Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer.

1998 ◽  
Vol 16 (9) ◽  
pp. 3078-3081 ◽  
Author(s):  
D H Lau ◽  
J J Crowley ◽  
D R Gandara ◽  
M B Hazuka ◽  
K S Albain ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Southwest Oncology Group ◽  
Poor Risk ◽  
Risk Patients ◽  
Stage Iii Nsclc

PURPOSE A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.

scholarly journals 244 Genomic determinants of response to chemoradiation and durvalumab consolidation for stage III non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A263-A263
Author(s):  
Matthew Guo ◽  
Joseph Murray ◽  
Paola Ghanem ◽  
Khinh Ranh Voong ◽  
Russell Hales ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Profiling ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Definitive Chemoradiation ◽  
Stage Iii Nsclc

BackgroundDurvalumab consolidation after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC) improves overall survival. However, up to 25% of patients progress within 18 months following durvalumab consolidation. Little is known regarding the genomic determinants of response to therapy.1 2MethodsWe retrospectively reviewed medical records of 76 patients with stage III NSCLC who received definitive chemoradiation and durvalumab consolidation between 2015–2020 at a large tertiary academic center. Tumor characteristics, molecular profiling, and clinical outcomes including response, progression-free survival (PFS), and overall survival (OS) were documented in an IRB-approved database. Outcomes were assessed by molecular alterations identified from diagnostic biopsy samples using Kaplan-Meier analysis.ResultsOf 76 patients with stage III NSCLC treated with definitive chemoradiation and durvalumab consolidation, 74 were evaluable for PFS and OS. Median age at diagnosis was 66.5 years and 43% were women (n=32). Histology included adenocarcinoma (55%, n=41) and squamous cell carcinoma (32%, n=24). Median follow-up time was 23.0 months from start of durvalumab. The cohort’s median PFS was 15.9 months with 36 patients having documented radiographic progression. Overall survival for the cohort was 32.0 months with 28 deaths. Molecular profiling was performed at time of diagnosis in 35 patients (47%), of which 30 had adenocarcinoma histology. 18 patients had KRAS mutations including KRAS p.G12C (n=8), which were mutually exclusive with 8 patients who had other clinically targetable alterations (EGFR mutations n=1, ALK fusion n=1, RET fusion n=1, MET exon 14 skipping mutation n=1, or ERBB2 mutation n=4). Three patients had non-targetable mutations (BRAF non-p.V600E, STK11, KEAP1) and the remaining six patients lacked an identifiable alteration. There was no significant difference in PFS (p=0.92 by log-rank) or OS (p=0.36 by log-rank) between patients with KRAS mutations, other targetable alterations, non-targetable mutations, or those without molecular profiling. Within patients with KRAS mutations, there was no significant difference in PFS (p=0.33 by log-rank) or OS (p=0.69 by log-rank) when comparing KRAS p.G12C to non-p.G12C mutations.ConclusionsOur study of real-world cohort of patients with stage III NSCLC examined genomic determinants of response to treatment with definitive chemoradiation and durvalumab. Results from this retrospective study suggest that patients with KRAS-mutated tumors derive similar benefit from therapy than patients with other targetable, non-targetable or no identifiable genomic alterations. Future directions for this cohort include analysis of post-progression therapy, subgroup analysis comparing genomic alterations to patterns of progression, and examination of molecular signatures of patients with progression.ReferencesAntonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med 2017;377(20):1919–1929. doi:10.1056/NEJMoa1709937Faivre-Finn C, Vicente D, Kurata T, et al. Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC—an update from the PACIFIC trial. Journal of Thoracic Oncology 2021;16(5):860–867. doi:10.1016/j.jtho.2020.12.015Ethics ApprovalThis retrospective chart review study has obtained ethics approval from the Institutional Review Board at the Johns Hopkins School of Medicine (number: IRB00232313).

scholarly journals Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252053
Author(s):  
Samuel P. Heilbroner ◽  
Eric P. Xanthopoulos ◽  
Donna Buono ◽  
Daniel Carrier ◽  
Ben Y. Durkee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
High Frequency ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
The Impact

Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. Results Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. Conclusion hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805.

