Presenter(s)
A. E. Silberstein1, P. S. Pathak2, B. Y. Yeap3, C. R. Blaszkowsky4, J. L. Koenig4, H. Singh2, L. S. Blaszkowsky2, C. Weekes2, J. N. Allen2, D. P. Ryan2, A. R. Parikh2, M. L. Peters2, Z. Guan3, C. Fernandez-del Casti5, M. Qadan6, P. J. Fagenholz7, J. Harrison7, J. Y. Wo4, T. S. Hong8, and H. J. Roberts4; 1Harvard Radiation Oncology Program, Boston, MA, 2Division of Medical Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 3Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 4Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5Massachusetts General Hospital, Boston, MA, 6Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Department of Surgical Oncology, Mass General Brigham, Boston, MA, 8Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
Purpose/Objective(s): Pancreatic cancers contain high densities of immunosuppressive myeloid cells, which are felt to promote carcinogenesis and contribute to resistance to chemotherapy and immunotherapy (Kemp Cell Mol Gastroenterol Hepatol 2021). We hypothesize that removal of the primary pancreatic mass may modulate resistance of pancreatic cancer by removing its surrounding immunosuppressive microenvironment. To explore this, we investigated patterns of recurrence comparing resected and unresected pancreatic cancers.
Materials/Methods: Patients with borderline resectable or locally advanced pancreatic cancer treated with chemotherapy followed by chemoradiation (CRT) from 2016-2025 were included. Unresected patients did not have surgery or underwent exploration with or without intraoperative radiation therapy. Patients who did not complete CRT or developed metastases within 60 days after CRT were excluded. Survival outcomes were assessed from end of CRT using log-rank tests, and patterns of failure were compared with Fisher’s exact tests.
Results: Of 297 patients with a median follow-up of 17.8 months, there were 207 (70%) recurrences: 44 (15%) local, 126 (42%) distant, 37 (13%) synchronous local and distant. Recurrence rate was 67% (116/174) among resected and 74% (91/123) among unresected patients (p=0.22). We explored patterns of failure by recurrence sites in the table below. There were higher absolute rates of lung-only metastasis (11% vs. 6%) and lower rates of local failure (10% vs. 21%) in resected vs. unresected patients, respectively; however, overall distribution of sites was not significantly different (p=0.12). Resected patients had improved progression free survival (PFS), distant metastasis free survival (DMFS), overall survival (OS), and survival from time of metastatic onset. Among patients with initial lung-only recurrence, resected patients had extended median post-progression survival (PPS) at 38.2 months vs. 15.1 months.
*P value in table compares PPS in resected lung failures vs. all other sites, as survival was similar among all other subgroupsConclusion: Patients with resected pancreatic cancer had higher rates of recurrence in the lung, a site associated with a less aggressive disease course, and had improved post-metastasis survival vs. unresected patients. Further studies to explore mechanisms driving these differences and relation to removal of tumor immunosuppressive microenvironment are warranted.
Abstract 2223 – Table 1
| Median Survival Outcomes (Months) | Resected (n=174) | Unresected (n=123) | P value |
| PFS | 14.7 | 8.6 | <0.001 |
| DMFS | 20.7 | 11.0 | 0.004 |
| Post-Metastasis Survival | 10.2 | 5.6 | 0.001 |
| OS | 29.7 | 14.3 | <0.001 |
| PPS: Local Failure | 11.4 | 6.8 | <0.001* |
| PPS: Local and Distant Failure | 7.3 | 7.4 | |
| PPS: Lung Only Metastasis (n=26) | 38.2 | 15.1 | |
| PPS: Liver Only Metastasis | 11.1 | 11.9 | |
| PPS: Peritoneum Only Metastasis | 7.4 | 5.6 | |
| PPS: Other Distant Metastasis (includes multi-site metastasis) | 6.6 | 10.5 |