D. Blanchard

Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: Preliminary results

INTRODUCTION Osteoradionecrosis (ORN) is a severe, generally irreversible complication of radiotherapy due to failure of healing. The pentoxifylline-tocopherol combination decreases the superficial fibrosis induced by radiotherapy. Potentiation by Clodronate (PENTOCLO) appears to be effective in ORN of the mandible. The objectives of this study were to evaluate the efficacy and safety of PENTOCLO to treat osteoradionecrosis of the mandible. METHODS Retrospective study of 27 patients with a mean age of 65±12 years, managed for ORN of the mandible secondary to irradiation for head and neck cancer, treated by the PENTOCLO protocol between January 2010 and March 2011. The primary endpoint was regression of exposed bone until complete healing. Assessment was both clinical (measurement of mucosal ulceration) and radiological (panoramic dental x-rays) before treatment, after antibiotic-corticosteroid combination therapy for one month (M1), and then after 3, 6, 12 months of PENTOCLO. RESULTS An improvement of mucosal ulceration was observed in 16/21 patients after 3 months and in 12/17 patients after 6 months of PENTOCLO. Healing was obtained in 16 patients. Median healing time was 82 days (range: 32-266), and was shorter after surgery and radiotherapy (49 days) and longer after chemoradiotherapy (169 days). Radiological healing was achieved later than clinical healing with improvement in 9 out of 20 patients at 3 months. The safety and efficacy of treatment were evaluated by intraoral clinical examination, and assessment of feeding, weight and analgesic consumption. No patient discontinued treatment because of adverse effects. CONCLUSION The PENTOCLO protocol achieved clinical and radiological regression of ORN with, in parallel, a reduction of the indications for major surgery. These preliminary results need to be confirmed by prospective studies comprising quality of life assessment.

Prognostic Value of Microscopic Lymph Node Involvement in Patients With Papillary Thyroid Cancer

CONTEXT The impact of microscopic nodal involvement on the risk of persistent/recurrent disease (PRD) remains controversial in patients with papillary thyroid carcinoma (PTC). OBJECTIVE The goal of the study was to assess the risk of PRD and the 4-year outcome in PTC patients according to their initial nodal status [pNx, pN0, pN1 microscopic (cN0/pN1) or pN1 macroscopic (cN1/pN1)]. DESIGN We conducted a retrospective cohort study. PATIENTS The study included 305 consecutive PTC patients referred for radioiodine ablation from 2006 to 2011. MAIN OUTCOME MEASURE We evaluated the risk of structural PRD and the disease status at the last follow-up. At ablation, persistent disease was consistently assessed by using post-radioiodine ablation scintigraphy combining total body scan and neck and thorax single-photon computed tomography-computed tomography (SPECT-CT) acquisition. RESULTS Of 305 patients, 128 (42%) were pNx, 84 (28%) pN0, 44 (14%) pN1 microscopic, and 49 (16%) pN1 macroscopic. The 4-year cumulative risk of PRD was higher in pN1 macroscopic than in pN1 microscopic patients (49% vs 24%, P = .03), and higher in pN1 microscopic than in pN0 (12%, P = .01) or pNx patients (6%, P < .001). On multivariate analysis, tumor size of 20 mm or greater [relative risk (RR) 3.4; P = .0001], extrathyroid extension (RR 2.6; P < .003), pN1 macroscopic (RR 4.5; P < .0001), and pN1 microscopic (RR 2.5; P < .02) were independent risk factors for PRD. At the last visit, the proportion of patients with no evidence of disease decreased from pNx (98%), pN0 (93%), and pN1 microscopic (89%) to pN1 macroscopic patients (70%) (P < .0001, Cochran-Armitage trend test). Extrathyroid extension (odds ratio 9.7; P < .0001) and N1 macroscopic (OR 4.9; P < .001) independently predicted persistent disease at the last visit, but N1 microscopic did not. CONCLUSIONS PATIENTS with microscopic lymph node involvement present an intermediate outcome between that observed in pN0-pNx patients and pN1 macroscopic patients. These data may justify modifications to the risk recurrence staging systems.

Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: The impact of treatment preparation modalities and tumor burden

OBJECTIVE In patients with differentiated thyroid cancer (DTC), the stimulated serum thyroglobulin (Tg) level at radioiodine ablation is a known predictive factor of persistent disease. This prognostic value is based on data obtained after thyroid hormone withdrawal (THW), but little is known about this prognostic value after recombinant human TSH (rhTSH) stimulation and about the relationship between the stimulated Tg level and the burden of persistent tumor. We aimed to assess the impact of both radioiodine preparation modalities and persistent tumor burden on stimulated Tg levels. DESIGN AND METHODS The stimulated Tg level was measured at radioablation in 308 consecutive DTC patients without serum Tg antibodies. Of these, 123 (40%) were prepared with rhTSH and 185 with THW. Post-ablation scintigraphy included total-body scan and neck and thorax single photon emission computed tomography with computed tomography (SPECT-CT). During a mean follow-up of 43 months, persistent/recurrent disease (PRD) was found in 56 patients (18%). PRD was considered structural in the presence of lesions >1 cm and nonstructural otherwise. RESULTS Nonstructural PRD was more frequent in the rhTSH group than in the THW group (64 vs 26%, P=0.01). Stimulated Tg levels were lower after rhTSH than after THW in patients with (13.5 vs 99.5 ng/ml, P<0.01) and without (1.2 vs 3.2 ng/ml, P<0.001) PRD. Also, Tg levels were lower in nonstructural disease than in structural disease in both rhTSH (3.8 vs 127.0 ng/ml, P<0.01) and THW (13.0 vs 143.5 ng/ml, P<0.0001) patients. The best Tg cutoff to predict PRD was 2.8 in rhTSH and 28 ng/ml in THW patients. CONCLUSION Both radioiodine preparation modalities and the burden of persistent tumor affect the stimulated Tg level at ablation.

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.

Laryngeal preservation in ENT oncology. Retrospective series of 246 patients managed in the Caen University Hospital and François Baclesse Cancer Care Center between 1998 and 2008.

OBJECTIVES A 10-year retrospective study investigated factors for survival and laryngeal preservation in advanced laryngeal, hypopharyngeal or epilaryngeal neoplasia. MATERIAL AND METHOD Two hundred and forty-six patients with advanced cancer of the larynx (17.48%), hypopharynx (48.78%) or epilarynx (33.74%) undergoing primary organ-sparing treatment were included from 1998 to 2008. Treatment comprised chemotherapy followed by radiation therapy for 92.68% of patients, isolated radiation therapy for 1.6% and concomitant or sequential radiation-chemotherapy for 5.7%. General health status, history and tumor status were recorded. Factors influencing survival were analyzed by Kaplan-Meier estimator, log-rank test and Cox models. RESULTS Median overall survival of the population was 2.3 years and median laryngeal preservation 0.99 years in male patients and 2 years in female patients. Survival correlated significantly with body mass index (BMI; P=0.0004), WHO performance status (P=0.0064), alcohol consumption (P=0.0004) and cessation (P<0.0001) and also T stage (P=0.0038), initial laryngeal mobility (P=0.0002) and post-chemotherapy assessment (P<0.0001). Survival with functional larynx correlated with baseline BMI at first consultation (P=0.016), baseline WHO grade (P=0.0005), laryngeal mobility (P<0.0001), T staging (P=0.0009), and T and/or N chemotherapy response to a classical organ preservation protocol (P<0.0001). CONCLUSION Over and above established criteria, the present study highlighted the importance of general health and nutritional status during treatment.

Incremental Value of a Dedicated Head and Neck Acquisition during 18F-FDG PET/CT in Patients with Differentiated Thyroid Cancer.

Objectives 18F-FDG-PET/CT is a useful tool used to evidence persistent/recurrent disease (PRD) in patients with differentiated thyroid cancer and iodine-refractory lesions. The aim of this study was to compare the diagnostic value at the cervical level of the routine whole-body (WB) acquisition and that of a complementary head and neck (HN) acquisition, performed successively during the same PET/CT study. Methods PET/CT studies combining WB and HN acquisitions performed in 85 consecutive patients were retrospectively reviewed by two nuclear medicine physicians. 18F-FDG uptake in cervical lymph nodes (LN) or in the thyroid bed was assessed. Among the 85 patients, the PET/CT results of the 26 who subsequently underwent neck surgery were compared with surgical and pathological reports. The size of each largest nodal metastasis was assessed by a pathologist. Results In the 85 patients, inter-observer agreement was excellent for both WB and HN PET/CT interpretation. Of the 26 patients who underwent surgery, 25 had pathology proven PRD in the neck. Of these 25 patients, 15 displayed FDG uptake on either WB or HN PET. In these 15 patients, HN PET detected more malignant lesions than WB PET did (21/27 = 78% vs. 12/27 = 44%, P = 0.006). Node/background ratios were significantly higher on HN than on WB PET (P<0.0001). Three false-negative studies (20%) on WB PET were upstaged as true-positive on HN PET. The mean size of the largest LN metastasis was 3 mm for the LN detected neither on WB nor on HN PET, 7 mm for the metastasis detected on HN but not on WB PET, and 13 mm for those detected on both acquisitions (P = 0.0004). Receiver-Operating Characteristic analysis showed that area under the curve was higher for HN PET than for WB PET (0.97 [95%CI, 0.90–0.99] vs 0.88 [95%CI, 0.78–0.95], P = 0.009). Conclusions HN acquisition improves the ability to detect PRD in the neck compared with WB acquisition alone. We recommend systematically adding an HN acquisition when PET/CT is performed to detect PRD in the neck.

