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Insights into the dose-response relationship of hepatic radioembolization with resin yttrium-90 microspheres: a prospective cohort study in patients with colorectal cancer liver metastases
SUNDAY: Scientific Sessions
S6
’
Sunday
Scientific Session
instances of progression occurring after an initial CR, of which 9 (22.0%) were classified as target progression (RE: 1, MWA: 8). Median (95% CI) overall TTP (m) was 11.1 (8.8-25.6) in the RE group and 12.1 (7.7-19.1) in the MWA group (p¼1.0). Mean survival (m) was 30.8 in the RE group and 42.7 in the MWA group (p¼0.8). After matching (41:41), the following outcomes were not significantly different between the two groups: target CR rate (p*¼0.62), overall CR rate (p*¼0.78), TTP (p*¼0.81), and survival (p*¼1.0). Conclusions: Response and progression outcomes of patients with solitary HCC ≤3 cm treated with radiation segmentectomy were not significantly different compared to MWA ablation.
3:18 PM
Abstract No. 5
Insights into the dose-response relationship of hepatic radioembolization with resin yttrium-90 microspheres: a prospective cohort study in patients with colorectal cancer liver metastases A. van den Hoven1, C. Rosenbaum1, S. Elias1, H. de Jong1, M. Koopman1, H. Verkooijen1, A. Alavi2, M. van den Bosch1, M. Lam1; 1University Medical Center Utrecht, Utrecht, The Netherlands; 2University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Purpose: Randomized controlled trials are investigating the benefit of hepatic radioembolization added to systemic therapy in the first/second-line treatment of patients with colorectal liver metastases (CRLM). Remarkably, administered activity may still be suboptimal, because a dose-response relationship has not been defined. The purpose of this study was to characterize the relationship between tumor absorbed dose and response after 90Y-radioembolization treatment for CRLM. Materials: 30 patients with unresectable chemorefractory CRLM were treated with resin 90Y-microspheres in a prospective phase II clinical trial. Tumor absorbed dose was quantified on 90Y-PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on 18F-FDG-PET, was measured at baseline and 1 month posttreatment. The relationship between tumor absorbed dose and posttreatment metabolic activity was assessed per metastasis, with a linear mixed effects regression model. Results: 133 treated metastases were identified. Mean tumor absorbed dose was 47 ± 24 Gy (range 5 – 136 Gy). A 50% reduction in TLG* was achieved in 46% of metastases, and in 11/ 30 (37%) patients for the sum of metastases. The latter was associated with prolonged median overall survival (11.6 vs. 6.6 months, p ¼ 0.02). A strong, and statistically significant doseresponse relationship was found (p o 0.001). The dose-effect depended on baseline TLG* (p o 0.01). Effective tumor absorbed dose was conservatively estimated at a minimum of 40 – 60 Gy. Conclusions: A strong dose-response relationship exists for the treatment of CRLM with resin microspheres 90Yradioembolization. Treatment efficacy is however still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.
