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Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

ABSTRACT: INTRODUCTION:Concurrent chemoradiotherapy (cCRT) was the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, however, patients also received single modality therapy. This study identified predictors of therapy and differences in overall survival (OS). METHODS:This retrospective study included stage III NSCLC patients aged ?65 years, with ?1 claim for systemic therapy (ST) or radiotherapy (RT) within 90 days of diagnosis, identified in SEER-Medicare data (2009-2014). Patients who had overlapping claims for chemotherapy and RT ?90 days from start of therapy were classified as having received cCRT. Patients who received sequential CRT or surgical resection of tumor were excluded. Predictors of cCRT were analyzed using logistic regression. OS was compared between therapies using adjusted Cox proportional hazards models. RESULTS:Of 3,799 patients identified, 21.7% received ST; 26.3% received RT; and 52.0% received cCRT. cCRT patients tended to be younger (p <0.001), White (p = 0.002), and have a good predicted performance status (p<0.001). Patients who saw all three specialist types (medical oncologist, radiation oncologist, and surgeon) had increased odds of receiving cCRT (p<0.001). ST and RT patients had higher mortality risk versus cCRT patients (hazard ratio [95% CI]: ST: 1.38 [1.26-1.51]; RT: 1.75 [1.61, 1.91]); p<0.001). CONCLUSIONS:Several factors contributed to treatment selection, including patient age and health status, and whether the patient received multidisciplinary care. Given the survival benefit of receiving cCRT over single-modality therapy, physicians should discuss treatment within a multidisciplinary team, and be encouraged to pursue cCRT for patients with unresectable stage III NSCLC.

SUBMITTER: Bobbili P

PROVIDER: S-EPMC7080248 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

Bobbili Priyanka P Ryan Kellie K DerSarkissian Maral M Dua Akanksha A Yee Christopher C Duh Mei Sheng MS Gomez Jorge E JE

PloS one 20200318 3

<h4>Introduction</h4>Concurrent chemoradiotherapy (cCRT) was the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, however, patients also received single modality therapy. This study identified predictors of therapy and differences in overall survival (OS).<h4>Methods</h4>This retrospective study included stage III NSCLC patients aged ≥65 years, with ≥1 claim for systemic therapy (ST) or radiotherapy (RT) within 90 days of di ...[more]

PMID: 32187231

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Project description:ObjectiveHigh activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T-cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes.Materials and methodsSystemic IDO1 activity was calculated by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. The dynamic change of IDO1 activity was followed in 24 patients by measuring the Kyn : Trp ratio before, during, and after RT administration.ResultsIn 24 patients with dynamic tracking of plasma IDO1 activity, there were no significant alterations observed among the three time points (Friedman test, p = 0.13). The changing pattern of the Kyn : Trp ratio was divided into four groups: decreased consistently during RT, first increased, then decreased, increased consistently, first decreased then increased. Patients whose Kyn : Trp ratio kept decreasing or first increased then decreased were defined as the good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p = 0.04; p = 0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than the bad-change group (p = 0.01, HR = 0.22). In 113 stage III NSCLC patients with pre-radiation Kyn : Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p = 0.079).ConclusionFavorable change in IDO1 activity during RT was associated with superior OS, PFS, and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients.

Project description:<p><strong>OBJECTIVES:</strong> High activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes.</p><p><strong>MATERIALS AND METHODS:</strong> Systemic IDO1 activity was calculated by Kyn:Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. Dynamic change of IDO1 activity was followed in 24 patients by measuring Kyn:Trp ratio before, during and after RT administration.</p><p><strong>RESULTS:</strong> In 24 patients with dynamic tracking of plasma IDO1 activity, there was no significant alterations observed among the 3 time points (Friedman test, p=0.13). The changing pattern of Kyn:Trp ratio was divided into 4 groups: decreased consistently during RT, first increased then decreased, increased consistently, first decreased then increased. Patients whose Kyn:Trp ratio kept decreasing or first increased then decreased were defined as good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p=0.04; p=0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than bad-change group (p=0.01, HR=0.22). In 113 stage III NSCLC patients with pre-radiation Kyn:Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p=0.079).</p><p><strong>CONCLUSION: </strong>Favorable change of IDO1 activity during RT was associated with superior OS, PFS and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients.</p>

Project description:BackgroundThe treatment of stage III non-small cell lung cancer (NSCLC) is very challenging because it is a heterogeneous group of diseases. This study was to investigative whether concurrent immunotherapy with chemoradiotherapy was associated with improved outcomes compared to consolidative immunotherapy following chemoradiotherapy in patients with unresectable stage III NSCLC, which may provide evidence-based medical evidence for the treatment of stage III NSCLC.MethodsA total of 78 epidermal growth factor receptor or anaplastic lymphoma kinase (EGFR/ALK) negative patients from the clinical database of the shanghai pulmonary hospital with locally advanced unresectable NSCLC and we evaluated them for baseline clinical factors, follow-up. Patients underwent concurrent immunotherapy with chemoradiotherapy or consolidative immunotherapy after chemoradiotherapy. Patients were classified based on initial site of progression (primary versus non-primary site). The study endpoints were progression-free survival (PFS) and time to death or distant metastasis (TDDM). Cox proportional hazards analysis was used to assess the factors affecting PFS and TDDM.ResultsThe median follow-up time for both groups was 26 months, and there was no significant difference in baseline clinical characteristics (P>0.05). The patients receiving concurrent immunotherapy (n=36) had a longer PFS than those receiving consolidative immunotherapy (n=42) (median 32.4 vs. 15.5 months; P<0.01). The TDDM was also longer in patients with concurrent immunotherapy than those with consolidative immunotherapy (median 57.3 vs. 31.0 months; P=0.01). Furthermore, in a subset of patients with initial site of progression at a non-primary-site, patients undergoing concurrent immunotherapy had longer PFS than those undergoing consolidative immunotherapy (median 22.7 vs. 11.9 months; P=0.03).ConclusionsConcurrent immunotherapy with chemoradiotherapy may be associated with improved disease progression outcomes as compared to consolidative immunotherapy following chemoradiotherapy.

