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).

Role of T0 status in overall survival for unresectable stage III non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9026-9026
Author(s):  
Takefumi Komiya ◽  
Emily Powell ◽  
Charles Vu ◽  
Achuta Kumar Guddati
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

9026 Background: Occult (T0) primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Its prognosis has not been evaluated well in the literature. Methods: Using National Cancer Database (NCDB), cases diagnosed between 2004 and 2016 with unresectable clinical stage III NSCLC with N2 or N3 involvement were selected and assigned to T0 or T1-4 group according to AJCC staging version 6th or 7th. Clinical demographics including use of chemotherapy/immunotherapy in first course of treatment were collected. As validation, independent data using Surveillance, Epidemiology, and End Results Program (SEER) was analyzed accordingly. Survival analyses were conducted using Kaplan-Meier and log-rank tests. Results: A total of 458 and 84,263 cases met criteria for unresectable, N2/N3 stage III NSCLC with T0 and T1-4 status, respectively. T0 status was associated with younger age, recent diagnosis, adenocarcinoma histology, N3, and use of chemotherapy. Overall survival (OS) was improved in T0 over T1-4 group (p < 0.0001) with a five-year survival rate of 30.5% and 12.7%, respectively, with a validation with multivariate proportional hazard models. Propensity score matching analyses using all 458 patients in each group demonstrated a significant difference in OS (p < 0.0001). The difference was also significant in a subset of those who have undergone chemoradiation (p < 0.0001). Independent analysis using SEER data confirmed its superior survival of T0 over T1-4 with a five-year survival rate of 35.3% and 13.5%, respectively. Conclusions: Both NCDB and SEER analyses demonstrated better survival of T0 than T1-4 counterpart in the setting of unresectable stage III NSCLC, irrespective of chemotherapy status. This group may require a distinct assignment to new staging group after further investigation.

Doubling of median overall survival in a nationwide cohort of veterans with stage III non-small cell lung cancer in the durvalumab era.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8546-8546
Author(s):  
Kamya Sankar ◽  
Alex K. Bryant ◽  
Michael Green ◽  
Nithya Ramnath
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Median Number ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
The Pacific ◽  
Stage Iii Nsclc

8546 Background: The standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy followed by durvalumab maintenance based on outcomes from the PACIFIC trial. However, PACIFIC did not include Veterans, a unique population with significant co-morbidities; thus, the impact of durvalumab on survival of Veterans with stage III NSCLC is unknown. Methods: Using the U.S. Department of Veterans Affairs Corporate Data Warehouse, patients with stage III non-small cell lung cancer who received chemoradiotherapy and at least one dose of durvalumab were selected. Kaplan-Meier survival analysis and univariate Cox proportional hazards modeling were used to determine progression-free survival (PFS), overall survival (OS) and independent predictors of PFS and OS. PFS was manually extracted by review of serial surveillance scans. All statistical computations were performed using SAS 9.4 software. Results: 1106 Veterans met our inclusion criteria. The median age was 69. 95.1% (n = 1052) were male. The median Charlson Comorbidity Index was 1. 86.4% (n = 956) reported current or former tobacco use. 48.1% (n = 532) had adenocarcinoma histology, 48.4% (n = 535) squamous cell, 0.5% (n = 5) large cell, 0.3% (n = 3) neuroendocrine, and 0.1% (n = 1) sarcomatoid. 60% (n = 619) had AJCC 8th edition stage IIIA disease, 34.5% (n = 382) stage IIIB, and 3.3% (n = 36) stage IIIC. Median PFS was 19.9 months (95% CI: 16.9 – 23.6) and median OS was 34.9 months (95% CI: 29.7 – not reached). In univariate survival analyses, adenocarcinoma histology (HR 1.14, p = 0.03) predicted progression. Older age (HR 1.03, p < 0.0001) and stage IIIB/IIIC disease (HR 1.05, p = 0.008) predicted inferior OS. 18.4% (n = 204) of patients completed all planned cycles of adjuvant durvalumab. The median number of durvalumab infusions received was 6 (range: 1 – 38). Among evaluable patients, 175 (19.4%) discontinued durvalumab for progression, 211 (23.4%) discontinued for suspected immune-related toxicity and 17 (1.9%) died during treatment. Conclusions: While several factors have led to the improvement of OS in patients with stage III NSCLC over time, we report a doubling of median OS in Veterans with stage III NSCLC who received chemoradiotherapy plus durvalumab as compared to historical cohorts who received chemoradiotherapy alone (1). Veterans in our study received a lower median number of durvalumab infusions as compared to patients in the PACIFIC trial (6 vs. 14), and a significant proportion discontinued durvalumab due to suspected immune-mediated toxicity (23.4%). If further analyses confirm our findings, investigation of alternative dosing regimens and/or dosing intervals of durvalumab in order to balance safety and efficacy of durvalumab therapy in Veterans is warranted. (1) Santana-Davila R et al. J Clin Oncol. 2015 Feb 20;33(6):567-74.

