Neoadjuvant Stereotactic Body Radiotherapy After Upfront Chemotherapy Improves Pathologic Outcomes Compared With Chemotherapy Alone for Patients With Borderline Resectable or Locally Advanced Pancreatic Adenocarcinoma Without Increasing Perioperative Toxicity

Abstract

Background Patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) are at high risk of margin-positive resection. Neoadjuvant stereotactic body radiation therapy (SBRT) may help sterilize margins, but its additive benefit beyond neoadjuvant chemotherapy (nCT) is unclear. The authors report long-term outcomes for BRPC/LAPC patients explored after treatment with either nCT alone or nCT followed by five-fraction SBRT (nCT-SBRT). Methods Patients with BRPC or LAPC from 2011 to 2016 who underwent resection after nCT alone or nCT-SBRT were retrospectively reviewed. Baseline characteristics were compared, and the propensity score with inverse probability weighting (IPW) was used to compare pathologic/survival outcomes. Results Of 198 patients, 76 received nCT, and 122 received nCT-SBRT. The nCT-SBRT cohort had a higher proportion of LAPC (53% vs 22%; p < 0.001). The duration of nCT was longer for nCT-SBRT (4.6 vs 2.9 months; p = 0.03), but adjuvant chemotherapy was less frequently administered (53% vs 67.1%; p < 0.001). Adjuvant radiation was administered to 30% of the nCT patients. The nCT-SBRT regimen more frequently achieved negative margins (92% vs 70%; p < 0.001), negative nodes (59% vs 42%; p < 0.001), and pathologic complete response (7% vs 0%; p = 0.02). In the multivariate analysis, nCT-SBRT remained associated with R0 resection (p < 0.001). The nCT-SBRT cohort experienced no significant difference in median overall survival (OS) (22.1 vs 24.5 months), local progression-free survival (LPFS) (13.5 vs. 15.4 months), or distant metastasis-free survival (DMFS) (11.7 vs 16.3 months) after surgery. After SBRT, 1-year OS was 77.0% and 2-year OS was 50.4%. Perioperative Claven-Dindo grade 3 or greater morbidity did not differ significantly between the nCT and nCT-SBRT cohorts (p = 0.81). Conclusions Despite having more advanced disease, the nCT-SBRT cohort was still more likely to undergo an R0 resection and experienced similar survival outcomes compared with the nCT alone cohort.

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer—A Critical Review and Practical Consideration

“…In addition to 90-day perioperative toxicity, a recent study by Hill et al [ 93 ] describes long-term outcomes in a group of patients who underwent subsequent surgical resection after receiving neoadjuvant chemotherapy alone or neoadjuvant chemotherapy followed by SBRT. Doses of 33 Gy (10–15% heterogeneity allowed) were administered in five fractions on five consecutive working days.…”

Tissue clearing and 3D reconstruction of digitized, serially sectioned slides provide novel insights into pancreatic cancer

“…Close to 50% of surgically resected patients with stage T1 or T2 disease are alive five years after surgery (Allen et al, 2017). Radiation therapy is often also given, particularly in the United States, to achieve better local control of the disease, and for patients with locally advanced pancreatic cancer to shrink the cancer to the point where surgery is an option (Hill et al, 2022).…”

Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies

“…Although SBRT presented the highest response rate, the overall and progression-free survival were found to be comparable to Three-Dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) [ 200 ]. Similarly, the overall survival and toxicity in patients receiving SBRT were similar to that of Conventional Fractionated Chemoradiation (CRT) or chemotherapy alone [ 201 , 202 ]. In the preclinical setting, SBRT was reported to induce immunogenic tumour death in PDAC [ 203 ].…”