Assessment of the efficacy and toxicity of 131I-metaiodobenzylguanidine therapy for metastatic neuroendocrine tumours

Abstract

131 I-metaiodobenzylguanidine ( 131 I-MIBG) is a licensed palliative treatment for patients with metastatic neuroendocrine tumours. We have retrospectively assessed the consequences of 131 I-MIBG therapy in 48 patients (30 gastroenteropancreatic, 6 pulmonary, 12 unknown primary site) with metastatic neuroendocrine tumours attending Royal Liverpool University Hospital between 1996 and 2006. Mean age at diagnosis was 57.6 years (range 34 -81). 131 I-MIBG was administered on 88 occasions (mean 1.8 treatments, range 1 -4). Twenty-nine patients had biochemical markers measured before and after 131 I-MIBG, of whom 11 (36.7%) showed 450% reduction in levels post-therapy. Forty patients had radiological investigations performed after 131 I-MIBG, of whom 11(27.5%) showed reduction in tumour size post-therapy. Twenty-seven (56.3%) patients reported improved symptoms after 131 I-MIBG therapy. Kaplan -Meier analysis showed significantly increased survival (P ¼ 0.01) from the date of first 131 I-MIBG in patients who reported symptomatic benefit from therapy. Patients with biochemical and radiological responses did not show any statistically significant alteration in survival compared to non-responders. Eleven (22.9%) patients required hospitalisation as a consequence of complications, mostly due to mild bone marrow suppression. 131 I-MIBG therefore improved symptoms in more than half of the patients with metastatic neuroendocrine tumours and survival was increased in those patients who reported a symptomatic response to therapy.

Long-Term Outcome and Toxicity After Dose-Intensified Treatment with 131I-MIBG for Advanced Metastatic Carcinoid Tumors

“…In agreement with previous reports, hematotoxicity was the primary side effect of 131 I-MIBG therapy in the present study (1,10,(24)(25)(26)34,35); this side effect was noted at a higher frequency (10%-20% perpatient incidence of grade 3 or 4) with the studied treatment regimen than with previously reported treatment regimens with lower single activities (23,24,26,27). However, it was of a transient nature in our cohort and triggered no hospitalization, granulocyte stimulation, or thrombocyte substitution, except in 1 patient with grade 4 thrombocytopenia (cumulative activity of 66.6 GBq).…”

“…This finding was particularly encouraging considering the difficulty in controlling carcinoid symptoms, which frequently determine patients' quality of life and increase morbidity rates (22). A morphologic tumor response after 131 I-MIBG therapy, on the other hand, was less frequently observed for carcinoid tumors, with reported response rates of 0%-35% (10,11,(23)(24)(25)(26)(27). The main observed outcome in the present study was disease stabilization (with or without minor remission) in 80%-90% of patients.…”

“…Three of 11 patients (27%) with symptomatic carcinoid tumors had a complete resolution of symptoms after treatment, and 6 patients (55%) had a partial resolution of symptoms after treatment. This symptomatic relief resulted in a reduction in the required doses of somatostatin analog treatment in 9 patients ($50% reduction in 5 patients); this effect lasted for a mean of 14 mo (range, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] from the completion of 131 I-MIBG therapy. Only 2 patients (18%) had no significant symptomatic improvement.…”

Molecular radiotheranostics for neuroendocrine tumours

“…An example of a patient with good uptake on the MIBG imaging scan that went on to have MIBG therapy is demonstrated in Fig 4 . Approximately 40-50% of patients develop good symptomatic response to treatment. [33][34][35] Not many studies evaluated progression-free survival, but most studies showed a median overall survival of over 40 months following MIBG therapy. Interestingly, Sywak et al compared two groups of patients with midgut NETs.…”

“…Myelodysplasia is another possible rare side effect, which may occur in patients heavily pre-treated with chemotherapy or radiotherapy. [33][34][35] Tumour and critical organ dosimetry Dosimetry is the measurement of absorbed radiation dose imparted by ionising radiation. Dosimetry can be performed both to calculate critical organ radiation dose (to limit toxicity) and to optimise tumour dose.…”