Hugo Levillain1, Ivan Duran Derijckere2, Lieveke Ameye3, Thomas Guiot4, Arthur Braat5, Carsten Meyer6, Bruno Vanderlinden4, Nick Reynaert4, Alain Hendlisz7, Marnix Lam5, Christophe M Deroose8, Hojjat Ahmadzadehfar9, Patrick Flamen2. 1. Nuclear Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium. hugo.levillain@bordet.be. 2. Nuclear Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium. 3. Data Center Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium. 4. Medical Physics Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium. 5. Radiology and Nuclear Medicine Department, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands. 6. Radiology Department, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. 7. Digestive Oncology Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium. 8. Department of Imaging and Pathology, Nuclear Medicine, University Hospitals Leuven and Nuclear Medicine and Molecular Imaging, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. 9. Nuclear Medicine Department, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Abstract
PURPOSE: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome. METHODS: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox's proportional hazards model. RESULTS: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy). CONCLUSION: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.
PURPOSE: Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome. METHODS: This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin 90Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline 18F-FDG-PET/CT. 99mTc-MAA tumor to liver uptake ratio (TLRMAA) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox's proportional hazards model. RESULTS: Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLRMAA < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy). CONCLUSION: Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.
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