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Definitive radiochemotherapy versus surgery within multimodality treatment in stage III non-small cell lung cancer (NSCLC) - a cumulative meta-analysis of the randomized evidence.

ABSTRACT: Randomized trials were analyzed comparing surgery with definitive radiotherapy as local curative treatment options within the framework of different multimodality treatments for patients with locally advanced non-small cell lung cancer (NSCLC). Endpoints for comparison of treatment results were overall survival, progression-free survival, and toxicity.Hazard ratios (HR) were taken to measure treatment effects and pooled using a random effects model.Overall survival was not significantly different between surgical and definitive radiotherapy arms (HR=0.92 [95%CI 0.82-1.04], p=0.19, χ2-test). There was heterogeneity with respect to survival at 2 years (p<0.0001, Cochran Mantel Haenszel (CMH)-test). Latter trials using concurrent radiochemotherapy (ccRT/CT) showed better survival at 2 years (risk ratio of death=0.80 [95%CI 0.73-0.88], p<0.0001, CMH-test). In the ccRT/CT trials, survival in the surgical arms tended to have an excess early mortality before 6 months of follow-up and a lesser hazard rate in comparison to definitive ccRT/CT thereafter (HR=0.78 [95%CI 0.63-0.98]). Over all trials, treatment associated mortality was higher in the surgical arms (risk ratio=3.56 [95% CI: 1.65-7.72], p=0.0005, CMH test). With respect to progression-free survival, no significant differences were found (HR=0.91 [95%CI: 0.73 - 1.13]), although the largest conducted trial found an advantage for the surgical arm (HR=0.77 [95%CI: 0.62-0.96]).Induction therapy followed by resection or definitive radiochemotherapy represent valuable curative treatment options for patients with stage III NSCLC, the individual treatment choice deserves careful interdisciplinary evaluation and counseling. Based on the broad heterogeneity of patient groups in these stages further research on predictive factors supporting individual therapy selection is necessary.

SUBMITTER: Pottgen C

PROVIDER: S-EPMC5522187 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description:BackgroundTo investigate the potential impact of fractionation regimes and overall treatment time (OTT) on lymphopenia during definitive radiotherapy (RT) and its associations with patient outcomes in non-small cell lung cancer (NSCLC).MethodsSubjects consisted of 115 patients who had received definitive chemoradiation therapy (CRT) with different doses and fractions for unresectable stage III NSCLC. Clinical and laboratory records were reviewed to assess the changes in total lymphocyte counts (TLCs) during definitive RT. The associations of the TLCs with the clinical and treatment features, and outcomes were analyzed.ResultsThe median reduction of TLCs in the entire cohort was 1300 cells/μL (interquartile range [IQR], 950-1510 cells/μL). Of all patients, 63 (54.8%) experienced severe lymphopenia (SL) (TLC nadir < 500 cells/μL), which occurred at a median of the 5th week following RT initiation, not at the completion of RT or upon treatment with maximal doses. SL risk was increased over the first 5 weeks (odds ratio [OR] = 3.455, P = 0.007), after which, no increased risk was observed (OR = 0.562, P = 0.216). The median TLCs remained low and failed to recover to the initial normal values of their pre-RT level after 2 months of RT completion. Patients without SL exhibited significantly improved progression-free survival (hazard ratio [HR] = 0.544, P = 0.010) and overall survival (HR = 0.463, P = 0.011) after controlling for confounding variables in multivariate analyses. The incidence of SL was significantly lower (71.1% reduction in risk (OR = 0.289, P = 0.007)) in patients who received hypofractionated RT with an OTT within 4 weeks, compared to those who had an OTT of more than 4 weeks (32.1% vs 62.1%, P = 0.006). Multivariate analyses revealed that OTT within 4 weeks (OR = 0.322, P = 0.032) was significantly associated with a decreased risk of developing SL after controlling for confounding factors.ConclusionsHypofractionated RT was significantly associated with a decreased risk of SL and improved survival during definitive radiotherapy for unresectable stage III NSCLC.

