T2 or T3 non-small cell lung cancer: a retrospective study

    International Nuclear Information System (INIS)

    Sakaguchi, Masakuni; Maebayashi, Toshiya; Aizawa, Takuya; Ishibashi, Naoya; Fukushima, Shoko; Abe, Osamu; Saito, Tsutomu

    2016-01-01

    Hypofractionated three-dimensional conformal radiation therapy (3D-CRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically unable to tolerate surgery and who are not amenable to treatment with stereotactic body radiotherapy. This study assessed the efficacy and safety of 3D-CRT as a monotherapy in patients with localized stage T2 or T3 NSCLC. This retrospective study consisted of 29 patients (20 males) aged 56–89 years (median, 76 years) with histologically confirmed NSCLC who underwent 3D-CRT between 2005 and 2014. The median duration of patient observation was 17.0 months (range, 1.0–64.0 months). Complete and partial responses occurred in 13.8 and 44.8 % of patients, respectively, and the overall response rate was 58.2 %. Meanwhile, the 1- and 3-year survival rates were 65.8 and 33.8 %, respectively. In T2 NSCLC, the median survival time (MST) was 12 months, and the 1- and 3-year survival rates were 62.4 and 21.4 %, respectively. In T3 NSCLC, the MST was 17 months, and the 1- and 3-year survival rates were 72.9 and 48.6 %, respectively. Severe toxicities (Common Terminology Criteria Grade 3) were not observed. The mean biologically effective dose required to improve local control exceeded 80 Gy (range, 67.2–96.0 Gy). These findings support a role for 3D-CRT as a treatment option for patients who refuse or could not tolerate surgical therapy with early-stage NSCLC. Although this was a small, retrospective study, it may form the basis for future, larger controlled studies on 3D-CRT as a monotherapy for NSCLC

  10. 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.

  11. Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer.

    Science.gov (United States)

    Watanabe, Shun-Ichi; Nakagawa, Kazuo; Suzuki, Kenji; Takamochi, Kazuya; Ito, Hiroyuki; Okami, Jiro; Aokage, Keiju; Saji, Hisashi; Yoshioka, Hiroshige; Zenke, Yoshitaka; Aoki, Tadashi; Tsutani, Yasuhiro; Okada, Morihito

    2017-12-01

    The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. 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

  13. Computed 88% TCP dose for SBRT of NSCLC from tumour hypoxia modelling

    International Nuclear Information System (INIS)

    Ruggieri, Ruggero; Naccarato, Stefania; Stavreva, Nadejda; Stavrev, Pavel

    2013-01-01

    In small NSCLC, 88% local control at three years from SBRT was reported both for schedule (20–22 Gy ×3) (Fakiris et al 2009 Int. J. Radiat. Oncol. Biol. Phys. 75 677–82), actually close to (18–20 Gy ×3) if density correction is properly applied, and for schedules (18 Gy ×3) and (11 Gy ×5) (Palma et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 82 1149–56). Here, we compare our computed iso-TCP = 88% dose per fraction (d 88 ) for three and five fractions (n) with such clinically adopted ones. Our TCP model accounts for tumour repopulation, at rate λ (d −1 ), reoxygenation of chronic hypoxia (ch-), at rate a (d −1 ) and fluctuating oxygenation of acute hypoxia (ah-), with hypoxic fraction (C) of the acutely hypoxic fractional volume (AHF). Out of the eight free parameters whose values we had fitted to in vivo animal data (Ruggieri et al 2012 Int. J. Radiat. Oncol. Biol. Phys. 83 1603–8), we here maintained (a(d −1 ), C, OER ch , OER ah /OER ch , AHF, CHF) = (0.026, 0.17, 1.9, 2.2, 0.033, 0.145) while rescaling the initial total number of clonogens (N o ) according to the ratio of NSCLC on animal median tumour volumes. From the clinical literature, the usually assumed (α o /β o (Gy), λ(d −1 )) = (10, 0.217) for the well-oxygenated (o-)cells were taken. By normal (lognormal) random sampling of all parameter values over their 95% C.I., the uncertainty on present d 88 (n) computations was estimated. Finally, SBRT intra-tumour dose heterogeneity was simulated by a 1.3 dose boost ratio on 50% of tumour volume. Computed d 88 (±1σ) were 19.0 (16.3; 21.7) Gy, for n = 3; 10.4 (8.7; 12.1) Gy, for n = 5; 5.8 (5.2; 6.4) Gy, for n = 8; 4.0 (3.6; 4.3) Gy, for n = 12. Furthermore, the iso-TCP = 88% total dose, D 88 (n) = d 88 (n)*n, exhibited a relative minimum around n = 8. Computed d 88 (n = 3, 5) are strictly consistent with the clinically adopted ones, which confirms the validity of LQ-model-based TCP predictions at the doses used in SBRT if a highly

  14. nab-paclitaxel/carboplatin induction in squamous NSCLC: longitudinal quality of life while on chemotherapy

    Directory of Open Access Journals (Sweden)

    Thomas M

    2017-10-01

    Full Text Available Michael Thomas,1,2 David R Spigel,3 Robert M Jotte,4 Michael McCleod,5 Mark A Socinski,6 Ray D Page,7 Laurent Gressot,8 Jeanna Knoble,9 Oscar Juan,10 Daniel Morgensztern,11 Dolores Isla,12 Edward S Kim,13 Howard West,14 Amy Ko,15 Teng Jin Ong,15 Nataliya Trunova,15 Cesare Gridelli16 On behalf of ABOUND.sqm investigators 1Department of Thoracic Oncology/Internal Medicine, Thoraxklinik im Universitätsklinikum Heidelberg, 2Translational Lung Research Center Heidelberg, Heidelberg, Germany; 3Sarah Cannon Research Institute, Nashville, TN, 4Department of Medical Oncology/Hematology, Rocky Mountain Cancer Centers, Denver, CO, 5Florida Cancer Specialists, Fort Myers, 6Florida Hospital Cancer Institute, Orlando, FL, 7The Center for Cancer and Blood Disorders, Fort Worth, 8North Cypress Cancer Center, Cypress, TX, 9The Mark H. Zangmeister Center, Columbus, OH, USA; 10Department of Medical Oncology, Hospital Universitari i Politécnic La Fe, Valencia, Spain; 11Department of Medical Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; 12Department of Medical Oncology, University Hospital Lozano Blesa, Zaragoza, Spain; 13Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, 14Thoracic Oncology Program, Swedish Cancer Institute, Seattle, WA, 15Celgene Corporation, Summit, NJ, USA; 16Department of Oncology/Hematology, S.G. Moscati Hospital, Avellino, Italy Background: Longitudinal data on the impact of treatment on quality of life (QoL in advanced non-small cell lung cancer (NSCLC are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ≤4 cycles of nab-paclitaxel/carboplatin combination chemotherapy. Methods: Patients received nab-paclitaxel 100 mg/m2 days 1, 8, 15 + carboplatin area under the curve 6 mg•min/mL day 1 (q3w for four cycles. QoL was assessed by the Lung Cancer Symptom Scale (LCSS and

  15. Staging in Patients with Small-Cell Lung Carcinoma; PET-CT versus Standard Staging Procedures

    Directory of Open Access Journals (Sweden)

    Burcu Yalçın

    2016-12-01

    Full Text Available Objective: The most important factor for accurate treatment of patients with small cell lung carcinoma (SCLC is accuracy of the initial staging. The aim of this study was to determine how often patients, staged as local or local-advanced disease by standard staging procedures (SSPs, would be staged to have a metastatic disease based on the findings of the positron emission tomography–computed tomography (PET-CT scan. Methods: Patients with SCLC who were staged as I, II, or III disease by SSPs (according to the American Joint Committee on Cancer Staging, 7th edition formed the study population. SSPs included computed tomography of chest, abdomen, brain (or magnetic resonance imaging of brain, and bone scintigraphy. These patients were re-staged with 18F-FDG PET-CT scan. Results: Between 2013 and 2015, 27 patients were prospectively studied. Of these patients, 92.5% were male and the median age was 61. Among 27 patients, distant metastasis was detected by PET-CT in 7 (25.9% patients. Two of 7 patients were determined as stage IIIA by SSPs and 5 of 17 patients that were determined as stage IIIB by SSPs were upstaged to metastatic disease by PET-CT. All of the 7 patients had bone metastasis by PET-CT. But bone metastasis could not be detected with bone scintigraphy. Conclusion: PET-CT detected distant metastasis in one quarter of SCLC stage III patients by SSPs. Patients who staged local-advanced SCLC with CT of the chest have to be assessed by PET-CT for extracranial distant metastasis.

  16. 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

  17. 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

  18. 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

  19. Stage design

    International Nuclear Information System (INIS)

    Shacter, J.

    1975-01-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage

  20. Prognostic factors and long term results of neo adjuvant therapy followed by surgery in stage IIIA N2 non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Jing

    2009-01-01

    Full Text Available Background: Prognosis of stage IIIA N2 non-small cell lung cancer (NSCLC remains poor despite the changes in therapeutic strategies. Objectives: To assess long term results of neo adjuvant therapy followed by surgery for patients with stage IIIA N2 NSCLC and to analyze factors influencing survival. Materials and Methods: The methods adopted include: Retrospective review of medical records of 91 patients with stage IIIA N2 NSCLC, who received neo adjuvant therapy followed by surgery; collection of information on demographic information, staging procedure, preoperative therapy, clinical response, type of resection, pathologic response of tumor, status of lymph nodes and adjuvant chemotherapy; survival analysis by Kaplan-Meier and calculation of prognostic factors using log-rank and Cox regression model. Results: All patients received a platinum-based chemotherapy and 23 (29.1% had an associated radiotherapy. Eighty four patients underwent thoracotomy. Median survival was 26 months (95%CI, 22.6-30.8 months with three and five year survival rates of 31.6 and 20.9%, respectively. Prognostic factors for survival on univariate analysis was clinical response (P = 0.032, complete resection (P = 0.002, pathologic tumor response ( P < 0.001, and lymph nodal down staging (P = 0.001. Multivariate analyses identified complete resection, pathologic tumor response and lymph nodal down staging as independent prognostic factors. Conclusion: Survival of patients with stage IIIA N2 NSCLC who received neo adjuvant therapy is significantly influenced by clinical response, complete resection, pathologic tumor response, and lymph nodal down staging. These results can be helpful in guiding standard clinical practice and evaluating the outcome of neo adjuvant therapy followed by surgery in patients with stage IIIA N2 NSCLC.

  1. 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.

  2. 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...

  3. 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...

  4. 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.

  5. Aberrant trafficking of NSCLC-associated EGFR mutants through the endocytic recycling pathway promotes interaction with Src@

    Directory of Open Access Journals (Sweden)

    Band Vimla

    2009-11-01

    Full Text Available Abstract Background Epidermal growth factor receptor (EGFR controls a wide range of cellular processes, and altered EGFR signaling contributes to human cancer. EGFR kinase domain mutants found in non-small cell lung cancer (NSCLC are constitutively active, a trait critical for cell transformation through activation of downstream pathways. Endocytic trafficking of EGFR is a major regulatory mechanism as ligand-induced lysosomal degradation results in termination of signaling. While numerous studies have examined mutant EGFR signaling, the endocytic traffic of mutant EGFR within the NSCLC milieu remains less clear. Results This study shows that mutant EGFRs in NSCLC cell lines are constitutively endocytosed as shown by their colocalization with the early/recycling endosomal marker transferrin and the late endosomal/lysosomal marker LAMP1. Notably, mutant EGFRs, but not the wild-type EGFR, show a perinuclear accumulation and colocalization with recycling endosomal markers such as Rab11 and EHD1 upon treatment of cells with endocytic recycling inhibitor monensin, suggesting that mutant EGFRs preferentially traffic through the endocytic recycling compartments. Importantly, monensin treatment enhanced the mutant EGFR association and colocalization with Src, indicating that aberrant transit through the endocytic recycling compartment promotes mutant EGFR-Src association. Conclusion The findings presented in this study show that mutant EGFRs undergo aberrant traffic into the endocytic recycling compartment which allows mutant EGFRs to engage in a preferential interaction with Src, a critical partner for EGFR-mediated oncogenesis.