scholarly journals Real-Life Long-Term Cohort of Patients With Stage IIIA Non–Small-Cell Lung Cancer: Overall Survival Related to Patients' Characteristics and Multiple Treatment Models

2021 ◽  
pp. 1572-1585
Author(s):  
Fernando Conrado Abrão ◽  
Frederico Rafael Moreira ◽  
Igor Renato Louro Bruno de Abreu ◽  
Marcelo Giovanni Marciano ◽  
Riad Naim Younes
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real Life ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Cancer Specific Survival ◽  
Stage Iii Nsclc

PURPOSE This real-life cohort of patients describes the treatment patterns and compares the overall survival (OS) and hazard risk of utilization of multiple therapies. MATERIALS AND METHODS Electronic medical registries of patients with stage III non–small-cell lung cancer (NSCLC) regularly attended in 72 hospitals were included. Univariate and multivariate analyses were conducted to evaluate the primary patients' characteristics leading to better OS and cancer-specific survival. RESULTS A total of 3,363 patients with stage III NSCLC followed over 19 years were included in this study. The median age was 66.00 (58.00-72.00) years, 65% male, and 41.2% with squamous cell carcinoma followed by adenocarcinoma (34.6%) and undifferentiated carcinoma (13.1%) in clinical stage T3 (50.3%), T2 (29.3%), and T4 (12.3%). The median survival (in months) was 18.4 (95% CI, 16.9 to 19.5) in patients submitted to radiotherapy plus chemotherapy, 11.2 (95% CI, 10.5 to 12.1) to chemotherapy, 31.5 (95% CI, 25.9 to 37.7) to surgery plus chemotherapy, and 33.8 (95% CI, 28.3 to 47.8) to chemotherapy plus radiotherapy plus surgery. The median cancer-specific survival (in months) was 19.3 (95% CI, 17.9 to 20.9) in patients submitted to radiotherapy plus chemotherapy, 12.1 (95% CI, 11.1 to 12.9) to chemotherapy, 36.9 (95% CI, 29.6 to 43.2) to surgery plus chemotherapy, and 41.3 (95% CI, 32.1 to 61.3) to chemotherapy plus radiotherapy plus surgery. The patients treated with multiple chemotherapy plus radiotherapy followed by surgery had significantly better OS and lower mortality rates than those treated with other treatments (adjusted hazard ratio, 0.55; 95% CI, 0.45 to 0.66; P < .001). At the end of the study, 11.2% and 10.7% of the patients were living with and without cancer, respectively. CONCLUSION Our real-life 19-year cohort study has shown that only 30.3% of the total patients with stage III NSCLC have been submitted to standard chemotherapy and radiotherapy treatment. This may show a substantial difference between the recruited clinical trials' patients and the real-life patients' characteristics in daily routine treatment.

scholarly journals Treatment patterns and overall survival among patients with unresectable, stage III non-small-cell lung cancer

2019 ◽  
Vol 15 (29) ◽  
pp. 3381-3393 ◽  
Author(s):  
Priyanka Bobbili ◽  
Kellie Ryan ◽  
Mei S Duh ◽  
Akanksha Dua ◽  
Ancilla W Fernandes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Patterns ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

Aim: To analyze treatment patterns and overall survival (OS) across time (2009–2014) among patients with unresected, stage III non-small-cell lung cancer (NSCLC). Patients & methods: Stage III NSCLC patients aged ≥65 years who initiated therapy were identified using SEER-Medicare data. Results: Among 4564 patients, 84% received chemotherapy (with or without radiotherapy), and 59% received chemoradiotherapy (CRT). Carboplatin + paclitaxel was the most frequent regimen. Median (interquartile range) OS among chemotherapy patients was 13.2 (6.0–28.9) months, and 14.8 (6.7–33.4) months among CRT patients. Among CRT patients, there was no difference in OS across years of CRT initiation. Conclusion: OS remained static across 2009–2014, indicating stagnancy in clinical outcomes for stage III NSCLC patients and a need for more effective therapeutic options.

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.

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.

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