1995 ◽  
Vol 13 (8) ◽  
pp. 1880-1892 ◽  
Author(s):  
K S Albain ◽  
V W Rusch ◽  
J J Crowley ◽  
T W Rice ◽  
A T Turrisi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Small Cell ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Term Survival ◽  
Southwest Oncology Group

PURPOSE To assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB. PATIENTS AND METHODS Biopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found. RESULTS The median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and 61% were only distant. There were 26 brain relapses, of which 19 were the sole site or cause of death. There was no survival difference (P = .81) between stage IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v 18%; P = .0005). CONCLUSION This trimodality approach was feasible in this Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival rate. An Intergroup study is currently being conducted to determine whether surgery adds more to the risk or to the benefit of chemoRT.

scholarly journals Identification of Potential Prognostic and Predictive Immunological Biomarkers in Patients with Stage I and Stage III Non-Small Cell Lung Cancer (NSCLC): A Prospective Exploratory Study

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6259
Author(s):  
Rianne D. W. Vaes ◽  
Kobe Reynders ◽  
Jenny Sprooten ◽  
Kathleen T. Nevola ◽  
Kasper M. A. Rouschop ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Exploratory Study ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Stage I ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Stage Iii Nsclc

Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). In this prospective study, patients with stage I NSCLC treated with stereotactic body radiation therapy (n = 26) and patients with stage III NSCLC treated with concurrent chemoradiotherapy (n = 18) were included. Blood samples were collected before (v1), during (v2), and after RT (v3). In patients with stage I NSCLC, CD244 (HR: 10.2, 95% CI: 1.8–57.4) was identified as a negative prognostic biomarker. In patients with stage III NSCLC, CR2 and IFNGR2 were identified as positive prognostic biomarkers (CR2, HR: 0.00, 95% CI: 0.00–0.12; IFNGR2, HR: 0.04, 95% CI: 0.00–0.46). In addition, analysis of the treatment-induced changes of circulating protein levels over time (Δv2/v3−v1) also identified CXCL10 and IL-10 as negative predictive biomarkers (CXCL10, HR: 3.86, 95% CI: 1.0–14.7; IL-10, HR: 16.92 (2.74–104.36)), although serum-induced interferon (IFN) response was a positive prognostic. In conclusion, we identified several circulating immunogenic proteins that are correlated with PFS in patients with stage I and stage III NSCLC before and during treatment.

Southwest Oncology Group: Two Decades of Experience in Non-Small Cell Lung Cancer

2005 ◽  
Vol 32 ◽  
pp. 119-121 ◽  
Author(s):  
Andrew T. Turrisi ◽  
John Crowley ◽  
Kathy Albain ◽  
Laurie Gaspar ◽  
David Gandara
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Southwest Oncology Group

Time From Treatment to Subsequent Diagnosis of Brain Metastases in Stage III Non–Small-Cell Lung Cancer: A Retrospective Review by the Southwest Oncology Group

2005 ◽  
Vol 23 (13) ◽  
pp. 2955-2961 ◽  
Author(s):  
Laurie E. Gaspar ◽  
Kari Chansky ◽  
Kathy S. Albain ◽  
Eric Vallieres ◽  
Valerie Rusch ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Disease Progression ◽  
Small Cell ◽  
Stage Iii ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Southwest Oncology Group ◽  
The Brain

Purpose A retrospective review of the Southwest Oncology Group (SWOG) database was undertaken to review the incidence and timing of diagnosis of brain metastases in patients undergoing combined-modality therapy for stage III non–small-cell lung cancer (NSCLC). Patients and Methods Four hundred twenty-two eligible, assessable patients with stage IIIA/B NSCLC were treated on four SWOG protocols. Treatment varied with protocol but consisted of concurrent cisplatin-etoposide and radiation in all patients, with a surgery arm in two of the four protocols. Results Of the 422 total patients, 268 (64%) have experienced disease progression; 54 relapses (20%) were in brain only, 17 (6.5%) were in brain and other sites simultaneously, and 197 (63.5%) were in sites other than brain. Of the 268 patients with disease progression, progression in the brain only, in the brain and other sites, and not in the brain occurred in 20%, 6%, and 74% of patients, respectively. Time from treatment to diagnosis of disease progression in the brain in 71 patients was as follows: during treatment, 16 relapses (22.5%); 0 to 16 weeks after treatment, 17 relapses (24%); 16 weeks to 6 months after treatment, 10 relapses (14%); 6 to 12 months after treatment, 16 relapses (22.5%); and more than 12 months after treatment, 12 relapses (17%). Nonsquamous histology and young patient age were the only significant predictors for increased risk of early relapse with brain metastases. Conclusion Brain metastases often develop early in the course of treatment for stage IIIA/B NSCLC. The statistical designs of ongoing trials of prophylactic cranial irradiation in stage III NSCLC have taken this into account.

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