  6. 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.

  7. Next-Generation Sequencing Workflow for NSCLC Critical Samples Using a Targeted Sequencing Approach by Ion Torrent PGM™ Platform.

    Science.gov (United States)

    Vanni, Irene; Coco, Simona; Truini, Anna; Rusmini, Marta; Dal Bello, Maria Giovanna; Alama, Angela; Banelli, Barbara; Mora, Marco; Rijavec, Erika; Barletta, Giulia; Genova, Carlo; Biello, Federica; Maggioni, Claudia; Grossi, Francesco

    2015-12-03

    Next-generation sequencing (NGS) is a cost-effective technology capable of screening several genes simultaneously; however, its application in a clinical context requires an established workflow to acquire reliable sequencing results. Here, we report an optimized NGS workflow analyzing 22 lung cancer-related genes to sequence critical samples such as DNA from formalin-fixed paraffin-embedded (FFPE) blocks and circulating free DNA (cfDNA). Snap frozen and matched FFPE gDNA from 12 non-small cell lung cancer (NSCLC) patients, whose gDNA fragmentation status was previously evaluated using a multiplex PCR-based quality control, were successfully sequenced with Ion Torrent PGM™. The robust bioinformatic pipeline allowed us to correctly call both Single Nucleotide Variants (SNVs) and indels with a detection limit of 5%, achieving 100% specificity and 96% sensitivity. This workflow was also validated in 13 FFPE NSCLC biopsies. Furthermore, a specific protocol for low input gDNA capable of producing good sequencing data with high coverage, high uniformity, and a low error rate was also optimized. In conclusion, we demonstrate the feasibility of obtaining gDNA from FFPE samples suitable for NGS by performing appropriate quality controls. The optimized workflow, capable of screening low input gDNA, highlights NGS as a potential tool in the detection, disease monitoring, and treatment of NSCLC.

  8. 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.

  9. 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.

  10. NSCLC: primary tumor size - radiation dose-related accelerated, twice daily radiotherapy by target splitting, preceded by 2 cycles of chemotherapy. First results of a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Wurstbauer, K.; Deutschmann, H.; Kopp, P.; Kranzinger, M.; Merz, F.; Nairz, O.; Sedlmayer, F. [Univ. Clinic of Radiation Oncology, Salzburger Landeskliniken und Paracelsus Medizinische Privatuniversitaet, Salzburg (Austria); Studnicka, M. [Univ. Clinic of Pneumology, Salzburger Landeskliniken und Paracelsus Medizinische Privatuniversitaet, Salzburg (Austria)

    2007-12-15

    Ensuing a phase I trial of accelerated, twice daily high dose radiotherapy showing good tolerability, a prospective study relating primary tumor size with radiation dose in non-operated patients with non-small cell lung cancer (NSCLC) was started. From 01/2004 until 12/2006 79 patients with 81 histologically/cytologically proven NSCLC tumors were treated, representing 94% of all referred non-operated NSCLC patients in stage Mo, malignant pleural effusions excluded. For the majority of patients the conformal target splitting technique has been employed. The target is split into a cranial and a caudal part; beam arrangements in the two parts are completely independent. In order to reduce internal margins slow planning CTs (4 sec./slice) were used, patients freely breathing, 7 mm margins from gross tumor volume to planning target volume. We formed 4 groups with primary tumor sizes (mean number of 3 perpendicular diameters) < 2,5; 2,5-4,5; 4,5-6,0; > 6,0 cm (11/41/22/7 patients, respectively); tumor doses of 73,8, 79,2, 84,6 and 90,0 Gy (ICRU) were applied to the primary tumors of the patients in the respective groups. Single dose 1,8 Gy; twice daily, interval 11 h; 5 days/week; duration 33 days median (range 29-42). Macroscopically involved nodes 61,2 Gy median (range 54,0-75,6 Gy), nodes electively 45,0 Gy (to volume about 6 cm cranial to apparently involved nodes). In 62 patients chemotherapy before radiotherapy was given, 2 cycles median, generally a cisplatin or carboplatin containing doublet; no concurrent chemotherapy. Median follow-up of all patients 16,7 months, of patients alive 19,3 months. Until now 10 local failures (0/11, 3/41, 5/22, 2/7 in the respective groups) and 2 regional failures occured, resulting in an actuarial local and regional tumor control of 80,1% and 96% at 2 years, respectively. Local failures relate to the primary tumor site, regional failures to the regional node sites. Overall actuarial 1-, 2-year survival rate for all patients: 76

  11. Panels of tumor-derived RNA markers in peripheral blood of patients with non-small cell lung cancer: their dependence on age, gender and clinical stages.

    Science.gov (United States)

    Chian, Chih-Feng; Hwang, Yi-Ting; Terng, Harn-Jing; Lee, Shih-Chun; Chao, Tsui-Yi; Chang, Hung; Ho, Ching-Liang; Wu, Yi-Ying; Perng, Wann-Cherng

    2016-08-02

    Peripheral blood mononuclear cell (PBMC)-derived gene signatures were investigated for their potential use in the early detection of non-small cell lung cancer (NSCLC). In our study, 187 patients with NSCLC and 310 age- and gender-matched controls, and an independent set containing 29 patients for validation were included. Eight significant NSCLC-associated genes were identified, including DUSP6, EIF2S3, GRB2, MDM2, NF1, POLDIP2, RNF4, and WEE1. The logistic model containing these significant markers was able to distinguish subjects with NSCLC from controls with an excellent performance, 80.7% sensitivity, 90.6% specificity, and an area under the receiver operating characteristic curve (AUC) of 0.924. Repeated random sub-sampling for 100 times was used to validate the performance of classification training models with an average AUC of 0.92. Additional cross-validation using the independent set resulted in the sensitivity 75.86%. Furthermore, six age/gender-dependent genes: CPEB4, EIF2S3, GRB2, MCM4, RNF4, and STAT2 were identified using age and gender stratification approach. STAT2 and WEE1 were explored as stage-dependent using stage-stratified subpopulation. We conclude that these logistic models using different signatures for total and stratified samples are potential complementary tools for assessing the risk of NSCLC.

  12. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    because they are hard to use and interpret, and tools for age and stage structured populations are missing. We present easily interpretable expressions for the sensitivities and elasticities of life expectancy to vital rates in age-stage models, and illustrate their application with two biological......Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  13. P13.10 Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases

    Science.gov (United States)

    Yust-Katz, S.; Dudnik, E.; Perlov, E.; Zer, A.; Flex, D.; Peled, N.; Siegal, T.

    2016-01-01

    Abstract Background: Central nervous system (CNS) metastases occur in about 30% of patients (pts) with advanced non-small cell lung cancer (NSCLC). Local treatment strategies (e.g., radiotherapy or surgery) result in delays in systemic therapy administration and are frequently associated with neurocognitive impairment. Nivolumab is an anti-PD1 immune check-point inhibitor which has been recently approved by the FDA as a second line treatment of NSCLC. Data regarding its intracranial activity is lacking. Methods: We retrospectively reviewed efficacy and safety of nivolumab administered intravenously at a dose of 3mg/kg q2 weeks in five pts with advanced NSCLC and new or progressing intracranial metastases which were diagnosed before or within 1 month after starting the treatment. Results: Pt baseline characteristics were as follows: median age 78y (range, 52–84); 2 males; 4 smokers; ECOG PS 0/1/2 - 2 pts/1 pt/2 pts; histological subtype: adenocarcinoma/ squamous-cell carcinoma/NSCLC NOS 3 pts /1 pt/1 pt; EGFR WT/ALK neg/KRAS M all/all/2 pts. Four pts had parenchymal brain metastases, three pts had leptomeningeal disease. All pts were asymptomatic and did not require corticosteroids or immediate brain irradiation. Dramatic response in the brain was observed in two pts (including 1 pt with leptomeningeal spread demonstrating a complete response in the CNS); time-to-response comprised 5 weeks and 9 weeks; all responses are still ongoing at the time of the report (18+ weeks, 19+ weeks). In one pt stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved. Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS-metastases related grade ≥ 3 adverse events were observed. Conclusions: Nivolumab has a promising intracranial activity and favorable safety profile in pts with NSCLC and untreated/progressing CNS metastases. Nivolumab CNS activity warrants further evaluation.

  14. Combination treatment with erlotinib and ampelopsin overcomes erlotinib resistance in NSCLC cells via the Nox2-ROS-Bim pathway.

    Science.gov (United States)

    Hong, Seung-Woo; Park, Nam-Sook; Noh, Min Hye; Shim, Ju A; Ahn, Byul-Nim; Kim, Yeong Seok; Kim, Daejin; Lee, Hyun-Kyung; Hur, Dae Young

    2017-04-01

    Erlotinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), has been shown to have a dramatic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the presence of primary resistance or acquired resistance to EGFR-TKI is the most common reason for switching to other anti-cancer agents. Even though there are newer agents that have activity in the presence of the T790M mutation, identification of potential agents that could overcome resistance to EGFR-TKI is still needed for the treatment of NSCLC patients. In this study, we used erlotinib-resistant NSCLC cell lines to investigate the effects of combination treatment with erlotinib and ampelopsin. After treatment with either single or combination, cell viability and cell death were determined with WST-1 assay, trypan blue exclusion method, colony forming assay, annexin-V staining assay and western blot assay. The content of ROS was evaluated by FACS analysis using H 2 DCF-staining method. To determine the effect of Nox2 and Bim on the combined treatment with erlotinib and ampelopsin-induced cell death, we transfected with Nox2 or Bim specific siRNA and performed with western blot assay for evaluation of its expression. Combined treatment with erlotinib and ampelopsin at non-cytotoxic concentrations significantly induced caspase-dependent cell death in erlotinib-resistant NSCLC cells. Furthermore, cell death resulted in the accumulation of reactive oxygen species (ROS) through upregulation of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2) expression, a direct source of ROS. The expression level of Bim increased with combination treatment, but not with either treatment alone. Here in this study, we demonstrate that the combination of erlotinib and ampelopsin induces cell death via the Nox2-ROS-Bim pathway, and ampelopsin could be used as a novel anti-cancer agent combined with EGFR-TKI to overcome resistance to erlotinib in EGFR-mutant NSCLC

  15. Cmr1 enables efficient RNA and DNA interference of a III-B CRISPR–Cas system by binding to target RNA and crRNA

    Science.gov (United States)

    Li, Yingjun; Zhang, Yan; Lin, Jinzhong; Pan, Saifu; Han, Wenyuan; Peng, Nan; Liang, Yun Xiang

