Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls

Abstract

Background For progressive metastatic medullary thyroid carcinoma (MTC), the available treatment options with tyrosine kinase inhibitors result in grade 3–4 adverse events in a large number of patients. Peptide Receptor Radionuclide Therapy (PRRT), which has also been suggested to be a useful treatment for MTC, is usually well tolerated, but evidence on its effectivity is very limited. Methods Retrospective evaluation of treatment effects of PRRT in a highly selected group of MTC patients, with progressive disease or refractory symptoms. In addition, a retrospective evaluation of uptake on historical 111 In-DTPA-octreotide scans was performed in patients with detectable tumor size > 1 cm. Results Over the last 17 years, 10 MTC patients were treated with PRRT. Four out of 10 patients showed stable disease at first follow-up (8 months after start of therapy) whereas the other 6 were progressive. Patients with stable disease were characterized by a combination of both a high uptake on 111 In-DTPA-octreotide scan (uptake grade ≥ 3) and a positive somatostatin receptor type 2a (SSTR2a) expression of the tumor by immunohistochemistry. Retrospective evaluation of historical 111 In-DTPA-octreotide scans of 35 non-treated MTC patients revealed low uptake (uptake grade 1) in the vast majority of patients 31/35 (89%) with intermediate uptake (uptake grade 2) in the remaining 4/35 (11%). Conclusions PRRT using 177 Lu-octreotate could be considered as a treatment in those patients with high uptake on 111 In-DTPA-octreotide scan (uptake grade 3) and positive SSTR2a expression in tumor histology. Since this high uptake was present in a very limited number of patients, this treatment is only suitable in a selected group of MTC patients.

Clinical utility of 177Lu‐DOTATATE PRRT in somatostatin receptor‐positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity

“…However, none of these treatments were able to promote complete remission and cure of the disease and had some important and serious side effects such as ECG alterations, diarrhea and hypertension. 34,35 We found median a PFS of 24 months (95% CI: 15.1-32.9 months) after first 177 Lu-DOTATATE PRRT, which was between cabozantinib group (PFS-11.2 months) and vandetanib group (PFS-30.5 months) reported in the literature; also PRRT welltolerated with fewer side effects of low grade severity was demonstrated in our study. However, retrospective nature of our study was major limitation.…”

An Alternative Therapy Option in Metastatic Thyroid Cancer: Peptide Receptor Radionuclide Therapy

“…Therefore, alternative treatment options with fewer side effects were needed. With the detection of SSTR expression in MTC, PPRT has become the new treatment option (9). According to previous studies, the response rates were 29-80%, in our study we found stable disease response in all 3 patients who underwent treatment response evaluation (18,24).…”

Novel Targeted Therapies for Metastatic Thyroid Cancer—A Comprehensive Review

“…There were small pilot studies performed in Europe that documented the utility of treatment of progressive RAI-non-avid metastatic DTC and MTC with SSTR agonists radiolabeled with 177 Lutetium or 86 Ytrium. The overall response rate was similar to current standard-of-care therapy with TKIs, while the quality of life was better and complication rate was lower after the therapy with PRRT (Table 2) [111][112][113][130][131][132].…”