The role of biological dose-escalation for pancreatic cancer

The role of chemo-radiotherapy for treatment of locally advanced pancreatic cancer (LAPC) has been discussed for many years, and the absence of an overall survival benefit compared to gemcitabine chemotherapy alone in the recent LAP07 study seems to have increased the controversy. However, even in this study, chemo-radiotherapy resulted in decreased local progression (p = 0.03). In combination with increased efficacy of novel systemic therapy consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX), radiation dose-escalation may show to be beneficial in LAPC. Stereotactic body radiation therapy (SBRT) can be expected to be the most suitable approach to perform local radiation dose-escalation, and has been shown to be both effective and tolerable at doses of 25-35 Gy in 3-5 fractions. Whether further dose-escalation for LAPC will be both feasible and useful is debatable, because of dose restrictions to adjacent critical organs at risk, and the observation that thus far a benefit of delivering BED₁₀ in excess of 70 Gy has not shown to improve local control significantly. If an attempt to further dose-escalate is performed, stereotactic MR-guided adaptive radiation therapy (SMART) theoretically has the highest potential. In addition to superior soft-tissue setup without the need for implanted fiducial markers and online MR-guidance during delivery with minimal safety margins, daily plan adaptation directed at avoiding undue high doses to critical organs such as the duodenum, stomach and bowel are advantages of this technique over current SBRT. This paper aims to illustrate the SMART technique, which has been delivered in 300 fractions for LAPC or locally recurrent pancreatic cancer at Amsterdam UMC since early 2016.