Systemic immune–inflammation index changes predict outcome in stage III non-small-cell lung cancer patients treated with concurrent chemoradiotherapy

2021 ◽  
Author(s):  
Taosheng Huang ◽  
Huanqian Zhang ◽  
Yunzheng Zhao ◽  
Yanping Li ◽  
Guofeng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Operating Characteristic ◽  
Concurrent Chemoradiotherapy ◽  
Characteristic Curve ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Operating Characteristic Curve ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

Background: Although the systemic immune–inflammation index (SII) has been used to predict recurrence and survival in non-small-cell lung cancer (NSCLC) patients, the prognostic significance of change in SII (ΔSII) is unclear for stage III NSCLC patients treated with concurrent chemoradiotherapy (CCRT). In the present study we aimed to explore the association between ΔSII and the clinical outcomes of 142 patients with stage III NSCLC treated with CCRT. Methods: A total of 142 patients were included in this retrospective study. The SII values were calculated based on laboratory data regarding platelet, neutrophil and lymphocyte counts, and ΔSII was calculated using data acquired before and approximately 2 weeks after CCRT. The receiver operating characteristic curve was used to determine the optimal cut-off value for the peripheral blood inflammation index. Kaplan–Meier analysis and Cox proportional regression were used to analyze the prognostic value of ΔSII for overall survival (OS) and progression-free survival (PFS). Results: The area under the receiver operating characteristic curve for ΔSII (0.708) was larger than those for pre-CCRT SII (0.578) and post-CCRT SII (0.610). The optimal cut-off point for ΔSII was defined as 43. OS and PFS were better in patients with low ΔSII and in multivariate analysis, the ΔSII was an independent predictor of OS and PFS (p = 0.006 and p = 0.017, respectively). Conclusions: ΔSII is related to progression and death in patients with stage III NSCLC. The ΔSII can provide a detailed prognostic prediction for stage III NSCLC.

Machine-Learning and Stochastic Tumor Growth Models for Predicting Outcomes in Patients With Advanced Non–Small-Cell Lung Cancer

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Kien Wei Siah ◽  
Sean Khozin ◽  
Chi Heem Wong ◽  
Andrew W. Lo
Keyword(s):  
Machine Learning ◽  
Lung Cancer ◽  
Clinical Trials ◽  
Operating Characteristic ◽  
Advanced Nsclc ◽  
Characteristic Curve ◽  
Small Cell ◽  
Small Cell Lung ◽  
Out Of Sample ◽  
Operating Characteristic Curve

PURPOSE The prediction of clinical outcomes for patients with cancer is central to precision medicine and the design of clinical trials. We developed and validated machine-learning models for three important clinical end points in patients with advanced non–small-cell lung cancer (NSCLC)—objective response (OR), progression-free survival (PFS), and overall survival (OS)—using routinely collected patient and disease variables. METHODS We aggregated patient-level data from 17 randomized clinical trials recently submitted to the US Food and Drug Administration evaluating molecularly targeted therapy and immunotherapy in patients with advanced NSCLC. To our knowledge, this is one of the largest studies of NSCLC to consider biomarker and inhibitor therapy as candidate predictive variables. We developed a stochastic tumor growth model to predict tumor response and explored the performance of a range of machine-learning algorithms and survival models. Models were evaluated on out-of-sample data using the standard area under the receiver operating characteristic curve and concordance index (C-index) performance metrics. RESULTS Our models achieved promising out-of-sample predictive performances of 0.79 area under the receiver operating characteristic curve (95% CI, 0.77 to 0.81), 0.67 C-index (95% CI, 0.66 to 0.69), and 0.73 C-index (95% CI, 0.72 to 0.74) for OR, PFS, and OS, respectively. The calibration plots for PFS and OS suggested good agreement between actual and predicted survival probabilities. In addition, the Kaplan-Meier survival curves showed that the difference in survival between the low- and high-risk groups was significant (log-rank test P < .001) for both PFS and OS. CONCLUSION Biomarker status was the strongest predictor of OR, PFS, and OS in patients with advanced NSCLC treated with immune checkpoint inhibitors and targeted therapies. However, single biomarkers have limited predictive value, especially for programmed death-ligand 1 immunotherapy. To advance beyond the results achieved in this study, more comprehensive data on composite multiomic signatures is required.

