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Incidence and dose-volume relationship of radiation pneumonitis after concurrent chemoradiotherapy followed by durvalumab for locally advanced non-small cell lung cancer.

ABSTRACT: Background and purpose:We investigated the incidence and dose-volume relationships of radiation pneumonitis (RP) after concurrent chemoradiotherapy (CCRT) followed by durvalumab for locally advanced non-small-cell lung cancer (LA-NSCLC). Materials and methods:We retrospectively analyzed records of 36 patients with LA-NSCLC who underwent CCRT followed by durvalumab. Incidence of RP was analyzed for correlations with clinical factors and dose-volume parameters of lung in radiotherapy. Results:All patients received 60 Gy in 30 fractions of radiotherapy with concurrent chemotherapy. Over a median follow-up period of 7 months, incidence of grade ?2 RP was 36% (including grade 3 RP: 5% and grade 5 RP: 3%). Age, sex, Brinkman index, and blood test results did not significantly differ between patients with grade ?2 RP and grade ?1 RP. Dose-volume parameters (lung volumes that received 5 Gy, 10 Gy, 20 Gy, 30 Gy, 40 Gy, 50 Gy, and mean lung dose) were significantly higher among patients with grade ?2 RP compared with patients with grade ?1 RP. Conclusion:Incidence of grade ?2 RP was 36% after CCRT followed by durvalumab for LA-NSCLC, but did not significantly differ from those of patients treated with CCRT alone. Lung dose-volume parameters were significantly correlated with RP.

SUBMITTER: Saito S

PROVIDER: S-EPMC7283100 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Incidence and dose-volume relationship of radiation pneumonitis after concurrent chemoradiotherapy followed by durvalumab for locally advanced non-small cell lung cancer.

Saito Satoshi S Abe Takanori T Kobayashi Nao N Aoshika Tomomi T Ryuno Yasuhiro Y Igari Mitsunobu M Hirai Ryuta R Kumazaki Yu Y Miura Yu Y Kaira Kyoichi K Kagamu Hiroshi H Noda Shin-Ei SE Kato Shingo S

Clinical and translational radiation oncology 20200530

<h4>Background and purpose</h4>We investigated the incidence and dose-volume relationships of radiation pneumonitis (RP) after concurrent chemoradiotherapy (CCRT) followed by durvalumab for locally advanced non-small-cell lung cancer (LA-NSCLC).<h4>Materials and methods</h4>We retrospectively analyzed records of 36 patients with LA-NSCLC who underwent CCRT followed by durvalumab. Incidence of RP was analyzed for correlations with clinical factors and dose-volume parameters of lung in radiotherap ...[more]

PMID: 32529055

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Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Project description:BackgroundPatients with bladder cancer (BC) who are cisplatin ineligible or have unresectable disease have limited treatment options. Previously, we showed targeting programmed death-ligand 1 (PD-L1) with durvalumab (durva) and radiation therapy (RT) combination was safe in BC. We now report results from a phase II study evaluating the toxicity and efficacy of durva and RT in localized BC.MethodsThis is a single-arm, multi-institutional phase II study; N=26. Enrolled patients had pure or mixed urothelial BC (T2-4 N0-2 M0) with unresectable tumors and were unfit for surgery or cisplatin ineligible. Patients received durva concurrently with RT ×7 weeks, followed by adjuvant durva × 1 year.Primary endpoints(A) progression-free survival (PFS) at 1 year and (B) disease control rate (DCR) post adjuvant durva. Key secondary endpoints: (A) complete response (CR) post durvaRT (8 weeks), (B) overall survival (OS), (C) PFS and (D) toxicity. Correlative studies included evaluation of baseline tumor and blood (baseline, post durvaRT) for biomarkers.ResultsMedian follow-up was 27 months. Evaluable patients: 24/26 post durvaRT, 22/26 for DCR post adjuvant durva, all patients for PFS and OS. Post adjuvant durva, DCR was seen in 72.7%, CR of 54.5%. 1-year PFS was 71.5%, median PFS was 21.8 months. 1-year OS was 83.8%, median OS was 30.8 months. CR at 8 weeks post durvaRT was 62.5%. Node positive (N+) patients had similar median PFS and OS. DurvaRT was well tolerated. Grade ≥3 treatment-related adverse events: anemia, high lipase/amylase, immune-nephritis, transaminitis, dyspnea (grade 4-COPD/immune), fatigue, rash, diarrhea and scleritis. No difference in outcome was observed with PD-L1 status of baseline tumor. Patients with CR/PR or SD had an increase in naïve CD4 T cells, a decrease in PD-1+CD4 T cells at baseline and an increase in cytokine-producing CD8 T cells, including interferon gamma (IFNγ) producing cells, in the peripheral blood.ConclusionDurva with RT followed by adjuvant durva was safe with promising efficacy in localized BC patients with comorbidities, including N+ patients. Larger randomized studies, like S1806 and EA8185, are needed to evaluate the efficacy of combining immunotherapy and RT in BC.Trial registration numberNCT02891161.

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Incidence and dose-volume relationship of radiation pneumonitis after concurrent chemoradiotherapy followed by durvalumab for locally advanced non-small cell lung cancer.

Publications

Incidence and dose-volume relationship of radiation pneumonitis after concurrent chemoradiotherapy followed by durvalumab for locally advanced non-small cell lung cancer.

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