PG-LGBCL in early stage can be cured with local radiotherapy, and this study resulted that pathologic CR after IFRT was achieved in all patients, suggesting radiation dose of 25–30 Gy showed adequate tumor control. Previous studies also reported a high response rate of 90% to radiotherapy in cases diagnosed with PL-LGBCL, with RFS rate of 90–100% and an OS rate of 75–100% [11–15]. However, the clinical factors that affect the response time and oncologic outcome of delayed response to radiation therapy have not yet been evaluated in previous studies.
The current study demonstrated that local tumor control was good even with delayed response to radiotherapy. Only one patient in early responder group developed out-field recurrence and there was no recurrence in delay responder group. This results suggested that the lesion can be cured without further treatment even if the response to radiation therapy was delayed. In addition, initial evaluation of radiotherapy after 6 months or interval increases could reduce unnecessary invasive tests.
For treatment of H.pylori-positive gastric lymphoma, eradication therapy using antibiotics is the first-line treatment and highly invasive lymphomas are known to respond later more than 6 months or not [16, 17]. Previous studies have shown that patients with lymphoma extending beyond the submucosal layer can respond after 1 year of HPE, so endoscopy and biopsy are recommended every 6 months for the first 2 years [18–20]. The heterogeneity of H.pylori strain may result in different responses or different tumor location might affect different responses to HPE [17, 21, 22]. Therefore, secondary treatment after eradication therapy is recommended if the gross lesion persists for 6 months and microscopic lymphomatous infiltration occurs up to 2 years [23]. A delayed response to eradication therapy indicates poor prognosis warranting secondary treatment such as radiotherapy.
On the other hand, few studies investigating delayed response to radiotherapy have been conducted. Cheson et al. [24] and the NCCN guidelines recommended an evaluation of endoscopy and biopsy at 3 to 6 months after radiotherapy. However, 8 of the 43 patients manifested the delayed response after > 6 months, which may require further follow-up to evaluate the final response to radiotherapy.
Interestingly, clinical and endoscopic factors that affect delayed response after radiation therapy were analyzed in this study. In multivariate logistic regression analysis, the depth of invasion beyond mucosal layer showed a significant difference between two responder groups. Other characteristics such as age, stage, LDH, and IPI score did not show statistical difference between two groups. Previous studies reported differences in eradication therapy depending on sex or tumor location; however, no significant difference in response time of radiotherapy was demonstrated [16, 21]. Although there were delayed response in deeply invasive lymphoma, the patients were observed without salvage treatment and all achieved CRs finally.
The endoscopic findings such as ulcerative pattern indicated the high grade lymphoma in previous study [25]. In the endoscopic findings of current study, there was no significant difference in endoscopic patterns between two responder groups. However, the first endoscopic finding of the 7 patients in 8 delayed responders was characterized by diffuse or deep nodularity and ulceration rather than erosion or erythema at the initial examination. The number of patients was small so there was no difference between endoscopic findings and delayed response.
The aim of the current study was not only to evaluate the response rate but also to analyze the factors associated with the delayed response. The study was conducted as a retrospective design with a small number of patients at a single institution. In addition to selection bias, the small sample size prevents generalization of the results to larger populations. A prospective large-scale study is needed to analyze the factors that may cause delayed response and to establish a protocol for evaluation of response to radiotherapy of PG-LGBCL.
In conclusion, PG-LGBCL showed an adequate response rate, RFS, and OS with limited toxicity with radiotherapy. And there were no significant difference of recurrence and local control between response time to radiotherapy. Furthermore, deep invasion beyond mucosal layer affected delayed response to radiotherapy. This study suggested more studies of factors and prognosis affecting the delayed response. Additional clinical studies are needed, but PG-LGBCL with response to radiation therapy may be followed up without further treatment.