title: Epstein-Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B-cell lymphoma.
abstract: Primary gastric diffuse large B-cell lymphomas are generally well controlled by non-surgical treatment with combination chemotherapy followed by radiotherapy. We have previously reported that over 90% of patients achieved complete response (CR) with this therapeutic strategy: three cycles of cyclophosphamide, adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy). Although the CR rate was very high, some patients still showed resistance to this combination therapy. In order to clarify the factors related to therapy resistance, we examined the relationship between Epstein-Barr virus (EBV), which was examined using an in situ hybridization technique, and the patients' clinical courses. Out of the 50 patients, four were EBV positive; over half of lymphoma cells were positive for EBV by in situ hybridization. Of the three EBV-positive patients, two showed progressive disease and one achieved partial response (PR). Two of the patients died of disease progression. The other patient achieved CR, but the lymphoma recurred with distant metastasis in the cerebellum 3 months after remission. In the present study, eight patients did not achieve CR or they relapsed, four patients showed progressive disease, one patient achieved PR, and three patients achieved CR with recurrence. Therefore, half of these unfavorable patients were EBV positive. This finding strongly indicated that EBV-associated gastric diffuse large B-cell lymphomas frequently show resistance to standard chemoradiotherapy, although some other adverse factors remain unclear.
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 2-5-1, Shikata-cho, Okayama 700-8558, Japan. yoshino@md.okayama-u.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Takio
authors.initials: T
authors.lastname: Yokoi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitadai
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Oda
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Mera
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishikura
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000556:secondary / Q000628:therapy / Q000821:virology; D003520:Cyclophosphamide / Q000627:therapeutic use; D018450:Disease Progression; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000821:virology; D009367:Neoplasm Staging; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D011836:Radiation Tolerance; D012074:Remission Induction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D012367:RNA, Viral; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone