Interventional procedure overview of selective internal radiation therapy for neuroendocrine tumours that have metastasised to the liver

Alsultan, A.A., Smits, M.L.J., Barentsz, M.W. et al (2019). The value of yttrium‑90 PET/CT after hepatic radioembolization: a pictorial essay, Clinical and Translational Imaging, 7, 303–312.

Retrospective case reports

n=1 mNET (n=5 total)

Patients were followed until the article was submitted.

Patient alive at submission of article. Severe pain in liver, fever, abscess in necrotic tissue requiring surgical drainage and antibiotics following treatment. Authors recommend that PET/CT used to improve dose planning and that treatment went as planned.

Studies with prospective designs, larger samples and more clinical outcomes measures were included.

Andrews, J.C., Walker, S.C., Ackermann, R.J. et al., (1994). Hepatic Radioembolization with Yttrium-90 Containing Glass Microspheres: Preliminary Results and Clinical Follow-Up, J NucI Med, 35,1637-1644.

Prospective dose escalation study

n=6 mNET (n=24 total)

Follow-up until disease progression

16 weeks after therapy, 3 people had minimal response and 3 people showed stable disease. Four of 6 people (66%) survived with stable disease for 16 months after SIRT.

Studies with larger samples and more clinical outcome measures in the sample of interest were included.

Arslan, N., Emi, M., Alagoz, E., et al (2011). Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for hepatic neuroendocrine metastases: initial experience at a single center, Vojnosanit Pregl, 68(4), 341–348.

Retrospective case series

n=10

Mean follow-up= 6 months

Overall response rate was 90% (9/10). Complete response in 30%, partial response in 50%, stable disease in 1 person and disease progression in 1 person. Tolerance was satisfactory for most. Almost all people reported some degree of mild-to-moderate abdominal pain, nausea, lethargy, anorexia, and fever from 1 week to 1 month after the treatment. No cases of radiation pneumonitis or radiation induced liver disease.

This study was included in the meta-analysis by Frilling (2019). Studies with prospective designs, larger samples and longer follow up periods were included in Table 2.

Barbier, C.E., Garske-Roman, U., Sandstrom, M., et al., (2016). Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. Eur J Nucl Med Mol Imaging , 43, 1425–1431.

Retrospective case series

n=40

Mean follow-up=20 months

At a mean of 3 months, disease control was seen in 94% of people. At a mean of 20 months, disease control was seen in 57%. Mean overall survival from the first SIRT was 34.8 months and survival rates at 1, 2, 3 and 5 years were 76%, 59%, 52% and 35% respectively. Adverse effects were generally mild and easily manageable except in one patient who died from radiation-induced liver failure.

This study was included in the Frilling (2019) meta-analysis. Studies with larger samples, prospective designs, longer follow-up periods were included.

Benson, A.B., Geschwind, J.F., Mulcahy, M.F., et al., (2013). Radioembolisation for liver metastases: Results from a prospective 151 patient multi-institutional phase II study, European Journal of Cancer, 49, 3122-130.

Prospective multicentre case series

n=43 people with mNETs (n=151 total)

People were followed up every 6 months until deceased.

No patients had complete response; 21% had partial response; 72% had stable disease and 7% had progressive disease. Hepatic progression free survival was 17.9 months (95%CI=13.6 to n/a). Overall survival at 2 years was 79%.

This study was included in the Frilling (2019) meta-analysis. More recent studies and studies with larger samples were included. A long list of adverse events was reported but not specific to mNETs.

Braat, A.J.A.T, Ahmadzadehfar, H., Kappadath, S.C., et al (2020). Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy. Cardiovasc Intervent Radiol, 43, 246–253

Retrospective case series

n=44

All data that was collected between December 2006 and May 2016.

All procedures followed PRRT. Median overall survival was 3.5 years (95%CI 1.8 to 5.1). Disease control rate was 91% at 3 months. Clinical response was 65% (15/23 symptomatic patients). Clinical toxicity was observed in 26% of people, lymphocytopenia in 42% but other grade 3 or 4 toxicities in less than or equal to 10%.

Studies with larger samples, prospective designs and longer follow-up periods were included.

Cao, C.Q., Yan, T.D., Bester, L., et al. (2010). Radioembolization with yttrium microspheres for

neuroendocrine tumour liver metastases, British Journal of Surgery Society Ltd, 97, 537-543.

Prospective database from 2 centres analysed retrospectively

n=58

Follow-up included all data collected between 2003 and 2008

10% had complete response, 24% partial response, 24% had stable disease and 29% had disease progression. Overall survival rates at 1, 2 and 3 years were 86%, 58% and 47% respectively; median survival was 36 (range 1–61) months.

This study was included in the Frilling (2019) meta-analysis. More recent studies have been included in Table 2.

Celeen, F., Theisen, D., Garcia de Albeniz, X., et al., (2015). Towards New Response Criteria in Neuroendocrine Tumors: Which Changes in MRI Parameters Are Associated With Longer Progression-Free Survival After Radioembolization of Liver Metastases? JOURNAL OF MAGNETIC RESONANCE IMAGING, 41, 361–368.

Retrospective case series

n=45

Follow-up= 3 months

At 3 months, no patients were in complete remission, 13% showed partial response, 82% showed stable disease and 5% showed progressive disease. Decreases in tumour arterial enhancement, increase in necrosis and decrease in tumour diameter were statistically significantly associated with increased progression free survival.

Studies with larger samples prospective designs, longer follow-up periods and more clinical outcomes were included.

Chasanti, O., Jahangiri, Y., Matsui, Y. et al (2017). Tumor Dose Response in Yttrium-90 Resin Microsphere Embolization for Neuroendocrine Liver Metastases: A Tumor- Specific Analysis with Dose Estimation Using SPECT-CT. J Vasc Interv Radiol, 28, 1528–1535.

Retrospective case series from a single centre

n=15

Median follow-up= 7.6 months.

In this sample of people for whom surgery was not suitable, 67% (8/12) showed complete or partial response at follow-up. The mean absorbed dose of radiation was higher in responders than non-responders (p=.007). mNET cell differentiation, tumour grade, and overall tumour burden, were not associated with response.

This study was included in the meta-analysis by Frilling (2019). Studies with larger samples prospective designs, longer follow-up periods and more clinical outcomes were included.

Chen, J.X., Rose, S., White, S.B., et al., (2017). Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival, Cardiovasc Intervent Radiol, 40, 69-80.

