Unexpectedly frequent hepatitis B reactivation by chemoradiation in postgastrectomy patients

Authors

  • Jason Chia-Hsien Cheng M.D., M.S.,

    Corresponding author
    1. Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
    2. Cancer Research Center, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
    3. Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
    • Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan
    Search for more papers by this author
    • Fax: (011) 886 223711174

  • Mei-Ching Liu M.D.,

    1. Department of Medical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
    Search for more papers by this author
  • Stella Y. Tsai M.D.,

    1. Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
    Search for more papers by this author
  • Wei-Tse Fang M.D.,

    1. Department of Medical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
    Search for more papers by this author
  • James Jer-Min Jian M.D.,

    1. Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
    Search for more papers by this author
  • Juei-Low Sung M.D.

    1. Department of Internal Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
    Search for more papers by this author

  • Presented in part at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, New Orleans, Louisiana, October 6–9, 2002.

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 ≥ 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.

Ancillary