Pattern of Marginal Local Failure in a Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy for Resectable and Borderline Resectable Pancreas Cancer

Abstract

Objectives: The main objectives of this study were to prospectively evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Materials and Methods: Eighteen patients were enrolled from November 2014 to June 2017. Following 3 cycles of chemotherapy, SBRT was delivered to the tumor and abutting vessel and a 3 mm planning target volume (PTV) margin to 33 Gy (6.6 Gy×5) with an optional elective PTV to 25 Gy (5 Gy×5) customized to the nodal space and mesenteric vessels. The primary endpoint is ≥grade 3 acute and late gastrointestinal toxicity. Results: Fifteen patients had borderline resectable tumors due to arterial abutment (n=7) or superior mesenteric vein encasement (n=8); 3 patients had resectable tumors. There were no ≥grade 3 acute or late gastrointestinal events. Following SBRT, surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. The median overall survival and progression-free survival was 21 months (95% CI: 18-29) and 11 months (95% CI: 8.4-16). Progression occurred in 83% (10/12) of resected patients (distant [n=4, 40%], local-only [n=4, 40%], and local and distant [n=2, 20%]). The cumulative incidence of local failure (LF) at 12 months from resection was 50% (95% CI: 20-80). All LF were outside to the PTV33. Conclusions: Neoadjuvant SBRT was well tolerated, however LFs were predominantly observed outside the PTV33 volume that would have been covered with conventional RT volumes. The durability of local control after SBRT in the neoadjuvant setting merits examination relative to chemoradiation before incorporation into routine practice.

Ablative 5-Fraction Stereotactic Magnetic Resonance–Guided Radiation Therapy With On-Table Adaptive Replanning and Elective Nodal Irradiation for Inoperable Pancreas Cancer

“…Fifth, most patients were treated to elective nodal regions, which is unconventional and frankly controversial. 6,9,25 The role of ENI remains debated and owing to potentially severe toxicity, at least using CT image guidance, some have recommended against it. 11 Electively treated regions typically received an ablative dose prescription, and although this was tolerated well the long-term effects of this need to be closely evaluated.…”

“…After it was apparent that treatment was tolerated well we eventually adopted the routine use of elective nodal irradiation (ENI); this decision was influenced by patterns of failure data indicate that ENI may reduce locoregional failures. 6,25 As such, ENI was delivered to the more recently treated 20 patients (57.1%) and the electively treated region gradually evolved to include a 5 to 10 mm radial expansion around the celiac axis, superior mesenteric vein, and superior mesenteric artery; up to the proximal 10 to 15 mm of these vessels was also included. Instead of routinely creating a clinical target volume, electively treated regions were typically included within the GTV to minimize the number of structures, expedite daily adaptive replanning, and reduce time patients were in the treatment unit.…”

Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

“…143 Unfortunately, the study was recently suspended following an interim analysis of 30 patients revealing crossing of the futility boundary for R0 resection rates for the SBRT arm. 127,144 Taking into account all these data, and despite the lack of level I evidence, the NCCN, ASCO, ASTRO and the American College of Radiobiology (ACR) guidelines have already listed SBRT as an optional treatment for localized PDAC in experienced, high-volume centres. 2,14,58,59,145 It is essential to continue to improve the pancreatic SBRT technique, in particular by trying to deliver very high BED to the target while maintaining a safe toxicity profile.…”

“…149 These perivascular tissues are not systematically covered by pancreatic SBRT and could explain the important rates of LF reported in some studies. 127,150 A recent example is provided by the phase II study from Kharofa et al in which 18 BR patients were treated with 3 cycles of multi-agent CT followed by SBRT (33 Gy in 5 fractions with an optional elective 25 Gy volume to the at-risk vasculature). Surgery was performed in 12 patients with 92% of R0 resections.…”

Basics and Frontiers on Pancreatic Cancer for Radiation Oncology: Target Delineation, SBRT, SIB Technique, MRgRT, Particle Therapy, Immunotherapy and Clinical Guidelines

“…For resected patients, median OS was not reached and PFS was 29.6 months. More recently, a phase II trial on SBRT [122] enrolled 18 patients (15 BRPCs and 3 resectable). After 3 cycles of FOLFIRINOX, SBRT was delivered to the tumor and abutting vessel (33 Gy in 5 fractions) with an optional elective PTV (25 Gy in 5 fractions) including lymph nodes and mesenteric vessels.…”