Preoperative survivin, ERCC1, and PTEN expression in stage III non-small cell lung cancer (NSCLC) patients (pts) treated with neoadjuvant and definitive chemoradiation and association with overall survival (OS).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7067-7067
Author(s):  
Marta Batus ◽  
Mary J. Fidler ◽  
Kelly Kaiser Walters ◽  
Mark Pool ◽  
Brett Mahon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Repair ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Stage Iii ◽  
Term Survival ◽  
Modest Improvement ◽  
Thoracic Radiation ◽  
Nsclc Patients

7067 Background: Thoracic radiation and concurrent chemotherapy consisting of platinum based doublets has produced modest improvement in long term survival for patient with locally advanced (LA) NSCLC. There is relatively little information regarding molecular profiles and outcome in LA-NSCLC patients (pts) treated with chemoradiation. The objective of this retrospective study is to evaluate potential relationships between expression of DNA repair enzyme ERCC1 and enzymes involved in cell survival – survivin and PTEN. Methods: Stage III NSCLC pts who were treated with chest radiation (40-60Gy) and concurrently with platinum doublet and who had sufficient pretreatment tissue were included in this study. Immunohistochemistry was used to detect nuclear and cytoplasmic expression (frequency 0-4 and intensity 0-4) of survivin, and PTEN, and for nuclear expression of ERCC1. Product of intensity and frequency was calculated for all markers and correlated with overall survival (OS). Results: 97 pts had adequate tumor samples for analysis. 53 women, median age 67. 48 pts with ERCC1 prod <=6 had longer OS than 41 pts with ERCC1 prod >6 (19.6 vs 1.0 months, p=0.034). 16 pts with ERCC1 prod >6, PETN prod <=6 and survivin prod >4 had significantly lower OS than 68 pts with ERCC1<=6, PETN >6 and survivin <=4 (17.2 vs 40.2 months, p<0.001). Conclusions: The association of inferior survival in LA-NSCLC pts whose tumors express high survivin, low PTEN, and high ERCC1, suggests that combining inhibitors of survivin and or of PI3KCA with chemoradiation and developing strategies to inhibit DNA repair might improve outcomes in this group of pts.

scholarly journals Long-term survival of locally advanced stage III non-small cell lung cancer patients treated with chemoradiotherapy and perspectives for the treatment with immunotherapy

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Martina Vrankar ◽  
Karmen Stanic
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Term Survival ◽  
Long Term Survival ◽  
Stage Iii Nsclc

Abstract Background Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.

scholarly journals Long-term survival of locally advanced stage III non-small cell lung cancer patients treated with chemoradiotherapy and perspectives for the treatment with immunotherapy

2018 ◽  
Vol 52 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Martina Vrankar ◽  
Karmen Stanic
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Term Survival ◽  
Long Term Survival ◽  
Stage Iii Nsclc

Abstract Background Standard treatment for patients with inoperable locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year overall survival rates range between 15 and 25%, while long term survival data are rarely reported. Patients and methods A total of 102 patients with stage III NSCLC treated between September 2005 and November 2010 with induction chemotherapy and CCRT were included in this long term survival analysis. All patients were tested for PD-L1 status and expression of PD-L1 was correlated with overall survival (OS), progression free survival (PFS) and toxicities. Results The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year-survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1 months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1 status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005. The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to 21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and are significantly shorter for patients with PD-L1 expression. New treatment with check-point inhibitors combined with RT therefore seems reasonable strategy to improve these results.

Predictive factors for achieving a pathologic complete remission (pCR) rate after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer: Results of a multivariant analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11556-e11556
Author(s):  
Edwin Boelke ◽  
Christiane Matuschek ◽  
Stephan L. Roth ◽  
Hans Bojar ◽  
Johann Wolfgang Janni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Complete Remission ◽  
Predictive Factors ◽  
Locally Advanced ◽  
Time Interval ◽  
Term Survival ◽  
Long Term Survival ◽  
Pathologic Complete Remission

