In summary, we have demonstrated that 131I-MIBG therapy resulted in symptomatic improvement in more than half of a group of 48 patients with metastatic NETs. Patients who reported a symptomatic improvement also showed a 37-month increase in median survival from the date of first 131I-MIBG administration. Although some evidence of treatment-related toxicity was found in up to a third of patients, this toxicity was mild and self-limiting in most cases.
The proportion of patients experiencing symptomatic benefit from 131
I-MIBG therapy (56.3%) was similar to that reported in previous studies (Safford et al, 2004
; Sywak et al, 2004
). As in one previous similar study (Safford et al, 2004
), survival after 131
I-MIBG therapy was best predicted by a subjective symptomatic response to treatment. Median survival was increased by 37 months in symptomatic responders compared to non-responders in this study, compared to 32 months in the previous study (Safford et al, 2004
). As also previously demonstrated by Safford et al (2004)
, patients who demonstrated improvement in biochemical parameters (serum chromogranin A or 24
h urine 5HIAA) or decreased tumour burden on follow up radiological scans post-131
I-MIBG therapy showed no statistically significant differences in survival. This finding may partly reflect the small sample size of patients who had complete biochemical and radiographic measurements available. Nonetheless, our data suggest that routine monitoring of biochemical and radiographic parameters post-131
I-MIBG therapy is unlikely to provide useful information about an individual patient's prognosis.
Overall median survival in our cohort of patients (79±7.2 months) was similar to that reported in previous studies. In our study, although symptomatic responders to 131I-MIBG therapy showed significantly increased survival compared to non-responders when assessed from the date of first 131I-MIBG treatment, when survival of this group was assessed from the date of initial diagnosis with a NET, there was no statistically significant difference compared to those patients who did not demonstrate a symptomatic response to 131I-MIBG therapy. It is therefore possible that the responders to 131I-MIBG therapy were treated earlier in the course of their illness. It is not currently known whether a patient's response to radionuclide therapies alters during the course of disease progression. A randomised prospective trial in a less heterogeneous group of patients would be necessary to definitively determine whether 131I-MIBG therapy improves overall survival in patients with metastatic NETs.
Toxicity post-131I-MIBG therapy was not infrequent, occurring in 29.2% patients and leading to hospitalisation in 22.9%. Bone marrow suppression was observed most commonly, but in most cases this was mild (NCI grade 1 or 2) and resolved spontaneously without specific measures. There was one death within 30 days of treatment, but this was as a result of tumour progression rather than due to treatment side effects. Two patients developed hypothyroidism despite thyroid blockade.
Patients with NETs do benefit from a multidisciplinary approach to their care. All patients should be evaluated in a standardised manner using a range of biochemical assays as well as with anatomical and functional imaging techniques. Several treatment options are often possible for an individual patient at a particular stage in the course of his/her illness and the choice of treatment should therefore be discussed by the multidisciplinary team and with the patient concerned. Our study confirms previous observations that 131
I-MIBG therapy is a generally safe and reasonably well-tolerated treatment option and confers symptomatic benefit in >50% patients with metastatic NETs. Symptomatic responders to 131
I-MIBG therapy may have an improved prognosis. However, as responders in this study were often treated earlier in the course of their illness, current data do not confirm a significant increase in survival from the date of initial diagnosis. It therefore appears that the use of small-fractionated doses of 131
I-MIBG probably does not affect the overall survival of patients with metastatic NETs, although therapy does appear to have a major effect on symptoms in many patients. The efficacy of larger doses of 131
I-MIBG should therefore be evaluated, but as this is likely to be associated with an increased incidence of bone marrow toxicity risk/benefit analyses will have to be undertaken. Recently, other novel forms of radionuclide therapy have been developed. Direct comparisons of 131
I-MIBG with other radionuclide therapies such as 90
Y-DOTATOC (Bodei et al, 2004
; Forrer et al, 2006
; Frilling et al, 2006
) should therefore be performed to determine the optimal treatment regimes for individual patients.