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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Role of SBRT in patients who do not respond to NACT is not yet well defined. We conducted this study to evaluate the impact of SBRT in borderline resectable pancreatic cancer patients with suboptimal response to NACT All consecutive patients staged as BRPC at our center from 2016 to 2020 were included. All received NACT with mFOLFIRINOX or NAB-PACLITAXEL (4-6 cycles) followed by surgical assessment. Patients with radiological partial response (PR) were surgically explored, those with poor response or stable disease not amenable to R0 resection received SBRT and additional chemotherapy followed by surgical assessment. SBRT consisted of 42 -45 Gy over 5 fractions in 10 days. A total of 151 patients with BRPC were registered. During NACT, 44(29%) patients either defaulted or progressed and 107 (69.9%) patients completed at least 4 cycles of NACT and response assessment CECT scan was done. Post NACT, 36(33.6%) patients with partial response were surgically explored, 22(73%) underwent R0 and 8 (24%) had R1 resection (Group 1, n = 30). Remaining 71(66.3%) patients had suboptimal response to NACT and were not feasible for R0 resection received additional SBRT and CT. Post SBRT 28(26.1%) patients were surgically explored and 17 (77%) underwent R0 resection whereas 5 (23%) had R1 resection (Group 2, n = 22). Remaining 43(40%) (Group 3, n = 43) patients continued to receive palliative chemotherapy. At median follow up of 18 months, Median overall survival (OS) and 2-year OS for the whole group (107 patients) was 18 (13-22) months and 37.1% respectively. Group 1 (Patients undergoing curative resection after NACT) had median OS of 26 (19-32) months and 2-year OS of 56 % while Group 2 (patients with addition of SBRT after NACT to achieve curative resection) had median OS of 21 (13-28) months and 2-year OS was 40.9 %. (p value = 0.572). Median OS for the patients in non-resected group (Group 3, n = 43) was 13 months and 2-year OS was 25.6%. There was no significant difference in DFS of the R0 resection patients in Group 1vs 2. (p value = 0.250). Median OS and 2-year OS of the patients who had R0 resection was significantly better than the patients who had R1 resection (27 vs 18 months, 55.9% versus 30.8% respectively, p value = 0.046). There was no difference in surgical complications or postoperative mortality between the two groups. Only 1 patient had grade 2 and 1 patient had grade 3 RT related late GI toxicity. 7 (23%) in Group 1 and 8 (36%) patients had Surgical morbidity. Patients diagnosed with BRPC with suboptimal response to NACT precluding resection, benefit from addition of SBRT by increasing the resectability rate and outcomes similar to the patients having partial or good response to NACT alone. SBRT does not lead to additional surgical or RT related late toxicity. [ABSTRACT FROM AUTHOR]