Radioiodine sinus uptake related to mucosal thickening or aspergilloma: a case series of an unrecognized event well evidenced by SPECT/CT

BackgroundFalse-positive radioiodine (RAI) uptake related to chronic sinusitis and mucocele has only rarely been reported in patients with differentiated thyroid cancer (DTC) even with the recent use of single photon emission tomography with computed tomography (SPECT/CT) acquisition. No other etiology of sinus RAI uptake has been mentioned to date.ObjectivesWe report five cases of DTC patients with sinus RAI uptake on post-RAI scintigraphy. SPECT/CT clearly localized RAI uptake either in the sphenoid, the maxillary or the frontal sinus and highly suspected mucosal thickening in four patients and sinus aspergilloma in one patient.ConclusionThese data confirm the possibility of false-positive sinus RAI uptake, provide a new cause of such benign uptake, i.e. sinus aspergilloma, and demonstrate the clinical relevance of head and neck SPECT/CT acquisition in the diagnosis of such uptake. Nuclear medicine physicians should be aware of this pitfall when interpreting post-RAI scintigraphy.

Cancer de l’oropharynx

Oropharyngeal carcinomas, contrary to other head and neck carcinomas are of increasing frequency, mostly due to a frequent association with human papillomavirus infection. Pluridisciplinary management is necessary. New techniques as transoral surgery or intensity-modulated radiation therapy have the potential to reduce toxicities and morbidity while offering equivalent local control rates. Early stages may be treated with single modality treatment (surgery or radiotherapy) with five-year overall survival rate exceeding 80%. Advanced stages need therapeutic associations and five-years survival rates are inferior to 40%.

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.

Récidive des cancers glottiques classés T1N0M0 ou T2N0M0 après traitement par radiothérapie exclusive

larynx ou de l’hypopharynx ayant bénéficié d’examen tomodensitométrique préopératoire et d’une chirurgie carcinologique par laryngectomie totale. Trois critères d’envahissement du cartilage sont colligés : l’érosion ou la lyse, la condensation ou sclérose, la présence de tumeur de part et d’autre du cartilage. Deux critères anatomopathologiques sont présents : l’atteinte microscopique du cartilage et l’atteinte macroscopique. Les mesures de l’angle thyroïdien antérieur se font grâce à la méthode de Waldeyer et sont comparées en fonction de l’envahissement microscopique, macroscopique, et de la radiothérapie. Résultats.— La sensibilité et la spécificité de la détection de l’envahissement cartilagineux sont respectivement de 70,45 et de 80,95 %. La radiothérapie influence négativement la détection de l’envahissement du cartilage avec une sensibilité de 46,6 % (p = 0,0185). L’association d’au moins 2 des 3 critères d’envahissement permet de détecter 82 % de l’envahissement du cartilage thyroïde. L’angle thyroïdien antérieur est mesuré à 64,9◦ ± 14,7 dans notre population. Il est de 67,22◦ ± 12 chez les patients présentant un envahissement cartilagineux (p = 0,24). Il est de 65,1◦ pour les patients ayant bénéficié d’un traitement par radiothérapie. Conclusion.— Le scanner est un bon examen pour détecter l’envahissement du cartilage thyroïde mais la détection est plus délicate en cas d’envahissement microscopique et de traitement par radiothérapie. Le diagnostic d’envahissement du cartilage est plus précis si on associe plusieurs critères d’envahissement et notamment le critère de lyse du cartilage, même si ce dernier est soumis aux variations des centres d’ossification. La croissance tumorale au contact du cartilage ou le traitement par radiothérapie n’influence pas les mesures de l’angle thyroïdien antérieur.