Retrospective case series from multiple institutions.

N=155

Data between 2004 and 2015 were analysed.

Radioembolisation tended toward worse overall survival than TACE and TAE. There were no significant differences in hepatic progression free survival between types of embolotherapy.

This study was included in the meta-analyses by Frilling (2019) and Ngo (2021). Larger studies reporting similar outcomes were also included.

Currie, B.M., Hoteit, M.A., Ben-Josef, E., et al., (2019). Radioembolization-Induced Chronic Hepatotoxicity: A Single-Center Cohort Analysis. J Vasc Interv Radiol, 30, 1915–1923

Retrospective case series from a single centre

n=53 mNET (n=98 total)

Follow-up data collected between 2005 and 2014.

SIRT-induced chronic hepatotoxicity (occurring at least 6 months after therapy and persisting) was observed in 7/53 people with mNETs.

Studies with larger samples, prospective designs and more clinical outcomes were included. Another study included in the main evidence explicitly reported the effects of SIRT on long term clinical toxicity (Su, 2017).

Currie, B.M., Nadolski, G., Mondschein, J. et al., (2020). Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization, J Vasc Interv Radiol, 31, 1627–1635

Retrospective cohort

n=91 total (n=28 had SIRT; n=63 had TACE)

Follow-up was until death, loss to follow up or initiation of alternative treatment

A statistically significant difference in the number of people who had intrahepatic disease progression favoured SIRT over TACE (43% and 75%, respectively, p=.005). There was no statistically significant difference but a trend for more embolotherapy induced chronic hepatic toxicity in the SIRT than TACE cohort (14% and 3%, respectively, p=0.07). There was no statistically significant difference but a trend for more grade 4 and 5 injuries in the SIRT than TACE cohort (27% and 5% of people, p=.06). Delayed hepatotoxicity was observed at a median of 2 (range 1 to 6 years) and 2.3 (range 6 months to 5 years) in the TACE and SIRT groups, respectively.

Studies with larger samples prospective designs were included. Another study included in the main evidence explicitly reported the effects of SIRT on long term clinical toxicity (Su, 2017).

Devcic, Z., Rosenberg, J., Braat, A.J.A., et al., (2014). The Efficacy of Hepatic ⁹⁰Y Resin Radioembolization for Metastatic Neuroendocrine Tumors: A Meta-Analysis, The Journal of Nuclear Medicine, 55(9), 1404-1410.

Systematic review and meta-analysis

n=12 studies (n=435 procedures)

Follow-up information was not reported.

Pooled objective response rate was 50% (95%CI= 38 to 62%) and disease control rate was 86% (95%CI= 78 to 92%). Median overall survival was 28.5 months (range 14 to 70 months).

The Frilling (2019) meta-analysis in Table 2 is more recent and has more studies. The findings were similar in both studies.

Do Minh, D., Chapiro, J., Gorodetski, B., et al., (2017). Intra-arterial Therapy of Neuroendocrine Tumor Liver Metastases: Comparing conventional TACE, Drug-Eluting Beads TACE and ⁹⁰Yttrium Radioembolization as Treatment Options using a Propensity Score Analysis Model, Eur Radiol, 27(12), 4995–5005

Retrospective cohort

n=192 (n=44 SIRT, n=122 TACE, n=26 DEB-TACE)

Median follow-up=75.6 months

Median overall survival for TACE, DEB-TACE and SIRT was 33.8 months, 21.7months and 23.6 months, respectively. TACE demonstrated significantly longer median overall survival compared with DEB-TACE(p=.04) and SIRT (p=.03). The five-year survival rate after initial TACE, DEB-TACE and SIRT was 28.2%, 10.3% and 18.5%, respectively. Adverse events were considered similar across groups.

This study was included in Ngo et al., (2021) and the Frilling (2019) meta-analyses. Larger studies with prospective data were included.

Ebbers, S.C., Roekel, C, Braat ,M.N.G.J.A., et al., (2022). Dose–response relationship after yttrium‑90‑radioembolization with glass microspheres in patients with neuroendocrine tumor liver metastases, European Journal of Nuclear Medicine and Molecular Imaging, 49, 1700-1710.

Retrospective case series for dose response analysis

n=26

Follow-up=3 months

There is a clear dose-response relationship such that higher doses of 90Y was related to better response outcomes on RECIST v1.1. The authors recommend a minimum planned tumour absorbed dose of 150Gy.

Larger, prospective studies with longer follow-up and more outcomes were included.

Ebbers, Brabander, T., Tesselaar, M.E.T., et al., (2022). Inflammatory markers and long term hematotoxicity of holmium‑166‑radioembolization in liver‑dominant metastatic neuroendocrine tumors after initial peptide receptor radionuclide therapy, EJNMMI Research, 12(7).

Secondary analysis of prospective single arm trial (HEPAR PLuS trial) data for a toxicity analysis

n=31

Follow-up=12 months

Toxicity after sequential treatment with PRRT and ¹⁶⁶Ho-radioembolization is limited and temporary. No significant relationship with survival was found. Thombocyte-to-lymphocyte ratio 3 weeks after treatment may be a predictor of tumour response.

All participants were from the HEPAR plus study which is included. This study reported laboratory toxicity, there was no focus on clinical toxicity.

Elf, A.K., Andersson, M., Henrikson, O., et al., (2018). Radioembolization Versus Bland Embolization for Hepatic Metastases from Small Intestinal Neuroendocrine Tumors: Short- Term Results of a Randomized Clinical Trial, World Journal of Surgery, 42, 506-513.

Pilot RCT comparing SIRT with TAE.

n=11 (n=6 had SIRT; n=5 had TAE)

Median follow-up=195 days

There were no responders in the SIRT group at 3 months (0/6). All people who had TAE showed partial response (5/5, p=.002). At 6 months, there was no significant difference in the proportion of people who showed tumour response (p=0.24). Median hospital stay was significantly longer for people who had TAE compared with SIRT (p=0.02).

Studies with larger samples and longer follow-up were included.

Engelman, E.S., Leon-Ferre, R., Naraev, B.G. et al., (2014). Comparison of Transarterial Liver-Directed Therapies for Low-Grade Metastatic Neuroendocrine Tumors in a Single Institution. Pancreas, 43(2), 219–225.

Retrospective case series from a single centre comparing TACE, HAE and SIRT outcomes.

n=42 (n=12 had SIRT).

