F. Bidault

Antiangiogenic Tyrosine Kinase Inhibitors: Occurrence and Risk Factors of Hemoptysis in Refractory Thyroid Cancer

BACKGROUNDnAntiangiogenic tyrosine kinase inhibitors (TKIs) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity.nnnOBJECTIVEnTo determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment.nnnMETHODSnWe analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of computed tomography scan images for airway invasion assessment. Occurrence of grade 1-2 or grade 3-5 hemoptysis according to Common Terminology Criteria for Adverse Events version 4.03 and risk factors for hemoptysis were investigated.nnnRESULTSnA total of 140 patients (89 males; median age, 52 y) with medullary (56%), differentiated (33%), and poorly differentiated (11%) TC were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy in 41 (32% with therapeutic purpose and 68% with adjuvant purpose). Patients received from 1 to 4 lines of TKI (median 1). Median follow-up was 24 months. Airway invasion was found in 65 (46%) cases. Hemoptysis occurred in 9 patients: grade 1-2 in 7 cases (5%) and grade 3-5 in 2 (1.4%) cases (fatal in 1). Hemoptysis was associated with presence of airway invasion (P = .04), poorly differentiated pathology (P = .03), history of therapeutic external-beam radiotherapy (P = .003), and thyroidectomy without neck dissection (P = .02).nnnCONCLUSIONnAirway invasion, poorly differentiated pathology, therapeutic external-beam radiotherapy, and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during antiangiogenic TKI treatment. Further research is needed to confirm this data and to sort out interactions between these risk factors. A careful assessment of airway invasion is mandatory before TKI introduction.

Screening in asymptomatic SDHx mutation carriers: added value of 18F-FDG PET/CT at initial diagnosis and 1-year follow-up

PurposeSpecific recommendations on screening modalities for paraganglioma (PGL) and phaeochromocytoma (PCC) in asymptomatic SDHx mutation carriers (relatives) are still lacking. We evaluated the added value of 18F-FDG PET/CT in comparison with morphological imaging at initial diagnosis and 1xa0year of follow-up in this population.MethodsThe study included 30 consecutive relatives with a proven SDHx mutation who were investigated by 18F-FDG PET/CT, gadolinium-enhanced magnetic resonance angiography of the head and neck, thoracic/abdominal/pelvic (TAP) contrast-enhanced CT and/or TAP MRI. 123I-MIBG scintigraphy was performed in 20 subjects and somatostatin receptor scintigraphy (SRS) in 20 subjects. The gold standard was based on pathology or a composite endpoint as defined by any other positive imaging method and persistent tumour on follow-up. Images were considered as false-positive when the lesions were not detected by another imaging method or not confirmed at 1xa0year.ResultsAt initial work-up, an imaging abnormality was found in eight subjects (27xa0%). The final diagnosis was true-positive in five subjects (two with abdominal PGL, one with PCC and two with neck PGL) and false-positives in the other three subjects (detected with 18F-FDG PET/CT in two and TAP MRI in one). At 1xa0year, an imaging abnormality was found in three subjects of which one was an 8-mm carotid body PGL in a patient with SDHD mutaion and two were considered false-positive. The tumour detection rate was 100xa0% for 18F-FDG PET/CT and conventional imaging, 80xa0% for SRS and 60xa0% for 123I-MIBG scintigraphy. Overall, disease was detected in 4xa0% of the subjects at the 1-year follow-up.Conclusion18F-FDG PET/CT demonstrated excellent sensitivity but intermediate specificity justifying combined modality imaging in these patients. Given the slow progression of the disease, if 18F-FDG PET/CT and MRI are normal at baseline, the second imaging work-up should be delayed and an examination that does not expose the patient to radiation should be used.

Surgery for Neck Recurrence of Differentiated Thyroid Cancer: Outcomes and Risk Factors

BackgroundnPersistent/recurrent disease in the neck is frequent in patients with differentiated thyroid cancer (DTC).nnnObjectivenAssess efficacy, safety, and prognostic factors of first neck reoperation in DTC.nnnMethodsnRetrospective study of consecutive patients undergoing neck reoperation for recurrent/persistent DTC in a referral cancer center. Response after reoperation was defined according to the 2015 American Thyroid Association guidelines.nnnFindingsnOne hundred sixty-one DTC patients were enrolled (64% females, median age 35 years, 96% papillary DTC). Initial stage was pT3 in 43% and pT4 in 10%, pN1 in 74%. Aggressive histology was present in 25% of the patients, in both primary and persistent/recurrent tumor. Four patients had no malignancy in the reoperative specimen, and 1 patient died due to postoperative hematoma and was excluded from further analysis. Following reoperation, 15 patients (10%) had persistent structural disease, 16 (10%) had biochemical incomplete response, 26 (17%) had indeterminate response, and 99 (63%) had complete response (CR), among whom 24 relapsed later. After a median follow-up of 5 years, only 83 patients (53%) had CR without the need for further treatments. The rate of permanent complications was: hypoparathyroidism 2%, laryngeal nerve palsy 0.6%, other 6%. Age ≥45 years, aggressive histology, and lymph node ratio ≥0.6 at initial surgery were independent risk factors for incomplete response after reoperation. Male sex, aggressive histology, and ≥10 metastases at reoperation were independent risk factors of secondary relapse following CR achieved with reoperation.nnnConclusionnA careful risk-benefit analysis should guide surgical decision, particularly in patients with risk factors for incomplete response.

Revisiting vascular contraindications for transoral robotic surgery for oropharyngeal cancer: TORS and Retropharyngeal Carotid Arteries

We analyzed the outcomes for patients with a retropharyngeal internal carotid artery (ICA) who underwent a transoral robotic surgery (TORS) procedure involving a cervical‐transoral robotic oropharyngectomy course with free flap reconstruction.

