Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma

Inclusion criteria translational part of the study: In order to be eligible to participate in the translational part of the study, a subject must be discussed in a liver tumor board, should be eligible for gemcitabine-based chemotherapy (and immunotherapy, if applicable), and should meet all of the following criteria pre-chemotherapy: * Perihilar cholangiocarcinoma (pCCA) according to the criteria of the Mayo Clinic, Rochester: a positive or strongly suspicious intraluminal brush cytology or biopsy, or a radiographic malignant appearing stricture plus either: CA 19-9\>100 U/ml in the absence of acute bacterial cholangitis, or polysomy on fluorescence in situ hybridization (FISH), or a well-defined mass on cross sectional imaging * One tumor mass * Unresectable tumor or patient deemed unfit for surgery * T1-T4 (AJCC staging 8th edition), N0-N2-M0 (AJCC staging 8th edition), radiologically or pathologically suspect. N1 is defined as one to three affected lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. N2 is defined as four or more affected lymph nodes from the sites described for N1. Endoscopic ultrasound (EUS) is leading in identifying pathological lymph nodes compared to CT. * In case of (underlying) liver cirrhosis: Child-Pugh A * Age ≥ 18 years * ECOG performance status 0-1 * Written informed consent for the translational part of the study Inclusion criteria SBRT part of the study: In addition to the criteria mentioned above, patients should meet the following criteria to be eligible for the treatment with SBRT: * Measurable disease to be selected as a target on a computed tomography (CT) or magnetic resonance imaging (MRI) scan, according to RECIST 1.1 criteria * Finished gemcitabine-based chemotherapy treatment, preferably 8 cycles. If less cycles are given, patients are still eligible for this study * Bilirubin ≤3.0 times normal value, aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤5 times ULN * Platelets ≥ 50x10E9/ l, Leukocytes \> 1.5x10E9/l, Hemoglobin (Hb) \> 6 mmol/l * Willing and able to comply to the follow-up schedule * Able to start SBRT within 12 weeks after completion of chemotherapy and immuno-therapy (if applicable) * Written informed consent for the SBRT part of the study Exclusion criteria translational part of the study: * Prior surgery or transplantation of the liver * Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall * Ascites * Prior radiotherapy to the liver * Current pregnancy * Affected lymph nodes outside the regions described in the inclusion criteria Exclusion criteria SBRT part of the study: Progression (local or distant) during or after chemotherapy