Unexpectedly frequent hepatitis B reactivation by chemoradiation in postgastrectomy patients

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...

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Published in:Cancer 2004-11, Vol.101 (9), p.2126-2133
Main Authors: Cheng, Jason Chia‐Hsien, Liu, Mei‐Ching, Tsai, Stella Y., Fang, Wei‐Tse, Jer‐Min Jian, James, Sung, Juei‐Low
Format: Article
Language:English
Subjects:
adjuvant chemoradiotherapy
Biological and medical sciences
Combined Modality Therapy
Female
Gastrectomy - adverse effects
gastric carcinoma
hepatic toxicity
hepatitis B viral reactivation
Hepatitis B virus - physiology
Human viral diseases
Humans
Infectious diseases
Liver Diseases - etiology
Male
Medical sciences
Stomach Neoplasms - complications
Stomach Neoplasms - therapy
Tumors
Viral diseases
Viral hepatitis
Virus Activation
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Summary: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 (defined 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. Cancer 2004. © 2004 American Cancer Society. Hepatitis B virus (HBV) carriers had a higher incidence of chemoradiation‐induced liver disease (CRILD) after postgastrectomy adjuvant, concomitant chemoradiotherapy, probably related to HBV reactivation. Dosimetric parameters modulated the risk of CRILD in noncarriers, but not in carriers.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.20591