The study included data from medical records between 2001 and 2011.

Time to progression in patients treated with SIRT was 33.4 months, compared with HAE (12.1 months) or TACE (15.1 months; comparisons were not significant). SIRT did not have increased toxicity compared to HAE or TACE and the toxicity profile overall was acceptable for all modalities.

This study was included in the meta-analysis by Ngo (2021). More recent studies with larger samples prospective designs and more clinical outcomes were included.

Ezziddin, S., Meyer, C., Kahancova, S., et al (2012). ⁹⁰Y Radioembolization After Radiation Exposure from Peptide Receptor Radionuclide Therapy. The Journal of Nuclear Medicine, 53(11), 1663–1669.

Retrospective case series from a single centre

n=23

Median follow-up=38 months

All procedures followed PRRT. Median overall survival was 29 months (95%CI= 4 to 54) months after SIRT. Tumour response indicated disease control in 91% at 3 months. Symptomatic response at 3 months was 80%. No grade 4 toxicity. One grade 2 gastroduodenal ulcer.

This study was included in the Frilling (2019) meta-analysis. Studies with larger samples prospective designs, longer follow-up periods and more clinical outcomes were included.

Fan, K.Y., Wild, A.T., Halappa, V.G., (2016). Neuroendocrine tumor liver metastases treated with yttrium-90 radioembolization. Contemporary Clinical Trials, 50, 143–149.

Retrospective case series

n=38

Median follow-up= 17 months

Median survival was 29.2 months. Disease control in 86% and 5 people (14%) developed progressive disease. Grade 3 non-serologic toxicities included abdominal pain (11%),

fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnoea (3%), diarrhoea (3%), and peripheral oedema (3%). No grade 4 or 5 toxicity was reported.

This study was included in the Frilling (2019) meta-analysis. Studies with larger samples, prospective designs and longer follow-ups were included.

Fidelman, N., Kerlan, R.K., Hawkins, R.A., et al., (2014). ⁹⁰Y Glass Microspheres for the Treatment of Unresectable Metastatic Liver Disease from Chemotherapy-Refractory Gastrointestinal Cancers: A Pilot Study, Journal of Gastrointestinal Cancer, 45, 168-180.

Prospective cohort study

n=9 people with mNETs (n=30 total sample)

Follow-up= 6 months

No people with mNETs reached complete response. Partial response was observed in 78% (7/9) and stable disease in 22% (2/9). Two of 3 SAEs were reported in mNET patients (1 person had carcinoid crisis at the time of SIRT which required hospitalisation for 6 days. After stabilised they received a second dose of SIRT. The other patient had grade 4 gastric ulcer).

This publication was included in the meta-analysis by Frilling (2019). A more recent publication of this sample is also in the appendix.

Fidelman, N., Kerlan, R.K., Hawkins, R.A., et al., (2016). Radioembolization with ⁹⁰Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory

gastrointestinal cancers: final report of a prospective pilot study. Journal of gastrointestinal Oncology, 7(6), 860-874.

Prospective cohort study

n=11 people with mNETs (n=30 total sample)

Median follow-up=48.2 months

100% (6/6) patients that had carcinoid syndrome reported near or complete remission of symptoms within 1 month of SIRT. Median time to maximum response was 11 months (range= 5 to 29.6 months). After median follow-up of 48.2 months, 73% had disease progression in the treated lobe. Median response duration was 23.4 months (range=9.3 to 48 months).

This study was included in the meta-analysis by Frilling (2019). Prospective studies with larger samples were included. This study does not report adverse events by indication.

Filippi, L., Ciorra, A., Sardella, B., et al., (2014). Sequential Use of ⁹⁰Y Microspheres Radioembolization and ¹⁷⁷Lu-Dotatate in Pluri-Metastatic Neuroendocrine Tumors: A Case Report. Nuclear Medicine and Molecular Imaging, 48, 321-325.

Case study

n=1

Follow-up= 3 months

SIRT was applied before PRRT to downstage the gross hepatic lesion and also after PRRT as consolidation therapy for the liver residual disease. They suggest SIRT can be safely used in combination with PRRT, especially in case of liver-dominant tumour.

Studies with more participants and more outcomes were included.

Filippi, L., Scorpinaro, F., Pelle, G., et al., (2016). Molecular response assessed by 68Ga-DOTANOC and survival after ⁹⁰Y microsphere therapy in patients with liver metastases from neuroendocrine tumours. Eur J Nucl Med Mol Imaging, 43, 432–440.

Case series

n=15

Minimum follow-up= 36 months or until death

In this sample of people with unresectable mNETs, mean overall survival was 31 months (95%CI= 27 to 35); 9/15 were classed as responders. 7/15 people had nausea and mild abdominal pain within 10 hours of treatment. Late complications included grade 2 gastritis (2/15) and grade 2 cholecystitis (1/15).

This study is included in the Frilling (2019) meta-analysis. Studies with more people were included.

Gozstonyi, B., Pestalozzi, B., Kenkel, D., et al., (2022). A descriptive analysis of the characteristics, treatment response and prognosis of hepatic dominant solid tumors undergoing selective internal radiation therapy (SIRT). J Gastrointest Oncol, 13(6), 3240-3253.

Retrospective case series

n=182 (n=18 mNETs)

This study analysed medical records of people who had SIRT between Jan 2015 and May 2019.

Neuroendocrine tumours showed the third longest median post-SIRT survival (12.4 months) and the second longest median progression-free survival (5.2 months), compared to other indications treated with SIRT.

Studies with prospective designs, more clinical outcomes and larger samples in the group of interest were included.

Gulec, S.A., Mesoloras, G., Dezarn, W.A., et al (2007). Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio. Journal of Translational Medicine 5(15).

Retrospective case series

n=10 mNET (n=40 total)

Mean follow-up= 19 weeks

mNET tumour response was 100%. None of the patients had clinical venoocclusive disease or therapy-induced liver failure.

Studies with prospective designs, more clinical outcomes in the group of interest and larger samples were included.

Habibollahi, P., Bai, H.X., Sanampudi, S., et al (2020). Effectiveness of Liver-Directed Therapy for the Management of Intractable Hypoglycemia in Metastatic Insulinoma. Pancreas, 49, 763–767.

Retrospective case studies

n=2 people who had SIRT (n=7 total)

Follow-up = up to 75 months

Both people had chemoembolization before SIRT for intractable hypoglycemia resultant from insulinoma. There was a 100% symptomatic response rate. At 75 months, 1 person was alive and 1 person died at 22 months from liver failure.

