Upfront F18-choline PET/CT versus Tc99m-sestaMIBI SPECT/CT guided surgery in primary hyperparathyroidism: the randomized phase III diagnostic trial APACH2.

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.

F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study.

PURPOSE: To evaluate the sensitivity of F18-choline (FCH) PET/CT for parathyroid adenoma detection prior to surgery in patients with primary hyperparathyroidism and negative or inconclusive cervical ultrasound and Tc99m-sestaMIBI SPECT/CT. METHODS: We conducted a prospective bicentric study (NCT02432599). All patients underwent FCH PET/CT. The result was scored positive, inconclusive or negative. The number of uptakes and their sites were recorded. The FCH PET/CT result guided the surgical procedure (minimally invasive parathyroidectomy, bilateral cervical exploration, or other in case of multiple or ectopic foci). FCH PET/CT results were compared to the surgical and pathological findings and the follow-up. RESULTS: Twenty-five patients were included. Mean calcium and PTH levels prior to surgery were 2.76 ± 0.17 mmol/l and 94.8 ± 37.4 ng/l. Nineteen (76%) FCH PET/CTs were scored positive, 3 (12%) inconclusive and 3 (12%) negative, showing 21 cases of uniglandular disease, including 1 ectopic localization and 1 case of multiglandular (3 foci) disease. Mean lesion size was 13.1 ± 8.6 mm. Twenty-four patients underwent surgery. FCH PET/CT guided surgery in 22 (88%) patients, allowing for 17 minimally invasive parathyroidectomies, 1 bilateral cervical exploration for multifocality and 4 other surgical procedures. Two patients with negative FCH-PET/CT underwent bilateral cervical exploration. When dichotomizing the FCH PET/CT results, thereby classifying the inconclusive FCH PET/CT results as positive, the per lesion and per patient sensitivities were 91.3% (95%CI: 72.0-98.9) and 90.5% (95%CI: 69.6-98.8) and the corresponding positive predictive values were 87.5% (95%CI: 67.6-97.3) and 86.4% (95%CI: 65.1-97.1), respectively. Twenty-one (88%) patients were considered cured after surgery. Their mean calcium level after surgery was 2.36 ± 0.17 mmol/l. CONCLUSIONS: Preoperative FCH PET/CT has a high sensitivity and positive predictive value for parathyroid adenoma detection in patients with primary hyperparathyroidism and negative or inconclusive conventional imaging results. Bilateral cervical exploration could be avoided in the majority (75%) of patients.

F18-Choline PET/CT or MIBI SPECT/CT in the Surgical Management of Primary Hyperparathyroidism: A Diagnostic Randomized Clinical Trial.

Importance: Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear. Objective: To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery. Design, Setting, and Participants: A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible. Interventions: Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery. Main Outcomes and Measures: The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality. Results: Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported. Conclusions: This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity. Trial Registration: ClinicalTrials.gov Identifier: NCT04040946.

[Management of adverse effects of targeted therapy toxicities in oncology]. / Principes de prise en charge des effets indésirables des thérapies ciblées en cancérologie.

During the past few years, medical treatments of cancer have improved thanks to the discovery of targeted therapies. These therapies are today widely used in cancer treatment. The mechanism of action of targeted therapies and the adverse effects they induce are different from the classic chemotherapies, and require a specific management. Most of these drugs are taken at home and orally, and as a consequence, general practitioners should be able to manage these side effects. The most current toxicities in general medicine are fatigue, high blood pressure, dermatologic, gastrointestinal and metabolic side effects. These effects, often moderate are frequent and diverse, and can impact the patient's quality of life and reduce treatment compliance. Management of these toxicities should then be well known by general practitioners in order to optimize care and improve patient wellness.

Major hyperestrogenism in a feminizing adrenocortical adenoma despite a moderate overexpression of the aromatase enzyme.

A 30-year-old male was referred for the rapid development of gynecomastia, and dramatic hyperestrogenemia was assessed: plasma estrone, estradiol but also cortisol were not suppressed by high-dose dexamethasone, while gonadotropin pulsatility was completely abolished. A 60-mm right adrenal tumor was evidenced on computed tomography-scan, and the patient underwent adrenalectomy. The tumor was found to express a moderate increase in aromatase activity compared with adjacent non-neoplastic adrenal tissue. Quantitative RT-PCR also showed a weak and non-significant increase in total aromatase mRNA in the tumor compared with normal adrenal tissue. Aromatase transcripts were mainly promoter PII-derived, but different patterns of aromatase minor transcripts were found: promoter I.3- and I.6-derived transcripts were identified in the tumor, while only promoter I.4-derived transcripts were found in normal adrenal. This case report demonstrates that a sharp aromatase overexpression is not a prerequisite for clinical and biochemical hyperestrogenism, and further characterizes the aromatase promoter utilization in this feminizing adrenocortical tumor and in the normal adrenal cortex.

Efficacy of continuous subcutaneous insulin infusion in type 2 diabetes mellitus: a survey on a cohort of 102 patients with prolonged follow-up.

OBJECTIVES: We evaluated the long-term efficacy of continuous subcutaneous insulin infusion (CSII) for treating type 2 diabetes patients uncontrolled by multiple daily injections. RESEARCH DESIGN AND METHODS: All 102 type 2 diabetes patients who began insulin pump therapy at Caen University Hospital (Caen, France) between January 1998 and August 2008 were included in a retrospective observational study. Ninety-three percent of the patients were previously treated by insulin with a mean duration of 5.6 years. RESULTS: The median duration of follow-up with CSII was 24 months. A1c glycated hemoglobin (HbA1c) improved from baseline (9.3 ± 1.8%) to the 1-year evaluation (7.8 ± 1.4%) (P < 0.001). The magnitude of HbA1c improvement was highly dependent on (1) pretreatment HbA1c level, (2) degree of patient's autonomy, and (3) previous antidiabetes treatment. HbA1c decreased by 0.9 ± 1.6% (P = 0.002) in the group previously treated by a basal-bolus regimen. HbA1c decrease was maintained at follow-up until 6 years (P < 0.05). Mean body weight gain was 3.9 ± 8.6 kg at 1 year (P < 0.001) and remained stable at follow-up. No significant change in insulin requirement was observed. CONCLUSIONS: The use of CSII in patients with type 2 diabetes is safe and effective for improving glycemic control, particularly in those patients with baseline HbA1c above 8%. Such beneficial effect of CSII may persist until 6-year follow-up, suggesting the durability of CSII efficacy in our study population.