    2017-01-01

    Abstract CRISPR–Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems provide adaptive immunity against invasive nucleic acids guided by CRISPR RNAs (crRNAs) in archaea and bacteria. Type III CRISPR–Cas effector complexes show RNA cleavage and RNA-activated DNA cleavage activity, representing the only known system of dual nucleic acid interference. Here, we investigated the function of Cmr1 by genetic assays of DNA and RNA interference activity in the mutants and biochemical characterization of their mutated Cmr complexes. Three cmr1α mutants were constructed including ΔβΔ1α, Δβ1α-M1 and Δβ1α-M2 among which the last two mutants carried a double and a quadruple mutation in the first α-helix region of Cmr1α. Whereas the double mutation of Cmr1α (W58A and F59A) greatly influenced target RNA capture, the quadruple mutation almost abolished crRNA binding to Cmr1α. We found that Cmr2α-6α formed a stable core complex that is active in both RNA and DNA cleavage and that Cmr1α strongly enhances the basal activity of the core complex upon incorporation into the ribonucleoprotein complex. Therefore, Cmr1 functions as an integral activation module in III-B systems, and the unique occurrence of Cmr1 in III-B systems may reflect the adaptive evolution of type III CRISPR–Cas systems in thermophiles. PMID:28977458

  16. Cmr1 enables efficient RNA and DNA interference of a III-B CRISPR-Cas system by binding to target RNA and crRNA.

    Science.gov (United States)

    Li, Yingjun; Zhang, Yan; Lin, Jinzhong; Pan, Saifu; Han, Wenyuan; Peng, Nan; Liang, Yun Xiang; She, Qunxin

    2017-11-02

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems provide adaptive immunity against invasive nucleic acids guided by CRISPR RNAs (crRNAs) in archaea and bacteria. Type III CRISPR-Cas effector complexes show RNA cleavage and RNA-activated DNA cleavage activity, representing the only known system of dual nucleic acid interference. Here, we investigated the function of Cmr1 by genetic assays of DNA and RNA interference activity in the mutants and biochemical characterization of their mutated Cmr complexes. Three cmr1α mutants were constructed including ΔβΔ1α, Δβ1α-M1 and Δβ1α-M2 among which the last two mutants carried a double and a quadruple mutation in the first α-helix region of Cmr1α. Whereas the double mutation of Cmr1α (W58A and F59A) greatly influenced target RNA capture, the quadruple mutation almost abolished crRNA binding to Cmr1α. We found that Cmr2α-6α formed a stable core complex that is active in both RNA and DNA cleavage and that Cmr1α strongly enhances the basal activity of the core complex upon incorporation into the ribonucleoprotein complex. Therefore, Cmr1 functions as an integral activation module in III-B systems, and the unique occurrence of Cmr1 in III-B systems may reflect the adaptive evolution of type III CRISPR-Cas systems in thermophiles. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell...... proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7......) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7...

  18. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-01-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived ≥ 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  19. [Resistances to targeted therapies and strategy for following therapeutic lines in metastatic NSCLC].

    Science.gov (United States)

    Brosseau, Solenn; Oulkhouir, Youssef; Naltet, Charles; Zalcman, Gérard

    2015-06-01

    EGFR, ALK, ROS1 Tyrosine Kinase Inhibitors (TKis) have changed natural history of 12 to 15% of patients with metastatic Non-Small Cell Lung Cancer (NSCLC) and molecular alterations (mutations or translocations) in these genes. Median Progression Free Survival (PFS) of these patients has increased from 12 months with a platinum-based chemotherapy associated with bevacizumab, to 18 months with TKIs, overall survival reaching several years in these patients. However, rare primary resistance have been described in less than 10% of patients with EGFR or ALK-mutated cancer, whereas secondary resistance occur systematically. New generations TKIs are currently in clinical development, which are active on tumor clones harboring a resistance mutation, and some of them diffuse perfectly well into brain, a classical sanctuary for metastasis. Strategies are developed to delay secondary resistance apparition, to prolong PFS, and then overall survival. These strategies use combinations, as soon as first linesetting, of TKIs with either an anti-angiogenic drug (bevacizumab), or with an immunological checkpoint inhibitors, or with Heat-Shock Protein (Hsp) inhibitors. In order to delay acquired resistance to EGFR TKIs, the French Intergroup (IFCT) has launched a combination trial of EGFR TKIs with an anti-estrogen (fulvestrant) in postmenopausal women, whereas other trials associate EGFR TKIs with EFGR monoclonal antibody cetuximab, or with a monoclonal antibody targeting c-met. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

  20. A Model to Predict the Use of Surgical Resection for Advanced-Stage Non-Small Cell Lung Cancer Patients.

    Science.gov (United States)

    David, Elizabeth A; Andersen, Stina W; Beckett, Laurel A; Melnikow, Joy; Kelly, Karen; Cooke, David T; Brown, Lisa M; Canter, Robert J

    2017-11-01

    For advanced-stage non-small cell lung cancer, chemotherapy and chemoradiotherapy are the primary treatments. Although surgical intervention in these patients is associated with improved survival, the effect of selection bias is poorly defined. Our objective was to characterize selection bias and identify potential surgical candidates by constructing a Surgical Selection Score (SSS). Patients with clinical stage IIIA, IIIB, or IV non-small cell lung cancer were identified in the National Cancer Data Base from 1998 to 2012. Logistic regression was used to develop the SSS based on clinical characteristics. Estimated area under the receiver operating characteristic curve was used to assess discrimination performance of the SSS. Kaplan-Meier analysis was used to compare patients with similar SSSs. We identified 300,572 patients with stage IIIA, IIIB, or IV non-small cell lung cancer without missing data; 6% (18,701) underwent surgical intervention. The surgical cohort was 57% stage IIIA (n = 10,650), 19% stage IIIB (n = 3,483), and 24% stage IV (n = 4,568). The areas under the receiver operating characteristic curve from the best-fit logistic regression model in the training and validation sets were not significantly different, at 0.83 (95% confidence interval, 0.82 to 0.83) and 0.83 (95% confidence interval, 0.82 to 0.83). The range of SSS is 43 to 1,141. As expected, SSS was a good predictor of survival. Within each quartile of SSS, patients in the surgical group had significantly longer survival than nonsurgical patients (p < 0.001). A prediction model for selection of patients for surgical intervention was created. Once validated and prospectively tested, this model may be used to identify patients who may benefit from surgical intervention. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mark Brenneman

    2018-01-01

    Full Text Available Pleuropulmonary blastoma (PPB is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of PBB patients lack predisposing germline or mosaic mutations and have sporadic (rather than syndromic disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development.

  2. Quality of Life Following Stereotactic Ablative Radiation Therapy Versus Surgery for Early-Stage Lung Cancer : Results From the ROSEL Randomized Controlled Trial and a Systematic Review

    NARCIS (Netherlands)

    Louie, A V; Chen, H.; Van Werkhoven, E; Smit, E.; Palma, D A; Paul, M A; Warner, A; Widder, J; Groen, H. J. M.; van Den Borne, B; De Jaeger, K; Rodrigues, G; Slotman, B J; Senan, S

    2016-01-01

    Purpose/Objective(s) One of the purported advantages of stereotactic ablative radiation therapy (SABR) as an alternative treatment option to surgery for early-stage non-small cell lung cancer (ES-NSCLC) is health-related quality of life (HRQOL). The objectives of this study are 1) to assess HRQOL

  3. Mediastinal staging of non-small-cell lung cancer among Australasian thoracic physicians: clinical practice and constraints on minimally invasive techniques.

    Science.gov (United States)

    Dabscheck, E J; Steinfort, D P; Irving, L B; Hew, M

    2012-06-01

    We determined current practice among Australasian thoracic physicians in the mediastinal staging of non-small-cell lung cancer (NSCLC). We focused on the availability of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) and constraints to its use, as there has been no systematic analysis regarding the availability and uptake of this new technology among thoracic physicians. Physician members of the Thoracic Society of Australia and New Zealand were emailed a survey seeking their current approach to three scenarios requiring mediastinal staging of NSCLC. Respondents were also asked for their preferred investigation for each scenario if any current constraints were removed. Relevant demographic information was sought. We received 164 responses from 512 Australasian physicians (34%). Without constraints, EBUS-TBNA was the preferred investigation for all three clinical scenarios, but only 33% of respondents had access to EBUS-TBNA. Constraints included lack of availability and lack of expertise. Reduced EBUS-TBNA access was associated with a number of clinician factors. Australasian thoracic physicians prefer EBUS-TBNA for the mediastinal staging of NSCLC, but access to EBUS-TBNA services is limited. We recommend targeted measures to improve access to EBUS-TBNA use and optimise mediastinal staging of NSCLC. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  4. Impact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Liang, Wenhua; He, Jiaxi; Shen, Yaxing

    2017-01-01

    Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non-small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institution...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  6. Preoperative Geriatric Nutritional Risk Index: A predictive and prognostic factor in patients with pathological stage I non-small cell lung cancer.

    Science.gov (United States)

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

    2017-12-01

    Surgical outcomes of early-stage non-small cell lung cancer (NSCLC) are poor. The Geriatric Nutritional Risk Index (GNRI) is a useful parameter for evaluating nutritional status. We aimed to investigate if preoperative GNRI could be a predictive factor for pathological stage I NSCLC patients. We retrospectively selected 141 consecutive pathological stage I NSCLC patients treated from August 2005 to August 2010. We analyzed their preoperative GNRI in univariate and multivariate Cox regression analyses for postoperative recurrence-free survival (RFS). A preoperative abnormal GNRI was significantly associated with postoperative recurrence (P = 0.0107). Univariate analyses showed that serum carcinoembryonic antigen (CEA) levels (P = 0.0013), preoperative serum albumin level (P preoperative GNRI (P = 0.0009), pleural invasion (P preoperative GNRI (P = 0.0084), CEA level (P = 0.0031), preoperative serum albumin level (P = 0.0041) and pleural invasion (P = 0.0018) were independent prognostic factors. In Kaplan-Meier analysis of RFS, cancer-specific survival (CS), and overall survival (OS) by preoperative GNRI, the abnormal GNRI group had significantly shorter RFS, CS, and OS (5-year RFS, CS, and OS: 52.81% vs. 89.15%; P Preoperative GNRI is a novel prognostic factor for pathological stage I NSCLC patients, which can identify high-risk patients for postoperative recurrence and cancer-related death. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.

    NARCIS (Netherlands)

    Meerbeeck, J.P. van; Kramer, G.W.P.M.; Schil, P.E. van; Legrand, C.; Smit, E.F.; Schramel, F.M.; Tjan-Heijnen, V.C.; Biesma, B.; Debruyne, C.; Zandwijk, N. van; Splinter, T.A.; Giaccone, G.

    2007-01-01

    BACKGROUND: Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to

  8. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer

    NARCIS (Netherlands)

    J.P. van Meerbeeck (Jan); G.W.P.M. Kramer (Gijs); P.E.Y. van Schil (Paul); C. Legrand; E.F. Smit (Egbert); F.M.N.H. Schramel (Franz); V.C.G. Tjan-Heijnen (Vivianne); B. Biesma (Bonne); C. Debruyne (Channa); N. van Zandwijk (Nico); T.A.W. Splinter (Ted); G. Giaccone (Giuseppe)

    2007-01-01

    textabstractBackground: Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non - small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be

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

    Directory of Open Access Journals (Sweden)

    Diana Rosa Fernández Ruiz

    2017-02-01

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

  10. Staging atmospheres

    DEFF Research Database (Denmark)

    Bille, Mikkel; Bjerregaard, Peter; Sørensen, Tim Flohr

    2015-01-01

    The article introduces the special issue on staging atmospheres by surveying the philosophical, political and anthropological literature on atmosphere, and explores the relationship between atmosphere, material culture, subjectivity and affect. Atmosphere seems to occupy one of the classic...

