Treatment strategy in laryngeal chondrosarcoma: a multicenter study of 43 cases.

PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.

ORGAVADS: establishment of tumor organoids from head and neck squamous cell carcinoma to assess their response to innovative therapies.

BACKGROUND: Radiotherapy is one of the cornerstones of the treatment of Head and Neck Squamous Cell Carcinomas (HNSCC). However, radioresistance is associated with a high risk of recurrence. To propose strategies (such as combinations with drugs) that could over intrinsic radioresistance, it is crucial to predict the response to treatment. Patient-Derived Tumor Organoids (PDTO) are in vitro tridimensional microtumors obtained from patient' own cancer samples. They have been shown to serve as reliable surrogates of the tumor response in patients. METHODS: The ORGAVADS study is a multicenter observational trial conducted to investigate the feasibility of generating and testing PDTO derived from HNSCC for the evaluation of sensitivity to treatments. PDTO are obtained after dissociation of resected tumors remaining from tissues necessary for the diagnosis. Embedding of tumor cells is then performed in extracellular matrix and culture in medium supplemented with growth factors and inhibitors. Histological and immunohistochemical characterizations are performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovating combinations are assessed, as well as response to immunotherapy using co-cultures of PDTO with autologous immune cells collected from patient blood samples. Transcriptomic and genetic analyses of PDTO allow validation of the models compared to patients' own tumor and identification of potential predictive biomarkers. DISCUSSION: This study is designed to develop PDTO models from HNSCC. It will allow comparing the response of PDTO to treatment and the clinical response of the patients from whom they are derived. Our aim is to study the PDTO ability to predict the clinical response to treatment for each patient in view of a personalized medicine as well as to establish a collection of HNSCC models that will be useful for future innovative strategies evaluation. TRIAL REGISTRATION: NCT04261192, registered February 7, 2020, last amendment v4 accepted on June, 2021.

Head and neck cancer patients under radiotherapy undergoing skin application of hydrogel dressing or hyaluronic acid: results from a prospective, randomized study.

PURPOSE: Acute radiodermatitis (ARD) is a frequent side effect of radiotherapy, a therapeutic option for head and neck squamous cell carcinoma (HNSCC). It is responsible for pain, quality of life (QoL) impairment, and increased risk of treatment discontinuation, which may compromise the prognosis for patients. Local therapies to prevent or alleviate ARD have been proposed without providing any high level of evidence to establish recommendations. METHODS: We implemented a prospective multicenter randomized study on patients with HNSCC treated with definitive radiotherapy to assess the impact on ear, nose, and throat (ENT) pain of the application of a hydrogel-based skin dressing (HydroTac®) compared with the application of hyaluronic acid (Ialuset®) during radiotherapy. RESULTS: Out of 130 enrolled patients, 48 patients per group were assessable for the main endpoint. No difference between groups was found: a worsening of ENT pain of 3 points or more on a visual analog scale from the initiation to 1 month after the end of the radiotherapy was observed for 8 patients (16.7%) who received HydroTac® compared to 13 patients (27%) who received Ialuset® (p = 0.342). The proportion of patients who experienced ARD and grades of ARD (CTCAE v4.0 criteria) were similar between groups. Patient compliance with radiodermatitis treatment was poor, with 56.1% of patients in the HydroTac® group having their treatment temporarily stopped. CONCLUSION: The application of a hydrogel dressing to prevent ARD during radiotherapy for HNSCC patients has failed to demonstrate a benefit. These results may be limited by the difficulties of applying the dressing.

Social and sexual health of thyroid cancer survivors 2 and 5 years after diagnosis: the VICAN survey.

PURPOSE: Thyroid cancer (TC) incidence is increasing. With its good prognosis and the young population concerned, the number of survivors is rising. However, their quality of life appears worse than expected. This study aims to assess the social and sexual health (SSH) of TC survivors and associated factors after a 2- and 5-year follow-up. METHODS: This study belongs to the National VICAN Survey implemented in France among TC patients diagnosed between January and June 2010. Data were collected via phone interviews, medical surveys, and from medico-administrative register in 2012 and 2015. We used multivariable logistic regressions to qualify TC impact on SSH. RESULTS: Across 146 patients, 121 were women, 50.7% were less than 42 years old, 77.5% were diagnosed at an early-stage, and 97.6% underwent thyroidectomy. At 2 years, 60.0% experienced social life discomfort because of cancer, 40.6% reported a decreased sexual desire, 37.4% fewer intercourse, 31.9% felt dissatisfied with this frequency, 30% reported difficulties achieving orgasm, and 15.2% considered that cancer had a negative influence for procreation. No significant difference was observed at 5 years. SSH was never discussed with medical professionals for 96.7% patients, as it was not proposed as a topic of concern (79.1%). In multivariable analysis, depression, embarrassment regarding their physical appearance since treatment, and reduced gestures of affection remained associated with decreased sexual desire. CONCLUSION: This study highlights that TC is associated with an alteration of SSH which remains even at 5 years post-diagnosis. SSH should be discussed during diagnosis and considered during follow-up.

Correlations between long-term quality of life and patient needs and concerns following head and neck cancer treatment and the impact of psychological distress. A multicentric cross-sectional study.

OBJECTIVES: To assess patient needs and concerns after head and neck squamous cell carcinoma (HNSCC) treatment and their possible correlations with long-term quality of life (QoL) and to examine the potential impact of psychological distress on these results. METHODS: Alive and disease-free HNSCC patients at least 1 year after treatment were enrolled in this cross-sectional multicentric study and completed the EORTC QLQ-C30 and H&N35 QoL questionnaires, the head and neck cancer-specific patient concerns inventory (PCI-HN) questionnaire and the hospital anxiety and depression scale (HADS). Correlations between QoL outcomes and patient needs and concerns were investigated using Spearman's correlation tests. RESULTS: Seventy-two patients were enrolled in the study. Fear of cancer recurrence was the main patient concern followed by dental, salivary, fatigue, speech, and eating problems. The leading patient needs in terms of consultation were to be referred to the surgeon, the speech, and swallow therapist and the oral rehabilitation team. The number of patient concerns correlated negatively (r < .40) with functioning scales score and positively (r > .40) with general and head and neck symptoms. Psychological distress was the main determinant of QoL outcomes (p < .0001). We found a significant impact of gender (p = .002) on the number of patient concerns, and of patient age (p = .003) on the number of staff members selected by patients. CONCLUSION: Identification of patient needs and concerns along with multidisciplinary management of persistent symptoms and psychological distress seem essential steps towards improving QoL of HNSCC patients.

Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome.

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.

French Therapeutic Education Programme Aimed at Improving the Quality of Life of Laryngectomised Patients and their Close Relations: the Three Stages (Observational and Interventional Randomised) of the Study "PETAL".

The therapeutic education of patients and their close relations is, as yet, poorly developed in France in the field of oncology. Total laryngectomy is a mutilating surgical procedure having a major impact on the patient's life, due to its physical and functional sequelae. Its psychosocial consequences are also important and alter the quality of life of patients and their close relations. Currently, care for laryngectomised patients consists essentially in informing and educating them on some technical procedures during hospital admission. The intervention of a speech therapist, often serves as the link between the patient and the hospital care team. These healthcare modalities often insufficiently account for the social, environmental and personal factors that interact in health-related problems. This report presents the therapeutic education programme protocol "PETAL" for laryngectomised patients and their close relations to improve their quality of life. The trial will be conducted over three phases: (1) the "pilot" phase aims at developing knowledge on the consequences of laryngectomy on the quality of life of patients and their close relations and developed a pluridisciplinary therapeutic education program, (2) the prospective intervention "replication" phase aims at evaluating the programme's transferability in three centres and (3) the cluster-randomised multicentric comparative intervention phase, will assess the benefits of the developed programme. Phase I identified nine themes of workshops related to therapeutic education, training and coordination of care. The developed programme should reinforce town-hospital links to improve help, follow-up and support for patients and their close relations.

Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC.

Median survival for recurrent/metastatic head and neck squamous cell cancer (HNSCC) patients is about 10 months after first-line best systemic treatment. We aimed to assess current approaches of oligometastatic HNSCC patients by the analysis of current concept and published data (1995-2017) in this population. Five-year survival rates are over 20% in selected patients who undergo metastasis-directed therapy by either surgery or stereotactic irradiation. Human papillomavirus(+) HNSCC patients have more disseminated metastases but respond more favorably and also benefit from ablative treatments. Treatments of oligometastases are expanding rapidly. Unmet needs include revised imaging follow-up strategies to detect metastases earlier, identification of predictive noninvasive biomarkers for treatment guidance, assessment and corrections of biases in current studies and randomized clinical trials.

