Abstract
Background
Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare and aggressive extranodal lymphoma, with no consensus on optimal treatment strategies. For unresectable cases, current evidence is insufficient to determine whether the addition of radiotherapy (RT) to chemotherapy (CT) provides a survival benefit. To address this gap, we used data from the Surveillance, Epidemiology, and End Results (SEER) database to compare survival outcomes between combined modality therapy (CMT) and CT alone in patients with unresectable PP-DLBCL.
Methods
Data on patients with unresectable PP-DLBCL were extracted from the SEER database of the National Cancer Institute, using SEER*Stat software (v8.4.3). Propensity score matching (PSM) was applied to adjusted confounding factors. Overall survival (OS) and cancer-specific survival (CSS) were estimated using Kaplan-Meier methods, and differences between groups were assessed using the log-rank test. Hazard ratios (HRs) were calculated using Cox proportional hazards models.
Results
A total of 880 patients with unresectable PP-DLBCL diagnosed between 2000 and 2021 met the inclusion criteria and the median follow-up were 87 months. The estimated 5-year OS rate was 65.4% [95% confidence interval (CI): 60.1–70.7%]. Of these patients, 719 received CT alone and 161 received CMT. Significant differences in primary tumor site and laterality were observed between the two groups (P<0.001). The analysis revealed a significant association between CMT and improved OS (HR, 0.77; 95% CI: 0.59–0.99), and this association remained consistent in the sensitivity analysis using PSM. Additionally, univariate and multivariate Cox regressions indicated that sex, age and Ann Arbor stage were independent prognosis factors of OS.
Conclusions
Our findings suggest that CMT may improve survival in patients with unresectable PP-DLBCL. Moreover, the prognostic factors identified in this study may help in identifying high-risk patients. Our findings provide new evidence to support the clinical management of this rare patient population.
Keywords: Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL), combined modality therapy (CMT), chemotherapy (CT), radiotherapy (RT), prognostic factors
Highlight box.
Key findings
• Our study suggests that combined modality therapy (CMT) improves prognosis for unresectable primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL).
What is known and what is new?
• PP-DLBCL is a rare and aggressive form of extranodal lymphoma, with no consensus on the optimal treatment strategies, particularly for unresectable cases.
• The Cox proportional hazard models identified Ann Arbor stage, age, and sex as independent prognostic factors for overall survival (OS) in patients with PP-DLBCL.
What is the implication, and what should change now?
• CMT has been shown to potentially improve OS, offering a promising benefit for the treatment of PP-DLBCL.
• Prospective studies with larger cohorts and more detailed clinical data are needed to enhance the accuracy and broader applicability of the model.
Introduction
Primary pulmonary lymphoma (PPL) is a rare form of extranodal lymphoma, comprising 0.4% of all lymphomas and 3.6% of extranodal lymphomas (1). The median age of PPL patients is 60 years, with younger cases being relatively uncommon and a slightly higher incidence rate observed in women (2,3). The most common pathological type is extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is the second most common type, constituting 5–20% of PPL cases (4,5). Compared to pulmonary MALT lymphoma, PP-DLBCL is more malignant and aggressive, with a relatively shorter median survival (6). Furthermore, research focusing on prognostic differences among extranodal DLBCLs suggests that those originating in the respiratory tract exhibit a poorer prognosis compared to those arising from other extranodal sites (7).
Given the rarity of PP-DLBCL, current evidence is limited to case reports and small retrospective studies. As a result, the optimal clinical management of this patient population remains controversial (3,8-11). Imaging examinations are essential diagnostic tools for various rare lymphomas (12,13), including PP-DLBCL, and selecting the appropriate timing and modality of treatment after a confirmed diagnosis is critical (14). Chemotherapy (CT), surgery and radiotherapy (RT) are the main treatments for PP-DLBCL, either alone or in combination. Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), serves as the standard treatment (15). Additionally, some studies suggest that the surgery may be beneficial for localized lesions, such as relatively indolent MALT lymphoma (16). However, due to the aggressive nature of PP-DLBCL, the tumors are frequently disseminated beyond a single region (2), making surgery ineffective for complete lesion removal. Adjuvant CT and subsequent radical surgical resection may not improve survival outcomes (1,4). In this context, the addition of RT may lead to improved prognosis (8). Nonetheless, the role of RT in the treatment of DLBCL remains controversial (17-19). Combined modality therapy (CMT), which involves the use of both CT and RT, has not been extensively studied in large-scale trials for unresectable PP-DLBCL.
