Major impact of personalized dosimetry using 90Y loaded glass microspheres SIRT in HCC: Final overall survival analysis of a multicenter randomized phase II study (DOSISPHERE-01).

Abstract

516 Background: 90Y loaded microsphere SIRT (radioembolization) is a treatment option in advanced HCC. However, no personalized dosimetric endpoints are currently used. The goal of this study was to compare the efficacy of 90Y loaded glass microsphere SIRT in HCC using a standard versus a personalized dosimetric approach. Methods: DOSISPHERE-01 was a multicenter, randomized phase 2 trial in unresectable HCC patients with at least one tumor ≥7cm. Treatment arm was randomly assigned (1:1) to standard dosimetry arm (SDA), with a goal to deliver 120±20Gy to the treated volume or to personalized dosimetry arm (PDA) with a goal to deliver at least 205Gy to the index lesion. The primary endpoint was the response rate (RR) of the index lesion according to EASL criteria. Secondary endpoints included dose response evaluation, safety and overall survival (OS). Results: Sixty HCC patients were randomized (PDA 31, SDA 29, intent to treat population-ITTP-), and 56 treated (28 in each arm). RR was significantly increased in the PDA versus the SDA, in the ITTP, respectively 64.5% versus 31% (p=0.0095) as in the safety population -SP- (treatment effectively received, personalized 35, standard 21), respectively 74.3% versus 14.3% (p<0.0001). Median OS was significantly increased in the PDA versus the SDA, in the ITTP, respectively 26.7m (CI 95%:11.7-NR) versus 10.6m (CI 95%:6-16.8), p=0.0096, HR=0.421 (95%CI:0.215-0.826), p=0.0119, as in the SP, respectively 26.7m (CI 95%:11.7- NR) versus 9.5m (CI 95%:4.8-14.9), p=0.0015, HR=0.342 (95%CI:0.171-0.683), p=0.0023. Median OS was 26.7m (CI 95%:13.5-NR) versus 6.0m (CI 95%:3.8-14.9) for the patients who received a tumor dose ≥205 Gy or <205 Gy respectively, p=0.0106, HR=0.336 (95%CI:0.154-0.735), p=0.0063. Treatment-related clinically relevant hepatic ≥grade 3 AEs were observed in 5.7% and 14.2% of the patients of the PDA and SDA arms, respectively, (p=ns). Conclusions: MAA SPECT/CT based personalized dosimetry is safe and dramatically increased RR and OS of HCC patients. These results question the interpretation of all phase 3 trials of SIRT designed without personalized dosimetry in HCC. Clinical trial information: 2015-A00894-45.

Personalised Dosimetry in Radioembolisation for HCC: Impact on Clinical Outcome and on Trial Design

“…The results of a multicentre randomized phase 2 study comparing personalized dosimetry and standard dosimetry with glass microspheres in patients with a least one lesion larger than 7 cm were recently communicated [53]. In this study, 60 patients were randomized to receive standard dosimetry (perfused liver dose of 120 ± 20 Gy) or personalized dosimetry (targeting more than 205 Gy to the tumor).…”

“…Whether to choose a tumor load of less than 70% or less than 50% is also a matter of debate, and tumor extension (unilobar or bilobar) has to be discussed regarding the safety. In DOSISPHERE-01 study exclusion of patients, where it is not possible to spare from radiation, at least 30% of the liver volume is a good point, because it is possible to increase doses without increasing liver toxicities [53].…”

Diagnosis, Staging, and Patient Selection for Locoregional Therapy to Treat Hepatocellular Carcinoma

“…A recent RCT assessing boosted doses of TARE with ablative intent (>205 Gy) in intermediate-and advanced-staged patients with tumors greater than 10 cm, many with portal vein thrombosis, has also shown promising overall survival improvements of approximately 20 months. 48 Currently, there is no role for surgery (other than transplantation) or minimally invasive, image-guided procedures for the treatment of end-stage HCC (BCLC D, HKLC V). Management is mostly directed at symptom control rather than prolonging life.…”

Mode of progression after radioembolization in patients with colorectal cancer liver metastases

“…These methods can lead to underdosing [59,60]. A personalized treatment approach, as was used in the DOSISPHERE study in HCC patients, could have led to a much higher response rate [61]. The results of earlier studies on the dose-response relations in mCRC patients treated with 90 Y-resin or 166 Ho prove this point: a significant dose-response relationship was found in both studies [22,62].…”