Primary gastric non-Hodgkin's lymphoma comprises about 4-20% of all non-Hodgkin lymphomas [6, 11, 16]. PGL is also the most common extranodal NHL in the Hong Kong Chinese population, accounting for up to 80% of all extranodal NHL. This is higher than the numbers reported in western countries . Our analysis of 57 DLBCL patients among the PGL cases showed that the ratio of the GCB to non-GCB subtype was 1:1.85 and is similar to a previous study from Hong Kong. In the Hong Kong study, 32 patients with DLBCL were comprised of 10 (31.2%) GCB and 22 (68.8%) non-GCB phenotypes . However, in a study of 141 patients with primary gastric DLBCL from Japan, Italy and France, the ratio of GCB to non-GCB phenotypes was about 1.04:1 . The ratio of GCB to non-GCB subtypes in Chinese patients with DLBCL of PGL has not been extensively investigated and the sample sizes analyzed so far, including in our study, have been small [17, 18]. It will be interesting to explore differences in the distribution of pathology subtypes between Chinese and non-Chinese patients with PGL.
In the 69 patients who received H. pylori detection, the incidence of H. pylori infection for cases with DLBCL was lower than those with MALT lymphoma: 79% versus 92%, respectively. H. pylori is considered linked to the development of MALT lymphoma, although its role in DLBCL is a matter of debate [9, 10, 19].
The value of possible prognostic factors such as B symptoms, LDH levels and PS remains controversial. No risk factors have been clearly identified in PGL so far and the International Prognostic Index (IPI) is a commonly used predictive model for aggressive non-Hodgkin's lymphoma. However, the role of IPI in PGL is doubtful [1, 20, 21]. Since the modified-stage IPI proposed by S. Cortelazzo et al. was applied in a limited manner to patients with localized primary gastric DLBCL (stage I-IIE) , the predictive value of stage-modified IPI in advanced stage or other subtypes lymphoma remains unexplored. In our study, we analyzed the clinical characteristics of Chinese patients with different subtypes (predominantly DLBCL) of PGL presenting at both limited and advanced Lugano stages. We found that performance status and stage-modified IPI could effectively predict prognosis of PGL.
In recent years, surgery has gradually been replaced by radiotherapy in the treatment of PGL. However, surgery has been seen to benefit patients who present with hemorrhage, perforation or ileus [11, 22, 23]. We found no significant difference when we compared the overall survival of patients treated either with chemotherapy alone or with combination therapy (chemotherapy combined with radiation or with surgery). Approximately two thirds of the patients recruited in our study presented at an advanced Lugano stage (≥ II2). We propose that surgery or radiotherapy work by improving overall survival in early stage PGL patients rather than advanced cases. This might explain why we saw no significant differences between different treatment modalities in our analysis. The small sample size analyzed in our study could be a possible reason for the lack of OS difference between the different treatment modalities.
Rituximab, a chimeric anti-CD20 antibody, was found to be effective in terms of improving survival rate as well as eliciting an effective clinical response when used in combination with conventional chemotherapy for various subtypes of B-cell lymphoma patients [24–26]. As far as we know, there were no previous studies directly compared immunotherapy-chemotherapy with chemotherapy alone in PGL. The study of Wohrer et al. showed that rituximab in addition to chemotherapy was promising in early-stage gastric DLBCL . A retrospective study of 75 patients in Japan also displayed an excellent result in gastric DLBCL . However, a phase II clinical trial showed that the addition of rituximab to standard chemotherapy did not improve the outcome in early-stage PGL . The role of rituximab in PGL remained controversial.
In this series, our data suggested that rituximab might improve the efficacy of chemotherapy in patients with primary gastric B-cell lymphoma. It was speculated that since conventional chemotherapy showed excellent results for early-stage PGL, adding rituximab may only have added limited incremental value . The situation was quite different in our report. Of the 36 patients who received rituximab therapy in our study, 22 patients (61%) had advanced disease and carried a worse prognosis. The effect of rituximab could well display in patients with advanced stage. The effect of rituximab combined with chemotherapy in B-cell PGL remains controversial [26, 27, 30]. It will be very informative to study the exact role of rituximab in patients with PGL in large prospective randomized clinical trials.