The Timing of Surgery Following Stereotactic Body Radiation Therapy Impacts Local Control for Borderline Resectable or Locally Advanced Pancreatic Cancer

SIMPLE SUMMARY: The role of radiation therapy in localized pancreatic cancer is controversial. The interval of time from the end of radiotherapy to surgery has been shown in some cancer disease sites to affect subsequent outcomes but has not been studied in pancreatic cancer. We aimed to characterize the optimal timing of surgery following stereotactic body radiation therapy (SBRT) in patients with borderline resectable or locally advanced pancreatic cancer. We found that patients who underwent surgery more than 6 weeks after completing SBRT had improved local control outcomes compared to those who had received surgery within 6 weeks of completing SBRT, even when controlling for other clinical factors such as the pathological response to neoadjuvant chemotherapy. These findings could be used to inform future studies, including prospective trials to better select patients with localized pancreatic cancer who may benefit from radiotherapy. ABSTRACT: We aimed to evaluate the impact of time from stereotactic body radiation therapy (SBRT) to surgery on treatment outcomes and post-operative complications in patients with borderline resectable or locally advanced pancreatic cancer (BRPC/LAPC). We conducted a single-institutional retrospective analysis of patients with BRPC/LAPC treated from 2016 to 2021 with neoadjuvant chemotherapy followed by SBRT and surgical resection. Covariates were stratified by time from SBRT to surgery. A Cox regression model was used to identify variables associated with survival outcomes. In 171 patients with BRPC/LAPC, the median time from SBRT to surgery was 6.4 (range: 2.7–25.3) weeks. Hence, patients were stratified by the timing of surgery: ≥6 and <6 weeks after SBRT. In univariable Cox regression, surgery ≥6 weeks was associated with improved local control (LC, HR 0.55, 95% CI 0.30–0.98; p = 0.042), pathologic node positivity, elevated baseline CA19-9, and inferior LC if of the male sex. In multivariable analysis, surgery ≥6 weeks (p = 0.013; HR 0.46, 95%CI 0.25–0.85), node positivity (p = 0.019; HR 2.09, 95% CI 1.13–3.88), and baseline elevated CA19-9 (p = 0.002; HR 2.73, 95% CI 1.44–5.18) remained independently associated with LC. Clavien–Dindo Grade ≥3B complications occurred in 4/63 (6.3%) vs. 5/99 (5.5%) patients undergoing surgery <6 weeks and ≥6 weeks after SBRT (p = 0.7). In summary, the timing of surgery ≥6 weeks after SBRT was associated with improved local control and low post-operative complication rates, irrespective of the surgical timing. Further investigation of the influence of surgical timing following radiotherapy is warranted.