e11556 Background: In contrast to neoadjuvant chemotherapy they are no predictive factors to estimate the pathologic complete remission (pCR) rate after preoperative chemotherapy (NRT-CHX) in locally advanced breast cancer (LABC). Methods: 315 LABC patients were included in this trial. They were treated during 1991-1998. The last follow up was in November 2011. Radiotherapy was applied with 50 Gy (5x2 Gy / week) to the breast and the supra-/infraclavicular lymph nodes. 101 patients received a 10 Gy interstitial boost (breast conservation). Chemotherapy (CMF, EC or Mitoxantron was applied in 192 patients prior to radiotherapy and in 113 patients simultaneously. Ten patients had no chemotherapy. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time period up to surgery were examined in multivariate terms for pCR and overall survival. Results: The pCR rate for NRT-CHX after surgery was 29.2%. In multivariante analysis a longer time interval to surgery increased the probability of a pCR (HR 1,17 [95% CI 1,05-1,31], p<0,01). In term of overall survival, the achievement of a pCR is the strongest predictor for long term survival (HR 0,28 [95% CI 0,19-0,56], p<0,001). Conclusions: A long time interval to surgery (> 2 months) increases the probability of a pCR after NRT-CHX. Like in neoadjuvant CHX the achievement of a pCR is an important prognostic factor for long term survival.

Randomized trial of amifostine in locally advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and hyperfractionated radiation (HRT): Long-term survival results of Radiation Therapy Oncology Group (RTOG) 9801

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7529-7529
Author(s):  
B. Movsas ◽  
J. Moughan ◽  
C. Langer ◽  
M. Werner-Wasik ◽  
N. Nicolaou ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Radiation Therapy Oncology Group ◽  
Disease Free Survival ◽  
Rank Test ◽  
Term Survival ◽  
Long Term Survival ◽  
Patient Reported ◽  
Nsclc Patients

7529 Purpose: This analysis was conducted to address the potential antitumor effect of amifostine (AM) in NSCLC patients enrolled on RTOG-9801. The long-term survival results of RTOG-9801 are presented here. Methods: 243 patients (pts) with stage II/IIIAB NSCLC received induction paclitaxel (P) 225 mg/m2IV days 1, 22 and carboplatin (C) AUC 6 days 1, 22 and then concurrent weekly P (50 mg/m2) and C (AUC 2) and HRT (69.6 Gy at 1.2 Gy BID). Pts were randomly assigned to AM 500 mg IV 4x/week or no-AM during chemoradiation. Treatment differences for overall and disease-free survival (OS & DFS) were analyzed with the log-rank test; Gray's test was used for time to progression (TTP). Results: 118 pts were randomly assigned to receive AM and 121 to no-AM (4 pts were ineligible). The median follow-up for pts still alive is 52.3 months (mo) for the AM-arm and 58.3 mo for the no-AM arm (16.6 vs 17.9 for all pts). There are no significant differences in OS, DFS or TTP between arms. The median survival, 3-yr, and 5-yr OS are 17.1 mo, 27% and 17% (AM-arm) vs 18.4 mo, 28% and 16% (no-AM arm) (p=0.97). Grade 3/4/5 late-RT toxicities are similar (11%/3%/2% AM-arm vs 14%/4%/2% no-AM arm). Conclusion: While an earlier publication reported that amifostine did not reduce objective measures of severe esophagitis in RTOG-9801, patient-reported outcome analyses suggested a possible advantage to AM with decreased pain and swallowing symptoms (J Clin Oncol 23:2145–2154, 2005). This long-term follow-up analysis on survival shows no evidence of tumor radioprotection due to amifostine. The promising 5-yr OS suggests that induction paclitaxel/carboplatin (P/C) followed by concurrent RT and weekly low-dose P/C is comparable to other regimens using cisplatin doublets at higher dosages every 3–4 weeks. Research supported by NCI and Medimmune Oncology. No significant financial relationships to disclose.

scholarly journals Can local treatment prolong the sensitivity of metastatic prostate cancer to androgen deprivation or even prevent castration resistance?

