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.

Risk factors for hypothyroidism following hemithyroidectomy.

OBJECTIVE: Hypothyroidism is the most common complication of hemithyroidectomy for thyroid nodules. This retrospective cohort study investigated the prognostic factors for hypothyroidism following hemithyroidectomy. METHODS: We included patients who underwent hemithyroidectomy between 2016 and 2017, excluding those with history of preoperative hypothyroidism or malignancy on histopathological examination. The primary endpoint was development of hypothyroidism during follow-up (TSH≥2 above normal). RESULTS: Twenty-six of the 128 included patients (20%) developed postoperative hypothyroidism. The following independent prognostic factors were found: preoperative TSH level>1.5 mIU/L (OR 2.11; P=0.013), and remaining thyroid volume adjusted for body surface area<4.0mL/m2 (OR 1.77; P=0.015). Twenty-one patients (81%) had first TSH values above the upper limit of normal. Postoperatively, first TSH level correlated significantly with the preoperative value (R=0.5779, P<0.001). Levothyroxine was prescribed to 16% of patients, with a mean dose of 0.92µg/kg/day. CONCLUSION: Patients with TSH>1.5 mIU/or remaining thyroid volume adjusted for body surface area<4.0mL/m2 should have intensified clinical and biological follow-up in the first year after surgery.

Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab.

BACKGROUND: Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity. OBJECTIVE: We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck. PATIENTS AND METHODS: Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%). RESULTS: Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47-75) compared to 51 days (47-65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3-107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively). CONCLUSIONS: Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.

Diagnostic performance of FDG PET/CT to detect subclinical HNSCC recurrence 6 months after the end of treatment.

PURPOSE: Posttreatment follow-up for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination or conventional imaging. Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is widely validated for the diagnosis of suspected recurrence. Moreover, we have shown in a previous prospective study the high effectiveness of FDG PET/CT in the assessment of subclinical recurrence 12 months after treatment. The aim of this prospective study was to evaluate the effectiveness of an earlier FDG PET/CT, at 6 months after the end of treatment. METHODS: All patients treated for histologically proven HNSCC from April 2009 to May 2012 at the University Hospital of Brest who did not show any findings suggestive of recurrence at 6 months of their usual follow-up underwent an FDG PET/CT examination. FDG PET/CT findings were correlated with histopathology or imaging follow-up. RESULTS: The study included 116 patients. FDG PET/CT examinations were performed within a mean period ± SD of 5.6 ± 1.8 months after treatment. FDG PET/CT examinations exhibited abnormal FDG uptake in 34 patients and found no suspected recurrence in 82 cases. Of these 82 FDG PET/CT considered as negative, only 1 had a recurrence. Among the 34 positive FDG PET/CT, 22 relapsed whereas 12 did not show evidence of recurrence. The sensitivity and specificity of FDG PET/CT in this study for the diagnosis of occult HNSCC recurrence were 96 (22/23) and 87 % (81/93), respectively. The positive predictive value was 65 % (22/34). The negative predictive value was 99 % (81/82). The overall accuracy was 89 % (103/116). Of the 116 patients, FDG PET/CT highlighted 22 (19 %) subclinical recurrences. CONCLUSION: Our study showed the high effectiveness of FDG PET/CT in the assessment of subclinical HNSCC recurrence 6 months after completion of treatment. These results confirmed that FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC, as we previously demonstrated in patients clinically asymptomatic at 12 months.

Early recurrence or submucosal residual of laryngeal squamous cell carcinoma: diagnosis by CT-guided endolaryngeal core biopsy on a transcutaneous approach.

BACKGROUND: Ultrasound and CT-guided biopsy is a common procedure for histologic diagnosis of recurrence of head and neck squamous cell carcinoma. The present study describes a novel CT-guided endolaryngeal puncture site. METHODS AND RESULTS: A 59-year-old man was treated for a T2N0M0 supraglottic laryngeal tumor by laser resection and bilateral lymph node dissection; exeresis was judged complete. Six-month follow-up found persistent dysphonia. Endoscopic examination and iterative biopsy gave reassuring results, but (18) fluorodeoxyglucose positron emission tomography-CT ((18) FDG PET-CT) found highly suspicious increased right hemilaryngeal metabolic activity. Diagnosis of residual tumor was confirmed on CT-guided endolaryngeal biopsy. CONCLUSIONS: Image-guided biopsy is the technique of choice in head and neck lesions that are deep or difficult to palpate and inaccessible to endoscopy. It is especially useful when recurrence is suspected after radiation therapy or cancer surgery. Many puncture sites have been reported in the literature; the present novel laryngeal approach extends the range of image-guided biopsy, although further studies will be needed to assess possible morbidity.

Prognostic value of fluorine-18 fluorodeoxyglucose positron-emission tomography imaging in patients with head and neck squamous cell carcinoma.

