Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial.

BACKGROUND: Erlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial. METHODS: NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE). RESULTS: A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments. CONCLUSION: Concurrent erlotinib with WBRT didn't improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: NCT01887795.

Comparison between the effects of elective nodal irradiation and involved-field irradiation on long-term survival in thoracic esophageal squamous cell carcinoma patients: A prospective, multicenter, randomized, controlled study in China.

BACKGROUND: This study's initial results revealed significant decreases in treatment-related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved-field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long-term trial results, specifically; overall survival (OS), progression-free survival (PFS), metastasis-free survival (MFS), and locoregional progression-free survival (LRFS). MATERIALS AND METHODS: Stage II-III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8-2.0 Gy fractions to a total dose of 60.0-66.0 Gy to the gross tumor volume and 50.0-54.0 Gy to the clinical target volume. The primary endpoints were acute treatment-related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS. RESULTS: Between April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS. CONCLUSION: IFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC.

Clinical observation on the thoracic esophageal cancer patients treated with elective nodal irradiation and involved field irradiation / 天津医药

Objective To observe the curative effect,failure pattern and treatment-related toxicities of elective nodal irradiation (ENI) and involved field irradiation (IFI) in patients with thoracic esophageal squamous cell carcinoma treated with radical radiotherapy, and determine the reasonable target delineation of radiotherapy. Methods Using prospective randomized controlled design, a total of 86 patients with thoracic esophageal squamous cell carcinoma were randomly allocated to two groups:ENI group(n=39)and IFI group(n=47).Both groups received concurrent chemoradiotherapy.In ENI group,the high-risk lymphatic drainage area received prophylactic irradiation on the basis of IFI group.After the treatment, all patients were followed up for 3~33 months.The median follow-up period was 15 months.The short-term effective rate, one year survival rate, progression free survival rate and the local control rate of two groups were calculated. The survival curve was drawn by the Kaplan-Meier method,and the survival rate was compared using the Log-rank method.Meanwhile, the treatment failure pattern and incidence of adverse reactions were analyzed in the two groups. Results There was no significant difference in effective rate between ENI group and IFI group (92.3% vs. 95.7%,χ 2=0.460, P>0.05). The one-year survival rates were 66.7% and 68.1% for the two groups,respectively.The progression-free survival rates were 56.4% and 53.2% respectively.The local control rates were 92.3% and 87.5% respectively,with no statistical difference(P>0.05). The median survival time was 15 months at the end of the follow-up for group ENI and group IFI, and there was no significant difference in survival rate between two groups(Log-rank χ2=1.520,P=0.218).There were 35 cases with treatment failure in all 86 patients, of which 17 cases were in group ENI and 18 cases in group IFI. The regional failure rates were 35.9% and 27.7% in ENI and IFI groups respectively,distant metastasis rates were 20.5% and 14.9% respectively,in-field failure rates were 30.8% and 23.4% respectively, and out-of-field failure rates were 4.3% and 5.1% respectively, which showed no significant differences (P>0.05). There were no significant differences in side effects, the incidence of bone marrow suppression,gastrointestinal reactions,radiation esophagitis and radiation-induced lung injury between two groups (P>0.05). Conclusion ENI shows similar recent efficacy, failure patterns, adverse reactions and prognosis with IFI for thoracic esophageal squamous cell carcinoma patients receiving radical radiotherapy. So IFI treatment is recommended to minimize the exposure dosage of normal tissue.