Project description:BackgroundHistorically, the standard of care for patients with unresectable, Stage III non-small cell lung cancer had been concurrent chemoradiotherapy. However, outcomes had been poor, with approximately 15% to 32% of patients alive at 5 years. In the placebo-controlled Phase III A PACIFIC trial, consolidation treatment with durvalumab after concurrent chemoradiotherapy significantly improved overall survival (OS) and progression-free survival in patients with unresectable, Stage III non-small cell lung cancer, establishing this regimen as a new standard of care in this setting. In the PACIFIC trial, crossover between treatment arms (durvalumab or placebo) was not permitted. However, after discontinuation from study treatment, patients from both arms of PACIFIC could switch to subsequent anticancer therapy, including durvalumab and other immunotherapies, which is known to influence standard intention-to-treat analysis of OS, potentially underestimating the effect of an experimental drug. Moreover, the introduction of immunotherapies has demonstrated marked improvements in the postprogression, metastatic non-small cell lung cancer setting.ObjectiveTo examine the influence of subsequent immunotherapy on OS in the PACIFIC trial.MethodsBoth a Rank Preserving Structural Failure Time Model (RPSFTM) and modified 2-stage method were used. RPSFTM assumes that a patient's survival time with no immunotherapy (counterfactual survival time) is equal to the observed time influenced by immunotherapy, multiplied by an acceleration factor, plus the time not influenced. The modified 2-stage method estimates the effect of immunotherapy by comparing postsubsequent-treatment-initiation survival times between patients with and without subsequent immunotherapy. In both models, OS was adjusted to reflect a hypothetical scenario in which no patients received subsequent immunotherapy. RPSFTM was also used for scenarios in which subsequent immunotherapy was received by increasing proportions of placebo patients but none of the durvalumab patients.ResultsIn the intention-to-treat analysis (3-year follow-up), durvalumab improved OS versus placebo (stratified hazard ratio = 0.69; 95% CI, 0.55-0.86). Overall, 10% and 27% of durvalumab and placebo patients, respectively, received subsequent immunotherapy. With subsequent immunotherapy removed from both arms, estimated hazard ratio was 0.66 (95% CI, 0.53-0.84) with RPSFTM and 0.68 (95% CI, 0.54-0.85) with the modified 2-stage method. With subsequent immunotherapy removed from the durvalumab arm only (RPSFTM), estimated hazard ratio increased as the proportion of placebo patients receiving subsequent immunotherapy increased, up to 0.75 (95% CI, 0.60-0.94) maximum (assuming all placebo patients with subsequent treatment received immunotherapy).ConclusionsResults were consistent with the intention-to-treat analysis, supporting the conclusion that durvalumab after chemoradiotherapy provides substantial OS benefit in patients with Stage III, unresectable non-small cell lung cancer. ClinicalTrials.gov identifier: NCT02125461 (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Project description:BackgroundCurrently, the value of induction chemoimmunotherapy before chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer (NSCLC) has not been explored. This study was designed to explore the efficacy and safety of induction chemoimmunotherapy in patients with unresectable stage III NSCLC.MethodsUnresectable stage III NSCLC patients who received CRT with or without induction chemoimmunotherapy between August 2014 and December 2021 were retrospectively enrolled. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and estimated by the Kaplan-Meier method. The potential factors affecting PFS and OS were analyzed by univariate and multivariate Cox regression models. One-to-one propensity score matching (PSM) was used to further minimize confounding.ResultsA total of 279 consecutive patients were enrolled, with 53 (19.0%) receiving induction chemoimmunotherapy followed by CRT (I-CRT group), and the remaining 226 (81.0%) receiving CRT alone (CRT group). After PSM, the median PFS was 24.8 months in the I-CRT group vs. 13.3 months in the CRT group (P=0.035). The median OS was not reached (NR) vs. 36.6 months ((P=0.142). The incidence of treatment-related adverse events (TRAEs) was similar in both groups, except that the incidence of hematological toxicity was higher in the I-CRT group (77.1% vs. 58.3%, P=0.049). Compared to induction chemotherapy, induction chemoimmunotherapy demonstrated a superior objective response rate (60.4% vs. 22.2%, P<0.001) and further prolonged PFS (median NR vs. 13.2 months, P=0.009) and OS (median NR vs. 25.9 months, P=0.106) without increasing the incidence of TRAEs in patients receiving concurrent chemoradiotherapy.ConclusionInduction chemoimmunotherapy is safe and may improve outcomes of CRT in patients with unresectable stage III NSCLC. Moreover, induction chemoimmunotherapy may further improve treatment response and survival outcomes compared to induction chemotherapy before cCRT.

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Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

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Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

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