The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single-Institution Experience

Abstract

Background Stereotactic body radiation therapy (SBRT) is a promising option for patients with pancreatic cancer (PCA); however, limited data support its efficacy. This study reviews our institutional experience of SBRT in the treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA. Methods Charts of all PCA patients receiving SBRT at our institution from 2010 to 2014 were reviewed. Most patients received pre-SBRT chemotherapy. Primary endpoints included overall survival (OS) and local progression-free survival (LPFS). Patients received a total dose of 25–33 Gy in five fractions. Results A total of 88 patients were included in the analysis, 74 with LAPC and 14 with BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively. Median OS from date of diagnosis was 18.4 months (LAPC, 18.4 mo; BRPC, 14.4 mo) and median PFS was 9.8 months (95 % CI 8.0–12.3). Acute toxicity was minimal with only three patients (3.4 %) experiencing acute grade ≥3 toxicity. Late grade ≥2 gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin-negative resections. Conclusions Chemotherapy followed by SBRT in patients with LAPC and BRPC resulted in minimal acute and late toxicity. A large proportion of patients underwent surgical resection despite limited radiographic response to therapy. Further refinements in the integration of chemotherapy, SBRT, and surgery might offer additional advancements toward optimizing patient outcomes.

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

“…Integrating these advances, a recent prospective, multi-institutional trial for patients with LAPC utilizing a 5-fraction regimen of 33 Gy reported rates of grade ≥2 gastritis, fistula, enteritis, and ulcer to be 2% (67). Furthermore, rates of resection among BRPC and LAPC patients are increasing, with 21.6% of patients (79% of whom were LAPC) in a series from Johns Hopkins undergoing resection and 51% of BRPC/24% of LAPC treated at Moffitt with induction FOLFIRINOX (leucovorin, fluorouracil, irinotecan, oxaliplatin) undergoing surgery (26,68). Integration of more active systemic therapies such as mFOLFIRINOX (neoadjuvant modified FOLFIRINOX) with SBRT is now being tested, with early data from a phase I trial using a strategy of 30-36 Gy in 3 fractions to the whole target and a focal 9 Gy integrated boost to the tumor/vessel interface showing no acute grade 3 or 4 complications and a median survival not yet reached (69).…”

Cytokinetic effects of Wee1 disruption in pancreatic cancer

“…This dose is similar to those being proposed for high dose stereotactic radiotherapy protocols in the clinic. 27 To assess the cell cycle effects over time we used a flow cytometry protocol that involves combined staining for DNA content, Cyclin A2, and H3S10 phosphorylation, as described by Jacobberger et al 28 This allows cells with a 4N DNA content to be separated into G2 phase (Cyclin A2 positive, pH3S10 negative), early mitosis (Cyclin A2 and pH3S10 positive), metaphase C anaphase (Cyclin A2 negative, pH3S10 positive), and mitotic exit (double negative). As seen in Figures 6A and 6B, there was a decrease in both Cyclin A2 and pH3S10 positive cells 6 h after treatment, followed by recovery of Cyclin A2, particularly in early Sphase, after 16 h, and buildup of Cyclin A2 positive cells at the 4N position after 24 h. At 24 h cells also appeared showing H3S10 phosphorylation, suggesting that the effect of radiation in vivo is to slow transit through G2, rather than G2 arrest.…”

Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

“…Despite the above mentioned characteristics which seem to improve some of the major limits of EBRT, the role of SBRT in LAPC and BRPC is not clearly defined yet, though some interesting preliminary evidence of its activity has been recently reported. As an example, in a single centre institution experience, the authors reported a median OS of 18.4 mo and median PFS of 9.8 mo in 88 patients affected by LAPC and BRPC treated with SBRT (2-30 Gy in five fractions on the planning target volume) with an acceptable toxicity profile (3.4% of > G3 gastrointestinal toxicity) [86] . Furthermore, SBRT led to improved pain control in five out of six studies in which this outcome has been evaluated [87] .…”