Ethan B. Ludmir, MD, an associate professor in the Department of Gastrointestinal Radiation Oncology at The University of Texas MD Anderson Cancer Center, spoke with CancerNetwork® ahead of the 2026 Chicago Cholangiocarcinoma Symposium about the rationale for moving radiation therapy into the neoadjuvant setting for borderline resectable or locally advanced cholangiocarcinoma.
Ludmir noted that most existing data support radiotherapy in the adjuvant setting, including the phase 2 SWOG S0809 trial (NCT00789958), where radiation served as a “cleanup crew” for patients with margin-positive resections or other adverse pathologic features. Drawing on experience in pancreatic cancer, a “sister disease” to distal extrahepatic cholangiocarcinoma, he explained that patients tend to tolerate neoadjuvant radiation better than adjuvant treatment and that preoperative radiation may improve the likelihood of an R0 resection. He also described variation in how surgeons view the effect of preoperative radiation on tissue planes around the vasculature.
Transcript:
CancerNetwork: What clinical rationale supports shifting radiation therapy into the neoadjuvant setting for borderline resectable or locally advanced cholangiocarcinoma, rather than reserving it for definitive or postoperative adjuvant management?
Ludmir: It speaks to a lot of the unknowns in treating cholangiocarcinoma. We have most of our data for using radiotherapy in the adjuvant setting; the SWOG S0809 trial and several others that use radiation, for lack of another way of putting it, as a cleanup crew, particularly for margin-positive resections. Those trials included anyone with any adverse pathologic features, such as pathologic T2 disease or higher or pathologic node positivity. Most patients with extrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, or gallbladder disease could qualify for adjuvant radiation if you use those trials as the paradigm.
We extrapolate from diseases like pancreatic cancer, which is a reasonable sister disease, in a way, if you think about distal extrahepatic cholangiocarcinoma, which often shows up in the head of the pancreas. Patients tend to tolerate neoadjuvant radiation a lot better than adjuvant radiation, so we tend to think that, from a patient-centric standpoint, it’s a little bit better tolerated in the neoadjuvant setting. If you believe data in the pancreas space, especially in borderline resectable pancreatic cancer, there seems to be some benefit of neoadjuvant radiation in achieving an R0 resection—getting everything out when the surgeon goes to the [operating room].
There are limitations and caveats there. Radiation can influence how things are for surgeons in the surgical field, and this gets down to individual practitioner variation and expertise. Some of our surgeons in the pancreas space, for instance, feel very strongly that neoadjuvant radiation, if delivered just so, 6 or 8 weeks before surgery, can help create edematous tissue planes that can help remove disease away from the vasculature. It might be a net positive, but there’s heterogeneity in how people practice.
Reference
Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33(24):2617-2622. doi:10.1200/JCO.2014.60.2219