Considering the relatively poor prognosis and limited research specifically on the treatment of PP-DLBCL, we conducted a retrospective analysis utilizing the large sample size provided by the Surveillance, Epidemiology, and End Results (SEER) program database. The aim was to evaluate the role of CMT in the rituximab era, focusing on its impact on overall survival (OS) and cancer-specific survival (CSS) in patients with unresectable PP-DLBCL. Further analysis of clinical characteristics was performed to identify prognostic factors and provide evidence for the identification of high-risk patients. We present this article in accordance with the STROBE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-34/rc).
Methods
Data sources and patient selection
Data on PP-DLBCL patients were extracted from the SEER database (SEER 17 registries, November 2023 data submission, 2000–2021) of the National Cancer Institute, using SEER*Stat software (v8.4.3). Importantly, the SEER database strictly upholds patient confidentiality; therefore, data analysis for this study was exempt from medical ethical review and did not require obtaining informed consent from participants. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
We identified patients diagnosed with lymphoma according to the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3), using the histology code 9680 (DLBCL, not otherwise specified). The primary site was selected based on the ICD-O-3 codes C34.0-C34.9. The inclusion criteria were: (I) patients who received CT; (II) patients for whom cancer-directed surgery was not recommended; (III) availability of follow-up information. The exclusion criteria were: (I) unknown RT method or refused; (II) patients who had undergone surgical procedures, refused recommended surgery, or had unknown surgical status; (III) patients with a survival duration less than 1 month; (IV) age <18 or >85 years.
Definitions and treatment
Rituximab was introduced into clinical practice in the early 21st century and had a substantial impact on DLBCL treatment, significantly improving patient prognosis while also reducing treatment-related toxicity and side effects (20,21). Therefore, data collection was focused on patients diagnosed from 2,000 onwards. Patient demographic and clinical data were obtained, including sex, race, age, marital status, Ann Arbor stage, primary site, B symptoms, and laterality. Age was categorized into two groups based on the International Prognostic Index (IPI): <60 and ≥60 years (22,23). Patients were classified into two groups based on the treatment received: the CT group, consisting of those who received CT only, and the CMT group, comprising those who received both beam RT and CT.
Endpoints
The primary endpoint was OS, defined as the time in months from the date of diagnosis to the date of death, the date last known to be alive, or the study cut-off date. CSS was defined as the time from diagnosis to death due to PP-DLBCL.
Statistical analysis
The Chi-squared test was applied to analyse the baseline clinical characteristics between the CT and CMT groups. The Kaplan-Meier method was employed to generate OS and CSS curves, and the log-rank test was conducted to evaluate differences in survival outcomes. The Cox proportional hazards models were utilized to assess whether the use of CMT improved OS and CSS. The initial multivariate Cox regression included a range of clinicopathological factors. To reduce the influence of confounding variables, propensity score matching (PSM) was applied, employing 1:4 matching without replacement and a caliper width of 0.25 for adjustment. Balance diagnostics using standardized mean differences (SMD) confirmed good balance, with all values below 0.1 (24,25). Subgroup analyses were conducted to investigate potential interactions between treatment modalities and other variables (26). In addition, nomogram-based prognostic models were developed for PP-DLBCL patients who received CMT (27). All statistical analyses were conducted using R version 4.2.3, with two-sided P values of <0.05 considered statistically significant.
Results
Patient characteristics and propensity score analysis
A total of 880 patients with unresectable PP-DLBCL who received CT or CMT were identified from the SEER database. Of these, 719 patients in the CT group and 161 in the CMT group comprised the study cohort, with a median follow-up duration of 111 months (Figure 1). The entire cohort of unresectable PP-DLBCL exhibited a slight female predominance, comprising 51.5%, with a male-to-female ratio of 0.94:1. In terms of race, Caucasians constituted the majority of patients (87.0%). A total of 66.6% of patients were aged 60 years or older. Among the known Ann Arbor stages, the CT group predominantly consisted of stage IV patients (28.5%), whereas the CMT group primarily included stage II patients (32.9%). Most patients receiving CT and CMT had unilateral lesions, with proportions of 82.8% and 93.8%, respectively (Table 1). These findings highlight the key differences in the distribution and treatment trends between the CT and CMT groups.
Figure 1.
Flow chart of this study. CI, confidence interval; CMT, combined modality therapy; CT, chemotherapy; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; NOS, not otherwise specified; PP-DLBCL, primary pulmonary diffuse large B-cell lymphoma.