4:03 PM
’
JVIR
Abstract No. 6
Radioembolization for unresectable hepatocellular carcinoma secondary to the hepatitis C virus: a analysis of survival and toxicity stratified by viral load D. Biederman1, J. Titano1, N. Swinburne1, V. Bishay1, G. Gunasekaran1, M. Schwartz1, M. Facciuto1, S. Florman1, A. Fischman1, R. Patel1, N. Tabori1, F. Nowakowski1, R. Lookstein1, E. Kim1; 1Icahn School of Medicine at Mount Sinai, New York, NY. Purpose: To evaluate the effect of viral load (VL) on the toxicity and survival of patients undergoing radioembolization (RE) therapy for unresectable hepatocellular carcinoma (HCC) secondary to the hepatitis C virus (HCV). Materials: A retrospective review of patients with HCC secondary to HCV undergoing glass-based RE therapy was performed. Patients with metastasis and prior RE were excluded from analysis. From 1/2010 to 6/2015 a total of 417 patients received RE therapy for HCC, of which 220 patients (age: 64.8±7.2y, male: 75%) met the above inclusion criteria. VL was examined in the 365 days before and after treatment. All recorded post-treatment laboratory values were analyzed using Kaplan-Meier methods to construct a time-to-toxicity (TTT) metric for grade 3/4 bilirubin (Bili) and AST toxicity. Patients were stratified according to the following variables: HCV genotype, ECOG, portal vein thrombosis (PVT), and tumor distribution. Outcome variables included TTT-Bili, TTT-AST, and overall survival (censored for transplant). Results: Sixty-five (29.5%) patients had an undetectable VL within 365 days of RE, 28 (43.1%) patients prior to RE (-197 ±120d) and 37 (56.9%) patients after RE (142±100d). Post RE grade 3/4 Bili and AST toxicities were observed in 61 (27.7%) and 62 (28.2%) patients respectively. The median (95% CI) TTT (d) was 513 (328-555) for Bili and 577 (423-959) for AST. An undetectable VL was predictive of lower Bili toxicity (p¼0.001, HR: 0.34, 95% CI: 0.20-0.57) and lower AST toxicity (p¼0.02, HR: 0.51, 95% CI: 0.30-0.86). The median overall survival for the cohort was 16.2 (13.7-25.9) months. Improved overall survival was seen in patients with an undectable VL (po0.0001, HR: 0.22, 95% CI: 0.14-0.37). Additional predictors of improved overall survival included ECOGo1 (po0.0001), absence of PVT (p¼0.006), solitary tumor (po0.0001), and a unilobar tumor distribution (p¼0.001). Conclusions: Preliminary analysis of outcomes in patients with HCC secondary to HCV treated with RE suggests VL to be predictive of toxicity and overall survival. A multivariate time dependent co-variate analysis will allow for more robust conclusions.
3:36 PM
Abstract No. 7
Safety of yttrium-90 radioembolization for patients with history of biliary tract instrumentation: a multicenter study N. Fidelman1, K. Devulapalli2, M. Miller3, M. Johnson4, C. Nutting5, J. Morrison6, K. Farsad6, J. Kaufman7, R. Lokken8, J. Bui9, R. Gaba9, J. Fleming10, D.B. Brown10, S. Kwan11, S. Rose12, K. Pennycooke13, D. Liu14, S. White15, C. Zhang2, R. Kerlan16; 1University of
S6
’
Sunday
Scientific Session
instances of progression occurring after an initial CR, of which 9 (22.0%) were classified as target progression (RE: 1, MWA: 8). Median (95% CI) overall TTP (m) was 11.1 (8.8-25.6) in the RE group and 12.1 (7.7-19.1) in the MWA group (p¼1.0). Mean survival (m) was 30.8 in the RE group and 42.7 in the MWA group (p¼0.8). After matching (41:41), the following outcomes were not significantly different between the two groups: target CR rate (p*¼0.62), overall CR rate (p*¼0.78), TTP (p*¼0.81), and survival (p*¼1.0). Conclusions: Response and progression outcomes of patients with solitary HCC ≤3 cm treated with radiation segmentectomy were not significantly different compared to MWA ablation.
3:18 PM
Abstract No. 5
Insights into the dose-response relationship of hepatic radioembolization with resin yttrium-90 microspheres: a prospective cohort study in patients with colorectal cancer liver metastases A. van den Hoven1, C. Rosenbaum1, S. Elias1, H. de Jong1, M. Koopman1, H. Verkooijen1, A. Alavi2, M. van den Bosch1, M. Lam1; 1University Medical Center Utrecht, Utrecht, The Netherlands; 2University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Purpose: Randomized controlled trials are investigating the benefit of hepatic radioembolization added to systemic therapy in the first/second-line treatment of patients with colorectal liver metastases (CRLM). Remarkably, administered activity may still be suboptimal, because a dose-response relationship has not been defined. The purpose of this study was to characterize the relationship between tumor absorbed dose and response after 90Y-radioembolization treatment for CRLM. Materials: 30 patients with unresectable chemorefractory CRLM were treated with resin 90Y-microspheres in a prospective phase II clinical trial. Tumor absorbed dose was quantified on 90Y-PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on 18F-FDG-PET, was measured at baseline and 1 month posttreatment. The relationship between tumor absorbed dose and posttreatment metabolic activity was assessed per metastasis, with a linear mixed effects regression model. Results: 133 treated metastases were identified. Mean tumor absorbed dose was 47 ± 24 Gy (range 5 – 136 Gy). A 50% reduction in TLG* was achieved in 46% of metastases, and in 11/ 30 (37%) patients for the sum of metastases. The latter was associated with prolonged median overall survival (11.6 vs. 6.6 months, p ¼ 0.02). A strong, and statistically significant doseresponse relationship was found (p o 0.001). The dose-effect depended on baseline TLG* (p o 0.01). Effective tumor absorbed dose was conservatively estimated at a minimum of 40 – 60 Gy. Conclusions: A strong dose-response relationship exists for the treatment of CRLM with resin microspheres 90Yradioembolization. Treatment efficacy is however still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.