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

AIM: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. RESULTS: Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). CONCLUSIONS: Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

Retrospective evaluation of concomitant cetuximab and radiotherapy tolerance for locoregional advanced head and neck squamous cell carcinoma treatment in patients unfit for platinum-based chemotherapy.

Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.

Intensive nutritional care for patients treated with radiotherapy in head and neck cancer: a randomized study and meta-analysis.

Nutritional care improves quality of life (QOL) in head and neck cancer patients treated with radiotherapy. The aim of our study was to determine whether intensive nutritional care (INC) would further improve QOL. In addition to a control group based on European and American guidelines, patients included in the INC group received six meetings with a dietitian. QOL was measured after radiotherapy using the EORTC QLQ-C30. We performed a meta-analysis to determine the best nutritional care. In the 87 patients, the QOL scores, weight, energy, and protein intakes were similar between the INC group (n = 43) and the control group (n = 44). The meta-analysis revealed no heterogeneity and significant differences in QOL (three studies) (p = 0.46) or weight changes after radiotherapy (four studies) (p = 0.06). The nutritional care specified in the European and American guidelines is composed of well-defined recommendations, and appears sufficient to maintain QOL without further intervention.

Health professionals and the early detection of head and neck cancers: a population-based study in a high incidence area.

BACKGROUND: In the context of early detection of head and neck cancers (HNC), the aim of this study was to describe how people sought medical consultation during the year prior to diagnosis and the impact on the stage of the cancer. METHODS: Patients over 20 years old with a diagnosis of HNC in 2010 were included from four French cancer registries. The medical data were matched with data regarding uptake of healthcare issued from French National Health Insurance General Regime. RESULTS: In 86.0 % of cases, patients had consulted a general practitioner (GP) and 21.1 % a dentist. Consulting a GP at least once during the year preceding diagnosis was unrelated to Charlson index, age, sex, département, quintile of deprivation of place of residence. Patients from the 'quite privileged', 'quite underprivileged' and 'underprivileged' quintiles consulted a dentist more frequently than those from the 'very underprivileged' quintile (p = 0.007). The stage was less advanced for patients who had consulted a GP (OR = 0.42 [0.18-0.99]) - with a dose-response effect. CONCLUSIONS: In view of the frequency of consultations, the existence of a significant association between consultations and a localised stage at diagnosis and the absence of a socio-economic association, early detection of HNC by GPs would seem to be the most appropriate way.

What are the real waiting times for therapeutic management of head and neck cancer: a study in the general population in the north-west of France.

Head and neck cancers (HNC) have a poor prognosis and a long treatment delay may have a negative impact on this. Some studies have investigated the determinants of this delay but not in the general population and rarely taking into account socio-economic factors. A high-resolution population-based study about cancer management was conducted, using registries in the north-west of France, on HNC diagnosed between 2008 and 2010. The median time between diagnosis and multidisciplinary team meeting (DMI) (N = 1631) was 14 days (Q1: 7 to Q3: 26). The median time between diagnosis and first treatment (DTI) (N = 1519) was 35 days (Q1: 21 to Q3: 54). When the first treatment was radiotherapy, the interval was 54.5 days (Q1: 40 to Q3: 71). In multivariate analysis, DTI was associated with the type of first treatment and place of treatment. For advanced stage HNC, DTI was associated with comorbidities, topography of the cancer and socio-economic status, underprivileged patients being treated later than privileged ones. Given the French governmental cancer plans which set out to coordinate care pathways via nursing coordinators and to improve the availability of radiotherapy, the waiting times observed in this study still seem long. The optimal care pathway should include adapted social management but the DTI was still longer for underprivileged patients.

