Prognostic Impact of Radiation Therapy in Stage I Nodal Marginal Zone Lymphoma

Purpose: Nodal marginal zone lymphoma (NMZL) localized to a single lymphatic region (i.e Stage I) is a relatively rare diagnosis. Current guidelines permit these patients to be either observed or treated with systemic therapy, radiotherapy (RT), or both modalities. The prognostic impact of systemic therapy or RT compared to observation has not been established. The purpose of this study is to assess the prognostic impact of therapy in Stage I NMZL.

Methodology: The National Cancer Database (NCDB) was queried (2004-2018) for patients with Stage I nodal marginal zone lymphoma. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for overall survival.

Results: A total of 3540 patients with median age 68 (IQR 58- 77) were included in this study. A total of 1136 (32%) were head/neck, 235 (7%) intrathoracic, 684 (19%) intraabdominal, 422 (12%) axilla or upper extremity, 310 (9%) inguinal or lower extremity, 98 (3%) pelvic, and 655 (19%) unspecified site. A total of 1728 (49%) were observed, 795 (23%) received systemic therapy alone, 886 (25%) received RT alone, and 131 (4%) received both systemic therapy and RT. Of the patients who received RT, 168 (17%) received ≤ 24Gy, 552 (54%) received 25- 30.6 Gy, and 297 (29%) received >30.6 Gy. The 10-year OS was 52% for patients observed, 51% for patients who received systemic therapy, 72% for patients who received RT, and 61% for patients who received both radiation and systemic therapy. On UVA, RT (HR 0.48, p< 0.001; CI 0.41- 0.56) was a positive prognostic factor while systemic therapy (HR 1.25, p= 0.02; CI 1.08-1.43), older age (HR 1.08, p< 0.001; CI 1.07-1.08), and CDCC comorbidity score (HR 1.95, p< 0.001; CI 1.69-2.25) were negative prognostic factors. On MVA, RT (HR 0.61, p< 0.001; CI 0.52- 0.72) remained a positive prognostic factor while systemic therapy (HR 1.21, p= 0.009; CI 1.05-1.40), older age (HR 1.08, p< 0.001; CI 1.07-1.08), and CDCC comorbidity score (HR 1.66, p< 0.001; CI 1.44- 1.92) remained negative prognostic factors.

Conclusions: This is the largest study to date on Stage I NMZL. Compared to both observation and systemic therapy, RT was a positive prognostic factor. Since acute toxicity from these relatively low doses of RT should be mild and late toxicity in this rather elderly population is of less concern, we advocate for RT as the preferred treatment option in the management of Stage I NMZL.

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