1160 - Heterogeneity within Oligometastatic Pancreatic Cancer: Impact of Metastatic Burden on Outcomes after Metastasis-Directed Therapy
Presenter(s)
E. E. Lee1, P. S. Pathak2, C. R. Blaszkowsky1, G. Lee3, J. N. Allen2, L. S. Blaszkowsky2, J. W. Clark2, C. Fernandez-del Casti4, T. S. Hong5,6, J. L. Koenig1, A. R. Parikh2, M. L. Peters2, M. Qadan4, D. P. Ryan2, H. Singh2, C. Weekes2, J. Y. Wo1, and H. J. Roberts1; 1Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 3Inova Schar Cancer Institute, Fairfax, VA, 4Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 6Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Purpose/Objective(s):
Oligometastatic pancreatic ductal adenocarcinoma (PDAC) represents a rare clinical state that may reflect less aggressive tumor biology than widely metastatic disease. While systemic therapy remains the standard of care, emerging data support metastasis-directed therapy (MDT), yet patient selection remains undefined. We report outcomes with ablative radiotherapy (RT) for oligometastatic PDAC.Materials/Methods:
We retrospectively analyzed patients with PDAC undergoing RT to metastatic lesions. Patients with de novo or metachronous oligometastatic disease (=5 radiographically evident metastatic lesions at MDT) were included. Time-to-event outcomes were calculated from index MDT. Cox models evaluated associations with outcomes.Results:
Ninety-nine patients met inclusion criteria, with median follow-up of 10.3 months (range 0.2-38.7). Median number of metastases was 1 (IQR, 1-2); 65 patients had 1, 22 had 2, and 4 each had 3, 4, and 5 lesions. Metastases were predominantly hepatic (88.9%), with lung involvement in 12.1% and other sites in 8.1%. Thirty-three patients (33.3%) presented with de novo oligometastatic disease, while 66 (66.7%) had metachronous presentation. Most patients (89.9%) received local therapy to the pancreatic primary prior to MDT including resection (52.5%) and/or radiation (73.7%). Among patients treated with metachronous metastases, the median time from diagnosis to MDT was 11.2 months (range 2.1-38.7). RT delivered was consolidative for stable/responding (48.5%) or progressive disease (51.5%), with a median 3.8 months (IQR 0.39-6.8) from oligometastatic diagnosis to MDT. Most received 50 Gy in 5 fractions (42.6%), and median BED10 was 100 Gy (range 37.5-102.6). Median treated-lesion local control (LC) was 25.3 months, progression-free survival (PFS) 4.9 months, overall survival (OS) 10.3 months, and chemotherapy-free interval (CFI) 8.1 months. 45.2% and 27.6% of patients remained off chemotherapy for 6 and 12 months, respectively. One-year LC, PFS, and OS were 66.8% (95% CI 51.9-78%), 21.3% (95% CI 13.2-30.7%), and 45.8% (95% CI 34.8-56.1%), respectively. On multivariate analysis, greater metastatic disease burden =3 lesions at start of MDT was associated with inferior LC, HR 4.8 (95% CI 1.01-22.9, p = 0.05) and shorter CFI, HR 12.7 (95% CI 1.5-107.5, p = 0.02). ECOG performance status independently predicted worse PFS, HR 1.59 (95% CI 1.1-2.31), and OS, HR 1.83 (95%CI 1.2-2.78). Higher BED10 was associated with improved PFS and OS, HR 0.79 and HR 0.73 per 10 Gy, respectively. De novo vs. metachronous presentation was not associated with outcomes.Conclusion:
Within patients meeting conventional oligometastatic criteria, metastatic burden at the time of MDT most consistently predicted outcomes. Patients with =2 lesions demonstrated more durable local control and systemic therapy-free intervals, suggesting heterogeneity within the current oligometastatic paradigm. Prospective study is needed to inform patient selection.