Primary Hepatic Lymphoma: Role of Low-Dose Radiotherapy at a Single Institution with Genetic Characterization and Paired Literature Review

Abstract

Purpose/Objective: Primary hepatic lymphomas (PHL) are an extremely rare form of non-Hodgkin Lymphoma (NHL) for which there are no established treatment guidelines, with available literature largely comprised of small case reports. Therefore, we evaluate our institutional experience treating PHL within the context of existing literature to better understand treatment modalities, role of radiotherapy (RT), and outcomes. Traditionally, radiotherapy for indolent lymphomas has involved treatment of up to 2400cGy in 12 fractions, however the use of low-dose radiotherapy of 400cGy in 1-2 fractions has been increasingly utilized. However to our knowledge, use of low-dose RT for liver lymphomas has not previously been reported in the literature. Materials/Methods: We conducted a single institutional retrospective analysis of all PHL patients (pts) diagnosed from 2000-2021 with a biopsy-proven liver lesion without other lymphomatous solid organ involvement, except for concurrently diagnosed splenic lymphomas. Subgroup analysis was performed for diffuse large B-cell lymphoma (DLBCL) and indolent lymphomas, which included marginal zone (MZL), follicular (FL), and low-grade B-cell lymphoma (BCL), NOS. Univariable (UVA) and multivariable analysis (MVA) for overall survival (OS) was performed using the Cox proportional hazards model. A literature review was also conducted using key words "liver", "lymphoma", and "treatment" to identify all available reported cases of PHL. An institutional targeted sequencing database was queried to identify patients with PHL of DLBCL histology. Results: We identified 30 PHL pts within the institutional cohort and 192 pts from comprehensive literature review. Sixteen patients were male (53%), and 25 (83%) were ECOG 0. Twenty five (83%) were Lugano Stage I, 3 (10%) were Stage III, and 2 (7%) were Stage IV. Six (20%) patients had bulky disease and 3 (10%) had nodal involvement. Systemic therapy was the most common treatment modality with 20 patients (67%), and 4 patients (13%) each received surgery, radiation and observation in our institutional cohort. In the paired literature review, 96 patients (50%) received systemic therapy, 69 (36%) underwent surgery, 10 (5%) received radiation and 11 (6%) underwent observation. Seventeen (57%) of patients were alive and 5 (17%) lost to follow-up within our institutional cohort, compared with 97 patients (51%) alive and 3 (2%) lost to follow-up. Median survival in our cohort was 6 years, compared with 2 years among the literature review cohort. Subgroup analysis of DLBCL included 15 pts (Table 1). On MVA for OS, only ECOG score (p=0.02) and Lugano stage (p=0.04) remained significant. Subgroup analysis of the indolent lymphoma group included 9 pts (Figure 1). On MVA for OS, only age remained significant. Six DLBCL patients with available targeted sequencing data were identified, with 4 mutations mutated more than once: TP53 (50%), MEF2B (33%), P2RY8 (33%), and IRF8 (33%). Pathway mapping of genetic mutations was notable for alterations in cell cycle pathway genes TP53 and ATM (17%). No other pathways had greater than one genetic alteration. Conclusion: PHLs are a rare subtype of NHL without clear treatment consensus. Primary hepatic DLBCL is predominantly treated with chemotherapy in both our institutional experience and as reported in the literature, with reasonable disease control. Importantly, indolent PHL patients in the institutional cohort have been treated with various modalities including low-dose radiotherapy, which appears to achieve comparable disease control. However radiotherapy was not utilized as a modality for indolent PHL within the literature review. Therefore, this is the first report of the use of low-dose radiotherapy for treatment of indolent liver lymphomas. Our RT data is limited by short follow-up duration of RT pts compared to pts who received chemotherapy, surgery or observation. However, our results are encouraging for the consideration of low-dose radiotherapy as a management option for appropriate patients with indolent PHL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal