Gastric adenocarcinoma treated with radiation with or without epirubicin-based chemotherapy: Evaluation of radiation-induced liver disease.

Abstract

110 Background: Anthracycline chemotherapy has been associated with radiation-induced liver disease (RILD). We sought to compare the incidence of liver toxicity among patients with gastric adenocarcinoma treated with radiotherapy (RT) with or without epirubicin-based chemotherapy. Methods: We performed a retrospective analysis of 94 patients with gastric adenocarcinoma treated at Massachusetts General Hospital since November 2005 and the Dana-Farber Cancer Institute since August 1998. All patients underwent definitive surgery and RT (median dose 45 Gray) with a minimum follow up of 6 months. Primary endpoints were development of ascites, radiographic liver change and elevations in liver function tests (LFTs), including alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT). Results: In total, 34 patients received epirubicin-based chemotherapy including 9 perioperatively (6 with oxaliplatin and capecitabine [EOX]; 2 with cisplatin and 5-flourouracil [ECF]; 1 with oxaliplatin and 5-flourouracil [EOF]) and 25 postoperatively (2 EOX; 22 ECF; 1 combination). Seven patients were treated with neoadjuvant RT; 87 received adjuvant RT a median of 88 days after surgery (interquartile range 73-108 days). Twenty-one patients developed ascites within 6 months of completing RT, all but one of whom developed peritoneal carcinomatosis or metastatic disease. Among 57 patients that did not develop metastases, maximum elevations in LFTs were similar in patients that received epirubicin-based chemotherapy compared to those who did not (ALP/AST/ALT 150/44/50 vs. 142/41/44, p=0.25/0.36/0.14, respectively), as were rates of radiographic liver change (22% vs. 13%, p=0.44). Conclusions: Epirubicin-based chemotherapy does not significantly increase the risk of RILD in a recent cohort of patients treated with modern RT techniques and dose-constraints. In this setting, treatment of gastric adenocarcinoma with RT and either pre- or postoperative chemotherapy is well tolerated with low rates of liver toxicities. Development of liver toxicity, particularly ascites, within six months of RT may be a harbinger of metastatic disease. No significant financial relationships to disclose.