Treatment of patients with Hurtle cell thyroid carcinoma using [Lu-177-DOTA0,Tyr3]octreotate

Objectives Hurthle cell thyroid carcinoma (HCTC) is a variant of follicular thyroid carcinoma. Although radioiodine (I-131) is frequently given for ablation of the thyroid remnant to enable thyroglobulin follow-up, the effectiveness of additional I-131 therapy for residual or metastatic disease is rather poor, related to the tumor’s poor capacity of taking up radioiodine. Since some thyroid tumor cells express somatostatin receptors, peptide receptor radionuclide therapy (PRRT) [Lu-177-DOTA0,Tyr3]octreotate (Lu-177-octreotate) has been proposed as a potential tool for treatment in HCTC.

Methods fifteen patients with pathology proven HCTC who had been treated with Lu-177-octreotate between January 2000 and April 2012 were studied. Pre-treatment In-111-octreotide planar scintigraphy was analyzed for extent (unifocal, limited and extensive) and intensity of disease using the Krenning score (Grade 1,2 and 3: tumor uptake less, equal or more than physiological liver uptake respectively and 4: intense uptake more than spleen or kidneys). CT or MRI scans were analyzed using mSWOG criteria (including the tumor response class minor response (MR) (decrease of 25‐50% for mSWOG)). Thyroglobulin levels before and after treatment were analyzed.

Results all fifteen patients had received radioiodine to ablate the thyroid remnant and 6 patients received an additional treatment dose of I-131 (total cumulative dose of I-131 range: 666 MBq to 14.8 GBq). Twelve patients received the intended cumulative dose (22-30 GBq) of Lu-177-octreotate whereas 3 patients did not due to persisting thrombocytopenia (1), concomitant cardiac atrial fibrillation (1), or diagnosis of a second primary carcinoma (1). The acute side effects nausea, vomiting, pain, and hairloss occurred in 22%, 2%, 8% and 27% respectively. WHO grade 3 bone marrow toxicity was present in 2% of all treatment cycles for both platelets and leukocytes. No long-term side effects such as myeloproliferative disorders or kidney failure were observed during follow-up. Analysis of all pre-treatment In-111-octreotide scans showed an uptake grade 2 in 9 (60%) patients, grade 3 in 5 (33%) and grade 4 in 1 (7%). Unifocal disease was present in 7 (47%) of all patients, limited in 7 (47%) and extensive in 1 (7%). In eleven of the 12 patients receiving the intended cumulative dose, sufficient follow-up data were available. Four (36%) patients achieved partial response (PR) at three months after the last treatment. Stable disease (SD) was found in seven (64%) patients of whom in six progressive disease was present defined with either anatomical imaging (5 patients) or an increase of thyroglobulin levels with more than 50% (1) within one year prior to treatment with Lu-177-octreotate. A decrease of more than 50% in serum thyroglobulin was found in four patients of whom three also demonstrated partial response on CT or MRI. Based on the pre-treatment scans neither extent nor uptake no significant prediction could be made on tumor response. Median time to progression was 32 months and median overall survival 36 months.

Conclusions Lu-177-octreotate therapy may be effective in patients with HCTC. PR was found in 36% of patients and SD in 64%, all of whom had proven progressive disease prior to PRRT.