Studies with prospective designs, more clinical outcomes in the group of interest and larger samples were included.

Ingenerf, M., Kiesl, S., Karim, S., et al., (2021). 68Ga-DOTATATE PET/CT and MRI with Diffusion-Weighted

Imaging (DWI) in Short- and Long-Term Assessment of Tumor Response of Neuroendocrine Liver Metastases (NELM) Following Transarterial Radioembolization (TARE). Cancers, 13, 4321.

Retrospective case series from a single centre

n=32

Median follow-up=58.7 months

Median overall survival was 68.8 months (95%CI=35 to 102). One year survival was 100% and 2 year survival was 84%. Median overall progression free survival was 12.7 months (95%CI=11 to 15).

Studies with prospective designs and larger samples were included.

Jia, Z., Paz-Fumagalli, R., Frey, G., et al., (2017). Single-institution experience of radioembolization with yttrium-90 microspheres for unresectable metastatic neuroendocrine liver tumors. Journal of Gastroenterology and Hepatology, 32, 1617–1623.

Retrospective case series from a single centre

n=36

Median follow-up=27 months

Median overall survival 41 months. Overall disease control rate was 88.9% (32/36) at 3 months. Symptomatic improvement in 94% (15/16) patients with carcinoid syndrome. Radiation induced gastrointestinal ulcers in 5.6% (2/36). Other side effects were fatigue (86%), anorexia (72%), nausea (42%), vomiting (39%), abdominal pain (28%), fever (22%).

This study was included in the meta-analysis by Frilling (2019). Studies with prospective designs and larger samples were included in Table 2.

Kalinowski, M., Dressler, M., Konig, A., et al., (2009). Selective Internal Radiotherapy with Yttrium-90 Microspheres for Hepatic Metastatic Neuroendocrine Tumors: A Prospective Single Center Study, Digestion, 79, 137-142.

Prospective single arm cohort

n=9

Mean follow up=21.7 months

No major complications. Survival rates were 100, 57 and 57% for 1, 2 and 3 years. Partial response in 66%, stable disease in 33% at 6 months meaning overall disease control was 99%. Quality of life at 6 months improved in 6 of 7 evaluable patients (p < 0.05). Quality of life later deteriorated but this was not significant and was usually related to recurrence of disease and/or other factors.

More recent studies with larger samples and longer follow up were included.

Kanabar, R., Barriusi, J., McNamara, M.G. et al., (2021). Liver Embolisation for Patients with Neuroendocrine Neoplasms: Systematic Review, Neuroendocrinology, 111, 354-369.

Systematic review and meta-analysis of all types of embolization for mNETs

n=20 studies with 772 patients (n=101 total studies)

Median follow-up=39.6 (95%CI=23.1 to 56.1)

Pooled weighted mean number of people that had symptomatic response was 77.4% (95%CI=47.1 to 100%). This was higher than the pooled mean for all types of liver directed therapy (55%). Pooled weighted mean overall survival was 40.1 months (95%CI=29.2 to 51). Pooled weighted mean progression free survival was 12.6 months (95%CI=0 to 30.4 months; n=2 studies).

The references for studies reporting SIRT outcomes were not available. Other reviews with more specific focus on SIRT were included.

Katharina-Ingenerf, M., Karim, H., Fink, N., et al., (2022). Apparent diffusion coefficients (ADC) in response assessment of transarterial radioembolization (TARE) for liver metastases of neuroendocrine tumors (NET): a feasibility study. Acta Radiologica, 63(7), 877-888.

Retrospective case series from a single centre

n=43

Mean= 74 days

According to RECIST 1.1: 23% (27/120) target lesions showed partial response, 73% (87/120) showed stable disease and 5% (6/120) showed progressive disease. According to mRECIST: 0.8% (1/120) showed complete response, 63% (76/120) showed partial, 23% (28/120) showed stable and 7% (8/120) showed progressive disease.

Studies with prospective designs, longer follow-up, more and clinical outcomes and larger samples were included.

Kennedy, A.S., Dezarn, W.A., McNeillie, P. (2008). Radioembolization for Unresectable Neuroendocrine Hepatic Metastases Using Resin 90Y-Microspheres: Early Results in 148 Patients. American Journal of Clinical Oncology, 31(3), 271–279.

Retrospective case series

n=148

Median follow-up=42 months

The median survival was 70 months. 33% of patients experienced grade 3 or 4 side effects. Fatigue (6.5%) was the most common side effect. Disease control was observed in 95% and progressive disease in 4.9%. No radiation induced liver failure occurred.

This study was included in the Frilling (2019) meta-analysis. More recent studies with prospective designs have been included.

King, J., Quinn, R., Glenn, D.M., et al., (2008). Radioembolization With Selective Internal Radiation Microspheres for Neuroendocrine Liver Metastases, American Cancer Society, 113, 921-929.

Prospective case series

n=34

Mean follow-up=35.2 months

Post-SIRT complications included mild to severe abdominal pain, nausea, fever, lethargy lasting between 1 week and 1 month, radiation gastritis, duodenal ulcer, 1 early death because of liver dysfunction and pneumonia. Symptomatic response was observed in 55% at 3 months and 50% at 6 months. Mean overall survival was 29.4 months and 50% has partial response or stable disease.

This study was included in the Frilling (2019) meta-analysis. More recent studies with larger samples were included.

Kukuk, G.M., Murtz, P., Traber, F., et al (2014). Diffusion-weighted imaging with acquisition of three b-values for response evaluation of neuroendocrine liver metastases undergoing selective internal radiotherapy. Eur Radiol 24, 267–276.

Retrospective case series

n=10

3 months

Greater than 20% reduction in the longest diameter of each tumour in 39% (12/31) metastases. These metastases were in 4/10 patients.

Studies with prospective designs, longer follow up, more and standardised clinical outcomes and larger samples were included.

Lacin, S., Oz, I, Ozkan, K., et al., (2011). Intra-Arterial Treatment with 90Yttrium Microspheres in Treatment-Refractory and Unresectable Liver Metastases of Neuroendocrine Tumors and the Use of 111In-Octreotide Scintigraphy in the Evaluation of Treatment Response. Cancer Biotherapy and Radiopharmaceuticals., 26, 631-639.

