Endocrine/Head and Neck
Aradhya Nigam, MD
Research Fellow
MSKCC
New York, New York, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Calcitonin doubling time (Ctn DT) predicts recurrence and outcomes after medullary thyroid cancer (MTC) resection. Tumor grade is a new validated prognostic factor for MTC. We aimed to describe how tumor grade affects post-operative Ctn DTs after curative surgery.
Methods:
Methods:
A retrospective analysis evaluated post-resection MTC patients at a single tertiary-care cancer center from 1986 to 2017. High-grade MTC was defined with either mitotic index ≥5 per 2mm2, the presence of tumor necrosis, or Ki67 proliferative index ≥5% on review by two head and neck pathologists. Ctn DT was calculated using a validated calculator with a minimum of three consecutive levels. Outcomes evaluated were locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS).
Results:
Amongst MTC patients, 98 (80.3%) had low-grade and 24 (19.7%) had high-grade tumors. Median follow-up was 70 months. Ctn DTs were significantly shorter in high-grade (8.51 ± 3.22mo) than low-grade (38.42 ± 11.19mo) patients (p< 0.001) with most high-grade patients having Ctn DTs less than one-year (66.7% v 1.0%; p< 0.001). Next, we grouped patients by Ctn DT less than 2 years and Ctn DT greater than 2 years- a clinically used prognostic cutoff point. When Ctn DT was greater than 2 years, 3% percent of tumors were high-grade and 97% were low-grade (p< 0.001). In the Ctn DT less than 2 years cohort, 70% of tumors were high-grade and 30% low-grade (p< 0.001). To determine the independent effect of grade and Ctn DT on outcomes, a multivariate analysis using Cox proportional hazards model was performed. Patients with high-grade tumors had worse LRRFS (HR 4.77, 95% CI 1.19-8.81), DMFS (HR 7.25 95%CI 2.36-22.28), and OS (HR 6.04, 95%CI 1.85-19.72; p< 0.05 for all) whereas patients with Ctn DT less than 2 years were associated with worse DMFS (HR 7.22, 95%CI 1.05-49.75).
Conclusions:
A majority of patients with high-grade MTC experience Ctn DTs of less than 2 years after surgical resection. High-grade patients and those with Ctn DTs less than 2 years are at risk for poor disease-specific outcomes and should be monitored closely for recurrence and be considered for adjuvant therapy trials.