4:03 PM
’
JVIR
Abstract No. 6
Radioembolization for unresectable hepatocellular carcinoma secondary to the hepatitis C virus: a analysis of survival and toxicity stratified by viral load D. Biederman1, J. Titano1, N. Swinburne1, V. Bishay1, G. Gunasekaran1, M. Schwartz1, M. Facciuto1, S. Florman1, A. Fischman1, R. Patel1, N. Tabori1, F. Nowakowski1, R. Lookstein1, E. Kim1; 1Icahn School of Medicine at Mount Sinai, New York, NY. Purpose: To evaluate the effect of viral load (VL) on the toxicity and survival of patients undergoing radioembolization (RE) therapy for unresectable hepatocellular carcinoma (HCC) secondary to the hepatitis C virus (HCV). Materials: A retrospective review of patients with HCC secondary to HCV undergoing glass-based RE therapy was performed. Patients with metastasis and prior RE were excluded from analysis. From 1/2010 to 6/2015 a total of 417 patients received RE therapy for HCC, of which 220 patients (age: 64.8±7.2y, male: 75%) met the above inclusion criteria. VL was examined in the 365 days before and after treatment. All recorded post-treatment laboratory values were analyzed using Kaplan-Meier methods to construct a time-to-toxicity (TTT) metric for grade 3/4 bilirubin (Bili) and AST toxicity. Patients were stratified according to the following variables: HCV genotype, ECOG, portal vein thrombosis (PVT), and tumor distribution. Outcome variables included TTT-Bili, TTT-AST, and overall survival (censored for transplant). Results: Sixty-five (29.5%) patients had an undetectable VL within 365 days of RE, 28 (43.1%) patients prior to RE (-197 ±120d) and 37 (56.9%) patients after RE (142±100d). Post RE grade 3/4 Bili and AST toxicities were observed in 61 (27.7%) and 62 (28.2%) patients respectively. The median (95% CI) TTT (d) was 513 (328-555) for Bili and 577 (423-959) for AST. An undetectable VL was predictive of lower Bili toxicity (p¼0.001, HR: 0.34, 95% CI: 0.20-0.57) and lower AST toxicity (p¼0.02, HR: 0.51, 95% CI: 0.30-0.86). The median overall survival for the cohort was 16.2 (13.7-25.9) months. Improved overall survival was seen in patients with an undectable VL (po0.0001, HR: 0.22, 95% CI: 0.14-0.37). Additional predictors of improved overall survival included ECOGo1 (po0.0001), absence of PVT (p¼0.006), solitary tumor (po0.0001), and a unilobar tumor distribution (p¼0.001). Conclusions: Preliminary analysis of outcomes in patients with HCC secondary to HCV treated with RE suggests VL to be predictive of toxicity and overall survival. A multivariate time dependent co-variate analysis will allow for more robust conclusions.
3:36 PM
Abstract No. 7
Safety of yttrium-90 radioembolization for patients with history of biliary tract instrumentation: a multicenter study N. Fidelman1, K. Devulapalli2, M. Miller3, M. Johnson4, C. Nutting5, J. Morrison6, K. Farsad6, J. Kaufman7, R. Lokken8, J. Bui9, R. Gaba9, J. Fleming10, D.B. Brown10, S. Kwan11, S. Rose12, K. Pennycooke13, D. Liu14, S. White15, C. Zhang2, R. Kerlan16; 1University of