Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I–II₁, diffuse large B‐cell lymphoma of the stomach

Abstract

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by radiotherapy is regarded as standard care for localized aggressive lymphoma; however, prospective confirmation of its applicability to localized primary gastric lymphoma is inadequate, and most patients in Japan have been initially treated with gastrectomy. We conducted a multicenter phase II study to evaluate the feasibility and efficacy of the non-surgical treatment. P rimary gastric lymphoma (PGL) is the most common among extranodal non-Hodgkin's lymphomas. PGL includes various histologic subtypes and management decisions are made depending on these subtypes. Eradication of Helicobacter pylori can achieve a 60-90% complete response for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma,(1) and this stomach-preserving treatment has been rapidly accepted. In contrast, the optimal treatment of localized gastric diffuse large B-cell lymphoma (DLBCL) still remains controversial. Surgery, alone or followed by chemotherapy with or without radiotherapy (RT), has been used as a primary therapy (2)(3)(4)(5) and has been supported by many physicians. Stomach-preserving treatment with chemotherapy with or without RT has also been reported with encouraging results, but no definitive conclusion could be drawn because most series were retrospective with small numbers of patients, heterogeneous histologic subtypes and various combinations of treatment. (6 -10) CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) has been used as a standard chemotherapy for DLBCL and three cycles of CHOP followed by RT has also been accepted for localized DLBCL.(11) However, prospective clinical trials to confirm its applicability to primary gastric DLBCL have rarely been conducted. To evaluate the feasibility and efficacy of nonsurgical treatment, we conducted a multicenter phase II study. Materials and methodsEligibility criteria and pretreatment evaluation. Eligibility criteria were as follows: pathologically proven primary gastric DLBCL; stage I-II 1 (Lugano staging system for gastrointestinal (GI) lymphomas (12) ); age 20 -75; performance status (based on Eastern Cooperative Oncology Group scale) 0 -1; no prior therapy; and adequate organ function. All patients gave written informed consent in accordance with our institutional review boards.Pretreatment evaluation included history and physical examination, complete blood count, serum chemistries, gastroscopy with biopsy, barium enema or colonoscopy, endoscopic ultrasound of the stomach, computed tomography (CT) scan of the chest and the abdomen, bone marrow aspiration, electrocardiogram and cardiac ultrasonography. Gallium scintigram and barium swallow were optional.Treatment details. The treatment consisted of three cycles of CHOP (day 1: cyclophosphamide, 750 mg/m 2 ; day 1: doxorubicin, 50 mg/m 2 , day 1: vincristine, 1.4 mg/m 2 (capped at 2 mg); and days 1-5: oral prednisone, 100 mg) every 3 weeks. RT delivered with megavoltage equipment began 3 -4 weeks after the third cycle ...

Rapid progression of Epstein-Barr-virus-positive gastric diffuse large B-cell lymphoma during chemoradiotherapy: a case report

“…In Japan, a multicenter phase II study involving 52 patients with primary gastric DLBCL was conducted to evaluate the feasibility and efficacy of nonsurgical treatment (three cycles of CHOP followed by radiotherapy to 40.5 Gy). A complete response was achieved in 92% (48/52) of patients, and 2-year progression-free survival and overall survival were 88% and 94%, respectively [2]. These findings suggested that stomachpreserving treatment should be considered a reasonable therapeutic option [5][6][7].…”

“…A complete response is seen in most patients with localized DLBCL, if treated with combination chemotherapy plus radiotherapy [2,3]. However, some cases are resistant to this therapeutic strategy.…”

Primary gastrointestinal non-Hodgkin’s lymphoma: clinicopathological and prognostic analysis

“…Two-year progression-free and overall survivals were 88% and 94%, respectively. This organ-preserving treatment should be considered as a very reasonable therapeutic option [17,18]. Lee et al [19] considered that the resection of localized intestinal DLBCL may be appropriate as the primary treatment.…”

Retrospective analysis of primary gastric diffuse largeB-cell lymphoma: a single center study from Turkey

“…Although radiotherapy in combination with R-CHOP was recommended in some studies, its effectiveness could not be proven in other studies (14,15,(22)(23)(24). Some series suggested that conservative nonsurgical treatment achieves equal or better results than surgery (5,7,8,25).…”