  11. Increasing Rates of No Treatment in Advanced Stage Non-Small Cell Lung Cancer Patients: A Propensity Matched Analysis

    Science.gov (United States)

    David, Elizabeth A; Daly, Megan E.; Li, Chin-Shang; Chiu, Chi-Lu; Cooke, David T; Brown, Lisa M; Melnikow, Joy; Kelly, Karen; Canter, Robert J

    2017-01-01

    Introduction Variation in treatment and survival outcomes for Non–Small Cell Lung Cancer (NSCLC) is high among patients with stage III or IV, but untreated NSCLC patients have not been critically analyzed to evaluate for improvable outcomes. We evaluated treatment trends and their association with oncologic outcomes for NSCLC, hypothesizing that there are a substantial number of untreated patients who are similar to patients who undergo treatment. Methods Linear regression was used to calculate trends in utilization of treatment. Kaplan-Meier and Cox regression modeling were used to determine predictors of receiving treatment. Propensity-matching was used to compare survival among subsets of treated versus untreated patients. Results Patients with primary NSCLC were identified from the National Cancer Data base from 1998–2012 and 21% (190,539) of patients received no treatment. For stage IIIA and IV, the proportion of untreated patients increased over the study period by 0.21% and 0.4% respectively (p= 0.003, <0.0001). Regardless of stage, untreated patients had significantly shorter OS (p<0.0001). Propensity-matched analyses of 6,144 stage IIIA patient pairs treated with chemoradiation vs no treatment confirmed shorter OS for untreated patients (Median, 16.5 vs 6.1 months, p <0.0001). For 19,046 stage IV patient pairs treated with chemotherapy vs no treatment, similar results were obtained (Median OS, 9.3 vs 2.0 months, p<0.0001). Conclusions The proportion of untreated stage IIIA and IV patients is increasing. Survival outcomes among advanced stage patients are superior with treatment, independent of selection bias. The benefits and risks of treatment should be carefully assessed prior to choosing to forego treatment. PMID:28109804

  12. Impact of staging with 18F-FDG-PET on outcome of patients with stage III non-small cell lung cancer: PET identifies potential survivors

    International Nuclear Information System (INIS)

    Eschmann, S.M.; Reimold, M.; Bares, R.; Friedel, G.; Paulsen, F.; Hehr, T.; Scheiderbauer, J.; Budach, W.; Kotzerke, J.

    2007-01-01

    The aim of this study was to analyse the impact of FDG-PET staging on treatment results of neo-adjuvant radiochemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We compared prospectively the outcome of two patient groups with stage III NSCLC undergoing the same neo-adjuvant radio-chemotherapy (NARCT). In one group, FDG-PET was part of the pretherapeutic staging, whereas in the other group, no PET scans were performed. One hundred and eighty-eight patients with advanced stage III NSCLC were selected for a phase II trial of NARCT. The first 115 patients underwent conventional workup (CWU) and FDG-PET before inclusion (group I); the remaining 73 patients underwent CWU only (group II). All patients were followed up according to a standardised protocol for at least 11 months (up to 64 months). Overall survival and disease-free survival were used as parameters of therapeutic success and analysed statistically. After staging, 157/188 patients were included in the clinical trial. Thirty-one were excluded owing to the results of FDG-PET, in most cases because of the detection of previously unknown distant metastases. Overall survival and metastasis-free survival were significantly longer in patients of group I stratified by FDG-PET than in group II (p=0.006 and 0.02 respectively). Another significant factor for survival was complete tumour resection (p=0.02). Gender, histological tumour type, tumour grade and UICC stage had no significant influence. Pretherapeutic staging by FDG-PET significantly influences the results of NARCT and subsequent surgery by identifying patients not eligible for curative treatment. (orig.)

  13. 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.

  14. 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

  15. Stereotactic body radiation therapy for stage I non-small cell lung cancer: a small academic hospital experience

    Directory of Open Access Journals (Sweden)

    Oren B Factor

    2014-10-01

    Full Text Available Purpose/Objective(s: Stereotactic body radiation therapy (SBRT has been shown to have increased local control and overall survival relative to conventional external beam radiation therapy in patients with medically inoperable stage I non-small cell lung cancer (NSCLC. Excellent rates of local control have been demonstrated both in clinical trials as well as in single-center studies at large academic institutions. However, there is limited data on the experiences of small academic hospitals with SBRT for Stage I NSCLC. The purpose of this study is to report the local control and overall survival rates in patients treated with SBRT for Stage I NSCLC at Winthrop-University Hospital (WUH, a small academic hospital. Materials/Methods: This is a retrospective review of 78 Stage I central and peripheral NSCLC tumors treated between December 2006 and July 2012 with SBRT at WUH. Treatment was given utilizing fiducials and a respiratory tracking system. If the fiducials were not trackable, a spine tracking system was used for tumor localization. CT-based planning was performed using the ray trace algorithm. Treatment was delivered over 4 consecutive days for central tumors to a dose of 4800 cGy delivered in 4 fractions. Peripheral tumors were treated to a dose of 6000 cGy in 3 consecutive fractions. The Kaplan-Meier method was used to calculate local control and overall survival. Results: The median age was 78.5 years. 54% of the patient population was female. 67% of the tumors were Stage IA, and 33% of the tumors were Stage IB. 53% of the tumors were adenocarcinomas and 29% were squamous cell carcinomas, with the remainder being of unknown histology or NSCLC, not otherwise specified The 2-year local control rate was 87%, and the two-year overall survival was 68%. Conclusions: Our findings support that local control and overall survival at a small academic hospital are comparable to that of larger academic institutions' published experiences with SBRT for

  16. Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and miRNA expression profiles.

    Science.gov (United States)

    Kumar, V Bharath; Yuan, Ta-Chun; Liou, Je-Wen; Yang, Chih-Jen; Sung, Ping-Jyun; Weng, Ching-Feng

    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. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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    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.)

  18. 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 

  19. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Stromal CD8+ T-cell Density—A Promising Supplement to TNM Staging in Non-Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Donnem, Tom; Hald, Sigurd M; Paulsen, Erna-Elise

    2015-01-01

    immunology is recognized as highly important. We have previously evaluated the prognostic impact of several immunological markers in NSCLC, yielding the density of stromal CD8(+) tumor-infiltrating lymphocytes (TIL) as the most promising candidate. Hence, we validate the impact of stromal CD8(+) TIL density...... as an immunoscore in NSCLC. EXPERIMENTAL DESIGN: The prognostic impact of stromal CD8(+) TILs was evaluated in four different cohorts from Norway and Denmark consisting of 797 stage I-IIIA NSCLC patients. The Tromso cohort (n = 155) was used as training set, and the results were further validated in the cohorts...... from Bodo (n = 169), Oslo (n = 295), and Denmark (n = 178). Tissue microarrays and clinical routine CD8 staining were used for all cohorts. RESULTS: Stromal CD8(+) TIL density was an independent prognostic factor in the total material (n = 797) regardless of the endpoint: disease-free survival (P

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

    Science.gov (United States)

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

    2017-08-01

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

  4. 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.

  5. Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

    Science.gov (United States)

    Ma, Ji-Yong; Yan, Hai-Jun; Gu, Wei

    2015-01-01

    BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

  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. EGFR Mutation Testing of non-squamous NSCLC: Impact and Uptake during Implementation of Testing Guidelines in a Population-Based Registry Cohort from Northern New Zealand.

    Science.gov (United States)

    McKeage, Mark; Elwood, Mark; Tin Tin, Sandar; Khwaounjoo, Prashannata; Aye, Phyu; Li, Angie; Sheath, Karen; Shepherd, Phillip; Laking, George; Kingston, Nicola; Lewis, Christopher; Love, Donald

    2017-10-01

    Since 2013, clinical practice guidelines recommend EGFR mutation testing of non-squamous NSCLC to select advanced-stage patients for first-line treatment using EGFR-TKIs. We aimed to determine population-based trends in the real-world uptake and impact in routine practice of these recently updated testing guidelines. A population-based observational study was conducted of notifications to the New Zealand Cancer Registry of patients eligible for EGFR testing diagnosed in northern New Zealand between January 2010 and April 2014. The main study variable was EGFR mutation testing. Main outcome measures (overall survival and dispensing of EGFR-TKIs) were extracted from prospectively archived electronic databases until October 2015. The population-based cohort of 1857 patients had an average age of 70 years. Most had adenocarcinoma and metastatic disease at diagnosis. EGFR testing was undertaken in 500 patients (27%) with mutations detected in 109 patients (22%). EGFR testing increased during the period of study from testing by all eligible patients was limited by a lack of availability of specimens for testing and variable testing referral practices. The proportion of patients treated with EGFR-TKIs decreased during the same time period, both among untested patients (from 12.2% to 2.8% (P testing was associated with prolonged overall survival (Adjusted HR = 0.76 (95% CI, 0.65-0.89) Log-rank P testing was achieved and associated with major changes in EGFR-TKI prescribing and improved health outcomes. Modifiable factors determined testing uptake. Study registration ACTRN12615000998549.

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2013-10-08

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

  11. 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.

  12. MiRNA 17 family regulates cisplatin-resistant and metastasis by targeting TGFbetaR2 in NSCLC.

    Directory of Open Access Journals (Sweden)

    Zeyong Jiang

    Full Text Available MicroRNAs (miRNAs have been proven to play crucial roles in cancer, including tumor chemotherapy resistance and metastasis of non-small-cell lung cancer (NSCLC. TGFβ signal pathway abnormality is widely found in cancer and correlates with tumor proliferation, apoptosis and metastasis. Here, miR-17, 20a, 20b were detected down-regulated in A549/DDP cells (cisplatin resistance compared with A549 cells (cisplatin sensitive. Over-expression of miR-17, 20a, 20b can not only decrease cisplatin-resistant but also reduce migration by inhibiting epithelial-to-mesenchymal transition (EMT in A549/DDP cells. These functions of miR-17, 20a, 20b may be caused at least in part via inhibition of TGFβ signal pathway, as miR-17, 20a, 20b are shown to directly target and repress TGF-beta receptor 2 (TGFβR2 which is an important component of TGFβ signal pathway. Consequently, our study suggests that miRNA 17 family (including miR-17, 20a, 20b can act as TGFβR2 suppressor for reversing cisplatin-resistant and suppressing metastasis in NSCLC.

  13. 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)

  14. 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

  15. 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

  16. Dual time point FDG PET/CT:Is it useful for lymph node staging in patients with non small cell lung cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Weung; Kim, Woo Hyoung; Kim, Chang Guhn [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

    2012-09-15

    Dual time point (DTP)FDG PET/CT has been shown to be useful for lymph node (LN)staging in patients with non small cell lung cancer (NSCLC). The aim of this study was to evaluate the LN staging ability of DTP FDG PET/CT in the predominant area of pulmonary tuberculosis. Sixty nine NSCLC patients underwent DTP PET/CT. Regions of interest were placed on each LN of each station, and the maximum SUVs were measured. Three variables were obtained: (1)the SUV on the early scan (SUV{sup early}), (2)the SUV on the delayed scan (SUV{sup delayed}), and (3)the retention index of the SUV (RI). Each patient had one final LN stage and three other LN stages according to the cutoff values of SUV{sup early}, SUV{sup delayed}, and RI. In the LN based analysis, the area under the ROC curve of SUV{sup delayed} (0.884)was significantly larger (p<0.01)than those of SUV{sup early} (0.868)and RI (0.717). Among the three variables, SUV{sup delayed} was more accurate (P<0.01)for detecting the mediastinal LN metastasis than SUV{sup early} and RI. In the patient based analysis, SUV{sup delayed} had correctly determined LN stages in 55 of 69 patients (sensitivity, specificity, and accuracy=88.7%, 50.0%, and 79.7%), whereas SUV{sup early} and RI correctly determined LN stages in 53 and 52 patients, respectively. In this study, comparing the diagnostic efficacy of SUV{sup early}, SUV{sup delayed}, and RI for LN staging in patients with NSCLC, SUV{sup delayed} was the most accurate variable for LN staging. DTP PET/CT could provide improved diagnostic accuracy for the LN staging of NSCLC.