Table 1. Baseline characteristics of primary pulmonary diffuse large B-cell lymphoma patients receiving CT or CMT, before and after propensity-score matching.
| Characteristic | Total patients (n=880) | Unmatched patients | Propensity-score matched patients | |||||
|---|---|---|---|---|---|---|---|---|
| CT (n=719) | CMT (n=161) | P | CT (n=500) | CMT (n=161) | P | |||
| Sex | 0.13 | 0.55 | ||||||
| Female | 453 (51.5) | 361 (50.2) | 92 (57.1) | 270 (54.0) | 92 (57.1) | |||
| Male | 427 (58.5) | 358 (49.8) | 69 (42.9) | 230 (46.0) | 69 (42.9) | |||
| Race | 0.29 | 0.89 | ||||||
| Black | 57 (6.5) | 51 (7.1) | 6 (3.7) | 19 (3.8) | 6 (3.7) | |||
| White | 766 (87.0) | 622 (86.5) | 144 (89.4) | 452 (90.4) | 144 (89.4) | |||
| Other | 57 (6.4) | 46 (6.4) | 11 (6.8) | 29 (5.8) | 11 (6.8) | |||
| Age (years) | 0.03 | 0.11 | ||||||
| <60 | 294 (33.4) | 228 (31.7) | 66 (41.0) | 168 (33.6) | 66 (41.0) | |||
| ≥60 | 586 (66.6) | 491 (68.3) | 95 (59.0) | 332 (66.4) | 95 (59.0) | |||
| Marital status | 0.12 | 0.54 | ||||||
| Divorced/separated/widowed | 204 (23.2) | 174 (24.2) | 30 (18.6) | 108 (21.6) | 30 (18.6) | |||
| Married | 501 (56.9) | 406 (56.5) | 95 (59.0) | 295 (59.0) | 95 (59.0) | |||
| Single/unmarried/domestic | 137 (15.6) | 105 (14.6) | 32 (19.9) | 79 (15.8) | 32 (19.9) | |||
| Unknown | 38 (4.3) | 34 (4.7) | 4 (2.5) | 18 (3.6) | 4 (2.5) | |||
| Ann Arbor stage | 0.002 | 0.16 | ||||||
| Stage I | 136 (15.5) | 108 (15.0) | 28 (17.4) | 80 (16.0) | 28 (17.4) | |||
| Stage II | 193 (21.9) | 140 (19.5) | 53 (32.9) | 119 (23.8) | 53 (32.9) | |||
| Stage III | 48 (5.5) | 42 (5.8) | 6 (3.7) | 19 (3.8) | 6 (3.7) | |||
| Stage IV | 239 (27.2) | 205 (28.5) | 34 (21.1) | 135 (27.0) | 34 (21.1) | |||
| Unknown | 264 (30.0) | 224 (31.2) | 40 (24.8) | 147 (29.4) | 40 (24.8) | |||
| Primary site | 0.001 | 0.38 | ||||||
| Main bronchus | 39 (4.4) | 30 (4.2) | 9 (5.6) | 23 (4.6) | 9 (5.6) | |||
| Upper lobe | 242 (27.5) | 181 (25.2) | 61 (37.9) | 163 (32.6) | 61 (37.9) | |||
| Middle lobe | 42 (4.8) | 29 (4.0) | 13 (8.1) | 25 (5.0) | 13 (8.1) | |||
| Lower lobe | 215 (24.4) | 185 (25.7) | 30 (18.6) | 108 (21.6) | 30 (18.6) | |||
| Overlapping lesion of lung | 16 (1.8) | 14 (1.9) | 2 (1.2) | 6 (1.2) | 2 (1.2) | |||
| Lung, NOS | 326 (37.0) | 280 (38.9) | 46 (28.6) | 175 (35.0) | 46 (28.6) | |||
| B Symptoms | 0.11 | 0.11 | ||||||
| Absent | 285 (32.4) | 231 (32.1) | 54 (33.5) | 156 (31.2) | 54 (33.5) | |||
| Present | 153 (17.4) | 134 (18.6) | 19 (11.8) | 95 (19.0) | 19 (11.8) | |||
| Unknown | 442 (50.2) | 354 (49.2) | 88 (54.7) | 249 (49.8) | 88 (54.7) | |||
| Laterality | <0.001 | 0.87 | ||||||
| Bilateral | 90 (10.2) | 87 (12.1) | 3 (1.9) | 12 (2.4) | 3 (1.9) | |||
| Unilateral | 746 (84.8) | 595 (82.8) | 151 (93.8) | 463 (92.6) | 151 (93.8) | |||
| Other | 44 (5.0) | 37 (5.1) | 7 (4.3) | 25 (5.0) | 7 (4.3) | |||
Data are presented as n (%). CMT, combined modality therapy; CT, chemotherapy.
