title: Unexpectedly frequent hepatitis B reactivation by chemoradiation in postgastrectomy patients.
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 (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 > or = 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.
authors.affiliation: Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan. jasoncheng@ha.mc.ntu.edu.tw
authors.forename: Jason Chia-Hsien
authors.initials: JC
authors.lastname: Cheng
authors.forename: Mei-Ching
authors.initials: MC
authors.lastname: Liu
authors.forename: Stella Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: Wei-Tse
authors.initials: WT
authors.lastname: Fang
authors.forename: James
authors.initials: J
authors.lastname: Jer-Min Jian
authors.forename: Juei-Low
authors.initials: JL
authors.lastname: Sung
mesh_terms: D003131:Combined Modality Therapy; D005260:Female; D005743:Gastrectomy / Q000009:adverse effects*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008107:Liver Diseases / Q000209:etiology*; D008297:Male; D013274:Stomach Neoplasms / Q000150:complications / Q000628:therapy*; D014775:Virus Activation