Neurological involvement in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by epistaxis, telangiectases, and multi-organ vascular dysplasia. Head and neck localizations of HHT are recurrent, frequent associated with serious complications. The aim of this study was to describe the clinical and imaging patterns of neurological involvement in HHT and to discuss the role of interventional radiology in the management of HHT patients. Based on a multidisciplinary experience of twenty years at our center, we report here the different aspects of neurological involvement of HHT. Depending on the genetic type of the disease, vascular abnormalities may affect different organs. The knowledge of neurological involvement according to specific localization of HHT makes detection easier. As cerebral or spinal arteriovenous fistula may be present in patients with epistaxis or pulmonary arteriovenous malformations (PAVMs), radiologists should be able to detect high-risk lesions and prevent related complications. Finally, we review indications and techniques of embolization for hemorrhagic lesions and emphasize that endovascular therapies are very effective and safe in experienced hands. Head and neck imaging is commonly used for the diagnosis of HHT. Imaging plays also a key role for patient evaluation before treatment as pluridisciplinary management is needed.

Management of surgical margins after endoscopic laser surgery for early glottic cancers: a multicentric evaluation in French-speaking European countries.

The aim of this study was to evaluate the practices of ENT surgeons for the management of surgical margins after endoscopic laser surgery for early glottic cancers. A questionnaire was sent to different surgeons managing cancers of the larynx in France, Belgium and Switzerland. A descriptive and comparative analysis of practices across centers was performed. Sixty-nine surgeons completed the questionnaire (58 in France, 10 in Belgium and 1 in Switzerland). In case of very close or equivocal resection margins after definitive histological examination, 67 % of surgeons perform close follow-up, 28 % further treatment and 5 % had no opinion. Factors resulting in a significant change in the management of equivocal or very close margins were: the country of origin (p = 0.011), the specialty of the multidisciplinary team leader (p = 0.001), the fact that radiation equipment is located in the same center (p = 0.027) and the access to IMRT technique (p = 0.027). In case of positive resection margins, 80 % of surgeons perform further treatment, 15 % surveillance, and 5 % had no opinion. The only factor resulting in a significant change in the management of positive margins was the number of cancers of the larynx treated per year (p = 0.011). It is important to spare, on one hand equivocal or very close margins and on the other hand, positive margins. Postoperative management should be discussed depending on intraoperative findings, patient, practices of multidisciplinary team, and surgeon experience. This management remains non-consensual and writing a good practice guideline could be useful.

Multicentric evaluation of strategies for treatment of T1a glottic carcinomas.

The aim of this study was to evaluate the practices of ENT surgeons for the management of early glottic cancers affecting only one vocal cord, i.e. classified T1a. A questionnaire was sent to different surgeons managing cancers of the larynx in France, Belgium and Switzerland. A descriptive and comparative analysis of practices across centers was performed. The decision-making parameters of the therapeutic strategy were analyzed. Sixty-nine surgeons completed the questionnaire (58 in France, 10 in Belgium and one in Switzerland). In the example of a 50-year-old man with active tobacco use and no oncologic history presenting a squamous cell carcinoma of the middle third of the vocal cord classified T1aN0M0, and with easy glottic exposition by laryngoscopy, 91 % of surgeons proposed endoscopic surgery laser, 2 % radiotherapy and 7 % proposed one of these two treatments without any preference. Therapeutic strategies were not influenced by the sex (p = 1.00), the smoking status (p = 0.58) or the age of the patient (more or less than 80 years, p = 0.27). A significant change was observed in the therapeutic strategy for tumors non-exposable by laryngoscopy (p = 0.032), tumors reaching the anterior commissure (p = 0.001) and patients using their voice professionally (p = 0.0003). The management strategy of T1a glottic carcinomas, in our series, is mainly surgical. The choice of therapeutic strategy seems to be based, in our series, on criteria such as the risk of a second location, cost, and duration of treatment.

Head and neck cancer survivors' pain in France: the VICAN study.

