Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90 Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study.

PURPOSE: To define a threshold radiation dose to non-tumoral liver from 90Y radioembolization that results in hepatic toxicity using pair-production PET. MATERIALS AND METHODS: This prospective single-arm study enrolled 35 patients undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with liver metastases) were included in the final analysis. Of 27 patients with underlying cirrhosis, 22 and 5 patients were Child-Pugh A and B, respectively. Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients, respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%) patients, respectively. Volumetric analysis was performed on post-radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE grade ≤ 1 compared to grade ≥ 2. RESULTS: The median dose delivered to the non-tumoral liver in the treated lobe was 49 Gy (range 0-133). A total of 15 patients had grade ≤ 1 hepatic toxicity, and 19 patients had grade ≥ 2 toxicity. Patients with a grade ≥ 2 change in composite toxicity (70.7 vs. 43.8 Gy), bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1 Gy) have significantly higher non-tumoral parenchymal doses than those with grade ≤ 1. Liver parenchymal dose and Child-Pugh status predicted grade ≥ 2 toxicity, observed above a dose threshold of 54 Gy. CONCLUSION: Increasing delivered 90Y dose to non-tumoral liver measured by internal pair-production PET correlates with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a dose threshold of 54 Gy. ClinicalTrials.gov identifier: NCT02848638.

Prospective Trial Using Internal Pair-Production Positron Emission Tomography to Establish the Yttrium-90 Radioembolization Dose Required for Response of Hepatocellular Carcinoma.

PURPOSE: To prospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. METHODS AND MATERIALS: A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. RESULTS: Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225 Gy vs 83 Gy, P < .01). Logistic regression models show tumor dose (P = .002) strongly predicted objective response. All nonresponders had tumor dose <200 Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders. CONCLUSIONS: Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225 Gy, compared with 83 Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.

Judgment analysis of prioritization decisions within a dialysis program in one United Kingdom region.

BACKGROUND: Some previous research on rationed clinical services has confused the conceptual differences underpinning prioritization decisions on the one hand and assessments of individual need on the other. The balance of the clinical and nonclinical drivers of these decisions can be different. Our objective was to study the basis and extent of variation among nephrologists in one NHS region in their views concerning prioritization for dialysis. DESIGN AND METHODS: In a clinical judgment analysis, multiple regression analysis was used to express the impact of clinical and nonclinical cues on nephrologists' decisions to offer dialysis and attribute priority to 50 "paper patients." Cues were selected for the decision-making models using stepwise (backward) elimination of variables. Further "policy" models for priority were derived by forcing in the doctors' views about the capacity of dialysis to extend life expectancy or improve its quality. RESULTS: Comparison of "propensity to offer" and "prioritization" decision models showed a modest degree of correspondence. Among the nonrenal cues, the patient's mental state made the single greatest contribution to the priority decision models (mean contribution to R2 = 12.1, with temporary or permanent confusional states in patients changing the priority [1-50] by an average of 15 rank places). Although patient age significantly influenced the decision models of half of the doctors, the beta-coefficients were very modest, suggesting a change in rank order of no more than one place. There was a significant improvement in the overall explained variance (R2) of the models when varying perceptions of the capacity of dialysis to improve the quality or extend the duration of the patient's life were forced into the model. Although, in general, temporary or permanent confusion in the patient down-graded the priority for dialysis by between 10 and 20 places, this tendency was largely unchanged when the doctors' perceptions of benefit were forced into the priority model. Among renal cues, the presence of uremic symptoms had the greatest impact on priority (mean contribution to R2 = 49.1, mean beta-coefficient -17.1), whereas the presence of other comorbid disease had relatively little effect. CONCLUSIONS: When forced to rank patients, the nonrenal factor that had the most significant bearing on perceived priority for dialysis was the patient's mental state. However, the impact of the patient's mental state on priority did not appear to be driven by its influence on the doctors' perceptions of how dialysis might improve quality of life.