Stereotactic Body Radiation Therapy and Immunotherapy in Abdominal and Pelvic Lymph Node Metastases.

PURPOSE/OBJECTIVE(S): This study characterizes the efficacy and safety of stereotactic body radiation therapy (SBRT) with immunotherapy in the treatment of abdominal and pelvic lymph node metastases, based on a pooled analysis of three prospective phase I trials. While SBRT is frequently utilized for metastases, its role in the treatment of abdominal and pelvic lymphadenopathy remains unclear. We hypothesize that local control will remain excellent for nodal SBRT, even with prioritization of organ-at-risk (OAR) constraints resulting in undercoverage of target metastases and with omission of elective treatment of regional nodal basins.

MATERIALS/METHODS: Patients with widely metastatic solid malignancies were enrolled on three Phase I trials between 2016 and 2020 (total 213 patients). Patients were treated with multisite SBRT (up to 4 sites). Metastases > 65cc were partially treated. Immunotherapy was administered either concurrently or sequentially. Immunotherapy regimens included pembrolizumab, ipilimumab with nivolumab, urelumab with nivolumab, or cabiralizumab with nivolumab. The study cohort included patients who underwent SBRT to at least one lymph node in the abdomen or pelvis, including the inguinal regions. Local control (LC) of irradiated metastases and regional control (RC) of the corresponding nodal basin were determined per RECIST 1.1 guidelines. Overall survival (OS) was calculated using the Kaplan-Meier method. For each irradiated lesion, the mean dose, V95%, and V100% to the ITV and PTV were recorded.

RESULTS: A total of 39 patients (mean age 59.2 years) underwent SBRT to 56 abdominal or pelvic lymph node metastases with median follow-up of 16.2 months. The median prescription dose was 45 Gy in 3 fractions. Median lesion volume was 17.0cc. Lymph node sites included 24 para-aortic/retroperitoneal (43%), 9 pelvic (16%), 11 inguinal (20%), 10 gastrohepatic/porta hepatis (18%), and 2 other (4%). Across all patients, the 1-year LC was 90.4%. Even without elective treatment of the corresponding nodal basins, 1-year RC was 81.9% (with only one isolated regional failure without concomitant distant progression). Median OS was 25 months, while 1-year and 2-year OS were 69.9% and 53.2%, respectively. ITV mean dose, V95%, and V100% were 47.3 Gy, 95.3%, and 89.5%, respectively (reported as medians across all 56 metastases). PTV mean dose, V95%, and V100% were 45.5 Gy, 84.2%, and 75.0%, respectively. The overall incidence of grade 3+ toxicity was 10.3%. The incidence of grade 3 colitis was 2.6% and grade 3 hepatitis was 2.6%, with no grade 4-5 colitis/hepatitis events.

CONCLUSION: In this pooled analysis of three prospective trials, SBRT to abdominal or pelvic lymph node metastases with immunotherapy is associated with acceptable toxicity and high rates of LC, even with target undercoverage to meet OAR constraints. This suggests a potential for this approach in clinical practice and study in future trials.