Abstract

NAJLA SLIM¹, Pietro Pacifico¹, Paolo Passoni¹, Roberta Tummineri¹, Monica Ronzoni², Federica Pedica³, Claudio Fiorino⁴, Anikò Maria Deli¹, Andrea Casadei Gardini⁵, Stefano Cascinu⁵, Francesco De Cobelli⁶, Luca Aldrighetti⁷, Nadia Gisella Di Muzio⁸

¹IRCCS San Raffaele Scientific Institute, Radiation Oncology, Milan, Italy; ²IRCCS San Raffaele Sientific Institute, Medical Oncology, Milan, Italy; ³IRCCS San Raffaele Scientific Institute, Pathologic Anatomy, Milan, Italy; ⁴IRCCS San Raffaele Scientific Institute, Medical Physics, Milan, Italy; ⁵IRCCS San Raffaele Scientific Institute, Medical Oncology, Milan, Italy; ⁶IRCCS San Raffaele Scientific Institute, Radiology, Milan, Italy; ⁷IRCCS San Raffaele Scientific Institute, Surgery, Milan, Italy; ⁸IRCCS San Raffaele Scientific Institute, Vita e salute University, Radiation Oncology, Milan, Italy

Adjuvant radiochemotherapy (RT/ChT) is controversial in patients (pts) with bile duct carcinoma. It improves outcome in pts with R1, lymph nodes (LNs) positive or stage ≥ T2. We report our results of hypofractionated adjuvant IGRT in bile duct carcinoma.

Pts with intra, extra-hepatic or gallbladder cancer were treated. Simulation consisted in contrast-enhanced computed tomography (c-e-CT) or FDG CT/PET, CTV included surgical bed and regional LNs depending on tumor site. PTV was defined adding standard margins (1, 1, 1.5 cm) to CTV. Median RT dose was 44.25 Gy (EQD2=54 Gy) in 15 fractions with SIB up to 50 Gy to R1 or PET + sites when possible respecting OARs. RT was delivered with tomotherapy or VMAT concomitant to capecitabine.

From 05/2009 to 07/2020, 57 pts (32 M; 25 F) were treated. Median age: 68 years (45-86). Twenty-six pts (46%) had Klatskin tumor, 17 pts (30%) common or distal bile duct carcinoma, 7 pts (12%) intrahepatic and 7 pts (12%) gallbladder carcinoma. Pathological staging is reported in the table. ChT was administered as follows: neoadjuvant 5 pts (9%), adjuvant 22 pts (39%), capecitabine concomitant to RT 43 pts (75%). CT/PET simulation was performed in 26 pts (46%) and 14 pts (25%) were PET positive. RT was delivered with tomotherapy: 35 pts (61%), VMAT: 22 pts (39%). Average PTV was 387 cc (110-861). No G3-G4 acute toxicity occurred; only 5 pts (9%) had G3 late toxicity (1 gastric ulcer, 2 stenotic fibrosis, 2 cholangitis). At a median follow up of 21 months (2 m- 118 m) the median overall survival (OS) was 31 months. Median time to local progression (TTLP) and time to local progression (TTDP) from the end of RT were 26 months for both. One, 3 and 5 years OS were 91%, 44% and 23%, respectively. One, 3 and 5 years local failure for survival (LFFS) were 84%, 32% and 11%, respectively. Grading was a significant prognostic factor for OS (G1-G2: 33 m vs G3: 20 m; p=0.038), a trend in favour of G1-G2 was shown for TTLP (G1-G2: 28 m vs G3: 18 m; p=0.08) and TTDP (G1-G2: 27 m vs G3: 19 m; p=0.065). Margin status showed a trend in favour of R0 in term of TTDP (R0: 31 m vs R1: 20 m; p=0.061) and OS (R0: 38 m vs R1: 27 m; p=0.081) but no difference in term of TTLP (R0: 31 m vs R1: 22 m; p=0.12). No significant difference in term of OS, TTLP and TTDP between pT1-T2/pT3-T4 (32 vs 30m, 27 vs 25m and 25 vs 20 m, respectively) and pN0/pN+ (31 vs 35 m, 29 vs 26 m and 29 vs 23 m, respectively).

Adjuvant hypofractionated RT concomitant to capecitabine in bile duct carcinoma is feasible with a good toxicity profile. Grading and margin status were the main predicting outcome factors. Neo/adjuvant ChT can explain the similarity between pT1-T2/pT3-T4 and pN0/pN+ in term of outcome The trend in favour of R0 in term of TTDP and OS while the no difference in term of TTLP suggests to consider RT in neoadjuvant setting to improve post-operative R0.