To mitigate these imbalances, PSM was employed as a sensitive analysis. The distribution of estimated propensity scores for CMT and CT is illustrated in Figure S1. After utilized a 1:4 PSM approach, 500 patients were assigned to the CT group and 161 to the CMT group. Baseline characteristics were well-balanced between the two groups, with all P values exceeding 0.05 (Figure S2).
Relationship between CMT with survival
The median OS for the entire study cohort was 87 months [95% confidence interval (CI): 72–105], with an estimated 5-year OS rate of 65.4% (95% CI: 60.1–70.7%), the median CSS not reached (95% CI: 233–NA) and an estimated 5-year CSS rate of 68.6% (95% CI: 65.4–72.0%).
Figure 2 illustrated the Kaplan-Meier survival curves comparing the CT and CMT groups. Log-rank test results indicated that CMT treatment significantly improved OS (P=0.004; HR, 0.69; 95% CI: 0.54–0.89) but had no statistical significance on CSS (P=0.07; HR, 0.75; 95% CI: 0.54–1.02). Similar results were observed in the cohort after PSM. In the entire cohort, multivariate Cox regression analysis revealed that CMT was significantly associated with improved OS (P=0.041, HR, 0.77; 95% CI: 0.60–0.99) (Table 2), PSM was performed as a sensitivity analysis and yielded similar results (P=0.042, HR, 0.76; 95% CI: 0.59–0.99) (Table 3). Despite CMT might improve the CSS, the results did not reach statistical significance (P=0.27, HR, 0.83; 95% CI: 0.59–1.16) (Table S1).
Figure 2.
Kaplan-Meier curves for overall survival and cancer-specific survival in the entire and PSM cohorts. (A,B) Overall survival and cancer-specific survival in the entire cohort. (C,D) Overall survival and cancer-specific survival in the PSM cohort. . CI, confidence interval; CMT, combined modality therapy; CT, chemotherapy; HR, hazard ratio; PSM, propensity-score matching.
Table 2. Univariable and multivariable Cox regression analyses for overall survival of entire study cohort.
| Characteristic | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | ||
| Sex | |||||
| Female | 1.00 (reference) | – | 1.00 (reference) | – | |
| Male | 1.157 (0.97–1.38) | 0.11 | 1.20 (1.00–1.44) | 0.044 | |
| Race | |||||
| Black | 1.00 (reference) | – | |||
| White | 1.09 (0.74–1.62) | 0.65 | |||
| Other | 0.85 (0.49–1.45) | 0.55 | |||
| Age (years) | |||||
| <60 | 1.00 (reference) | – | 1.00 (reference) | – | |
| ≥60 | 2.67 (2.14–3.32) | <0.001 | 2.70 (2.15–3.40) | <0.001 | |
| Marital status | |||||
| Married | 1.00 (reference) | – | |||
| Other | 1.09 (0.91–1.31) | 0.37 | |||
| Ann Arbor stage | |||||
| Stage I | 1.00 (reference) | – | 1.00 (reference) | – | |
| Stage II | 0.75 (0.57–0.98) | 0.04 | 0.70 (0.53–0.92) | 0.01 | |
| Stage III | 0.83 (0.54–1.27) | 0.39 | 0.78 (0.51–1.19) | 0.24 | |
| Stage IV | 1.09 (0.85–1.41) | 0.51 | 0.98 (0.76–1.27) | 0.89 | |
| Unknown | 0.73 (0.54–0.99) | 0.042 | 0.59 (0.44–0.80) | <0.001 | |
| Primary site | |||||
| Lower lobe | 1.00 (reference) | – | |||
| Upper lobe | 0.86 (0.66–1.12) | 0.27 | |||
| Middle lobe | 0.92 (0.58–1.45) | 0.71 | |||
| Main bronchus | 0.77 (0.46–1.28) | 0.31 | |||
| Overlapping lesion of lung | 1.09 (0.58–2.02) | 0.80 | |||
| Lung, NOS | 1.21 (0.96–1.54) | 0.11 | |||
| B Symptoms | |||||
| Absent | 1.00 (reference) | – | |||
| Present | 1.12 (0.82–1.53) | 0.47 | |||
| Unknown | 1.40 (1.12–1.75) | 0.003 | |||
| Laterality | |||||
| Bilateral | 1.00 (reference) | – | |||
| Unilateral | 0.79 (0.59–1.04) | 0.10 | |||
| Other | 0.79 (0.48–1.30) | 0.36 | |||
| Treatment | |||||
| CT | 1.00 (reference) | – | 1.00 (reference) | – | |
| CMT | 0.69 (0.54–0.89) | 0.004 | 0.77 (0.60–0.99) | 0.041 | |
CI, confidence interval; CMT, combined modality therapy; CT, chemotherapy; HR, hazard ratio; NOS, not otherwise specified.
