Prior stereotactic body radiotherapy (SBRT) experiences for treatment of locally advanced
pancreatic cancer entailed either single-fraction or multi-fraction approaches delivering
33 Gray (Gy) in 5 fractions. Excellent tolerance and tumor control has been demonstrated,
but median survival remained approximately 14 months. This highlights the strengths and
limitations of SBRT to current radiation doses for pancreatic cancer. A prior Washington
University institutional study and retrospective review has shown the safety of
delivering 67.5 Gy in 15 fractions for inoperable pancreatic cancer using a strict
'isotoxicity' approach of limiting the gastrointestinal (GI) organs at risk (stomach,
duodenum, small bowel and large bowel) to 45 Gy to 0.5 cm3 or less. This regimen resulted
in no grade 3 or higher GI toxicities, and only one death in the 19 patients with a
median follow-up of 15 months. This is significantly improved from prior experiences,
where approximately 15 months represents the median survival for most studies of
inoperable pancreatic cancer.
A recent retrospective analysis of 42 locally advanced pancreatic cancer patients treated
by magnetic resonance imaging (MRI) guided radiation therapy at four institutions
(University of California, Los Angeles, University of Wisconsin, Vrije Universiteit
Medical Center (VUmc), Amsterdam, and Washington University, St. Louis) demonstrated that
high-dose stereotactic body radiotherapy (SBRT) or hypofractionated radiation therapy
delivered using daily ADAPTIVE dose planning on an MRI-guided radiotherapy system
(MRIdian, ViewRay Inc.) has the potential to further improve overall survival. A control
group of 19 patients treated to more conventional radiation doses without frequent dose
adaptation showed a median survival of 14.8 months, while patients treated to high
radiation doses (n=23, maximum biologically equivalent dose at alpha/beta = 10 Gy, or
BED10 of > 90 Gy) under daily or almost daily adaptive re-planning had an estimated
median survival of 27.8 months (p=0.005). Interestingly, increased radiation dose
delivery using daily dose adaptation was correlated with less grade 3 toxicity (0% in the
high dose group vs 15.8% in patients treated to lower radiation doses without dose
adaptation).
The compelling data of this retrospective study prompted the development of this current
prospective clinical trial designed to assess the primary objective of grade 3 or greater
GI toxicity at 90 days for patients with borderline resectable or inoperable locally
advanced pancreatic cancer treated with MRI-guided on-table adaptive radiation therapy
and soft tissue tracking with radiation beam gating to 50 Gy in 5 fractions. Secondary
objectives include assessment of (1) overall survival at 2 years, (2) distant progression
free survival at 6 months, and (3) changes in patient-reported quality of life (QOL) from
pre-treatment to 3 and 12 months post-treatment.
