RET gene mutation analysis and long-term clinical outcomes of medullary thyroid cancer patients

Abstract

Objective Medullary thyroid carcinoma is a rare, potentially aggressive tumour, with relatively worse prognosis than well-differentiated thyroid cancer. We evaluated the long-term outcomes and prognosis of medullary thyroid carcinoma patients at a single institution in India and compared outcomes based on results of RET protooncogene mutation analysis. Methods Data were retrieved through a prospectively maintained thyroid cancer database from 1998 to June 2019, and medullary thyroid carcinoma patients were recruited. RET gene mutation status (exon 10–16) was assessed. Patient with a minimum follow-up of 12 months was eligible to be part of the long-term outcome analysis. Results Out of 149 peripheral blood samples, 42 were positive for RET gene mutation (prevalence of 28.1%). The median follow-up duration was 48 months, ranging from 12 to 240 months. Long-term clinical outcomes of 113 patients were assessed. Two deaths were noted in this series. Both 5- and 10-year survival was cent per cent. Overall survival was 98.2% (97.3% in RET positive and 98.7% in RET negative group). Progression-free survival was 55.4% in total (60% in RET positive and 53.3% in RET negative group). No statistically significant difference was found between RET positive and RET negative groups concerning overall survival (P = 0.6011) and progression-free survival (P = 0.5140). Univariate analysis revealed high calcitonin (>10 pg/mL), stage IV disease, and presence of lymph nodal metastasis to be significant predictors of disease recurrence, however, multivariate analysis demonstrated the presence of lymph node metastases as the only significant predictor of recurrence (P = 0.0005). Conclusions Medullary thyroid carcinoma patients had relatively favourable long-term outcomes. Long-term survival was similar irrespective of RET mutation status. Presence of lymph node metastases appeared to be the strongest predictor of overall and progression-free survival, followed by Calcitonin level and stage of the disease.

Landscape of gene mutation in Chinese thyroid cancer patients: Construction and validation of lymph node metastasis prediction model based on clinical features and gene mutation marker

“…Until now, univariate and multivariate analyses have both revealed LNM played a significant role in predicting disease recurrence 11 . Presence of LNM can cause five times more likely to relapse than the absence of LNM 11,13 . The study of Lee et al 14 found that the deaths can be up to 16 patients, who died of distant metastasis or locoregional failure, among 18 patients with recurrence, nearly 89% 14 .…”

“…The study of Nie et al 12 also found that the rate of lateral LNM and central LNM were 74.9% and 70.5%, respectively, in PTC patients in China. Until now, univariate and multivariate analyses have both revealed LNM played a significant role in predicting disease recurrence 11 . Presence of LNM can cause five times more likely to relapse than the absence of LNM 11,13 .…”

“…Surgery followed by radioactive iodine therapy or chemoradiation are both effective treatments and targeted treatment of the cancer for example BRAF inhibitors MEK inhibitors has also been a prospective method to cure of TC 5 . Although majority of patients have favorable prognoses, with the 5‐year‐survival rate of about 98.2% in PTC patients (PTCP) around the world and 84.3% in TC patients in China, 7–10 lymph node metastasis (LNM) is still a risk factor which contributes to the poor prognosis of TC patients 11 . Therefore, we aim to construct new models to predict LNM to optimize treatment of patients.…”

“… 5 Although majority of patients have favorable prognoses, with the 5‐year‐survival rate of about 98.2% in PTC patients (PTCP) around the world and 84.3% in TC patients in China, 7 , 8 , 9 , 10 lymph node metastasis (LNM) is still a risk factor which contributes to the poor prognosis of TC patients. 11 Therefore, we aim to construct new models to predict LNM to optimize treatment of patients.…”

“… 11 Presence of LNM can cause five times more likely to relapse than the absence of LNM. 11 , 13 The study of Lee et al 14 found that the deaths can be up to 16 patients, who died of distant metastasis or locoregional failure, among 18 patients with recurrence, nearly 89%. 14 Therefore, we could consider LNM as a poor prognostic factor.…”