Table 3. Univariable and multivariable Cox regression analyses for overall survival of patients after propensity score matching.
| Characteristic | Univariate | Multivariate | |||
|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | ||
| Sex | |||||
| Female | 1.00 (reference) | – | 1.00 (reference) | – | |
| Male | 1.27 (1.03–1.5) | 0.03 | 1.33 (1.08–1.64) | 0.008 | |
| Race | |||||
| Black | 1.00 (reference) | – | |||
| White | 0.99 (0.57–1.72) | 0.96 | |||
| Other | 0.64 (0.31–1.32) | 0.23 | |||
| Age (years) | |||||
| <60 | 1.00 (reference) | – | 1.00 (reference) | – | |
| ≥60 | 2.84 (2.21–3.64) | <0.001 | 2.97 (2.31–3.84) | <0.001 | |
| Marital status | |||||
| Married | 1.00 (reference) | – | |||
| Other | 0.96 (0.78–1.19) | 0.72 | |||
| Ann Arbor stage | |||||
| Stage I | 1.00 (reference) | – | 1.00 (reference) | – | |
| Stage II | 0.74 (0.54–0.99) | 0.046 | 0.62 (0.46–0.84) | 0.002 | |
| Stage III | 0.65 (0.35–1.20) | 0.17 | 0.72 (0.39–1.32) | 0.29 | |
| Stage IV | 1.11 (0.83–1.49) | 0.46 | 0.94 (0.70–1.26) | 0.68 | |
| Unknown | 0.69 (0.48–0.98) | 0.040 | 0.54 (0.38–0.77) | 0.008 | |
| Primary site | |||||
| Lower lobe | 1.00 (reference) | – | |||
| Upper lobe | 1.03 (0.76–1.39) | 0.86 | |||
| Middle lobe | 1.16 (0.71–1.89) | 0.56 | |||
| Main bronchus | 0.92 (0.52–1.61) | 0.77 | |||
| Overlapping lesion of lung | 0.77 (0.31–1.91) | 0.57 | |||
| Lung, NOS | 1.41 (1.05–1.90) | 0.02 | |||
| B Symptoms | |||||
| Absent | 1.00 (reference) | – | |||
| Present | 0.98 (0.67–1.42) | 0.90 | |||
| Unknown | 1.46 (1.13–1.90) | 0.004 | |||
| Laterality | |||||
| Bilateral | 1.00 (reference) | – | |||
| Unilateral | 0.64 (0.35–1.16) | 0.14 | |||
| Other | 0.67 (0.31–1.43) | 0.30 | |||
| Treatment | |||||
| CT | 1.00 (reference) | – | 1.00 (reference) | – | |
| CMT | 0.71 (0.55–0.92) | 0.008 | 0.76 (0.59–0.99) | 0.042 | |
CI, confidence interval; CMT, combined modality therapy; CT, chemotherapy; HR, hazard ratio; NOS, not otherwise specified.
Identification of prognostic factors in patients with unresectable PP-DLBCL
We performed univariate and multivariate Cox regression analyses in the entire cohort. The results showed that Ann Arbor stage II was associated with a 30% reduction in the risk of OS (HR, 0.70; 95% CI: 0.53–0.92). In contrast, male sex (HR, 1.20; 95% CI: 1.00–1.44) and age ≥60 years (HR, 2.70; 95% CI: 2.15–3.40) were associated with an increased risk of OS. For CSS, only sex and age emerged as independent prognostic factors. Furthermore, similar results were observed in the PSM cohort. In addition, to improve the clinical management of patients receiving CMT, we developed two nomograms to predict 1-, 2-, and 3-year OS and CSS in the patients with PP-DLBCL (Figures S3-S6).