BACKGROUND: High tumor uptake of fluorodeoxyglucose (FDG) is associated with an unfavorable outcome in patients with cancer. We evaluated FDG uptake as a prognostic factor in patients with head and neck squamous cell carcinoma. METHODS: Maximum standardized uptake values (SUVmax) of tumor, liver, and pulmonary artery were recorded. Ratios of SUVmax from tumor to liver (T/L) and from tumor to pulmonary artery (T/PA) were calculated for each patient. Clinical data, tumor, and SUVmax ratios were compared with disease-free survival (DFS) and overall survival (OS). RESULTS: Eighty-nine patients were included: 48 presented a local recurrent disease or distant metastases and 42 died. For both DFS and OS, tumor SUVmax value of 7 was the best cutoff value and 4 and 5 for T/L and T/PA ratios. Multivariate analysis confirmed the independent prognostic value of these 3 thresholds for DFS and OS. CONCLUSIONS: FDG uptake has a significant and independent relationship with recurrence and survival.

Does 18F-FDG PET/CT improve the detection of posttreatment recurrence of head and neck squamous cell carcinoma in patients negative for disease on clinical follow-up?

UNLABELLED: Posttreatment surveillance for the recurrence of head and neck squamous cell carcinoma (HNSCC) is a diagnostic challenge. Tissue distortion from radiation and surgery can obscure early detection of recurrence by conventional follow-up approaches such as physical examination, CT, and MRI. Several studies have shown that 18F-FDG PET may be an effective technique for the detection of persistent, recurrent, and distant metastatic HNSCC after treatment. The aim of this prospective study was to determine the benefits of hybrid 18F-FDG PET/CT in detecting a subclinical locoregional recurrence of HNSCC and distant metastases. The study patients were considered cured of HNSCC on the basis of 12 mo of negative findings on conventional follow-up. We also assessed the diagnostic accuracy of 18F-FDG PET/CT in these patients. METHODS: Ninety-one patients cured of HNSCC without any clinical evidence of recurrence were included. Whole-body 18F-FDG PET/CT examination was performed 11.6+/-4.4 mo after the end of the treatment. The gold standard was histopathology or 6 mo of imaging follow-up. RESULTS: The whole-body 18F-FDG PET/CT examinations had negative results in 52 patients and positive results in 39. Nine of these patients who exhibited abnormal 18F-FDG uptake in the head and neck area did not have recurrent HNSCC (false-positive). Thirty had proven recurrence. The sensitivity and specificity of 18F-FDG PET/CT in this study for the diagnosis of HNSCC recurrence were 100% (30/30) and 85% (52/61), respectively. The positive predictive value was 77% (30/39). The negative predictive value was 100% (52/52). The overall accuracy was 90% (82/91). CONCLUSION: The results of our study confirm the high effectiveness of 18F-FDG PET/CT in the assessment of HNSCC recurrence and suggest that 18F-FDG PET/CT is more accurate than conventional follow-up physical examination alone in the assessment of recurrence after previous curative treatment for HNSCC and could be proposed systematically at 12 mo of the usual follow-up.

Management of primary hyperthyroidism: toward minimal access surgery.

Fifteen years ago, bilateral exploration of the neck was dogma in parathyroid surgery. Now, less invasive procedures can be used to target lesions identified by new tests such as dual-phase Sestamibi scanning or intraoperative documentation of parathyroid hormone (PTH) level changes after removal of a parathyroid gland. A hand-held gamma probe can be used for intraoperative detection of high-uptake lesions, and video-assisted endoscopic surgery has been used successfully. With these new techniques, surgical exploration can be confined to one side of the neck through smaller incisions associated with better cosmetic results. The operating time is reduced, and in some cases the procedure can be done under local anesthesia. The objective of this article is to describe recent changes in the management of parathyroid adenoma requiring surgery.

CFTR transgene expression in primary DeltaF508 epithelial cell cultures from human nasal polyps following gene transfer with cationic phosphonolipids.

Cystic fibrosis (CF) is the most common autosomal lethal recessive disorder in the Caucasian population. The major cause of mortality is lung disease, owing to the failure of a functional protein from the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Today, even though the knowledge about the CFTR genomic is extensive, no efficient treatment has been developed yet. In this context, gene therapy represents a potential important advance on condition that it could develop efficient and safe transfection agents. Even though viral vectors have been used in most clinical trials owing to their high transfection efficiency, random integration and immunogenicity are still critical side effects. Consequently, all of these drawbacks brought forth the development of nonviral transfection systems. Although they engender few toxicity and immunogenicity problems, their low transfection efficiency is a hurdle that must be overcome. Over the past decade, we have developed an original family of monocationic lipids, cationic phosphonolipids, whose efficiency has been previously demonstrated both in vitro and in vivo. In this report, we observe that a new cationic phosphonolipid (KLN 30) can lead to the restoration of the CFTR protein following the ex vivo transfection of epithelial cells issuing from a F508 homozygous patient. The transgene expression and the cytotoxicity correlate with the charge ratio of the lipoplex. A kinetic study was performed, and a luminescent signal was detected until 35 d after transfection.