Pancreatic cancer is a leading cause of cancer death in the US.¹ For patients with localized disease, surgery and systemic therapy provide the best opportunity for durable cancer control. Resection with negative margins is associated with the best outcomes,² but is often hindered by mesenteric vessel involvement. Long-term survival associated with incompletely resected and unresected tumors has not surpassed a median of 12 months and 2-year rate of 20%. In randomized trials, conventional doses of radiation therapy (RT) as a consolidation strategy after gemcitabine for unresected tumors do not improve patient survival.^3-5 Multiagent chemotherapy regimens have since been shown to be superior to gemcitabine. However, the importance of local tumor control remains, and is illustrated by the survival limitation in patients with localized tumors who cannot have surgery compared with those who can. Recent technological advancements and innovative solutions for managing internal organ motion have enabled safe RT dose escalation. Early reports of dose escalation to an ablative threshold in small cohorts suggested that controlling the primary tumor can improve survival.^6,7 We report mature data on a 119-patient, uniformly treated cohort with regard to ablative RT (A-RT) as well as diagnostic, therapeutic, and supportive care pathways.

Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract. Advanced organ motion management, image guidance, and adaptive planning techniques enable delivery of ablative doses of radiation (> = 100Gy BED) when more protracted hypofractionated regimens or advanced image guidance and adaptive planning are used. This approach has resulted in encouraging improvements in survival in several studies. This review will summarize the evolution of the radiation technique over time from conventional to ablative and describe the practical aspects of delivering ablative doses near the GI tract using cone beam CT image (CBCT) guidance and online adaptive MRI guidance.

Intrahepatic cholangiocarcinoma often causes death due to obstruction of the biliary system or interruption of the vascular supply of the liver. This fact emphasizes the critical need for local tumor control in this disease. Successful local tumor control has traditionally been achievable through surgical resection for the small proportion of patients with operable tumors. Technological advances in radiation oncology and in interventional radiology have enabled the delivery of ablative radiation doses or other cytotoxic therapies for tumors in the liver. In some cases, this has translated into substantial prolongation of life for patients with this disease, but the indications for these different treatment options are still the subject of ongoing debate. Here, we review the technological advances and clinical studies that are changing the way intrahepatic cholangiocarcinoma is managed, and discuss ways to achieve individualized treatment of patients.

Ablative radiation therapy (A-RT) appears to improve outcomes in locally advanced pancreatic cancer (LAPC) yet requires solutions for respiratory and digestive motion. We report outcomes of A-RT for pancreatic cancer using 1.5 T MR-adaptive treatment delivery. Between March 2020 and July 2021, we treated 30 patients with pancreatic cancer with 50 Gy in 5 fractions (biologically effective dose [BED10] = 100 Gy10) using a novel compression belt workflow and remote planning on the Unity 1.5 T MR linac system. Cumulative incidence of progression was computed from A-RT initiation with death as a competing risk. Overall (OS) and progression-free survival (PFS) were calculated using Kaplan Meier methods. Of 30 patients, most (73 %) were locally advanced, 4 (13 %) were metastatic, 2 (7 %) were medically inoperable, and 2 (7 %) were locally recurrent. Most (73 %) received FOLFIRINOX prior to A-RT. Median follow-up times from diagnosis and A-RT were 17.6 (IQR 15.8–23.1) and 11.5 months (IQR 9.7–16.1), respectively. Cumulative incidences at 1-year of local and distant progression were 19.3 % (95 %CI 6.7–36.8 %) and 47.4 % (95 %CI 26.7–65.6 %), respectively. Median OS from diagnosis and A-RT were not reached. One-year OS from diagnosis and A-RT were 96.4 % (95 %CI 77.2–99.5 %) and 80.0 % (95 %CI 57.3–91.4 %), respectively. Median and 1-year PFS were 10.1 months (95 %CI 4.4–14.4) and 39.7 % (95 %CI 20.3–58.5 %), respectively. No grade 3 + toxicities were observed. A-RT using the 1.5 T Unity MR Linac resulted in promising LC and OS with no severe toxicity in patients with LAPC despite radiosensitive organs adjacent to the target volumes. Longer follow-up is needed to assess long-term outcomes.