  17. Control of Moderate-to-Severe Plaque Psoriasis with Efalizumab: 24-Week, Open-Label, Phase IIIb/IV Latin American Study Results.

    Science.gov (United States)

    Stengel, Fernando M; Petri, Valeria; Campbell, Gladys Am; Dorantes, Gladys Leon; López, Magdalina; Galimberti, Ricardo L; Valdez, Raúl P; de Arruda, Lucia F; Guerra, Mario Amaya; Chouela, Edgardo N; Licu, Daiana

    2009-12-01

    INTRODUCTION: Psoriasis is a debilitating, chronic inflammatory systemic disease affecting around 2% of the South American population. Biological therapies offer the possibility of long-term therapy with improved safety and efficacy. METHODS: We conducted a multicentre, open-label, single-arm, Phase IIIb/IV study of adult patients (18-75 years) with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. Patients received efalizumab subcutaneously (1.0 mg/kg/wk). The primary endpoint was the proportion of patients achieving a Physician Global Assessment (PGA) rating of "excellent" or "cleared" at Week 24. Safety outcomes were adverse events (AEs), serious AEs (SAEs) and abnormalities on laboratory tests. RESULTS: Of 189 patients included in the intent-to-treat and safety populations, 104 (55.0%) were of Hispanic or Latino ethnicity. At Week 24, 92/189 (48.7%) patients achieved or maintained a PGA rating of "excellent" or "cleared". AEs were reported by 161/189 (85.2%) patients, SAEs by 21/189 (11.1%). One patient died during the study (meningoencephalitis). Laboratory findings were consistent with previous experience. CONCLUSIONS: Efalizumab demonstrated sustained control of psoriasis up to 24 weeks in patients from Latin America, confirming results seen in Phase III studies conducted in North America and Europe.

  18. Fc gamma receptor IIIb polymorphism and systemic lupus erythematosus: association with disease susceptibility and identification of a novel FCGR3B*01 variant.

    Science.gov (United States)

    Santos, V C; Grecco, M; Pereira, K M C; Terzian, C C N; Andrade, L E C; Silva, N P

    2016-10-01

    The objective of this study was to evaluate the association between Fc gamma receptor IIIb polymorphism and susceptibility to systemic lupus erythematosus and clinical traits of the disease. Genomic DNA was obtained from 303 consecutive systemic lupus erythematosus patients and 300 healthy blood donors from the southeastern region of Brazil. The polymorphic region of the FCGR3B gene was sequenced and the alleles FCGR3B*01, FCGR3B*02 and FCGR3B*03 were analyzed. The FCGR3B*01 allele was more frequent in systemic lupus erythematosus patients (43.1%) while the FCGR3B*02 allele prevailed among controls (63.7%) (P = 0.001). The FCGR3B*03 allele was found equally in both groups. The FCGR3B*01/*01 (20.7%) and FCGR3B*01/*02 (41.1%) genotypes were more frequent among systemic lupus erythematosus patients (P = 0.028 and P = 0.012, respectively) while the FCGR3B*02/*02 genotype was more frequent in controls (45.5%) (P lupus erythematosus was associated with the FCGR3B*01 allele, as well as with the FCGR3B*01/*01 and FCGR3B*01/*02 genotypes. No association was found between FCGR3B genotypes and clinical manifestations, disease severity or the presence of autoantibodies. © The Author(s) 2016.

  19. Is it possible to predict limb viability in complex Gustilo IIIB and IIIC tibial fractures? A comparison of two predictive indices.

    LENUS (Irish Health Repository)

    O'Sullivan, S T

    2012-02-03

    The patient with severe lower limb trauma presents a management dilemma; whether to amputate primarily or to attempt limb salvage. In recent years, many predictive indices have been published which purport to identify limbs which are non-viable. We retrospectively applied two recently described indices, the Mangled Extremity Severity Score (MESS) and the Limb Salvage Index (LSI), to 54 limbs in 50 patients with either Gustilo IIIB or IIIC complex tibial fractures. There were 22 amputations (40.7 per cent) in the series. The mean MESS score in the limb salvage group was 3.8 (range 2-10), and the mean MESS score in the amputation group was 7.7 (range 4-13) (P < 0.0001). The mean LSI score in the limb salvage group was 3.6 (range 3-8), and the mean LSI score in the amputation group was 6.9 (P < 0.01). However, in the group with MESS scores > 7 (which recommends amputation), there were three limbs which were salvaged with acceptable functional outcome. Similarly, in those with LSI scores > 6 (which recommends amputation), there were seven limbs successfully salvaged. A MESS > 7 offered a greater relative risk of amputation (9.2) than a LSI score > 6 (5.3). We found both indices of use in predicting limb salvage and functional outcome. However, neither is sufficiently accurate to be considered absolutely reliable in clinical practice.

  20. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

    Science.gov (United States)

    Geisthoff, Urban W; Seyfert, Ulrich T; Kübler, Marcus; Bieg, Birgitt; Plinkert, Peter K; König, Jochem

    2014-09-01

    Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Survival in Operated Early and Local Advanced-Stage (IA-IIIA Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mahsuk Taylan

    2016-06-01

    Full Text Available Objective: The early and local advanced stages (IA-IIIA of non-small cell lung cancer (NSCLC warrant the curative treatment approach of surgery. However, despite the surgical approach, survival depends on a number of factors. The aim of the study was to examine the factors that affect survival in operated NSCLC patients with these stages. Methods: A cohort of 231 operated patients with IA, IB, IIA, IIB, and IIIA stages of NSCLC were analyzed. The effects of age, sex, comorbidity, performance status, histopathology of the tumor, T stage, N stage, pleural invasion, surgical resection type and postoperative resection margin invasion on the survival of the patients were examined with Kaplan-Meier and Cox Regression analyses. Results: Advanced age (OR=1.042 for every passing year, CI=1.020-1.064, adenocarcinoma histopathology (OR=1.676 CI=1.178-2.384, N2 invasion (OR=2.389 CI=1.46-4.239, pleural invasion (OR=2.403 CI=1.569-3.678, resection margin invasion (OR=2.401, CI=1.141-5.048 and pneumonectomy as the type of surgical operation (OR=2.313, CI=1.467-3.647 were found to be independent prognostic factors of mortality. Conclusion: Follow-up of the NSCLC cases with advanced age, an adenocarcinoma type, visceral pleural invasion, N2-lymph node invasion, a history of pneumonectomy, and a resection margin invasion should be undertaken more atten­tively during planning of surgical operation and postoperative period. J Clin Exp Invest 2016; 7 (2: 125-133

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

    Science.gov (United States)

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

    2017-04-01

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

  4. 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

  5. Staging Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    In recent years, the social sciences have taken a “mobilities turn.” There has been a developing realisation that mobilities do not “just happen.” Mobilities are carefully and meticulously designed, planned and staged (from above). However, they are equally importantly acted out, performed and li......, the book asks: what are the physical, social, technical, and cultural conditions to the staging of contemporary urban mobilities?...... that mobility is more than movement between point A and B. It explores how the movement of people, goods, information, and signs influences human understandings of self, other and the built environment. Moving towards a new understanding of the relationship between movement, interaction and environments...

  6. Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

    International Nuclear Information System (INIS)

    Gomez, Daniel R.; Liao, Kai-Ping; Swisher, Stephen G.; Blumenschein, George R.; Erasmus, Jeremy J.; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

    2015-01-01

    Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Viteri Santiago

    2010-12-01

    Full Text Available Abstract Background Immunohistochemistry (IHC with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93% patients with exon 21 EGFR mutations (all with L858R but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients.

  12. 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

  13. The impact of 18F-FDG PET/CT in staging of non-small cell lung cancer patients: the key to improve patient treatment strategy

    International Nuclear Information System (INIS)

    Bretas, Gustavo Oliveira; Guedes, Juliana Barroso; Carvalho, Fernanda Monteiro Castro; Viana, Marcelo; Amaral, Nilson; Lewer, Marcelo Mamede; Elcordis Centro de Diagnosticos Ltda., Contagem, MG; Fundacao Hospitalar do Estado de Minas Gerais; Hospital Julia Kubistchek, Cirurgia Toracica, Belo Horizonte, MG; Universidade Federal de Minas Gerais

    2016-01-01

    Lung cancer leads the cause of cancer-related deaths in men and women around the world. The most common is non-small cell lung cancer (NSCLC). Fast and accurate staging is essential for choosing treatment for NSCLC. The positron emission tomography (PET) with 18 F-fluorodeoxyglucose ( 18 F-FDG) can provide molecular and metabolic information, which acquired simultaneously with computed tomography (CT), has proved to be a very useful tool in the cancer diagnosis and staging. Identifying the stage of lung cancer is important to avoid unnecessary surgeries, reducing morbidity and treatment costs. This study aims to examine the impact of 18 F-FDG PET/CT in the initial evaluation of patients with NSCLC in the Brazilian reality. Twenty-six patients with histopathologic diagnosis of NSCLC were included. They underwent staging in two separated moments: first with morphological images (x-ray and computed tomography scan) and after with 18 F-FDG PET/CT. The performance of 18 F-FDG PET/CT changed lymph node staging in around 30% of the patients initially classified as potentially operable, with high sensitivity and negative predictive values. Regarding the stage of metastasis, 18 F-FDG PET/CT increased by 11.5% the detection of metastasis not previously detected. About the clinical staging, using the 1 '8F-FDG PET/CT significantly reduced the number of patients classified as potentially operable in the early stages, avoiding the use of unnecessary thoracotomies in 19.2% of patients. The metabolic information obtained by 18 F-FDG PET/CT demonstrated better accuracy when compared to anatomic methods in the detection of lymph node and distant metastases. Thus, having important impact on therapeutic strategy and treatment cost related. (author)

  14. 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

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

    Science.gov (United States)

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

    2017-10-01

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

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

    DEFF Research Database (Denmark)

    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...

  17. Meta-analysis study of lymph node staging by 18 F-FDG PET/CT scan in non-small cell lung cancer: Comparison of TB and non-TB endemic regions

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chih-Ying, E-mail: jine871@yahoo.com.tw [Department of Radiation Therapy and Oncology, Taichung Hospital, Department of Health, Executive Yuan, Taiwan (China); Institute of Integrated Medicine, China Medical University, Taichung, Taiwan (China); Chen, Jin-Hua, E-mail: chenjh12@gmail.com [Biostatistics Center and Graduate Institute of Biostatistics, China Medical University, Taichung, Taiwan (China); Liang, Ji-An, E-mail: hope.jal@msa.hinet.net [Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (China); Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); Yeh, Jun-Jun, E-mail: anvin.funlan@msa.hinet.net [Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (China); Department of Research, PingTung Christian Hospital and Meiho University, Pingtung, Taiwan (China); Kao, Chia-Hung, E-mail: d10040@mail.cmuh.org.tw [Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan (China); Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (China)

    2012-11-15

    Lymph node staging in non-small cell lung cancer (NSCLC) is challenging and important for deciding treatment policy. The role of PET/CT scans in lymph node staging of NSCLC remains controversial when comparing TB and non-TB endemic regions. This study systematically reviews the literature regarding the diagnostic performance of PET/CT in lymph node staging of patients with NSCLC, and determines its pooled sensitivity and specificity. Methods: The databases of PubMed, Medline, and Cochrane library were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. Results: Seven of 86 studies were included. These studies had moderate to good methodological quality. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for patient-based analyses (five studies) were 66%, 92.7%, 5.86%, and 0.41%, respectively, and those for lesion-based analyses (six studies) were 59.4%, 96.5%, 9.37%, and 0.31%, respectively. Subanalysis of endemic regions of tuberculosis (TB) showed that these regions had lower sensitivity and similar specificity to non-TB endemic regions. Conclusion: PET/CT showed high specificity in the lymph node staging of NSCLC and lower sensitivity in TB endemic regions.

