1161 - Neoadjuvant Therapy with Radiation for Locally Advanced Pancreatic Cancer: Outcomes from a Large Single-Institution Cohort
Presenter(s)
H. J. Roberts1, P. S. Pathak2, Z. Guan3, B. Y. Yeap3, C. R. Blaszkowsky1, J. L. Koenig1, A. E. Silberstein4, C. Weekes2, H. Singh2, J. N. Allen2, D. P. Ryan2, L. S. Blaszkowsky2,5, A. R. Parikh2, M. L. Peters2, C. fernandez-Del Castil6, M. Qadan5,7, P. J. Fagenholz8, J. Harrison8, K. Lillemoe8, T. S. Hong9, and J. Y. Wo1; 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, 3Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 4Washington University School of Medicine, Saint Louis, MO, 5Newton-Wellesley Hospital, Newton, MA, 6Deptartment of Surgical Oncology, Massachusetts General Brigham, Boston, MA, 7Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 8Department of Surgical Oncology, Mass General Brigham, Boston, MA, 9Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
Purpose/Objective(s): There is no standard approach to radiation (RT) in locally advanced pancreatic cancer (LAPC). Neoadjuvant chemoRT (CRT) may enable resection, while dose escalation may offer improved disease control in unresectable cases. We performed a large single institution retrospective analysis of outcomes following total neoadjuvant therapy (TNT).
Materials/Methods: This is a retrospective review of 332 patients with LAPC by NCCN criteria who underwent TNT with 4-6m of chemotherapy and RT (2016 - 25). OS and PFS were estimated from RT start using Kaplan–Meier. Multivariable (MV) logistic regression identified factors associated with resection, MV Fine-Gray regression with local control (LC), and MV Cox regression with OS and PFS. Resection model covariates included age (continuous), post-TNT CA19-9 response (normalization or =50% reduction with value <100 mg/dL vs not), and ECOG PS (0 vs >1). LC/OS/PFS models included age, CA19-9 response, and total RT dose (BED10 >/=90 Gy; EBRT + IORT courses) analyzed separately for resected and unresected cohorts (no LC MV analysis in resected cohort due to few events). pN+ was included in resected patients.
Results:
Median follow-up of 109 surviving patients was 18.8 mo (1.5-117.7). Neoadjuvant chemotherapy included FOLFIRINOX (84%), gemcitabine/nab-paclitaxel (20%), and/or other regimens (6%). RT dosing consisted of long course 50.4-58.8 Gy (76%), SBRT (median dose: 40 Gy/5 fractions, 14%), or other (10%); 92% was CRT (capecitabine (n=222, 73%). Surgical exploration was performed in 256 (77%); 124 (37%) underwent resection (R0 86% (n=107)), and 103 (31%) underwent IORT alone. 158 received BED10> 90. Among those resected, 38 (31%) were pN+ and 8 had a pCR (6%). 184 (72%) received IORT (median dose: 13 Gy (7-17)). 76 were not explored (progression = 38, comorbidity/PS = 5, other/unknown = 33). On MV analysis, CA19-9 response was associated with higher resection rates (OR 3.24, p<0.0001), improved OS in unresected (HR 0.6, p=0.008), and improved PFS in resected (HR 0.6, p=0.035) and unresected patients (HR 0.49, p<0.0001). BED10 >90 Gy was associated with improved OS (HR 0.46, p<0.0001) and PFS (HR 0.42, p<0.0001) in unresected patients. pN+ was associated with worse OS (HR 2.39, p=0.001) and PFS (HR 2.18, p=0.002).Conclusion: TNT including RT for LAPC was associated with meaningful rates of surgical conversion and R0 resection. CA19-9 response strongly predicted resection and OS/PFS, while pN+ status conferred worse OS/PFS. Dose escalation with IORT (BED10 >90 Gy) was associated with improved OS and PFS in unresected patients. These findings support ongoing prospective dose escalation studies in unresectable disease (NRG LAP100).
| Median OS (mo) | Median PFS (mo) | 2y OS | 2y PFS | 2y LC | |
| Overall (n=332) | 16.2 | 8.3 | 36% | 18% | 65% |
| Resected (n=124) | 27.9 | 12.5 | 59% | 33% | 71% |
| Unresected (n=208) | 12.5 | 6.3 | 20% | 8% | 61% |
| IORT Alone (n=103) | 18.2 | 9.5 | 30% | 13% | 54% |