2021 ◽  
Author(s):  
Christina Niklas ◽  
Matthias Saar ◽  
Alessandro Nini ◽  
Johannes Linxweiler ◽  
Stefan Siemer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Biochemical Recurrence ◽  
Metastatic Prostate Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Term Survival ◽  
Long Term Survival ◽  
Hormonal Manipulation

Abstract Purpose A number of observational clinical studies suggest that prior primary tumor treatment favorably influences the course of metastatic prostate cancer (PCa), but its mechanisms of action are still speculative. Here, we describe the long-lasting sensitivity to various forms of androgen deprivation in patients after radical prostatectomy (RP) for locally advanced PCa as one potential mechanism. Methods A consecutive series of 115 radical prostatectomies after inductive therapy for T4 prostate cancer was re-analyzed, and long-term survival, as well as recurrence patterns and responses to different forms of hormonal manipulation, were assessed. Results The estimated biochemical response-free, PCa-specific, and overall survival rates after 200 months were 20%, 65%, and 47% with a median overall survival of 156 months. The majority of patients, although not cured of locally advanced PCa (84/115), showed long-term survival after RP. PCa-specific and overall survival rates of these 84 patients with biochemical recurrence were 61% and 44% at 150 months. Long-term sensitivity to ADT was found to be the main reason for the favorable tumor-specific survival in spite of biochemical recurrence. Conclusions Sensitivity to primary or secondary hormonal manipulation was the main reason for the long-term survival of patients who had not been cured by surgery only. The results suggest that treatment of the primary tumor-bearing prostate delays castration-resistant PCa and enhances the effect of hormonal therapies in a previously unknown manner. The underlying cellular and molecular mechanisms need to be explored in more detailed analyses, which could profoundly impact treatment concepts of locally advanced and metastatic PCa.

Effect of adjuvant chemotherapy following pathologic complete response on long-term survival in rectal cancer: A propensity score matched analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 717-717 ◽  
Author(s):  
Ali Mokdad ◽  
Sergio Huerta ◽  
Rebecca M Minter ◽  
John C. Mansour ◽  
Michael A. Choti ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Term Survival

717 Background: The role of adjuvant chemotherapy following resection in patients with rectal cancer that achieve pathologic complete response (pCR) after neoadjuvant therapy is unclear. Current data have been limited by small sample size series. This study examined the impact of adjuvant chemotherapy following pCR on overall survival in a national cohort of patients. Methods: Patients with rectal adenocarcinoma were identified in the National Cancer Data Base between 2006 and 2012. Those with locally advanced tumor (clinical stage II or III) that achieved pCR (defined as ypT0N0 in surgical specimens) after neoadjuvant chemoradiotherapy (nCRT) were included in the study. We matched by propensity score patients that received adjuvant chemotherapy (ACT) and patients that did not receive postoperative treatment (no-ACT) controlling for demographic as well as perioperative patient and tumor characteristics. Overall survival was compared using a Cox proportional hazards model. Results: We identified 2,543 patients (ACT: 732, no-ACT: 1,811 patients) with resected locally advanced rectal adenocarcinoma that achieved pCR after nCRT. Among patients that received ACT, 711 were matched with 711 patients in the no-ACT group. Adjuvant chemotherapy was associated with improved overall survival compared to no-ACT (hazard ratio[HR] = 0.46, 95% confidence interval [CI] = 0.29 – 0.75). Overall survivals at 1, 3, and 5 years in the ACT and no-ACT groups were 100% vs 98% (P=0.1), 98% vs 94% (P<0.01), and 94% vs 89% (P<0.01), respectively. In subgroup analyses, adjuvant chemotherapy improved overall survival in patients with clinical stage II (HR = 0.43, 95% CI = 0.22 – 0.85) as well as stage III tumor (OR = 0.50, 95% CI = 0.26 – 0.98). Among patients that received adjuvant chemotherapy, there was no difference in overall survival between single agent and multiagent regimens (HR = 1.37, 95% CI = 0.57 – 3.29). Conclusions: Adjuvant chemotherapy may providea small long-term survival benefit in patients with resected locally advanced rectal cancer and pCR after nCRT.

Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder Cancer

2005 ◽  
Vol 23 (21) ◽  
pp. 4602-4608 ◽  
Author(s):  
Hans von der Maase ◽  
Lisa Sengelov ◽  
James T. Roberts ◽  
Sergio Ricci ◽  
Luigi Dogliotti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Visceral Metastases ◽  
Overall Survival Rates

Purpose To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). Patients and Methods Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. Results A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (≤ three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively. Conclusion Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.

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