Is There a Role for Peptide Receptor Radionuclide Therapy in Medullary Thyroid Cancer?

Vaisman, Fernanda; Rosado-de-Castro, Paulo Henrique; Lopes, Flávia Paiva Proença Lobo; Kendler, Daniel Barretto; Pessoa, Cencita H.N.; Bulzico, Daniel; Leal, Douglas de Carvalho; Vilhena, Bruno; Carneiro, Michel Pontes; Corbo, Rossana

doi:10.1097/rlu.0000000000000628

Cited by 44 publications

(40 citation statements)

References 22 publications

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“…Widespread skeletal pain was present in 10 patients before PRRT and complete disappearance of skeletal pain was found in 3 patients and PR was noted in 7 patients after PRRT. This was indicative of decrease in symptoms in sizeable fraction of metastatic MTC patients with few of them becoming completely symptom free following 177 Lu-DOTATATE PRRT, indirectly implying improvement in quality of life, which was also shown by Vaisman et al 30 in their study. The normalization of serum calcitonin level (CR) occurred in 5 (11%), more than 50% decrease in serum calcitonin level (PR) occurred in 13 (30%), stable serum calcitonin level (SD) was found in 4 (10%) patients after PRRT, suggestive of PRRT produces decrease in serum calcitonin levels in around half of the metastatic MTC patients.…”

Section: Discussionsupporting

confidence: 75%

“…The overall outcome (objective response and stable disease) was 42% in MTC and the objective complete or partial response rate was 0% in their study. 30 Makis et al reported two cases of metastatic MTC, who were treated with 177 Lu-DOTATATE PRRT. In their study, 67% MTC patients derived a clinical benefit from PRRT, which manifested as either an objective tumor response or stabilization of tumor burden.…”

Section: Discussionmentioning

confidence: 99%

“…All responders reported improvement in quality of life and cancer-related pain. 30 Makis et al reported two cases of metastatic MTC, who were treated with 177 Lu-DOTATATE PRRT. Both cases achieved stable disease after PRRT, based on 111 In-octreotide scintigraphy.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2019

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Background: The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor-positive metastatic medullary thyroid carcinoma (MTC), including progression-free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients.Methods: A total of 43 somatostatin receptor-positive metastatic MTC patients, treated with 177 Lu-DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post-treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68 Ga-DOTATATE, 18 F-FDG PET-CT, CeCT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (CtnDT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI-CTCAE v5.0 criteria. The observed Kaplan-Meier curves for both PFS and OS since first PRRT were compared with CtnDT (more than 24 months vs less than 24 months) by log-rank (Mantel-Cox) test. The prognostic variables were investigated for their association with CtnDT and response to PRRT using Cox proportional-hazards model. RESULTS:The median OS was 26 months (95% CI 16.6-35.3 months) and the median PFS 24 months (95%.CI: 15.1-32.9 months). Following 177Lu-DOTATATE PRRT, the observed median PFS and OS was longer in patients who had CtnDT more than 24 months compared to those with CtnDT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time-point of first 177 Lu-DOTATATE PRRT cycle, the patients with CtnDT more than 24 months had a significantly longer PFS (P < .001) and OS (P < .001) compared to those with less than 24 months. Less than 5 lesions, FDG uptake in lesions (SUVmax of <5) and patients alive at the time of analysis were the significant variables for association with CtnDT (more than 24 months). Out of 43 patients, 26 were responders (61%) and 17 nonresponders (39%) based upon PERCIST criteria, and 27 were responders (62%) while 16 patients were nonresponders (38%) based upon RECIST 1.1 criteria. The univariate analysis showed significant association between responses to PRRT with following prognostic variables:(a) size of lesions (<2 cm) and (b) FDG uptake in lesions (SUVmax of <5). PRRT was well tolerated in all patients without any major grade 3 or 4 toxicity. Conclusion:The results demonstrated that, 177 Lu-DOTATATE is a potentially efficacious and safe therapeutic option in SSTR avid metastatic MTC patients. K E Y W O R D S 177 Lu-DOTATATE, 68 Ga-DOTATATE PET-CT, calcitonin doubling time, medullary thyroid carcinoma, peptide receptor radionuclide therapy, progression-free survival and overall survival

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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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

et al. 2019

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“…A phase II trial in 31 patients with 90 Y-DOTA-TOC, which also targets SSTR2a, reported a partial response (PR) in 29% of the patients [13]. In a second trial treating 7 MTC patients with 177 Lu-octreotate, 3 patients had PR, 3 patients had stable disease (SD) and 1 patient progressive disease (PD) [14]. These results suggest that PRRT might be a useful treatment in patients with MTC, although the total number of treated patients is very limited so far.…”

Section: Patients and Treatmentmentioning

confidence: 99%

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

Beukhof¹,

Brabander²,

van³

et al. 2018

EJEA

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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.

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“…Therapy with 177 Lutetium-DOTATATE, a similar type of peptide receptor radionuclide targeting the SSTR, was reported to achieve stable disease for 9-10 months in two cases [63]. PRRT appears to be an alternative therapy for the minority of SSTR-positive MTC tumors, but long-term studies are still needed to understand efficacy and risk profiles of this novel therapy [64].…”

Section: • Radionuclide Therapymentioning

confidence: 99%

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

Li¹,

Simonds

2017

Int. J. Endo. Oncol.

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Hereditary hyperparathyroidism syndromes, such as multiple endocrine neoplasm type 1, type 2A and the hyperparathyroidism-jaw tumor syndrome, are associated with an increased incidence of malignancies involving the neuroendocrine tissue of the pancreas and thymus, parathyroid and thyroid glands. The natural history of these endocrine tumors can differ from nonhereditary malignancies. The surgical approach, the only potentially curative treatment option for these endocrine malignancies, has evolved considerably in recent years. Newer targeted therapies, such as small molecule kinase inhibitors, somatostatin analogs and peptide receptor radionuclide therapy, are being developed. We provide here a comprehensive review of the current standards of treatment and emerging novel therapies for the endocrine malignancies commonly associated with hereditary hyperparathyroidism syndromes.

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Is There a Role for Peptide Receptor Radionuclide Therapy in Medullary Thyroid Cancer?

Cited by 44 publications

References 22 publications

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

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

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

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

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Is There a Role for Peptide Receptor Radionuclide Therapy in Medullary Thyroid Cancer?

Cited by 44 publications

References 22 publications

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

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

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

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

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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

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