ABSTRACT
BACKGROUND: The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society. METHODS: We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1. DISCUSSION: FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications. In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs. TRIAL REGISTRATION: NCT04040946 , registered August 1, 2019. Protocol version Version 2.1 dated from 2020/04/23.
Subject(s)
Fluorine Radioisotopes/metabolism , Hyperparathyroidism, Primary/surgery , Positron Emission Tomography Computed Tomography/methods , Surgery, Computer-Assisted/methods , Technetium Tc 99m Sestamibi/metabolism , Tomography, Emission-Computed, Single-Photon/methods , Adolescent , Adult , Aged , Aged, 80 and over , Clinical Trials, Phase III as Topic , Female , Follow-Up Studies , Humans , Hyperparathyroidism, Primary/diagnostic imaging , Hyperparathyroidism, Primary/metabolism , Hyperparathyroidism, Primary/pathology , Male , Middle Aged , Multicenter Studies as Topic , Prognosis , Radiopharmaceuticals/metabolism , Randomized Controlled Trials as Topic , Young AdultABSTRACT
BACKGROUND: In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome. METHODS: This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or 18FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively. RESULTS: PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9-12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and 18FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit. CONCLUSIONS: The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.