Prospective case series

n=13

Mean follow-up=17.4 months

One year survival was 84.7%, overall survival was 20 months and median survival was 18 months. All patients experienced postradioembolization syndrome (mild abdominal pain, nausea, fever) which subsided within 15 days.

More recent studies with larger samples were included.

Loree, J.M., Tadaaki, H.M., Kennecke, H.F. (2016). Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases, Case Rep Oncol, 9, 76–82

Case report

n=1

Follow-up=49 months

Abdominal pain and nausea, biliary damage, postembolization oedema after one treatment. At approximately 49 months and after everolimus, liver cirrhosis was diagnosed and attributed to 90Y SIRT treatments. The authors report this possible long-term complication should be considered when considering SIRT for people with good prognosis.

Studies with prospective designs, more clinical outcomes and larger samples were included.

Ludwig, J.M., McIntosh Ambinder, E., Ghodadra, A., et al., (2016). Lung Shunt Fraction prior to Yttrium-90 Radioembolization

Predicts Survival in Patients with Neuroendocrine Liver Metastases: Single-Center Prospective Analysis, Cardiovasc Intervent Radiol, 39, . 1007-1014

Prospective case series

n=44

Patients were enrolled between 2006 and 2012 and data were censored at 2014.

Median overall survival was 27.4 months (95%CI= 12.7 to 55.2). High lung shunt fraction was a statistically significant prognostic factor of overall survival (p=.003); people with lung shunt fraction greater than 10% had median overall survival of 4.8 months (95 %CI 2.87–26.73) whilst people with lung shunt fraction less than 10% had median overall survival of 42.8 months (95 %CI 18.47–59.73).

This study was included in the Frilling (2019) meta-analysis. Larger studies with more outcomes were included.

Maccauro, M., Follacchio, G.A., Spreafico et al., (2019). Safety and efficacy of combined Peptide Receptor Radionuclide Therapy and liver Selective Internal Radiation Therapy in a patient with metastatic neuroendocrine tumor. Clin Nucl Med, 44(4), e286-e288

Case report

n=1

Follow-up= 16 months

PRRT followed by 2 SIRT treatments. From the end of PRRT and start of SIRT, the patient had 16 months of progression free survival. Liver and bone progression diagnosed at 16 months. No significant acute or delayed adverse effects or cumulative toxicity to healthy liver parenchyma.

Studies with prospective designs, more clinical outcomes and larger samples were included.

Maker, A.V., August, C., Maker, V.K. & Weisenberg, E. (2016). Hepatectomy after Yttrium-90 (Y90) Radioembolization-induced Liver Fibrosis. J Gastrointest Surg, 20(4), 869–870.

Case report

n=1

Last follow-up was not reported.

10 months after second SIRT treatment, the person was still symptomatic with flushing, diarrhoea, anxiety, myalgia, pain, and persistent night sweats, despite sandostatin administration. Histology showed Y90 induced fibrosis and microbeads in blood vessels around subsequently resected tumours which the authors believe demonstrates increased morbidity and mortality when resection previously radioembolised tumours.

Studies with prospective designs, more clinical outcomes and larger samples were included.

Mascarenhas, N.B., Mulcahy, M.F., Lewandowski, R.J. et al (2010). Hepatic Abscess After Yttrium-90 Radioembolization

for Islet-Cell Tumor Hepatic Metastasis

Case report

n=1

Last follow-up was not reported

Fever and abdominal pain after treatment which persisted with antibiotics. At 4-weeks post-treatment, an abscess in the treatment site was diagnosed. This was drained and several months after treatment the dominant hepatic metastases had decreased in size.

Studies with prospective designs, more clinical outcomes and larger samples were included.

Memon, K., Lewandowski, R.J., Mulcahy, M.F. et al., (2012). Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging and Long-term Outcomes. Int J Radiat Oncol Biol Phys, 83(3), 887–894.

Retrospective case series

n=40

Follow-up up to 3 years

Overall survival at 1, 2 and 3 years was 73%, 63% and 45%. Two classifications for response rate were used: WHO measures size (CR: 1.2%, PR: 62.7%) and EASL measures necrosis (CR: 20.5%, PR: 43.4%). Fatigue (63%), nausea/ vomiting (40%), abdominal pain (18%), fever (8%), diarrhoea and weight loss (5%). Symptom remission was reported in 84% (21/25) of people after treatment.

This study was included in the meta-analysis by Frilling (2019). Studies with prospective designs and larger samples were included.

Moir, J.A.G., Burns, J, Barnes, J. et al., (2015). Selective internal radiation therapy for liver malignancies. BJS, 102, 1533–1540.

Retrospective case series

n=6 mNET (n=44 total)

Median follow-up=10 months

Overall survival was 539 days (95%CI=350 to 617). Median percent change in tumour diameter was -30% (95%CI= -46 to -8; n=5). No significant difference in overall survival according to primary pathology (p=.065). No mNET patients required follow up resection.

Studies with prospective designs, larger samples and more outcomes specific to the group of interest were included.

Murthy, R., Kamat, P., Nunez, R., et al (2008). Yttrium-90 Microsphere Radioembolotherapy of

Hepatic Metastatic Neuroendocrine Carcinomas after Hepatic Arterial Embolization. J Vasc Interv Radiol, 19, 145–151.

Retrospective case series

n=8

Median follow-up= 9.5 months

Median overall survival was 14 months (range=3 to 15). Partial response was observed in 1/8 people, 50% (4/8) showed stable disease and 3/8 showed progressive disease in the liver. Disease progression was observed in 3/8. After 1 treatment, grade 2/3 abdominal pain was observed in 5/8 people, transient grade 1/2 fatigue in 3/8, pyrexia in 1 person and grade 2 nausea in 1 person. No radiation induced liver disease was observed.

Studies with prospective designs and larger samples were included.

Ozao-Choy, J., Friedman, M.L., Amanda, S.K. et al (2013). Radioembolization for Treatment of Liver Metastases From Neuroendocrine Tumors Correlation With Imaging and Biomarkers. Pancreas 42(2), 358-360.

Retrospective case series

n=18

Median follow-up= 5 months

Of 19 evaluated procedures, 11% (2/19) resulted in complete response, 47% (9/19) partial response and 32% (6/19) stable disease. Disease progressed in 11% (2/19). Toxicities included: radiation gastritis (2/18), gastric ulcer (1/18), biliary stricture requiring drainage (1/18), portal hypertension with refractory ascites (1/18), zone 3 injury with necrosis consistent with radiation induced liver disease (1/18).

