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4500 Background: Trastuzumab is a monoclonal antibody against human epidermal growth factor receptor 2 (HER2). The primary objective of RTOG 1010 was to determine if trastuzumab increases disease-free survival (DFS) when combined with trimodality treatment for patients with HER2 overexpressing esophageal adenocarcinoma. Methods: This open label, randomized phase III trial included patients with newly diagnosed stage T1N1-2, T2-3N0-2 adenocarcinoma of the esophagus involving the mid, distal, or esophagogastric junction and up to 5cm of the stomach. All patients received chemotherapy (C) of paclitaxel, 50mg/m2 and carboplatin AUC = 2, weekly for 6 weeks, with radiation (XRT: 3D-CRT or IMRT, 50.4 Gy in 28 fractions) followed by surgery. Patients were randomized 1:1 to receive weekly trastuzumab 4mg/kg week 1 then 2mg/kg/weekly x 5 during CXRT then 6 mg/kg for 1 dose prior to surgery and 6mg/kg every 3 weeks for 13 treatments after surgery. HER2 status was determined by IHC and gene amplification by FISH. With a 2-sided alpha of 0.05, 162 DFS events provide 90% power to detect a signal for an increase in median DFS from 15 to 25 months. DFS and overall survival (OS) were estimated by the Kaplan-Meier method. and arms were compared using the log rank test. The Cox proportional hazards model was used to analyze treatment effect. Results: 571 patients were entered for assessment of HER2 expression, 203 HER2+ patients randomized. The median follow-up for alive patients is 5.0 years. The estimated 2, 3, and 4-year DFS (95% CI) for the CXRT +trastuzumab arm were 41.8% (31.8%, 51.7%), 34.3% (24.7%, 43.9%), and 33.1% (23.6%, 42.7%), respectively, and for the CXRT arm were 40.0% (30.0%, 49.9%), 33.4% (23.8%, 43.0%), and 30.1% (20.7%, 39.4%), respectively; log-rank p = 0.85. The median DFS time is 19.6 months (13.5-26.2) for the CXRT +trastuzumab arm compared to 14.2 months (10.5-23.0) for the CXRT arm. The hazard ratio (95% CI) comparing the DFS of CXRT+trastuzumab arm to the CXRT arm was 0.97 (0.69, 1.36). The median OS time was 38.5 months (26.2-70.4) for the CXRT+trastuzumab arm compared to 38.9 months (29.0-64.5) for the CXRT arm, hazard ratio (95% CI): 1.01 (0.69, 1.47). There was no statistically significant increase in treatment-related toxicities with the addition of trastuzumab including no increase in cardiac events. Conclusions: The addition of trastuzumab to trimodality treatment did not improve DFS for patients with HER2 overexpressing esophageal adenocarcinoma. Supported by NCI grants U10CA180868, UG1CA189867, U10CA180822 and Genentech. Clinical trial information: NCT01196390 .

Hepatocellular Carcinoma (HCC) is one of the most common cancers and a leading cause of cancer related death worldwide. Until recently, systemic therapy for advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B or C, was limited and ineffective in terms of long-term survival. However, over the past decade, immune check point inhibitors (ICI) combinations have emerged as a potential therapeutic option for patients with nonresectable disease. ICI modulate the tumor microenvironment to prevent progression of the tumor. Radiotherapy is a crucial tool in treating unresectable HCC and may enhance the efficacy of ICI by manipulating the tumor microenvironment and decreasing tumor resistance to certain therapies. We herein review developments in the field of ICI combined with radiotherapy for the treatment of HCC, as well as look at challenges associated with these treatment modalities, and review future directions of combination therapy.

The prognostic nutrition index (PNI) has been shown to have prognostic value in several common cancers. We explore its clinical application value in the prognosis of patients with esophageal squamous cell carcinoma (ESCC) undergoing radical chemoradiotherapy (CRT) or radiotherapy (RT). Materials/Methods: Overall, 193 patients with ESCC who received radiotherapy with or without chemotherapy at Sichuan Cancer Hospital from March 20, 2012 to December 25, 2017 were retrospectively analyzed. Based on serum measurements before treatment, PNI at ESCC recurrence was calculated as albumin (g/L) + 5 Â total lymphocyte count. Kaplan-Meier method and Cox proportional regression model were used to analyze the relationship between PNI and overall survival. Results: The PNI of 193 ESCC patients was 49.01 AE 4.68. The optimal cutoff value of PNI was calculated to be 47.975, and the patients were divided into a low PNI group (<47.975) and a high PNI group (!47.975). PNI is related to tumor length, T-stage, and Synchronous chemotherapy in ESCC patients (P <0.05). The median OS for the entire group was 22.37 months. The median OS of patients in the high PNI group (PNI ! 47.975) and low PNI group (PNI <47.975) were 32.63 months and 15.4 months, respectively, and the 3-year survival rates were 47.5% and 32.2%, and 5year survival rates were 37.7% and 16.8%, respectively, and the differences were statistically significant (P Z 0.001). Univariate analysis showed that PNI, tumor length, T stage and Synchronous chemotherapy were related to the prognosis of ESCC patients (P <0.05). Multivariate analysis showed that tumor length (P Z 0.019), synchronous chemotherapy (P Z 0.009), and PNI (P Z 0.003) were independent prognostic factors affecting the prognosis of patients in ESCC treated with RT or CRT. Conclusion: The calculation of PNI value is simple, reliable and repeatable, which can improve the accuracy of patients' prognosis. And it needs to be further confirmed by the prospective study of large sample size.