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  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. Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC revealed by next generation sequencing: potential clinical implications.

    Directory of Open Access Journals (Sweden)

    Antonio Marchetti

    Full Text Available Microdeletions at exon 19 are the most frequent genetic alterations affecting the Epidermal Growth Factor Receptor (EGFR gene in non-small cell lung cancer (NSCLC and they are strongly associated with response to treatment with tyrosine kinase inhibitors. A series of 116 NSCLC DNA samples investigated by Sanger Sequencing (SS, including 106 samples carrying exon 19 EGFR deletions and 10 without deletions (control samples, were subjected to deep next generation sequencing (NGS. All samples with deletions at SS showed deletions with NGS. No deletions were seen in control cases. In 93 (88% cases, deletions detected by NGS were exactly corresponding to those identified by SS. In 13 cases (12% NGS resolved deletions not accurately characterized by SS. In 21 (20% cases the NGS showed presence of complex (double/multiple frameshift deletions producing a net in-frame change. In 5 of these cases the SS could not define the exact sequence of mutant alleles, in the other 16 cases the results obtained by SS were conventionally considered as deletions plus insertions. Different interpretative hypotheses for complex mutations are discussed. In 46 (43% tumors deep NGS showed, for the first time to our knowledge, subpopulations of DNA molecules carrying EGFR deletions different from the main one. Each of these subpopulations accounted for 0.1% to 17% of the genomic DNA in the different tumors investigated. Our findings suggest that a region in exon 19 is highly unstable in a large proportion of patients carrying EGFR deletions. As a corollary to this study, NGS data were compared with those obtained by immunohistochemistry using the 6B6 anti-mutant EGFR antibody. The immunoreaction was E746-A750del specific. In conclusion, NGS analysis of EGFR exon 19 in NSCLCs allowed us to formulate a new interpretative hypothesis for complex mutations and revealed the presence of subpopulations of deletions with potential pathogenetic and clinical impact.

  1. Gefitinib inhibits invasive phenotype and epithelial-mesenchymal transition in drug-resistant NSCLC cells with MET amplification.

    Directory of Open Access Journals (Sweden)

    Silvia La Monica

    Full Text Available Despite the initial response, all patients with epidermal growth factor receptor (EGFR-mutant non-small cell lung cancer (NSCLC eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs. The EGFR-T790M secondary mutation is responsible for half of acquired resistance cases, while MET amplification has been associated with acquired resistance in about 5-15% of NSCLCs. Clinical findings indicate the retained addiction of resistant tumors on EGFR signaling. Therefore, we evaluated the molecular mechanisms supporting the therapeutic potential of gefitinib maintenance in the HCC827 GR5 NSCLC cell line harbouring MET amplification as acquired resistance mechanism. We demonstrated that resistant cells can proliferate and survive regardless of the presence of gefitinib, whereas the absence of the drug significantly enhanced cell migration and invasion. Moreover, the continuous exposure to gefitinib prevented the epithelial-mesenchymal transition (EMT with increased E-cadherin expression and down-regulation of vimentin and N-cadherin. Importantly, the inhibition of cellular migration was correlated with the suppression of EGFR-dependent Src, STAT5 and p38 signaling as assessed by a specific kinase array, western blot analysis and silencing functional studies. On the contrary, the lack of effect of gefitinib on EGFR phosphorylation in the H1975 cells (EGFR-T790M correlated with the absence of effects on cell migration and invasion. In conclusion, our findings suggest that certain EGFR-mutated patients may still benefit from a second-line therapy including gefitinib based on the specific mechanism underlying tumor cell resistance.

  2. 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.

  3. Increasing Rates of No Treatment in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Propensity-Matched Analysis.

    Science.gov (United States)

    David, Elizabeth A; Daly, Megan E; Li, Chin-Shang; Chiu, Chi-Lu; Cooke, David T; Brown, Lisa M; Melnikow, Joy; Kelly, Karen; Canter, Robert J

    2017-03-01

    Variation in treatment and survival outcomes for NSCLC is high among patients with stage III or IV disease, but patients with untreated NSCLC have not been critically analyzed to evaluate for improvable outcomes. We evaluated treatment trends and their association with oncologic outcomes for NSCLC, hypothesizing that there are a substantial number of untreated patients who are similar to patients who undergo treatment. Linear regression was used to calculate trends in utilization of treatment. Kaplan-Meier and Cox regression modeling were used to determine predictors of receiving treatment. Propensity matching was used to compare survival among subsets of treated versus untreated patients. Patients with primary NSCLC were identified from the National Cancer Data base from 1998 to 2012, and 21% of patients (190,539) received no treatment. For stage IIIA and IV, the proportion of untreated patients increased over the study period by 0.21% and 0.4%, respectively (p = 0.003 and p < 0.0001). Regardless of stage, untreated patients had significantly shorter overall survival (OS) (p < 0.0001). Propensity-matched analyses of 6144 stage IIIA patient pairs treated with chemoradiation versus no treatment confirmed shorter OS for untreated patients (median 16.5 versus 6.1 months, p < 0.0001). For 19,046 stage IV patient pairs treated with chemotherapy versus no treatment, similar results were obtained (median OS 9.3 versus 2.0 months, p < 0.0001). The proportion of untreated patients with stage IIIA and IV disease is increasing. Survival outcomes among patients with advanced-stage disease are superior with treatment, independent of selection bias. The benefits and risks of treatment should be carefully assessed before choosing to forego treatment. Published by Elsevier Inc.

  4. 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...

  5. 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.

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

    Science.gov (United States)

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

    2017-12-01

    Although the skeletal muscle in the region of the third lumbar vertebra (L3) is generally assessed in order to judge sarcopenia, not every patient with non-small cell lung cancer (NSCLC) undergoes computed tomography including the L3 region. We hypothesized that immuno-nutritional parameters could predict the existence of sarcopenia in patients with NSCLC. The aim of this study was to retrospectively investigate the correlation between preoperative sarcopenia and immuno-nutritional parameters in patients with early-stage NSCLC. We selected 147 of patients with pathological stage I NSCLC who underwent preoperative measurement of immuno-nutritional parameters and CT including the L3 region. Preoperative sarcopenia was significantly associated with female gender (p=0.0003) and poor prognosis (p=0.0322). In Kaplan-Meier analysis of overall survival (OS) by preoperative sarcopenia status, the sarcopenic group had significantly shorter OS than the non-sarcopenic group (5-year OS: 87.27% vs. 77.37%, p=0.0131, log-rank test). In multivariate analysis, the preoperative sarcopenia status (hazard ratio=5.138; 95% confidence interval=2.305-11.676; pnutritional status score (p=0.0071) and Geriatric Nutritional Risk Index (GNRI) (p<0.0001). Spearman's correlation test showed good significant correlation between preoperative sarcopenia status and GNRI (r=0.348, p<0.0001). The preoperative GNRI is a simple and useful predictor for existence of preoperative sarcopenia which was associated with poor outcome in patients with early-stage NSCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. National patterns of care and outcomes after combined modality therapy for stage IIIA non-small-cell lung cancer.

    Science.gov (United States)

    Patel, Aalok P; Crabtree, Traves D; Bell, Jennifer M; Guthrie, Tracey J; Robinson, Clifford G; Morgensztern, Daniel; Colditz, Graham A; Kreisel, Daniel; Krupnick, A Sasha; Bradley, Jeffrey D; Patterson, G Alexander; Meyers, Bryan F; Puri, Varun

    2014-05-01

    The role of surgery in addition to chemotherapy and radiation for stage IIIA non-small-cell lung cancer (NSCLC) remains controversial. Because there are limited data on the benefit from surgery in this setting, we evaluated the use of combined modality therapy nationally and explored the outcomes with and without the addition of surgery. Patient variables and treatment-related outcomes were abstracted for patients with clinical stage IIIA NSCLC from the National Cancer Database. Patients receiving chemotherapy and radiation were compared with those undergoing chemotherapy, radiation, and surgery (CRS) in any sequence. Between 1998 and 2010, 61,339 patients underwent combined modality treatment for clinical stage IIIA NSCLC. Of these, 51,979 (84.7%) received chemotherapy and radiation while 9360 (15.3%) underwent CRS. Patients in the CRS group were younger, more likely female patients and Caucasians, and had smaller tumors and lower Charlson comorbidity scores. The 30-day surgical mortality was 200 of 8993 (2.2%). The median overall survival favored the CRS group in both unmatched (32.4 months versus 15.7 months, p therapy seem to have better long-term survival.

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

    Science.gov (United States)

    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.

  9. Thoracic staging with {sup 18}F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to {sup 18}F-FDG PET/CT?

    Energy Technology Data Exchange (ETDEWEB)

    Schaarschmidt, Benedikt M. [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Grueneisen, Johannes; Umutlu, Lale [University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Metzenmacher, Martin [University Duisburg-Essen, Medical Faculty, Department of Medical Oncology, Essen (Germany); Gomez, Benedikt; Ruhlmann, Verena [University Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Gauler, Thomas [University Duisburg-Essen, Medical Faculty, Radiation and Tumour Clinic, Essen (Germany); Roesel, Christian [University Duisburg-Essen, Ruhrlandklinik, Thoracic Surgery and Endoscopy, Essen (Germany); Heusch, Philipp; Antoch, Gerald; Buchbender, Christian [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany)

    2017-02-15

    To investigate whether differences in thoracic tumour staging between {sup 18}F-FDG PET/CT and PET/MR imaging lead to different therapeutic decisions in Non-Small Cell Lung Cancer (NSCLC). Seventy-seven NSCLC patients that underwent whole-body {sup 18}F-FDG PET/CT from the base of skull to the upper thighs and thoracic PET/MR were enrolled in this retrospective study. Thoracic PET/CT and PET/MR images were staged according to the 7th edition of the AJCC staging manual. Staging results of both modalities were discussed separately in a simulated interdisciplinary tumour board and therapeutic decisions based on both imaging modalities were recorded. Descriptive statistics were used to compare the results and reasons for changes in the therapeutic decision were investigated. Staging results differed in 35 % of patients (27 patients) between thoracic PET/CT and PET/MR. Differences were detected when assessing the T-stage in 18 % (n = 14), the N-stage in 23 % (n = 18), and the M-stage in 1 % (n = 1). However, patient therapy management was changed in only six patients (8 %). Despite the variability of thoracic {sup 18}F-FDG PET/CT and PET/MR in TNM-staging, both modalities lead to comparable therapeutic decisions in patients suffering from NSCLC. Hence, {sup 18}F-FDG PET/MR can be considered an possible alternative to {sup 18}F-FDG PET/CT for clinical NSCLC staging. (orig.)

  10. [Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy 
in the Treatment of Patients with Advanced Non-small Cell Lung Cancer
--A Retrospective Study].