Studies with prospective designs, larger samples and more outcomes were included.

Ozkan, F., Peynircioglu, B., E.Cil, B., et al (2013). Transarterial Chemo and Radioembolization (Yttrium90) of Hepatic Metastasis of Neuroendocrine Tumors: Single Center Experience. International Journal of Hematology and Oncology, 23(1), 20-27.

Retrospective cohort

n=14 (n=6 SIRT; n=8 TACE)

Median follow-up=17 months

Mean overall survival was 14.5 months in the SIRT group and 16.8 months in the TACE group (p=0.09). Progressive disease in 17% (1/6) SIRT group and 71% (5/8) of TACE group at intermediate follow up (greater than 3 months). 75% of people who had SIRT and 57% of people who had TACE had relief of carcinoid symptoms. No major complications were observed. One person who had SIRT had asymptomatic partial right portal vein thrombosis and almost all people had mild fatigue and fever. Grade 1 to 2 abdominal pain and nausea in 1/6 of the SIRT and 4/8 of the TACE group.

Study was included in the meta-analysis by Ngo (2021). Studies with prospective designs and larger samples were included.

Paprottka, P.M., Hoffmann, R.T., Haug, A., et al., (2012). Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres. Cardiovasc Intervent Radiol, 35, 334–342

Retrospective case series

n=42

Mean follow-up=16.2 months

At 3 months, 22.5% had partial response, 75% had stable disease and 2.5% had progressive disease. At mean follow-up of 16 months, 95.2% of people were alive. Hypovascularisation or partial necrosis was observed in 97.5% of lesions. 36 of 38 people showed remission of symptoms at 3 months. No radiation induced liver disease was observed and no acute or delayed toxicity above grade 2.

This study was included in the meta-analysis by Frilling (2019). Other studies with prospective designs and larger samples were included in Table 2.

Paprottka, K.J., Schoeppe, F., Ingrisch, M., et al (2017). Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients. Eur J Nucl Med Mol Imaging, 44, 1185–1193

Retrospective case series

n=389 (n=56 mNETs)

People had SIRT between January and February 2013 and followed up until December 2013.

22/56 people with mNETs (60%) were alive at the end of follow-up. Compared to other tumour types mNET showed best survival rates at last follow up.

Studies with prospective designs, more clinical outcomes and larger samples of people with the indication of interest were included.

Peker, A., Cicek, O., Soydal, C., et al., (2015). Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases. Diagn Interv Radiol, 21, 54–59.

Retrospective case series

n=30

Mean= 23 months

Median overall survival was 39 months (95% CI= 13 to 65). One and 2-year survival rates were 71% and 45%. Complete remission was observed in 3%, partial response in 43%, stable disease in 37% and progressive disease in 17%. Post-radioembolization syndrome was observed in all people and resolved with treatment in 30 days. Radiation induced gastritis was observed in 2/30 people; 1 of those had persistent ulceration at 9 months.

This study was included in the meta-analysis by Frilling (2019). Studies with larger samples and prospective designs were included.

Puleo, L., Agatem L., Bargellini, I., et al., (2022). Yttrium-90 transarterial radioembolization for liver metastases from medullary thyroid cancer, European Thyroid Journal, 11, e220130.

Prospective cohort study

n=8

Mean follow-up=18 months

Two people were excluded from analysis because of liver injury and death due to disease progression. Significant reduction in tumour mass observed after 1, 4 and 12 months (p<.01).

Studies with larger samples, longer follow-up and more clinical outcomes were included.

Rajekar, H., Bogommana, K., Stubbs, R.S. (2011). Selective Internal Radiation Therapy for Gastrointestinal Neuroendocrine Tumour LiverMetastases: A New and Effective Modality for Treatment. International Journal of Hepatology, 2011, 404916.

Retrospective case series

n=14

Up to 60 months

Median survival was 25 months. Partial response or stable disease in 100% of people. Carcinoid syndrome improved or resolved in 100% (10/10) instances. No treatment-related deaths or serious complications following SIRT. Anorexia and lethargy were experienced by all people. One person died 10 months after second SIRT treatment but this was not considered 'obviously' related to treatment.

More recent studies with prospective designs, more and standardised clinical outcomes and larger samples were included

Rhee, T.K., Lewandowski, R.J., Liu, D.M., et al., (2008). 90Y Radioembolization for Metastatic Neuroendocrine Liver Tumors: Preliminary Results From a Multi-institutional Experience. Annals of Surgery, 247, 1029-1035.

Prospective case series

n=42

Every 3 months until end of study (between June 2001 and June 2006)

92% of people that had SIRT with glass microspheres and 94% who had SIRT with resin were classed as having partial response or stable disease at 6 months. Median survival was 22 months with glass and 28 months with resin (p=0.82). 6 people had grade 3 or 4 toxicity during follow up.

This study was included in the Frilling (2019) meta-analysis presented in Table 2.

Rodrigues-Lago, I., Carretero, C., Maite, H., et al (2013). Long-term follow-up study of gastroduodenal lesions after radioembolization of hepatic tumors. World J Gastroenterol, 19(19), 2935-2940.

Retrospective case series

n=1 person with mNET (n=6 total)

Follow-up= 29 months

Gastroduodenal ulcers were observed between 1 and 12 weeks after SIRT. The person with mNETs had multiple erosions in the duodenal bulb, severe mucositis in gastric fundus, body and antrum with mucosal friability and superficial ulcers 5 weeks after SIRT. The person reported abdominal pain (Grade 1), nausea and vomiting (grade 1). Microspheres were detected in biopsies. The patient was free from severe symptoms at the end of follow up.

Studies with prospective designs and larger samples were included.

Sangro, P., Bilbao, I., Fernandez-Ros, N. et al (2017). Pneumatocele during sorafenib therapy: first report of an unusual complication. Oncotarget, 9(5), 6652-6656.

Case study

n=1

Follow-up= 5 years

A woman with pancreatic neuroendocrine tumours had SIRT. Her disease progressed after 9 months and required further intervention with Sorafenib. After this, pneumatocele were observed and the authors are unclear what the root cause of this was, but hypothesise it was Sorafenib.

Studies with prospective designs, more clinical outcomes and larger samples were included.