PURPOSE: Pain is an increasing concern in the growing number of head and neck cancer survivors. This study aimed to analyze the 5-year prevalence of pain in French survivors of head and neck cancer and to identify associated factors. METHODS: Analyses were performed among 296 5-year cancer survivors diagnosed in 2010. Using multivariable logistic regressions, we studied the associations between pain and factors collected in the French representative national "vie après le cancer" (VICAN) survey. Eligible participants were aged from 18 to 82 years; patients' living conditions, socioeconomic characteristics, and medical data were collected. RESULTS: Pain was reported by 72.6% of the participants. In the multivariable analyses, decreasing level of physical activity was the only determinant of increased overall pain (OR= 2.77, CI= 1.48-5.17). The chronic pain prevalence was 62.3%. The main risk factors found were tumor localization in the oropharynx (OR= 2.49, CI= 1.27-4.88), education (at least a high school's degree) (OR= 0.33, CI= 0.13-0.9), and decreased physical activity (OR= 2.20, CI= 1.24-3.9). CONCLUSIONS: Five years after diagnosis, pain is a very frequent sequelae that has a significant impact on quality of life in head and neck cancer survivors. Reduced physical activity, a low level of education, and tumor localization in the oropharynx are factors associated with pain. IMPLICATIONS FOR CANCER SURVIVORS: Pain frequency and its impact on patients' lives imply that an adaptation must be made in terms of both pain diagnosis and management and the training of healthcare professionals. CLINICAL TRIAL REGISTRATION: This is not a clinical trial. ISP number: INSERM C11-63.

Stroke in hereditary hemorrhagic telangiectasia patients. New evidence for repeated screening and early treatment of pulmonary vascular malformations: two case reports.

BACKGROUND: Paradoxical embolism due to pulmonary arteriovenous malformations is the main mechanism of brain infarction in patients with hereditary hemorrhagic telangiectasia. International Guidelines have recently been published to clarify the performance of screening tests and the effectiveness of treatment for pulmonary arteriovenous malformations. CASE PRESENTATION: We present two cases of hereditary hemorrhagic telangiectasia patients of our hospital who experienced an acute stroke secondary to paradoxical embolism. CONCLUSIONS: These two cases show that the guidelines must be followed to prevent the occurrence of ischemic stroke in patients with hereditary hemorrhagic telangiectasia, and that although they may be adequate in most cases, there are some patients who need a more personalized approach.

Management of total laryngectomy patients over time: from the consultation announcing the diagnosis to long term follow-up.

Throat cancer has always struck people's imagination. This type of cancer affects some of the patient's most essential physiological functions: speaking, swallowing and breathing. At advanced stages, radical surgery is disabling. The impact of a mutilated larynx corresponds to a very real trauma that is both individual and social. Our aim is to define how a total laryngectomy (TL) is represented by both the surgeon and the patient. The history of TL makes it possible to understand the changes that were needed for the key players in the subject to impose or accept this operation. Without doubt, the implementation of the "cancer plan" in the early 2000s was a major turning point in the management of patients with neoplasia. Increased awareness among the elite, encouraged by the mobilisation of patients and their families, is the explanation for the new role played by TL in 2008. The progress made in medical and surgical techniques, modifications to the patient-carer relationship and the appearance of the concept of Quality of Life are all themes that have changed the approach to this operation and the management of patients undergoing a TL.

18F-Fluorocholine Positron Emission Tomography/Computed Tomography is a Highly Sensitive but Poorly Specific Tool for Identifying Malignancy in Thyroid Nodules with Indeterminate Cytology: The Chocolate Study.

Background: Refining the risk of malignancy in patients presenting with thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) to predict malignancy. Methods: Between May 2016 and March 2019, 107 patients presenting with a thyroid nodule ≥15 mm with IC and eligible for surgery were included in this prospective study. Head-and-neck PET/CT acquisitions were performed 20 and 60 minutes after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard for diagnosis. Results: At pathology, 19 (18%) nodules were malignant, 87 were benign, and one was a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of FCH PET/CT in detecting cancer or NIFTP were 90%, 50%, 55%, 29%, and 96% at 20 minutes and 85%, 49%, 67%, 28%, and 94% at 60 minutes, respectively. Higher specificity (58% vs. 33%, p = 0.01) was observed in nononcocytic (n = 72) than in oncocytic IC nodules (n = 35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III-IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. In retrospective analysis, 42% of surgeries would have been unnecessary after PET/CT and 81% before (p < 0.001), resulting in a hypothetical 48% reduction (95% confidence interval [32-64]). Conclusions: FCH PET/CT offers high NPV to reliably exclude cancer in PET-negative IC nodules, but suffers from low PPV, particularly in those with oncocytic cytology. ClinicalTrials.gov identifier: NCT02784223.