Laser debulking or tracheotomy in airway management prior to total laryngectomy for T4a laryngeal cancer

PurposeRetrospective studies have shown that tracheotomy prior to total laryngectomy (TL) is associated with decreased survival. We sought to investigate whether this is due to higher local invasiveness associated with obstructive disease or whether it is the result of tracheotomy itself.MethodsWe reviewed patients with a T4a (AJCC 7th edition) laryngeal squamous-cell carcinoma treated with a primary TL followed by adjuvant radiotherapy between 2001 and 2013. We compared patients who had obstructive lesions with those who had non-obstructive lesions in terms of preoperative data, pathological features, and treatment outcomes. Second, we compared tracheotomized patients with patients who underwent endoscopic laser debulking (ELD).ResultsOne hundred patients were reviewed. Thirty-seven of them required an airway intervention prior to a TL (tracheotomy nu2009=u200924/ELD nu2009=u200913). Patients with obstructive tumors had more frequently subglottic extension (pu2009=u20090.0066) and a shorter disease-free survival (DFS) (pu2009=u20090.046), due to a higher incidence of additional distant metastases. Tracheotomy was associated with a shorter DFS (pu2009=u20090.035) and more frequent perineural invasion (pu2009=u20090.0272) as compared to ELD, but not with a higher incidence of stomal recurrence.ConclusionsA tracheotomy prior to a total laryngectomy is associated with decreased survival. We recommend laser debulking as the preferred treatment whenever management of an obstructive airway is required prior to a total laryngectomy.

L’intensité de fixation en 18FDG n’est pas un marqueur de la progression tumorale morphologique chez les patients atteints de carcinomes thyroïdiens différenciés métastatiques

Objectif Chez les patients avec cancer thyroidien differencie metastatique (CTD), le temps de doublement de la thyroglobuline (TDTg) et l’intensite de fixation du fluorodeoxyglucose (FDG) sont pronostiques. Chez les patients iodo-refractaires, les lesions fixant intensement le FDG sont considerees comme agressives. L’objectif de cette etude retrospective etait la recherche de correlation entre l’intensite de fixation du FDG et la croissance tumorale ( tumor growth rate TGR) exprimee en pourcentage d’augmentation sur 1xa0an et le TDTg. Patients et methode Cinquante-cinq patients (dont 47xa0iodo-refractaires) avec CTD et au moins une metastase mesurantxa0≥xa01xa0cm ayant eu une FDG-TEP/TDM (tomographie par emission de positon/tomodensitometrie) et une deuxieme TDM a plus de 3xa0mois du premier en absence de traitement local ou systemique ont ete inclus. Resultats Dans l’analyse par patient, la survie a 2xa0ans etait de 100xa0% pour les patients avec SUV max max xa0>xa05. Le TDTg median etait de 101xa0jours (extremesxa0:0–xa0>xa0100xa0%). Cent cinquante-six lesionsxa0: pulmonaires (63) ganglionnaires cervicales (22) ganglionnaires mediastinales (42) osseuses (11) hepatiques (2) ou autres (10) ont ete etudiees. La taille mediane etait de 16xa0mm, le SUVmax median de 8,7xa0; le volume metabolique median de 3,7xa0cm 3 . Le TGR median par lesion sur 1xa0an etait de 16xa0% (extremesxa0:0–xa0>xa0100xa0%). Le SUV max par lesion n’etait pas correle au TGR sur 1xa0an ( p xa0=xa00,28). Conclusion L’intensite de fixation du FDG de chaque lesion n’etait pas correlee a la progression tumorale morphologique et ne peut donc etre employee comme marqueur de substitution.

Cancers thyroïdiens différenciés (CTD) non résécables : des cancers de mauvais pronostics

Contexte La definition du caractere refractaire d’un CTD necessite au moins un traitement par iode 131 et donc une thyroidectomie totale. En cas de primitif non resecable, le caractere refractaire reste indetermine et l’acces aux essais therapeutiques par therapies ciblees est impossible. Le but de cette etude est d’evaluer leur pronostic. Patients et methode Analyse retrospective de 14 cas adultes de CTD juges non resecables (8 femmes, 6 hommesxa0; âge moyenxa0: 74xa0ans [extremesxa0: 52–91] diagnostiques entre 2000 et 2014. Resultats Les tumeurs etaient de type papillaire (4), vesiculaires (5) et peu differencie (5). Au diagnostic initial, 12 (86xa0%) patients presentaient des metastases a distance [pulmonaires (10), osseuses (8), hepatiques (2)]. La TEP FDG, disponible chez 10 patients, a montre une fixation anormale chez 9 (SUVmax medianxa0: 10 [4–33]). Les traitements administres ont comporte des inhibiteurs de tyrosine kinase (ITK) (36xa0%), de la radiotherapie externe (RTE) (43xa0%), des chimiotherapies systemiques (50xa0%), des traitements loco-regionaux (50xa0%). Apres RTE un patient a pu beneficier d’une thyroidectomie totale suivi d’iode radioactif. Dix patients (72xa0%) sont decedes en lien avec la maladie (5), une toxicite du traitement (1) ou une autre cause (4). Les survies globales a 1, 3 et 5xa0ans etaient de 77xa0%, 34xa0% et 22xa0%, respectivement. Discussion Le pronostic des CTD non resecables est mauvais justifiant de discuter, pour ces patients, l’interet des therapies ciblees. Leur rarete justifie d’un enregistrement national prospectif pour mieux decrire leur evolutivite.