    Science.gov (United States)

    Du, Shuhui; Qin, Da; Pang, Ruiqi; Zhang, Yeqing; Zhao, Siqi; Hu, Mu; Zhi, Xiuyi

    2017-10-20

    Radiofrequency ablation (RFA) combined with chemotherapy has a certain short-term therapeutic effect for the treatment of advanced non-small cell lung cancer (NSCLC), but whether it can improve the long-term survival rate of patients is still controversy. This study retrospectively analyzed the difference of long-term efficacy between RFA combined with chemotherapy and chemotherapy alone in the treatment of patients with advanced NSCLC. A total of 77 patients with stage IIIb and stage IV NSCLC who underwent radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery, Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to December 2015 were enrolled as the treatment group. Chemotherapy with no radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV NSCLC as the control group. Two groups of patients were followed up by telephone about their living conditions. "Survival" package of R software version 3.4.1 was used for statistical analysis. Two sets of data baseline levels were tested by chi-square test. The bias was processed by Cox regression model and the survival curve was plotted using covariate mean substitution method. The first-year survival rate of the treatment group was 70.74%, the two-year survival rate was 39.31% and the median survival time was 22.1 months. The one-year survival rate was 54.54% in the control group, the two-year survival rate was 19.49%, the median survival for 18.1 months. The long-term survival rate of the treatment group was better than that of the control group (PRadiofrequency ablation of lung cancer combined with chemotherapy can significantly improve the 2-year survival rate of patients with stage IIIb and stage IV NSCLC.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  13. CXCL5 overexpression is associated with late stage gastric cancer.

    Science.gov (United States)

    Park, Jeong Youp; Park, Kyung Hwa; Bang, Seungmin; Kim, Myoung Hwan; Lee, Ji-Eun; Gang, Jingu; Koh, Sang Seok; Song, Si Young

    2007-11-01

    Chemokines play multiple roles in the development and progression of many different tumors. Our cDNA array data suggested that chemokine CXCL5 was upregulated in gastric cancer. Here, we analyzed CXCL5 protein expression in gastric cancer and investigated the clinical implications of CXCL5 upregulation. Immunostaining for CXCL5 was performed on gastric tissue microarrays of tissue specimens obtained by gastrectomy. The intensity of immunostaining in tumor tissue was considered strong when tumor tissue staining was more intense than in normal tissue; the intensity was null when staining was weaker in the tumor than in normal tissue; and the intensity was weak when staining was similar in both tissues. Serum CXCL5 levels and microvascular density in tumor tissue were measured by ELISA and monoclonal antibody to Factor VIII. Strong CXCL5 expression correlated with tumor stage. CXCL5 expression did not correlate with T stage. However, N stage positively correlated with CXCL5 expression. Serum CXCL5 levels in late stage (IIIB, IV) gastric cancer patients were higher than in patients with benign conditions. Microvascular density was higher in tumors with strong CXCL5 expression, but the correlation with CXCL5 was not linear. Multiple logistic regression analyses showed that, compared to no or weak expression, strong expression of CXCL5 was a significant risk factor for high N stage (N2, N3). CXCL5 overexpression was associated with late stage gastric cancer and high N stage. These results suggest a role for CXCL5 in the progression of gastric cancer, specifically in lymph node metastasis.

  14. Multigene expression profile for predicting efficacy of cisplatin and vinorelbine in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Buhl, I. K.; Christensen, I. J.; Santoni-Rugiu, E.

    2016-01-01

    Background: There is a need for biomarkers to predict efficacy of adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Presented is a combined cisplatin and vinorelbine marker from a previously validated model system [1] tested in two cohorts. Methods: The profiles consist...... and vinorelbine (ACT) and 62 patients who had no adjuvant treatment (OBS) [2] and 2) 95 stage Ib-IIIb completely resected NSCLC patients who all received adjuvant cisplatin and vinorelbine [3]. Endpoint is cancer specific survival. Results: The combined cisplatin and vinorelbine profiles scored as a continuous...

  15. 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 the constraints of 31%, 18%, and 20 Gy, respectively.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  17. A Population-Based Comparative Effectiveness Study of Radiation Therapy Techniques in Stage III Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Jeremy P. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Murphy, James D. [Department of Radiation Medicine and Applied Science, University of California– San Diego, Moores Cancer Center, La Jolla, California (United States); Hanlon, Alexandra L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States)

    2014-03-15

    Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT.

  18. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Assessment of the prognostic value of the 8th AJCC staging system for patients with clinically staged prostate cancer; A time to sub-classify stage IV?

    Directory of Open Access Journals (Sweden)

    Omar Abdel-Rahman

    Full Text Available The American Joint Committee on Cancer (AJCC staging system (8th edition for prostate cancer has been published. The current study seeks to validate the prognostic performance of the changes in the new system among clinically staged prostate cancer patients registered within the surveillance, epidemiology and end results (SEER database.SEER database (2004-2014 has been accessed through SEER*Stat program and AJCC 7th and 8th edition stages were calculated utilizing T, N and M stages as well as baseline prostatic specific antigen (PSA and grade group. Cancer-specific and overall survival analyses according to 6th, 7th and 8th editions were conducted through Kaplan-Meier analysis. Moreover, multivariate analysis was conducted through a Cox proportional hazard model.A total of 110499 patients with prostate cancer were identified in the period from 2004-2014.For cancer- specific survival according to 8th AJCC, all pair wise P values for comparison were significant (<0.01 except for stage IIA vs. IIB; while for overall survival according to 8th AJCC, all pair wise P values for comparison were significant (<0.02 except for stage IIIA vs. IIIB. Results of c-index assessment for cancer-specific survival for the three AJCC editions were as follows: c-index for AJCC 6th edition was 0.816; c-index for AJCC 7th edition was 0.897; c-index for AJCC 8th edition was 0.907. For stage IVB prostate cancer (i.e.M1 disease, further sub-staging was proposed according to M1 sub-stage (i.e. M1a, M1b and M1c. Pair wise comparison between these proposed sub-stages was conducted for both cancer-specific and overall survival. For both cancer-specific and overall survival, all pair wise P values for comparisons were <0.0001.Compared to older staging systems (6th and 7th, the 8th system is more discriminatory. Further sub-classification of stage IV disease is suggested.

  20. 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

  1. The cost-effectiveness of a NSCLC patient assistance program for pemetrexed maintenance therapy in People's Republic of China

    Directory of Open Access Journals (Sweden)

    Shi Q

    2017-02-01

    Full Text Available Qiang Shi,1 Shanlian Hu,2 Wesley E Furnback,3 Gregory F Guzauskas,3 Jiejing Shen,1 Bruce CM Wang3 1Lilly Suzhou Pharmaceutical Company, Ltd., Shanghai, People’s Republic of China; 2Shanghai Health Development Research Center, Shanghai, People’s Republic of China; 3Elysia Group, Ltd., Taipei, Taiwan, Republic of China Background: Eli Lilly and the China Primary Health Care Foundation are currently implementing a patient assistance program (PAP in China, which allows first-line nonsquamous non-small-cell lung cancer (NSCLC patients who complete four cycles of pemetrexed induction therapy to receive free, continuous pemetrexed maintenance therapy.Objective: To estimate the cost-effectiveness of pemetrexed maintenance therapy vs basic standard care (BSC and the economic impacts of providing a PAP for pemetrexed maintenance therapy to NSCLC patients who have completed pemetrexed induction therapy in a Chinese health care setting.Methods: We developed a novel decision-analytic model to evaluate the long-term costs and clinical efficacy of pemetrexed plus BSC vs BSC alone. We utilized a three-state (progression-free survival, progressed disease, and dead partition survival model for both the clinical and economic aspects of the analysis. Cost and health utility estimates were derived from the literature. We performed a scenario analysis to estimate the real-world impact of introducing the PAP in China by comparing the use of the PAP vs non-PAP. Model uncertainty was evaluated using one-way and multivariate probabilistic sensitivity analysis.Results: Compared to BSC, pemetrexed plus BSC resulted in a gain of 0.22 years of life (95% credible range [CR]: 0.04–0.46 and 0.13 quality-adjusted life years (95% CR: 0.04–0.26 per patient, at an increased cost of $28,105 (95% CR: −$22,720 to $48,646 without a PAP and $3,068 (95% CR: −$1,263 to $9,163 with a PAP. The incremental cost-effectiveness ratio for pemetrexed plus BSC vs BSC alone was cost

  2. Patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase IIIb PSO-INSIGHTFUL study.

    Science.gov (United States)

    Hong, C-H; Papp, K A; Lophaven, K W; Skallerup, P; Philipp, S

    2017-11-01

    Poor adherence to topical therapy in psoriasis remains an issue; it is associated with poor clinical outcomes, reduced quality of life and increased costs. Treatment-related factors leading to poor adherence include lack of efficacy, excessive time applying medication and poor cosmetic characteristics (e.g. slow absorption, greasiness). To assess the topical treatment attributes that influence patient preference for fixed combination calcipotriol 50 μg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) foam vs. gel, as well as in comparison with the latest topical treatment (LTT) a patient received. PSO-INSIGHTFUL was a Phase IIIb, prospective, multicentre (Canada/Germany), open-label, randomized, two-arm crossover study in patients aged ≥18 years with mild-to-severe psoriasis (NCT02310646). Following a washout period of up to 4 weeks, patients were randomized 1 : 1 to once-daily Cal/BD foam for 1 week, followed by Cal/BD gel for 1 week, or vice versa. Patients completed six questionnaires evaluating patient preferences. A total of 213 patients were randomized; 118 had received a topical treatment in the previous 3 months. Based on the Subject's Preference Assessment, 50% of patients preferred Cal/BD foam and 50% preferred Cal/BD gel. Based on the Topical Product Usability Questionnaire (TPUQ), overall mean scores were high for both Cal/BD foam and gel, and were often significantly in favour of both products compared with LTT. Greater differences between Cal/BD foam and gel vs. LTT occurred when the previous treatment was an ointment or cream. Cal/BD foam was generally preferred by younger patients (aged 18-39 years), whereas Cal/BD gel tended to be preferred by older patients (aged ≥40 years). Results from other questionnaires were aligned with the TPUQ. Patients with psoriasis have diverse needs and different preferences for topical treatment. This knowledge may help prescribers to choose the right formulation for the right patient, potentially leading

  3. 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

  4. 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose positron-emission tomography is cost-effective in the initial staging of non-small cell lung cancer patients in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Cerci, Juliano Julio, E-mail: cercijuliano@hotmail.com [PET-CT Center, Quanta - Diagnostico e Terapia, Curitiba, PR (Brazil); Instituto do Coracao (InCor) - Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, SP (Brazil); Takagaki, Teresa Yae [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil); Trindade, Evelinda; Morgado, Roberta; Morabito, Fausto; Musolino, Rafael Silva; Meneghetti, Jose Claudio; Soares Junior, Jose [Instituto do Coracao (InCor) - Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, SP (Brazil)

    2012-07-15

    Objective: To evaluate the accuracy and cost-effectiveness of metabolic staging (MS) with FDG-PET as compared with the conventional staging (CS) strategy in the preoperative staging of non-small cell lung cancer (NSCLC). Materials And Methods: A total of 95 patients with initial diagnosis of NSCLC were staged before undergoing treatment. The MS and CS results were compared with regard to treatment definition and incidence of futile thoracotomies with both strategies. Results: Metabolic staging with FDG-PET upstaged 48.4% and down staged 5.3% of the patients, and would lead to change in the treatment of 41% of cases. Thoracotomy was considered as futile in 47% of the patients with CS, and in 19% of the patients with MS. The cost of futile thoracotomies in eight patients with MS was R$ 79,720, while in 31 patients with CS it would be R$ 308,915. Just such saving in costs would be more than enough to cover the costs of all FDG-PETs (R$ 126,350) or FDG-PET/CTs (R$ 193,515) for the 95 patients. Conclusion: The metabolic staging with FDG-PET is more accurate than CS in patients with NSCLC. Both FDG-PET and FDG-PET/CT are cost-effective methods and their utilization is economically justifiable in the Brazilian public health system. (author)