Oncologist decision drivers in stage III non-small cell lung cancer: Outcomes of a web-based survey.

2019 ◽  
Vol 37 (27_suppl) ◽  
pp. 35-35
Author(s):  
Adam Yagui-Beltran ◽  
Kellie Ryan ◽  
Marnie L. Boron ◽  
Ion Cotarla ◽  
Daryl S. Spinner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Decision ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Web Based ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Nsclc Patients ◽  
To Receive

35 Background: Clinical guidelines seek to optimize patient care. We investigated how oncologists manage stage III non-small cell lung cancer (NSCLC) patients from diagnosis through treatment decision-making and drivers impacting guideline adherence. Methods: A sample of US medical oncologists (n=150) participated in a 38-question, 25-min web-based quantitative survey in January 2019. Participation required at least 3 yrs in practice and 3 stage III NSCLC patients treated in the prior 6-mo period. Results: Surveyed oncologists (82% community; 18% academic), on average, had 15 yrs of clinical experience and treated 20 stage III NSCLC patients in the prior 6 mos. Time from first treatment decision to initiation averaged >2–4 wks in 31% and >4 wks in 20% of patients, respectively. Oncologists recommend definitive concurrent chemoradiation therapy (cCRT) in 48% of unresectable stage III NSCLC patients. Reasons for not recommending cCRT include patient unlikely to tolerate cCRT (64% of oncologists), presence of a targetable mutation (41%), patient inability to travel consistently to receive treatment/inconvenient dosing (41%), and patient cost/affordability (34%). Eighteen percent of unresectable stage III NSCLC patients decline recommended cCRT. Fifty-five percent of patients who receive cCRT go on to receive consolidation immunotherapy (IO). Insurance challenges led to oncologists not recommending consolidation IO in 19% of patients. In the 85% of oncologists who conduct EGFR or PD-L1 testing, positive EGFR or negative PD-L1 tests are reasons for not recommending consolidation IO in 27% of patients (12% and 15%, respectively). Over half (55%) of unresectable stage III NSCLC patients who receive definitive cCRT also receive consolidation chemotherapy, which is no longer recommended in guidelines. Patients receiving consolidation CT were less likely to receive consolidation IO than the overall cohort of patients receiving cCRT (42% vs. 55%). Conclusions: Oncologists reported important variances in guidelines and standards of care related to the stage III NSCLC patient treatment journey. While some deviations from both are expected, there may be areas of focus for quality improvement initiatives.

A national analysis of untreated stage III non-small cell lung cancer in black and white patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20561-e20561
Author(s):  
Elizabeth Blessing Elimimian ◽  
Rafael Arteta-Bulos ◽  
Hong Liang ◽  
Nadeem Bilani ◽  
Leah Elson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Black And White ◽  
Black Patients ◽  
Stage Iii Nsclc ◽  
Nsclc Patients ◽  
White Patients