Subgroup analysis after PSM
To delve deeper into the varying benefits of CMT across different populations, we conducted a subgroup analysis of the PSM cohort. The OS results demonstrated that the differences across all subgroups were not statistically significant (P for interaction >0.05) (Figure 3A). Likewise, the CSS outcomes across the most subgroups did not reach statistical significance (P for interaction >0.05). However, in the Ann Arbor stage subgroup, CMT significantly improved CSS in patients with stage I compared to other stages (HR, 0.30; 95% CI: 0.11–0.86, P=0.03, P for interaction =0.02) (Figure 3B).
Figure 3.
The subgroup analysis of the overall survival (A) and cancer-specific survival (B). CI, confidence interval; HR, hazard ratio.
Discussion
To the best of our knowledge, this study is the first comprehensive analysis of a substantial cohort of unresectable PP-DLBCL patients treated with CMT or CT, using data from the SEER database. After applying PSM to balance covariates, our findings demonstrated that CMT significantly improves prognosis in these patients.
Previous studies on PP-DLBCL have primarily been limited to small-scale retrospective analyses and case reports. Hu et al. research retrospective analyzed 50 cases of PPL, including 12 cases of PP-DLBCL, treated with or without additional therapies alongside CT, and found no significant difference in OS (P>0.05) (8). Similarly, other small retrospective studies have reported favorable outcomes with CT alone (3,28). However, a study using the SEER database for all PPL patients suggested that RT improved OS (P=0.03). Nevertheless, this study included patients with various pathological subtypes of lymphoma and did not account for baseline differences between treatment groups (29). In contrast, our study provides a more in-depth analysis of the impact of CMT on prognosis in unresectable PP-DLBCL patients using more robust statistical methods. Furthermore, a recent large-scale meta-analysis on DLBCL patients demonstrated that CMT significantly improves prognosis (30), further supporting our findings.
We further analyzed the prognostic factors for unresectable PP-DLBCL. Both univariate and multivariate Cox regression indicated that age over 60 years was an independent risk factor, consistent with previous reports on PPL. Elderly patients pose several challenges to the treatment of DLBCL due to unfavorable biological features, geriatric vulnerabilities, and the toxicities associated with cytotoxic therapy (31). Additionally, an earlier Ann Arbor stage was linked to better prognosis and influenced the choice of treatment regimen. In the multivariate Cox regression of the post-PSM cohort, Ann Arbor stage II emerged as an independent protective factor, while subgroup analysis revealed that CSS improved in stage I patients receiving CMT, indicating that CMT may confer better survival benefits for early-stage patients. For instance, Wang et al.’s research focused on early-stage DLBCL demonstrated that RT enhanced both OS and CSS (32). However, a study by Lamy et al. indicated that in the patients with non-bulky limited-stage DLBCL, adding RT to R-CHOP did not improve 5-year event-free survival (EFS) (P=0.18, HR, 0.61; 95% CI: 0.3–1.2) or OS (P=0.28) (33). Therefore, while controversy persists regarding the use of RT for early-stage PP-DLBCL, our findings indicate that although CMT does not improve OS in early-stage patients, it may still offer benefits in improving CSS.
Although our study has the advantages of a large sample size and the use of PSM to balance potential confounding factors, there are several limitations. First, due to the retrospective nature of the research, unmeasured confounders may still exist. Additionally, the SEER database lacks certain important prognostic markers, such as elevated beta-2 microglobulin and lactate dehydrogenase (LDH) levels, which are known to be associated with poor prognosis in PPL (34,35). Moreover, the SEER database does not provide details on CT regimens or RT doses, limiting a more comprehensive evaluation of the role of CMT. Furthermore, given the rarity of this disease, we were unable to collect sufficient samples in our institution to externally validate the prognostic model. We hope that future studies can incorporate multicenter data to achieve external validation.
Conclusions
In conclusion, our study demonstrates that patients with unresectable PP-DLBCL may benefit from CMT. In addition, we identified several independent prognostic factors for unresectable PP-DLBCL, which may contribute to optimizing the clinical management of this patient population.
Supplementary
The article’s supplementary files as
Acknowledgments
We are grateful to Yuna Sun (University of Sydney, Australia) for her thorough review and language editing assistance. We acknowledge the SEER database for generously providing complimentary data on PP-DLBCL.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-34/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-34/coif). The authors have no conflicts of interest to declare.
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