3058 - Increased Tumor Size and Progression Free Survival after 177Lu-DOTATATE for Metastatic Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

J. Patel¹, K. Zhang², O. B. Gbolahan³, D. M. Schuster⁴, S. Muzahir⁴, and P. R. Patel¹; ¹Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ²Emory University School of Medicine, Atlanta, GA, ³Department of Hematology and Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ⁴Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA

Purpose/Objective(s): The standard of care for well-differentiated, grade 1-2 GEP-NETs after somatostatin analog therapy includes ¹⁷⁷Lu-DOTATATE based on the results of the landmark NETTER-1 trial. A subgroup analysis demonstrated a reduction in 12-month progression free survival (PFS) from 95% to 75% in the presence of a lesion larger than 3 cm. We performed a retrospective review to characterize the distribution of disease and assess the impact of tumor size on PFS. Materials/

Methods: This single institution, retrospective study was IRB approved. Inclusion criteria included progressive, advanced GEP-NETs treated with ¹⁷⁷Lu-DOTATATE between 2018 and 2022. Patients who did not complete 4 cycles of therapy were excluded. Diagnostic imaging immediately preceding ¹⁷⁷Lu-DOTATATE and at the time of progression was reviewed. The size and location of the largest tumor prior to therapy was recorded and, when applicable, patterns of progression were assessed. The Kaplan-Meier method was used to assess PFS following ¹⁷⁷Lu-DOTATATE. The impact of tumor size was assessed using the Cox Proportional Hazards and Wilcoxon test.
Results: A total of 120 patients were included in this analysis. Primary tumors of the small bowel (44%) and pancreas (36%) were most common but rectal (6%), appendiceal (1%), and unknown primaries (13%) were also included. Well-differentiated tumors predominated (83%) and differentiation was unknown in 16%. In general, this was a more heavily pre-treated population compared to NETTER-1 with 50% undergoing resection of the primary, 50% receiving two or more lines of systemic therapy, and 22% receiving liver-directed therapy. Prior to ¹⁷⁷Lu-DOTATATE, metastases were identified in the liver (95%), lymph nodes (73%), and bone (34%). The mean size of the largest recorded tumor was 4.6 cm (standard deviation 2.81 cm). The largest tumor was most often found in the liver (70%) but mesenteric lymph node conglomerates (17%) and primary sites (6%) were also identified. With a median follow-up of 14 months (range 0.3-56), the 12-month PFS was 76%. Increasing tumor size was associated with inferior PFS (hazard ratio 0.12, 95% confidence interval 0.01- 0.21, p = 0.03). For those with tumor sizes exceeding 3 cm (n=73, 61%), the 12-month PFS was 69% compared to 84% for those with smaller tumors (p = 0.15). If tumor size exceeded 6 cm (n=28, 23%), the 12-month PFS was 57% versus 82% (p=0.04). Of the 47 patients who progressed, 60% were found to have progression in the largest lesion. In those without progression in the large lesion, progression was noted in a new lesion in 38% and the primary in 2%.
Conclusion: Increasing tumor size is a negative prognostic factor for PFS after ¹⁷⁷Lu-DOTATATE. Disease progression in the largest lesion is common. Strategies to improve outcomes in patients with large GEP-NET lesions are needed.