3060 - Matched Pair Analysis of Locally Advanced Pancreatic Cancer Patients Treated with Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy (MAPLAP)

M. Peddi¹, R. Engineer¹, M. Bhandare², V. Chaudhari², R. Krishnatry³, S. Gudi¹, V. Ostwal⁴, A. Ramaswamy⁴, and S. Shrikhande²; ¹Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ²Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ³Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ⁴Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India

Purpose/Objective(s): For patients having unresectable locally advanced pancreatic cancers (LAPC) the role of radiotherapy (RT) is not clear. The use of conventional fractionated RT has led to unsatisfactory outcomes. By adopting more precise and conformal Stereotactic Body Radiotherapy (SBRT), one can deliver higher biologically effective dose (BED) to the tumor with comparatively better sparing of organs-at-risk. This study aimed to assess the effect of RT in patients with LAPC who received RT in addition compared to chemotherapy (CT) alone. Materials/

Methods: We retrospectively analyzed, cases of LAPC, treated at our center from September 2015 till March 2022, who received neoadjuvant CT alone or neoadjuvant CT followed by RT. The CT regimen consisted of 6 to 8 cycles of m-FOLFIRINOX or Gemcitabine-based regimens whereas RT included both SBRT and conventional fractionated regimes. In order to balance potential confounding factors, Propensity score matching was performed on both groups for age, ECOG performance status, comorbidities, and site of the tumor in 1:3 ratio. The cumulative incidences of overall survival (OS), local progression-free survival (LPFS), progression-free survival - local or distant (PFS), Distant metastasis-free survival (DMFS), factors affecting outcomes and treatment related toxicities were analyzed in both the groups using the Kaplan-Meier, log rank and cox regression methods.
Results: Out of 152 patient, 33 (22%) who progressed, died during CT or could not complete at least 6 cycles of CT were excluded. Among the remaining 119 patients who received 6 cycles of CT and had a partial response or stable disease as per RECIST criteria, 22 (18%) continued to receive further CT only (Group 1) whereas the remaining 97 (82%) patients received RT followed by additional CT (Group 2). After matched pairing the two groups (Group 1, n = 22; Group 2, n = 66), Group 2 patients had better outcomes (median OS – 18.5 vs. 13.5mo.; median PFS - 12.8 vs. 10.1 mo.; median LPFS - 13.3 vs. 12.3 mo., all SS). In group 2, those who received SBRT (n=51) compared to other fractionated regimens (n = 15) had better median OS, PFS, LPFS, and DMFS (23.6 vs. 11.2, 14.2 vs. 7.7, 16.8 vs. 8.6, 16.8 vs. 10 in months, all SS). Patients who underwent resection (n = 16, 18.2 %) had a better median OS compared to those who did not (38.3 mo. vs. 16.2 mo., SS). In Group 2 in the unmatched cohort, those who had BED >75Gy (n=38) had better median OS (23.6 vs. 17.3 mo., SS). On multivariate analysis, factors contributing to better OS were SBRT, BED >75 Gy, serological (CA 19.9) and radiological response, and surgical resection. PFS was affected by the post-chemotherapy serological and radiological response, and surgical resection. Only 2 patients had RT-related >/= Grade II late GI toxicities.
Conclusion: Our results suggest that the addition of SBRT (at least >75Gy BED) to CT improves OS, LPFS, and PFS in LAPC patients. Further prospective studies are needed to substantiate the role of SBRT in LAPC.