Project description:BackgroundRetrospective studies have shown that adjuvant treatment improves survival of patients with stage IIB-III esophageal squamous cell carcinoma, but there is no evidence from prospective trials so far.Materials and methodsPatients with pathological stage IIB-III esophageal squamous cell carcinoma were randomly assigned to receive surgery alone (SA), postoperative radiotherapy (PORT), or postoperative concurrent chemoradiotherapy (POCRT). PORT patients received 54 Gy in 27 fractions; the POCRT group received 50.4 Gy in 28 fractions, plus concurrent chemotherapy with paclitaxel (135-150 mg/m2 ) and cisplatin or nedaplatin (50-75 mg/m2 ) every 28 days. The primary endpoint was disease-free survival (DFS), and the secondary endpoint was overall survival (OS).ResultsA total of 172 patients were enrolled (SA, n = 54; PORT, n = 54; POCRT, n = 64). The 3-year DFS was significantly better in PORT/POCRT patients than in SA patients (53.8% vs. 36.7%; p = .020); the 3-year OS was also better in PORT/POCRT patients (63.9% vs. 48.0%; p = .025). The 3-year DFS for SA, PORT, and POCRT patients were 36.7%, 50.0%, 57.3%, respectively (p = .048). The 3-year OS for SA, PORT, and POCRT patients were 48.0%, 60.8%, 66.5%, respectively (p = .048).ConclusionPORT/POCRT (especially POCRT) may significantly improve DFS and OS in stage IIB-III esophageal squamous cell carcinoma.Implications for practiceThe results of this phase III study indicated that postoperative radiotherapy/postoperative concurrent chemoradiotherapy (PORT/POCRT) could significantly improve disease-free survival and overall survival in stage IIB-III esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. In-field and out-of-field recurrences were comparable between the POCRT and PORT groups, which demonstrates the rationality and safety of the radiation field used in this study. The postoperative regimens in this trial might be accepted as standard treatment options for pathological stage IIB-III esophageal cancer. Larger sample size prospective randomized trials to identify the value are warranted.

Project description:BackgroundWith remarkable success and few side effects, induction chemoimmunotherapy has been used to improve the prognosis of patients with resectable or potentially resectable non-small cell lung cancer (NSCLC), even in stage III disease. However, for patients who are medically inoperable, unresectable or refuse surgery after induction chemoimmunotherapy, it is unclear whether patients should be treated with concurrent chemoradiotherapy (cCRT) or radiotherapy (RT) alone considering patient safety and tolerability. This study aimed to determine whether cCRT is safe and superior to RT alone after chemoimmunotherapy for stage III NSCLC.MethodsPatients diagnosed with stage III NSCLC who received chemoimmunotherapy followed by cCRT/RT alone without surgery at Tianjin Cancer Hospital between November 2018 to December 2021 were retrospectively collected. Patients were divided into two groups: induction chemoimmunotherapy followed by cCRT (cCRT cohort) or RT alone (RT alone cohort). Kaplan-Meier method was used to estimate survival. Univariate and multivariate Cox regression models were adopted to estimate risk factors for PFS.ResultsSixty-five patients were included, with 44 (67.7%) received RT alone and 21 (32.3%) received cCRT. Patients in the cCRT group had significantly prolonged PFS (HR = 0.155, p = 0.004), LPFS (HR = 0.225, p = 0.029) and DMFS (HR = 0.028, p = 0.006) than those in the RT alone group. Albeit nonsignificant, a trend toward improved OS (HR = 0.030, p = 0.069) was also observed in the cCRT group. The multivariate analysis further confirmed that cCRT (HR = 0.141, p = 0.008) was the independent factor for promoting a favorable PFS. Treatment-related adverse events were similar between groups (p > 0.05). Patients with consolidation immunotherapy exhibited a trend of improved PFS (HR = 0.398, p = 0.274) and numerically better OS (HR = 0.018, p = 0.209) compared with those without.ConclusionsFor patients with unresectable stage III NSCLC, cCRT following chemoimmunotherapy appears to be safe and may prolong survival compared with radiotherapy alone. Further investigations on the combination of chemoimmunotherapy and CRT are warranted.

Project description:BACKGROUND:Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0-28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer. METHOD:This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135-150 mg/m2) plus cisplatin or nedaplatin (50-75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT. DISCUSSION:This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma. TRIAL REGISTRATION:clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.

Project description:BackgroundBoth dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.MethodsThis multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity.FindingsWe included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs.InterpretationIn patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed.FundingDr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

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Definitive radiochemotherapy versus surgery within multimodality treatment in stage III non-small cell lung cancer (NSCLC) - a cumulative meta-analysis of the randomized evidence.

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