Survival and Toxicities after 90Y Transarterial Radioembolization of Metastatic Colorectal Cancer in the RESIN Registry.

Background Patients with unresectable, chemorefractory hepatic metastases from colorectal cancer have considerable mortality. The role of transarterial radioembolization (TARE) with yttrium 90 (90Y) microspheres is not defined because most reports are from a single center with limited patient numbers. Purpose To report outcomes in participants with colorectal cancer metastases treated with resin 90Y microspheres from a prospective multicenter observational registry. Materials and Methods This study treated enrolled adult participants with TARE using resin microspheres for liver-dominant metastatic colorectal cancer at 42 centers, with enrollment from July 2015 through August 2020. TARE was used as the first-, second-, or third-line therapy or beyond. Overall survival (OS), progression-free survival (PFS), and toxicity outcomes were assessed by line of therapy by using Kaplan-Meier analysis for OS and PFS and Common Terminology Criteria for Adverse Events, version 5, for toxicities. Results A total of 498 participants (median age, 60 years [IQR, 52-69 years]; 298 men [60%]) were treated. TARE was used in first-line therapy in 74 of 442 participants (17%), second-line therapy in 180 participants (41%), and third-line therapy or beyond in 188 participants (43%). The median OS of the entire cohort was 15.0 months (95% CI: 13.3, 16.9). The median OS by line of therapy was 13.9 months for first-line therapy, 17.4 months for second-line therapy, and 12.5 months for third-line therapy (χ2 = 9.7; P = .002). Whole-group PFS was 7.4 months (95% CI: 6.4, 9.5). The median PFS by line of therapy was 7.9 months for first-line therapy, 10.0 months for second-line therapy, and 5.9 months for third-line therapy (χ2 = 8.3; P = .004). TARE-attributable grade 3 or 4 hepatic toxicities were 8.4% for bilirubin (29 of 347 participants) and 3.7% for albumin (13 of 347). Grade 3 and higher toxicities were greater with third-line therapy for bilirubin (P = .01) and albumin (P = .008). Conclusion Median overall survival (OS) after transarterial radioembolization (TARE) with yttrium 90 microspheres for liver-dominant metastatic colorectal cancer was 15.0 months. The longest OS was achieved when TARE was part of second-line therapy. Grade 3 or greater hepatic function toxicity rates were less than 10%. Clinical trial registration no. NCT02685631 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Incidence and risk factors for sustained hepatic function toxicity 6 months after radioembolization: analysis of the radiation-emitting sir-spheres in non-resectable liver tumor (RESIN) registry.

BACKGROUND: To quantify rates and risk factors for toxicity after hepatic radioembolization using resin yttrium-90 microspheres. METHODS: Radiation-Emitting SIR-Spheres in Non-resectable liver tumor (RESIN) registry enrollees were reviewed with 614 patients included. Mean patient age was 63.1±12.5 years. The majority of patients were male (n=375, 61%) and white (n=490, 80%). Common tumor types were hepatocellular (n=197, 32%), colorectal (n=187, 30%) and neuroendocrine (n=56, 9%). Hepatotoxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE v 5). Potential risk factors for hepatotoxicity were tested using the Kruskal-Wallis or Pearson Chi-squared tests, and multivariate linear regressions. RESULTS: At 6 months, 115 patients (18.7%) died (n=91, 14.8%), entered hospice (n=20, 3.3%) or sought treatment elsewhere (n=4, 4%). Seven (1.1%) deaths were from liver decompensation. Grade 3 toxicity rates were: bilirubin (n=85, 13.8%), albumin (n=28, 4.6%), ALT (n=26, 4.2%) and AST (n=37, 6.0%). For each of these liver function test components, baseline abnormal labs predicted Grade 3 toxicity at follow-up by Kruskal-Wallis test (P<0.001) and linear regression (all P<0.03). Other significant factors predicting toxicity at regression included elevated Body-Mass Index (albumin P=0.0056), whole liver treatment (bilirubin P=0.046), and lower tumor volume (ALT and INR, P<0.035 for both). CONCLUSIONS: Baseline liver function abnormalities prior to radioembolization is the strongest predictor of post-treatment Grade 3 toxicity with rates as high as 13.8%. Toxicity rates for specific lab values are affected by large volume treatments especially with low tumor volumes.

Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation (SOLSTICE).

OBJECTIVE: To assess the safety and local recurrence-free survival in patients after cryoablation for treatment of pulmonary metastases. METHODS: This multicenter, prospective, single-arm, phase 2 study included 128 patients with 224 lung metastases treated with percutaneous cryoablation, with 12 and 24 months of follow-up. The patients were enrolled on the basis of the outlined key inclusion criteria, which include one to six metastases from extrapulmonary cancers with a maximal diameter of 3.5 cm. Time to progression of the index tumor(s), metastatic disease, and overall survival rates were estimated using the Kaplan-Meier method. Complications were captured for 30 days after the procedure, and changes in performance status and quality of life were also evaluated. RESULTS: Median size of metastases was 1.0 plus or minus 0.6 cm (0.2-4.5) with a median number of tumors of 1.0 plus or minus 1.2 cm (one to six). Local recurrence-free response (local tumor efficacy) of the treated tumor was 172 of 202 (85.1%) at 12 months and 139 of 180 (77.2%) at 24 months after the initial treatment. After a second cryoablation treatment for recurrent tumor, secondary local recurrence-free response (local tumor efficacy) was 184 of 202 (91.1%) at 12 months and 152 of 180 (84.4%) at 24 months. Kaplan-Meier estimates of 12- and 24-month overall survival rates were 97.6% (95% confidence interval: 92.6-99.2) and 86.6% (95% confidence interval: 78.7-91.7), respectively. Rate of pneumothorax that required pleural catheter placement was 26% (44/169). There were eight grade 3 complication events in 169 procedures (4.7%) and one (0.6%) grade 4 event. CONCLUSION: Percutaneous cryoablation is a safe and effective treatment for pulmonary metastases.

Imaged guided transarterial chemoembolization with drug-eluting beads loaded with doxorubicin (DEBDOX) for hepatic metastases from melanoma: early outcomes from a multi-institutional registry.

Patients with unresectable hepatic metastases from melanoma present a difficult clinical challenge due to lack of locoregional control and poor response to systemic chemotherapy. This study aims to examine the early outcomes of the novel treatment of unresectable hepatic metastases from melanoma with drug-eluting beads loaded with doxorubicin (DEBDOX) delivered via image guided transarterial chemoembolization. A multicenter prospective open registry of hepatic-directed therapy with drug-eluting beads was reviewed. Six patients underwent 12 DEBDOX treatments for liver-predominant, unresectable metastases from melanoma. Six adverse events (grade 1 or 2) were exhibited in three patients and were most commonly emesis, nausea, and pain. Over a median follow-up of 12 months (range: 6-17), response rates of 100 per cent, 83 per cent, and 60 per cent were observed at 3, 6, and 9 months respectively, based on standardized computed tomographic criteria. A median survival of 12.3 months after initial DEBDOX treatment was observed. Initial results for liver-directed therapy of hepatic-dominant metastatic disease from melanoma with DEBDOX demonstrate that this is a safe and well-tolerated treatment option with favorable response rates and survival characteristics at this point in follow-up. Salvage therapy with DEBDOX should be considered in the multidisciplinary therapy for this clinical dilemma.