  5. Prognostic and predictive role of FOXP3 positive tumor infiltrating lymphocytes (TILs in curatively resected non small cell lung cancer other than stage IA

    Directory of Open Access Journals (Sweden)

    Fatih Kose

    2017-12-01

    Full Text Available Lung cancer is the leading cause of cancer-related mortality and responsible for 1.6 million deaths per year through world-wide. Surgical resection with negative margin combined with the adjuvant therapy [except for stage IA and IB (<4 cm] is the Standard treatment for early-stage Non-small cell lung cancer (NSCLC. Early-stage NSCLC, however, has relapse rate over 40% mostly at distant sites. Therefore, high relapse rate necessitates urgent novel biomarker for these patients. In this study, we aim to evaluate the predictive and prognostic role of FOXP3+ Treg cells along with well defined Clinicohistopathological factors in early-stage non-small cell lung cancer (NSCLC. FOXP3 expression in tumor infiltrating lymphocytes (TIL was examined by immunohistochemical staining from resected early-stage 48 NSCLC patients. Data of patients and FOXP3 expression status along with common clinicohistopathological prognostic factors were evaluated retrospectively. Median age of patients was 62 years-old (range 43–78. Mean follow-up, median overall survival (OS, and disease-free survival (DFS were 49, 49 and 30 months, respectively. FOXP3 expression was positive in 23 (47.9% patients. Adjuvant chemotherapy (4 cycles of cisplatin-vinorelbine was given to 16 patients (33.3% at physician discretion. Patients with a FOXP3 expression of 25% or higher significantly lower OS and DFS when compared with patients with a FOXP3 staining lower than 25% with p-value of 0.016 and 0.032, respectively. In the patients with high FOXP3 expression, platin-based adjuvant chemotherapy had showed a detrimental effect on DFS and OS. These results suggest that FOXP3 expression may be used as useful prognostic biomarker in resected NSCLC. Our findings also suggest that resected NSCLC patients with FOXP3 expression of 25% or higher staining intensity may not get any benefit even disfavor from adjuvant platin chemotherapy.

  6. Expression and copy number gains of the RET gene in 631 early and mid stage non-small cell lung cancer cases.

    Science.gov (United States)

    Tan, Ling; Hu, Yerong; Tao, Yongguang; Wang, Bin; Xiao, Jun; Tang, Zhenjie; Lu, Ting; Tang, Hao

    2018-02-23

    To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China. RET expression was identified by Western blot. RET-positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription-PCR. ALK and ROS1 expression levels were tested by Western blot and EGFR mutation using Sanger sequencing. The RET-positive rate was 2.5% (16/631). RET-positive expression was related to poorer tumor differentiation (P < 0.05). In the 16 RET-positive samples, only two samples of moderately and poorly differentiated lung adenocarcinomas displayed RET rearrangement, both in RET-KIF5B fusion partners. Neither ALK nor ROS1 translocation was found. The EGFR mutation rate in RET-positive samples was significantly lower than in RET-negative samples (P < 0.05). RET-positive expression in early and mid stage NSCLC cases from south central China is relatively low and is related to poorer tumor differentiation. RET gene alterations (copy number gain and rearrangement) exist in all RET-positive samples. RET-positive expression is a relatively independent factor in NSCLC patients, which indicates that the RET gene may be a novel target site for personalized treatment of NSCLC. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  7. Clinical Application of Adjuvant Treatment after Operation in Patients with Stage IIIa Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yajie GAO

    2010-04-01

    Full Text Available Background and objective The efficacy of complete resection of the cancer for patients with stage IIIa non-small cell lung cancer (NSCLC is limited. Synthetic therapy is taken the lead in advocating at present. However, the value of post-operative radiotherapy is not still clear. The aim of this study is to evaluate the survival time and side effects of postoperative chemotherapy or chemoradiotherapy in the treatment of stage IIIa NSCLC. Methods Between December 2003 and June 2007, 52 cases that have completed followed-up data with stage IIIa of NSCLC received in the First Affiliated Hospital of Dalian Medical University. Twenty-three patients received postoperative chemoradiotherapy (group A and 29 patients received postoperative chemotherapy combined with radiotherapy (group B. Group A adopted platinum-based combination chemotherapy for 4-6 cycles. The chemotherapeutics included gemcitabine, vinorelbine and docetaxel. Group B used chemotherapy for 2-4 cycles and then received 3-dimensional conformal radiotherapy (3D-CRT. The prescribe dose of target volume was 50 Gy. The chemotherapy was same as for group A and needed 4 cycles in all. The impact of postoperative adjuvant treatment on survival and toxicity was observed in patients with stage IIIa NSCLC and the reason of disease progression was analyzed. Results The median survival was 32.5 months in group A and 31.9 months in group B (P=0.371. Progression-free survival extended about 6 months (P=0.044. The survival rate was 87% at 1 year, 0.1% at 2 year, 33% at 3 year for group A compared with 93%, 69%, 45% for group B. The major side effects were hematological and gastrointestinal toxicities, including nausea, vomiting and neutropenia. There was no significant difference in these toxicities between the two groups (P>0.05. Radioactiv esophageal infection occurred in 17.2% of the patients. Acute and late radioactive lung infection occurred in 13.8% and 27.6% of the patients. All these toxicities

  8. 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. 

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  10. Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  11. Long-term results of CT-guided percutaneous radiofrequency ablation of inoperable patients with stage Ia non-small cell lung cancer: A retrospective cohort study.

    Science.gov (United States)

    Huang, Bing-Yang; Li, Xin-Min; Song, Xiao-Yong; Zhou, Jun-Jun; Shao, Zhuang; Yu, Zhi-Qi; Lin, Yi; Guo, Xin-Yu; Liu, Da-Jiang; Li, Lu

    2018-03-16

    This study was performed to retrospectively evaluate the 10-year overall survival (OS), progression-free survival (PFS), and local control rates of patients with inoperable stage Ia non-small cell lung cancer (NSCLC) who underwent computed tomography (CT)-guided radiofrequency ablation (RFA) in a single center. Fifty patients with inoperable NSCLC underwent RFA between 2004 and 2016. Thoracic surgeons evaluated the patients and performed RFA under CT guidance. Follow-up CT and positron emission tomography/CT scans were obtained. Local control rates and recurrence patterns were analyzed. Seventy-three lesions in 50 patients (M:F = 22:28; median age: 73 years; range: 52-82 years) were treated with CT-guided RFA. The mean lesion size was 2.2 cm (range: 1-3 cm). No procedure-related deaths occurred. Low-grade fever was the most common post-ablation complication, with an incidence rate of 36%. The 1-, 2-, 3-, 5-, and 10-year OS rates of patients with Ia NSCLC were 96.0%, 86.5%, 67.1%, 36.3%, and 1%, respectively, and the 1-, 2-, 3-, and 5-year PFS rates were 94.0%, 77.5%, 43.5%, and 10.8%, respectively. The most common pattern of recurrence was local, and 15 patients with recurrence were treated with repeat RFA. Tumor size Ia NSCLC. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Tumour functional sphericity from PET images: prognostic value in NSCLC and impact of delineation method.

    Science.gov (United States)

    Hatt, Mathieu; Laurent, Baptiste; Fayad, Hadi; Jaouen, Vincent; Visvikis, Dimitris; Le Rest, Catherine Cheze

    2018-04-01

    Sphericity has been proposed as a parameter for characterizing PET tumour volumes, with complementary prognostic value with respect to SUV and volume in both head and neck cancer and lung cancer. The objective of the present study was to investigate its dependency on tumour delineation and the resulting impact on its prognostic value. Five segmentation methods were considered: two thresholds (40% and 50% of SUV max ), ant colony optimization, fuzzy locally adaptive Bayesian (FLAB), and gradient-aided region-based active contour. The accuracy of each method in extracting sphericity was evaluated using a dataset of 176 simulated, phantom and clinical PET images of tumours with associated ground truth. The prognostic value of sphericity and its complementary value with respect to volume for each segmentation method was evaluated in a cohort of 87 patients with stage II/III lung cancer. Volume and associated sphericity values were dependent on the segmentation method. The correlation between segmentation accuracy and sphericity error was moderate (|ρ| from 0.24 to 0.57). The accuracy in measuring sphericity was not dependent on volume (|ρ| value, although lower than that of volume, except for that derived using FLAB for which when combined with volume showed a small improvement over volume alone (hazard ratio 2.67, compared with 2.5). Substantial differences in patient prognosis stratification were observed depending on the segmentation method used. Tumour functional sphericity was found to be dependent on the segmentation method, although the accuracy in retrieving the true sphericity was not dependent on tumour volume. In addition, even accurate segmentation can lead to an inaccurate sphericity value, and vice versa. Sphericity had similar or lower prognostic value than volume alone in the patients with lung cancer, except when determined using the FLAB method for which there was a small improvement in stratification when the parameters were combined.

  13. 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.

  14. Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients.

    Science.gov (United States)

    Xu, Yujin; Wang, Liancong; Zheng, Xiao; Liu, Guan; Wang, Yuezhen; Lai, Xiaojing; Li, Jianqiang

    2013-05-01

    The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2- and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.

  15. RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRCA1, TUBB3 and RRM1 in NSCLC

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Garcia-Foncillas, J; Huarriz, M

    2012-01-01

    Customized chemotherapy is increasingly used in the management of patients with advanced non-small cell lung cancer (NSCLC). However, the most reliable methodology to determine biomarker status is neither fully elucidated nor agreed upon. Accordingly, we evaluated the predictive efficiency of q......RT-PCR and immunohistochemical analysis (IHC) on excision cross complementation group 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and class III ß-tubulin (TUBB3)....

  16. Understanding cancer staging

    Science.gov (United States)

    ... detailed information about the cancer stage. TNM Staging System The most common system for staging cancer in the form of solid tumor is the TNM system. Most providers and cancer centers use it to stage ...

  17. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial.

    Science.gov (United States)

    Brahmer, Julie R; Rodríguez-Abreu, Delvys; Robinson, Andrew G; Hui, Rina; Csőszi, Tibor; Fülöp, Andrea; Gottfried, Maya; Peled, Nir; Tafreshi, Ali; Cuffe, Sinead; O'Brien, Mary; Rao, Suman; Hotta, Katsuyuki; Zhang, Jin; Lubiniecki, Gregory M; Deitz, Anne C; Rangwala, Reshma; Reck, Martin

    2017-12-01

    In the phase 3 KEYNOTE-024 trial, treatment with pembrolizumab conferred longer progression-free survival than did platinum-based therapy in patients with treatment-naive, advanced non-small-cell lung cancer (NSCLC) with a programmed cell death-ligand 1 (PD-L1) tumour proportion score of 50% or greater (PD-L1-positive). Here we report the prespecified exploratory endpoint of pembrolizumab versus chemotherapy on patient-reported outcomes (PROs). In this multicentre, international, randomised, open-label, phase 3 trial, we recruited patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries. Eligible patients had measurable disease (per RECIST version 1.1) and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients were randomly assigned (1:1) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks (35 cycles) or investigator-choice platinum-doublet chemotherapy (4-6 cycles or until documented disease progression or unacceptable toxicity). Randomisation was stratified according to geography, ECOG performance status, and histology. PROs were assessed at day 1 of cycles 1-3, every 9 weeks thereafter, at the treatment discontinuation visit, and at the 30-day safety assessment visit using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), the EORTC Quality of Life Questionnaire Lung Cancer 13 items (QLQ-LC13), and the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) questionnaire. The key exploratory PRO endpoints (analysed for all patients who received a