LBA 08 - A Randomized, Phase II Clinical Trial of Stereotactic Body Radiation Therapy Or Conventionally Fractionated Concurrent Chemotherapy and Radiation Therapy Preoperatively for Pancreatic Adenocarcinoma, the SOFT Preop Study
Presenter(s)
W. A. Hall1, S. Tsai2, A. Banerjee3, D. Seo4, C. J. Small1, B. George5, M. Kamgar4, J. Thomas4, E. S. Paulson1, N. Lytle4, H. G. Nasief1, T. McFall4, K. Christians4, X. Chen1, G. Yavas6, H. Heaviland4, L. Schmitz4, C. N. Clarke7, D. B. Evans2, and B. A. Erickson1; 1Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, 2Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, 3Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, 4Medical College of Wisconsin, Milwaukee, WI, 5Mayo Clinic Comprehensive Cancer Center, Rochester, MN, 6Froedtert and Medical College of Wisconsin, Milwaukee, WI, 7Medical College of Wisconsin Department of Surgery, Milwaukee, WI
Neoadjuvant therapy for operable PDAC has become a standard of care, yet the optimal sequence and duration of therapies remain less well defined. We conducted a prospective, randomized, phase II trial testing two different modalities of RT preoperatively.
Materials/Methods:
Eligibility criteria included resectable, borderline, or locally advanced (LA) type A PDAC, ECOG 0-2, and > 1 month of neoadjuvant chemotherapy (chemo). Patients were enrolled and randomized 1:1 after neoadjuvant chemo to: RT with concurrent chemo (Chemo-RT: 50.4 Gy/28 fractions with weekly gemcitabine or capecitabine); versus, stereotactic body RT (SBRT: 25 Gy/5 to elective nodes and 33-40 Gy in 5 to the primary without concurrent chemo). Most patients in the SBRT cohort were treated using 1.5 T adaptive MRI guidance. The primary endpoint was pathologic node positivity hypothesizing that chemo-RT would have lower rates of nodal positivity. Secondary endpoints included: progression-free survival (PFS), overall survival (OS), patient-reported quality of life (QOL), physician-reported toxicity, surgical complications, and translational endpoints. 102 patients were targeted for enrollment, anticipating a 15% drop out before surgery. Patient-reported QOL was assessed using the PROMIS instrument.
Results:
102 patients were enrolled; 4 withdrew after enrollment. Median age was 65 (34-82), 38%/42%/20% were resectable, borderline, and LA type A respectively. 92% of patients had more than 2 months of chemotherapy before enrollment, including FOLFIRINOX (79%), gemcitabine/nab-paclitaxel (12%), or other (9%). 83/98 (84.7%) completed all intended therapy to include surgical resection; equal in both arms (41 SBRT and 42 Chemo-RT). The rate of node positivity was 41% (SBRT) vs 38% (Chemo-RT), p = 0.754. Median OS in all patients (measured from date of enrollment) was 26.04 mo (95% CI 17.9 to 59.28) in the SBRT cohort and 42.96 mo (95% CI 18.72 to 54.72) in the Chemo-RT cohort, p= 0.639. At 3 years from date of enrollment, 42.6% of the SBRT cohort, and 57.5% of the Chemo-RT cohort were alive, p = 0.198. PFS was 14.28 mo in the SBRT cohort (95% CI of 9-29.64) and 21.6 mo in the chemo-RT (95% CI 10.56-38.04), p = 0.96. Local/regional recurrence occurred in 8 (7.8%) of patients (6 SBRT and 2 chemo-RT) with a median follow-up among all enrolled patients of 3.4 [2.6, 5.1] years. There was no difference in surgical complications. Patient reported QOL was better preserved across physical function, global physical health, and fatigue using SBRT compared to Chemo-RT (p = < 0.05).
Conclusion:
In the first randomized trial comparing SBRT with Chemo-RT in the neoadjuvant setting for PDAC, there was no difference in node positivity, completed surgical resection, pathologic response, margin negativity, PFS, or OS. SBRT was associated with a significant preservation in QOL compared with Chemo-RT. This is one of the first prospective randomized trials comparing two different RT types and supporting SBRT in the neoadjuvant setting for PDAC.