Saxena, A., Chua, T.C., Bester, L., et al., (2010). Factors Predicting Response and Survival After Yttrium-90 Radioembolization of Unresectable Neuroendocrine Tumor Liver Metastases: A Critical Appraisal of 48 Cases, Annals of surgery, 251(5), 910-916

Prospective case series

n=48

Median follow-up=41 months

Median survival was 35 months. At follow-up, 15% (7/48) people had complete response, 40% (19/48) had partial response and 23% (11/48) had stable disease, 11% had progressive disease. One person showed grade 3 toxicity (cirrhosis, ascites) and died within 1 month of treatment. One patient developed biliary obstruction over the 6 month period.

Study is included in the Frilling (2019) meta-analysis in Table 2. More recent studies are also included.

Saxena, A., Chua, T.C., Zhao, J., Morris, D.L. (2012). Liver-Directed Therapy for Neuroendocrine Neoplasm Hepatic Metastasis Prolongs Survival Following Progression After Initial Surgery. Journal of Surgical Oncology, 105, 342–350.

Retrospective case series

n=15 people who had SIRT (n=50 total)

Median follow-up=29 months

Median progression free survival after SIRT was 18 months, following previous resection with or without ablation.

Studies with prospective designs, more clinical outcomes and larger samples in the group of interest were included.

Schuttler, D., Mouroizis, K., Auernhammer, C.J. et al (2021). Development of severe intrapulmonary shunting in a patient with carcinoid heart disease after closure of a persistent foramen ovale: a case report. European Heart Journal - Case Reports, 5(12), 1–5.

Case report

n=1

Follow-up=4 months

The patient had carcinoid heart disease. Four months after SIRT, disease progressed into the bone but symptoms of carcinoid syndrome (dyspnoea) were relieved.

Studies with prospective designs, more clinical outcomes and larger samples were included.

Shaheen, M., Hassanain, M., Aljiffry, M., et al (2011). Predictors of response to radio-embolization (TheraSphere®) treatment of neuroendocrine liver metastasis. HPB, 14, 60–66.

Retrospective case series

n=25

Median follow-up=21.7 months

Previous surgery predicted greater change in percent tumour necrosis. 63% showed complete or partial response. 28% had grade 1–2 toxicities within 30 days of surgery. 2/25 people had grade 3 to 4 toxicity. One person died from bleeding from a perforated duodenal ulcer. Change in tumour necrosis was greatest for people who had previous surgical therapy indicating less bulky disease was a predictor of better response to SIRT.

This study was included in the meta-analysis by Frilling (2019). Studies with prospective designs and larger samples were included.

Sheheta, M., Yan, K., Itoh, S., et al., (2009). Splenomegaly and tumor marker response following selective internal radiation therapy for non-resectable liver metastases from neuroendocrine tumor. Dokkyo Journal of Medical Sciences, 36(3), 131-134.

Retrospective review of prospective database

n=16

Splenic volume was measured 3 months after SIRT.

Oesophagal variceal bleeding due to portal hypertension, gastrointenstinal bleeding and duodenal ulceration causing death in one patient 9 months after treatment. Long-term splenomegaly and portal hypertension may be important complications of SIRT.

Studies with prospective designs, more clinical outcomes and larger samples were included. As this is an old article, the methods of SIRT may have evolved since.

Simon, N., Warner, R.R.P., Baron, M. et al., (1968). Intra-arterial irradiation of carcinoid tumors of the liver. The American journal of roentgenology, radium therapy, and nuclear medicine, 102(3), 552-561.

Retrospective case series

n=5

Followed up to 19 months

Two people died from side effects of extrahepatic irradiation. Two people had remission of carcinoid symptoms in the short term (up to 6 months and 10 months respectively) but later showed recurrence of symptoms. One person made complete recovery.

As this is an old article, the methods of SIRT may not reflect current practice. Studies with prospective designs, more clinical outcomes and larger samples were included.

Singla, S., LeVea, C.M., Pokuri, V.K., et al., (2016). Ki67 score as a potential predictor in the selection of liver directed therapies for metastatic neuroendocrine tumors: a single institutional experience. J Gastrointest Oncol, 7(3), 441-448

Case series.

n=72 (n=44 SIRT)

Median follow-up=54.5 months

No significant difference in overall survival between SIRT and TACE when used without selection (median= 69, 82 months, respectively; p=0.47). There was significant interaction between Ki-67 score and liver-directed treatment benefit.

This study was included in the meta-analyses by Ngo (2021) and Frilling (2019). Studies with more clinical outcomes and larger samples were included.

Smits, M.L.J., van den Hoven, Rosenbaum, C.E.N.M., et al (2013). Clinical and Laboratory Toxicity after Intra-Arterial Radioembolization with 90Y-Microspheres for Unresectable Liver Metastases. PLoS ONE, 8(7): e69448.

Retrospective case series

n=6 people with mNETs (n=59 people in total)

Follow-up until death end of study period (2009-2012).

Median overall survival was 40.3 months (95% CI = 0 to 107.9). Median time to progression for the target lesion was 36.4 months (95% CI= 0 to 88.7) and 11.7 months (95% CI= 0 to 24.8) overall. Grade 1 to 2 toxicity observed in majority of patients (fatigue, loss of appetite, pain/ discomfort in upper abdominal quadrant, nausea/vomiting, fever). No grade 3 or 4 toxicity was observed. No serious treatment-related complications.

Studies had more people in the group of interest, prospective designs and more information about the mNET subgroup.

Sommer, W.H., Celeen, F., Garcia-Albeniz, X., et al., (2013). Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin. Eur Radiol, 23, 3094–3103

Retrospective case series

n=45

Median=303 days

Median progression free survival was 727 days (95 % CI, 378–964). Best response to SIRT in terms of longer progression free survival was predicted by hypervascular metastases, Ki-67 less than 2% and low neuron specific enolase level.

Studies with prospective designs, longer follow-up, more clinical outcomes and larger samples were included.

Su, Y.K., Mackey, R.V., Riaz, A., (2017). Long-Term Hepatotoxicity of Yttrium-90 Radioembolization as Treatment of Metastatic Neuroendocrine Tumor to the Liver, J Vasc Interv Radiol, 28, 1520–1526

Retrospective case series

n=54

Development of cirrhosis-like morphology was more common in people who had whole-liver treatments than unilobar; 56.4% (22/39) of people who had whole-liver SIRT developed cirrhosis-like morphology.

Median time to cirrhosis-like morphology was 1.8 years (range 0.7 to 7.2 years).

