The Clinical Impact of Surgery on Overall Survival of Patients with Intestinal Non‑Hodgkin Lymphoma through a Nationwide Study

Introduction

The most common site of extranodal non‑Hodgkin lymphoma (NHL) is gastrointestinal tract. Previous studies revealed that surgical resection followed by chemotherapy might be recommended as an effective treatment strategy for localized intestinal NHL. However, because of its rarity, appropriate therapeutic approach to improve survival in intestinal NHL patients is still undefined. In this large cohort, we assessed the role of surgery on survival outcomes of patients with intestinal NHL.

Methods

A nationwide cohort of patients diagnosed with NHL was extracted from the using the Korean National Health Insurance System (NHIS) database between 2002 and 2021. Patients with NHLs were retrospectively identified using Korean Classification of Diseases (KCD), which is essentially based on the 10th amendment of the International Classification of Diseases (ICD). From 2002, the code is C82.0, C82.1, C82.2, C82.3, C82.4, C82.5, C82.7, C82.9 for follicular lymphoma (FL), C83.0 for lymphoplasmacytic lymphoma (LPL), C83.1 for mantle cell lymphoma (MCL), C83.3, C83.8, C83.9, C85.1, C85.7 for diffuse large B cell lymphoma (DLBCL), C83.7 for Burkitt lymphoma, C84.4 for peripheral T cell lymphoma (PTCL), C84.5, C84.9, C86.0, C86.4 for NK/T cell lymphoma (NKTCL), and C84.6, C84.7 for anaplastic large cell lymphoma (ALCL), C86.2 for enteropathy-associated T cell lymphoma (MEITL), and C86.5 for angioimmunoblastic T cell lymphoma (AITL) in the KCD classification. The primary intestinal sites were distinguished by the type of endoscopy and surgery. The exclusion criteria were as follows: patients whose type of reporting source was a biopsy code of stomach; patients who had 0-3 months survival; patients who are not treated with chemotherapy; the treatment mode of surgery was open and closure surgery; the mode of endoscopy or surgery were unknown; patients aged<18 years. Cox proportional-hazards model and Log-rank tests were used to assess the influence of surgery on overall survival (OS), and the OS was estimated from Kaplan-Meier curves.

Results

Of a total of 18,716 patients with intestinal NHLs, there were 24.7% (n = 4,613) of patients who had received surgery, while 75.4% (n=14,103) patients had not undergone surgery. The mean age was 59.5 years. Male patients were more frequent than females, accounting for 59.4% (n = 11,114). Male patients were slightly more common in the surgery group than in the non-surgery group (63.3% [2,918 patients] versus 58.1% [8,196 patients], respectively; p<.001). There were 74.2% (n = 13,878) patients with B cell lymphoma, and 7.3% (1,370) patients with T cell lymphoma. In B cell lymphoma, the majority of patients was diagnosed with DLBCL (n=11,344, 60.6%) followed by patients with FL (n=1,137, 6.1%), LPL (n=663, 3.5%), MCL (n=453, 2.4%), and Burkitt lymphoma (n=281, 1.5%). In T cell lymphoma, the majority of patients was diagnosed with PTCL (n= 598, 3.2%) followed by patients with NKTCL (n=356, 1.9%), AITL (n=214, 1.1%), ALCL (n=109, 0.6%), and MEITL (n=93, 0.5%). The NHLs location in the majority of patients (86.5%; n = 16,187) was in the colon followed by small intestine (7.1%; n = 1,330) and rectum (5.9%; n = 1,112). Univariate analysis for OS identified age over 60 years (p<.001), male sex (p<.001), T cell lymphoma (p<.001), Charlson comorbidity index (p<.001), and small bowel involvement (p<.001) as factors that predicted poor prognosis. Adjusted hazard ratio (HR) was calculated based on the Cox proportional hazard model with adjustment of age, sex, histologic diagnosis, tumor site and Charlson comorbidity index. Multivariable analysis identified non-surgery (adjusted HR=1.430, 95% confidence interval [CI]=1.338-1.527, p<.001) as independent factors for OS that predicted poor prognosis.

Conclusions

To our knowledge, this is the first Korean population based nationwide study to describe the clinical impact of surgery on OS of patients with intestinal NHLs. In the large cohort of intestinal NHLs patients with chemotherapy older than 18 years, surgery was associated with significantly improved OS. Strategies are warranted to improve the survival of intestinal NHLs patients through a prospective randomized study.