e20561 Background: Stage III non-small cell lung cancer (NSCLC) is treatable and potentially curable with surgical resection and/or chemoradiotherapy (CRT). Factors such as medical comorbidities and access to care may impact treatment decisions, including the decision to give no treatment. Using the National Cancer Database (NCDB), we analyzed the clinical presentation and proportion of Black and White Stage III NSCLC patients who received no form of treatment and compared their overall survival to patients who received other forms of management. Methods: Black and White stage III NSCLC’s diagnosed between 2004 and 2015 in the NCDB were included. Cases with multiple tumors and who received surgery were excluded. Patients who received no form of treatment (No-RT-nor-CT) were compared to patients treated with (CRT), RT only (RT), and CT only (CT). Univariate, multivariate, and Kaplan-Meier models were performed. Results: A total of n=22,459 Black and n=138,477 White stage III NSCLC patients were analyzed. Concurrent CRT given within 0-30 days was the most common management for Black (42.3%) and White patients (43.9%). No-RT-nor-CT was the second largest management group among Black (21.2%) and White patients (21.5%). A higher proportion of Black patients (14.2%) had a contraindication to CT than White patients (12.9%), p=0.0016; the same was true for those not managed with RT (6.1% vs. 5.3%, p=0.0051). Among patients managed without CT, the most common reason for not receiving CT among Black (63.31%) and White patients (63.0%) was that CT was not part of the planned 1st treatment course. Among patients managed without RT, the most common reason for not receiving RT among Black (77.0%) and White patients (78.2%) was that RT was not part of the planned 1st treatment course. A higher proportion of White patients versus Black patients did not receive CT (17.4% vs 14.0%, p<0.0001) nor RT (8.8% vs 7.7%, p=0.0013) because it was refused by the patient or guardian. The 2- and 5-year overall survival (OS) rates were lowest among the No-RT-nor-CT cohort of Black (13.9%, 5.4%, respectively) and White (12.1%, 4.6%, respectively) patients versus all other treatments. Median OS with No-RT-nor-CT was 4 months for Black patients and 3 months for White patients (p<0.0001). Conclusions: Concurrent CRT with or without surgery is an established standard of care for stage III NSCLC, but a significant proportion of White and Black patients are not receiving potentially curative therapy. A higher proportion of Black patients had contraindications to CT and RT than a similar cohort of White patients, which may reflect a higher rate of medical comorbidities. A higher proportion of White patients or their guardians refused CT and RT than a similar cohort of Black patients. Assessing and addressing the challenges that affect access to care and the type of care delivered remains an essential component of health care in America and influences survival outcomes.

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 Outcomes of Image-Guided Moderately Hypofractionated Radiotherapy for Stage III Non-Small-Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yang Zhang ◽  
Zongjuan Li ◽  
Yixing Chen ◽  
Han Xiao ◽  
Yongkang Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Hypofractionated Radiotherapy ◽  
Small Cell Lung ◽  
Image Guided ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

Objective. To evaluate the efficacy and toxicity of hypofractionated radiotherapy (hypo-RT) for stage III non-small-cell lung cancer (NSCLC) in the Chinese population. Methods. Eighty-six stage III NSCLC patients who received hypo-RT (60 Gy/20 fractions, BED = 78.00 Gy: 73 patients; 62.5 Gy/25 fractions, BED = 78.13 Gy: 13 patients) were recruited. Fifty-seven patients who received conventional radiotherapy (60 Gy/30 fractions, BED = 72.00 Gy) during the same period were enrolled as the control group. All hypo-RT treatments were conducted using image-guided technology. The efficacy and toxicity of the treatment were compared between the two groups. Results. The median duration of follow-up was 23.0 months (range: 4.0–82.0 months). Univariate and multivariate analyses of all 143 stage III NSCLC patients revealed that hypo-RT was an independent factor for progression-free survival (PFS) and overall survival (OS). The median PFS and OS of hypo-RT were significantly higher than in the conventional RT group (PFS: 14.30, 11.00 months, p = 0.035 ; OS: 43.30, 31.50 months, p = 0.045 ). The incidence rates of symptomatic radiation pneumonitis and radiation esophagitis (≥grade 2) were 17.77% and 27.91%, respectively, in the hypo-RT group. Compared to the conventional radiation therapy group (22.81% and 19.30%, respectively), no significant differences were found between the two common side effects ( p = 0.662 and p = 0.241 , respectively). Conclusion. For Chinese stage III NSCLC patients, image-guided hypo-RT offers favorable prognosis, and the treatment toxicity was totally acceptable. This radiation modality deserves further prospective clinical trials.

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 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.

Preoperative Concurrent Chemoradiotherapy of S-1/Cisplatin for Stage III Non-Small Cell Lung Cancer

2013 ◽  
Vol 96 (5) ◽  
pp. 1783-1789 ◽  
Author(s):  
Masafumi Yamaguchi ◽  
Gouji Toyokawa ◽  
Taro Ohba ◽  
Tomonari Sasaki ◽  
Takuro Kometani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung
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