Larger and more recent studies reporting similar long-term toxicity were included.

Retrospective case series

n=93

Median follow-up= 15 months

The toxicities in this study focus on laboratory not clinical toxicity. Another study from 2018 that focuses on long term clinical side effects of SIRT has been included.

Tsang, E.S., Loree, J.M., Davies, J.M., et al., (2020). Efficacy and Prognostic Factors for Y-90 Radioembolization (Y-90) in Metastatic Neuroendocrine Tumors with Liver Metastases. Canadian Journal of Gastroenterology and Hepatology, 2020, 5104082

Retrospective case series

n=49

Data collected between Jun 2011 and Jan 2017

Median overall survival was 27.2 months (95%CI 8 to 47). Partial response (53%), stable disease (33%), and progressive disease (12%) was observed. Grade 3-4 biochemical toxicities (2%) and grade 3 abdominal pain (6%) were observed. Grade 1 toxicities included fatigue (4%), gastric ulceration (2%), and odynophagia (2%).

Studies with prospective designs and larger samples of the group of interest were included.

Tudela-Lerma, M, Orcajo-Rincon, J., Ramon-Botella, E. et al., (2021). Efficacy and safety of Yttrium-90 radioembolization in the treatment of neuroendocrine liver metastases. Long-term monitoring and impact on survival. Revista Española de Medicina Nuclear e Imagen Molecular, 40, 82–90.

Retrospective case series

n=15

5 years

No patient developed postembolisation syndrome or carcinoid syndrome after treatment. There were no vascular complications associated with the procedure. At 6 months, 78.6% presented partial response and 21.4%

stable disease, there was no progression or complete response. Survival at 3 and 5 years was 73% in both cases.

Studies with prospective designs and larger samples of the group of interest were included.

Turkmen, C., Ucar, A., Poyanly, A et al. (2013). Initial Outcome After Selective Intraarterial Radionuclide Therapy with Yttrium-90 Microspheres as Salvage Therapy

for Unresectable Metastatic Liver Disease, Cancer and Radiotherapy Biopharmaceuticals, 28(7), 534-540

Retrospective case series

n=12 mNET (n=61 total)

Mean=11 months

Median overall survival was not reached. Mean overall survival was 29 months (SD=3).

Studies with prospective designs, more clinical outcomes and larger samples of the group of interest were included.

Xing, M., Lahti, S., Kokabi, N., et al. (2016). 90Y Radioembolization Lung Shunt Fraction in Primary and Metastatic Liver Cancer as a Biomarker for Survival, Clinical Nuclear Medicine, 41(1), 21–27

Retrospective case series

N=73 mNET patients (n=366 total)

Every 3 months until death

People with low lung shunt fraction (less than 10%) had significantly longer overall survival. Overall survival was 33 months for people with low (less than 10%) lung shunt fraction, compared with 9.1 months in people with high (greater than or equal to 10%) lung shunt fraction (p< 0.001).

Studies with prospective designs, more clinical outcomes and larger samples of the group of interest were included.

Yang, T.X., Hua, T.C., Morris, D.L., (2012). Radioembolization and chemoembolization for unresectable neuroendocrine liver metastases: A systematic review, Surgical Oncology, 21, 299-308.

Systematic review for SIRT and TARE

n=12 SIRT studies with 423 patients (n=37 studies in total)

median follow-up was reported in 8 of 12 studies ranged from 9.4 months to 42 months (median=22.9)

The objective response rate was 63.1% (range= 12.5-100%) for SIRT, compared to 58.4% (range= 11.1- 89%) of those treated with TACE. More people who had SIRT had stable disease (32.8% versus 22 %), while less had progressive disease (3.6% versus 8.7%). The clinical response rates were similar in patients treated with

SIRT and TACE (85% versus 88.5%) Median survival for SIRT was 28 months (range= 14 to 70 months). Rates of major complication were similar. Radioembolisation may allow downstaging of liver metastases and subsequent radiofrequency ablation, liver resection or bridge to transplantation, allowing for a complete response.

A more recent systematic review explicitly comparing SIRT with TARE with meta-analyses was included in table 2.

Yilmaz, E., Engin, M.N., Ozkan et al., (2020). Y90 selective internal radiation therapy and peptide receptor radionuclide therapy for the treatment of metastatic neuroendocrine tumors: combination or not? Nuclear medicine communications, 41(12), 1242-1249.

Retrospective case series

n=27 (n=15 SIRT, n=12 SIRT and PRRT)

Mean= 32 months

Objective response or stable disease was observed in 87% (13/15) people in the SIRT only group and 67% (8/12) in the SIRT and PRRT group. Median OS was 34.9 months in SIRT only group and 67.5 months in the SIRT plus PRRT group (=0.22). Mean progression free survival was 53.1 in the SIRT only group and 27.2 in the SIRT plus PRRT group (p=0.56).

Studies with prospective designs, more clinical outcomes and larger samples of the group of interest were included.

Zubiri, L., Bilbao, J.I., Rodriguez, J., Sangro, B., (2018). Selective internal radiation therapy: an effective treatment for hormonal syndromes in pancreatic neuroendocrine tumors. Hepat. Oncol, 5(2).

Case reports

n=2

24 to 28 months after treatment

Two people with severe carcinoid syndrome that was refractory to other treatments were successfully treated with SIRT. One person had no side effects, was asymptomatic for 2 years and showed decrease in lesion vascularity. One person's symptoms were brought under control after treatment and ongoing octreotide. They experienced mild hypertransaminasemia 2 months after treatment. Their tumour showed complete response at 8 months which was maintained until their death 28 months after treatment.

Studies with prospective designs, more clinical outcomes and larger samples of the group of interest were included.

Zuckerman, D.A., Kennard, R.F., Roy, A., et al., (2019). Outcomes and toxicity following Yttrium-90 radioembolization for hepatic metastases from neuroendocrine tumors- a single institution experience. J Gastrointest Oncol, 10(1), 118-127

Retrospective case series

n=59

Mean=2 years

Median overall survival was 31 months, and the 1- and 2-year overall survival was 80.4% and 65.6%, respectively. Median hepatic progression free survival and overall progression-free survival were 18 and 13 months, respectively. Three patients died of hepatic failure that was possibly therapy-related. Preliminary data regarding dose to normal liver is suggestive of a relation between dosimetry and toxicity.

Larger, prospective studies with longer follow-up were included.