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Purpose <p>The liver is the commonest site of metastases in neuroendocrine neoplasias (NENs) and is an independent predictor of poor outcome. Selective internal radiation therapy (SIRT) allows selective delivery of high dose radiation to liver tumours and has shown promise in the management of NENs. We determined the safety and efficacy of SIRT for inoperable liver metastases secondary to NENs. Dose-response and dose-toxicity relationship were assessed.</p> Methods <p>A prospective, multicentre, phase 2 study was conducted. Primary outcomes were objective response rate (ORR) in the treated liver volume according to RECIST 1.1 and mRECIST criteria, incidence and severity of adverse events (AEs) at 6 months. Secondary outcomes were hepatic specific progression free survival, PFS, overall survival (OS), change in quality of life (QoL). Tumour dose-response relationship was derived retrospectively from post therapy yttrium-90 bremsstrahlung single photon emission computed tomography/CT for both the tumour and perfused normal liver.</p> Results <p>21 patients were analysed; majority had grade 2 NEN (67%) and were heavily pretreated, 76% having received prior systemic therapy including peptide receptor radiotherapy (33%). ORR by RECIST 1.1 and mRECIST were 14% and 45%, respectively. Median hepatic specific PFS, PFS and OS were 48.1, 13.3 and 49.9 months respectively. Only 3 patients experienced grade 3 AEs; 2 radiation-induced liver disease that resolved without sequelae and one arterial plug migration. No significant deterioration in QoL was observed following SIRT. Dosimetry analysis found a clear tumour dose/response relationship for 3-month ORR. Mean tumour dose in responders was 372&#xa0;Gy versus 173&#xa0;Gy in non-responders (<i>p</i> &lt; 0.001). We identified a threshold tumour absorbed dose of 164&#xa0;Gy for PFS 48.1months compared to 8.8months (HR 0.2, 95%CI 0.05–0.96. <i>p</i> = 0.03).</p> Conclusion <p>In a prospective study of heavily pretreated patients, we have demonstrated clinical efficacy of SIRT for the management of liver metastases secondary to NENs. A tumour dose-response relationship was demonstrated and a threshold tumour dose for survival outcome. This work lends prospective evidence for personalised dosimetry in NENs.</p>

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Efficacy and evaluation of dose-response relationship of selective internal radiation therapy for the management of liver metastases in neuroendocrine neoplasia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月17日

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  • Qasim Ahmed,
  • Nikolaos Doumanoglou,
  • Joanne Evans,
  • Maria Martinez,
  • Caroline Ward,
  • Hooshang Izadi,
  • Florian Wernig,
  • Mark Bray-Parry,
  • Kuldip Nijran,
  • Laura Perry,
  • Neva Patel,
  • Chloe Bowen,
  • Ali Alsafi,
  • Rob Thomas,
  • Tahir Shah,
  • Priten Khagram,
  • Paul Tait,
  • Rohini Sharma

摘要

Purpose

The liver is the commonest site of metastases in neuroendocrine neoplasias (NENs) and is an independent predictor of poor outcome. Selective internal radiation therapy (SIRT) allows selective delivery of high dose radiation to liver tumours and has shown promise in the management of NENs. We determined the safety and efficacy of SIRT for inoperable liver metastases secondary to NENs. Dose-response and dose-toxicity relationship were assessed.

Methods

A prospective, multicentre, phase 2 study was conducted. Primary outcomes were objective response rate (ORR) in the treated liver volume according to RECIST 1.1 and mRECIST criteria, incidence and severity of adverse events (AEs) at 6 months. Secondary outcomes were hepatic specific progression free survival, PFS, overall survival (OS), change in quality of life (QoL). Tumour dose-response relationship was derived retrospectively from post therapy yttrium-90 bremsstrahlung single photon emission computed tomography/CT for both the tumour and perfused normal liver.

Results

21 patients were analysed; majority had grade 2 NEN (67%) and were heavily pretreated, 76% having received prior systemic therapy including peptide receptor radiotherapy (33%). ORR by RECIST 1.1 and mRECIST were 14% and 45%, respectively. Median hepatic specific PFS, PFS and OS were 48.1, 13.3 and 49.9 months respectively. Only 3 patients experienced grade 3 AEs; 2 radiation-induced liver disease that resolved without sequelae and one arterial plug migration. No significant deterioration in QoL was observed following SIRT. Dosimetry analysis found a clear tumour dose/response relationship for 3-month ORR. Mean tumour dose in responders was 372 Gy versus 173 Gy in non-responders (p < 0.001). We identified a threshold tumour absorbed dose of 164 Gy for PFS 48.1months compared to 8.8months (HR 0.2, 95%CI 0.05–0.96. p = 0.03).

Conclusion

In a prospective study of heavily pretreated patients, we have demonstrated clinical efficacy of SIRT for the management of liver metastases secondary to NENs. A tumour dose-response relationship was demonstrated and a threshold tumour dose for survival outcome. This work lends prospective evidence for personalised dosimetry in NENs.