To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer

Abstract

Purpose To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer. Methods A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded. Results A total of 3038 records were identified of which 487 were screened based on the full text. Ultimately, 37 studies were included for narrative analysis. Meta-analysis could not be performed due to the large heterogeneity in study and reporting designs. Out of 37 studies, 30 reported a ‘mean dose threshold’ that needs to be achieved in order to expect a response. This threshold appears to be higher for hepatocellular carcinoma (HCC, 100–250 Gy) than for colorectal cancer metastases (CRC, 40–60 Gy). Reported thresholds tend to be lower for resin microspheres than when glass microspheres are used. Conclusion Although the existing evidence demonstrates a dose-response relationship in SIRT for both primary liver tumours and liver metastases, many pieces of the puzzle are still missing, hampering the definition of standardized dose thresholds. Nonetheless, most current evidence points towards a target mean dose of 100–250 Gy for HCC and 40–60 Gy for CRC. The field would greatly benefit from a reporting standard and prospective studies designed to elucidate the dose-response relation in different tumour types.

Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery

“…Most importantly, it suggests that, in most cases, the maximum achievable mean tumour dose has not been reached, a maximum which can only be achieved by microsphere saturation of the tumour microvasculature. This leaves a room for personalized treatment optimization, as an increased tumour dose has been correlated with an improved response rate [9]. Using an image-guided approach, more microspheres could be injected until the point of complete tumour saturation, as long as the healthy liver dose remains below the toxicity threshold.…”

“…The treatment parameters such as injected activity and injection positions are partly based on a treatment simulation, and the resulting absorbed dose distribution is only assessed after treatment. As a result, not all tumours necessarily receive an adequate dose and, indeed, many patients have a suboptimal response to TARE [9].…”

Study Protocol: Adjuvant Holmium-166 Radioembolization After Radiofrequency Ablation in Early-Stage Hepatocellular Carcinoma Patients—A Dose-Finding Study (HORA EST HCC Trial)

“…Another possible synergetic result may be a radiation-induced inhibition of repair and recovery and increased free radical formation, as observed in animal tumour models with RFA and transarterial chemoembolization (TACE) [ 14 ]. Transarterial radioembolization (TARE) provides an alternative way of delivering adjuvant radiation therapy by means of radioactive microspheres that are administered selectively in the hepatic artery using a high tumour dose and a low toxicity to the healthy liver parenchyma [ 15 , 16 ].…”

Development of an MRI-Guided Approach to Selective Internal Radiation Therapy Using Holmium-166 Microspheres

“…A similar benefit of personalizing the radiation dose was demonstrated in SIRT in the DOSISPHERE-01 trial, leading to both an increase in local response (71% vs. 36%) and survival (26.6 mo vs. 7.1 mo), without an increase in adverse events [12]. Moreover, a lot of research has investigated the doseresponse relation in SIRT and it has been shown that an improved tumour dose leads to an improved response, both in terms of liver progression-free and in overall survival [13].…”