Unexpectedly frequent hepatitis B reactivation by chemoradiation in postgastrectomy patients
Journal
Cancer
Journal Volume
101
Journal Issue
9
Pages
2126-2133
Date Issued
2004
Author(s)
Abstract
BACKGROUND. Postgastrectomy patients undergoing chemoradiation risk chemoradiation-induced liver disease (CRILD). The objectives of this study were to investigate dosimetric implications and assess biologic susceptibility to CRILD in these patients. METHODS. Sixty-two patients with Stage IB-IV gastric/gastroesophageal adenocarcinoma without metastases underwent radical total/subtotal gastrectomy; regional lymph node dissection; and postoperative, adjuvant, concomitant chemoradiotherapy (CCRT). Among these, 8 patients developed CRILD (denned as Grade 3-4 liver toxicity), and 11 patients were chronic hepatitis B virus (HBV) carriers (HBV+). Chemotherapy consisted of 1 cycle of etoposide, leucovorin, and 5-fluorouracil (ELF); followed by 5 weekly high doses of 5-fluorouracil (2000-2600 mg/m2) and leucovorin concurrent with radiotherapy (median dose, 45 grays [Gy] to the tumor bed/regional lymphatics); followed by 3 cycles of ELF separated by a 21-day interval. Patients were followed for ? 4 months after CCRT. Patient-related and dosimetric factors were correlated with CRILD. RESULTS. HBV+ status was the only independent factor associated with CRILD. HBV+ patients had a higher CRILD incidence (6 of 11 patients vs. 2 of 51 patients; P < 0.001). HBV-negative patients with CRILD were recipients of a higher mean liver dose (MLD) (23.8 Gy vs. 15.2 Gy; P = 0.009) and a higher volume fraction of liver that received > 30 Gy (36.5% vs. 19.7%; P = 0.009) compared with noncarriers without CRILD, but no MLD difference was found between HBV+ patients with or without CRILD. Moreover, in four of six carriers with CRILD, HBV infection was reactivated during CRILD. Two of the toxicities were fatal. CONCLUSIONS. HBV carriers had a higher incidence of CRILD after postgastrectomy CCRT, probably related to HBV reactivation. Dosimetric parameters modulated the risk of CRILD in noncarriers, but not in carriers. These factors deserve attention in CRILD/HBV+ patients, and the underlying pathogenesis warrants investigation. ? 2004 American Cancer Society.
Subjects
Adjuvant chemoradiotherapy; Gastric carcinoma; Hepatic toxicity; Hepatitis B viral reactivation
SDGs
Other Subjects
etoposide; fluorouracil; folinic acid; adenocarcinoma; adult; aged; article; cancer adjuvant therapy; cancer chemotherapy; cancer radiotherapy; cancer staging; controlled study; dosimetry; female; follow up; gastrectomy; hepatitis B; Hepatitis B virus; human; liver toxicity; lymph node dissection; major clinical study; male; priority journal; radiation induced liver disease; radiation injury; stomach carcinoma; virus carrier; virus reactivation; Combined Modality Therapy; Female; Gastrectomy; Hepatitis B virus; Humans; Liver Diseases; Male; Stomach Neoplasms; Virus Activation
Type
journal article