[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

Afatinib maintenance therapy following post-operative radiochemotherapy in head and neck squamous cell carcinoma: Results from the phase III randomised double-blind placebo-controlled study BIB2992ORL (GORTEC 2010-02).

OBJECTIVE: We investigated the efficacy and safety of afatinib maintenance therapy in patients with head and neck squamous cell carcinoma (HNSCC) with macroscopically complete resection and adjuvant radiochemotherapy (RCT). METHODS: This French multicentric randomised phase III double-blind placebo-controlled study included adult patients with ECOG-PS≤2, normal haematological, hepatic and renal functions, and non-metastatic, histologically confirmed HNSCC of the oral cavity, oropharynx, larynx or hypopharynx, with macroscopically complete resection and adjuvant RCT (≥2 cycles of cisplatin 100 mg/m2 J1, J22, J43 and 66Gy (2Gy/fraction, 5 fractions/week, conventional or intensity modulated radiotherapy ≥60Gy). Randomised patients were planned to receive either afatinib (afa arm) or placebo (control arm (C)) as maintenance therapy for one year. Primary endpoint was disease free survival (DFS). A 15% improvement in DFS was expected at 2 years with afatinib (from 55 to 70%). RESULTS: Among the 167 patients with resected HNSCC included in 19 cancer centres and hospitals from Dec 2011, 134 patients were randomised to receive one-year maintenance afatinib or placebo (afa:67; C:67). Benefit/risk ratio was below assumptions and independent advisory committee recommended to stop the study in Feb 2017, the sponsor decided premature study discontinuation, with a 2-year follow-up for the last randomised patient. 2y-DFS was 61% (95% CI 0.48-0.72) in the afatinib group and 64% (95% CI 0.51-0.74) in the placebo group (HR 1.12, 95% CI 0.70-1.80). CONCLUSION: Maintenance therapy with afatinib compared with placebo following post-operative RCT in patients with HNSCC did not significantly improve 2y-DFS and should not be recommended in this setting outside clinical trials. CLINICALTRIALS: gov identifier NCT01427478.

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.

Induction chemotherapy followed by cisplatin or cetuximab concomitant to radiotherapy for laryngeal/hypopharyngeal cancer: Long-term results of the TREMPLIN randomised GORTEC trial.

BACKGROUND: In Europe, induction chemotherapy (ICT) followed by radiotherapy is preferred to conventional chemoradiotherapy to avoid total laryngectomy in patients with laryngeal/hypopharyngeal cancer. In comparison with conventional radiotherapy, bioradiotherapy with cetuximab significantly improves locoregional control rates (LCRs) and overall survival (OS) without any increase in unmanageable toxicity. METHODS: Patients included had untreated non-metastatic stage III-IV laryngeal/hypopharyngeal invasive squamous cell carcinoma. Good responders after three cycles of docetaxel-cisplatin-5-fluorouracil (TPF)-ICT (docetaxel and cisplatin, 75 mg/m2 each on day 1, and 5-fluorouracil, 750 mg/m2/day on days 1-5) every 3 weeks were randomised to receive radiotherapy (70 Gy) with concurrent cisplatin (100 mg/m2/day on days 1, 22 and 43 of radiotherapy) or cetuximab (400 mg/m2 of loading dose, 250 mg/m2/week during radiotherapy). The primary end-point was larynx preservation. The secondary end-points were laryngo-oesophageal dysfunction-free survival (LEDFS), LCR and OS. RESULTS: A total of 153 patients were enrolled. Among 126 TPF-ICT responders, 116 were randomised to receive either cisplatin (n = 60) or cetuximab (n = 56). The median follow-up was 77.5 months. Five-year OS rates were 66.6% (95% confidence interval [CI]: 0.54-0.79) versus 66.9% (95% CI: 0.54-0.79) (p = 0.9), respectively. Five-year LCRs were 79.8% (95% CI: 69.5-90.0) versus 67.8% (95% CI: 55.1-80.5%) (p = 0.18). Five-year LEDFS was 62.2% (95% CI: 49.7-74.8%) versus 56.2% (95% CI: 43.0-69.4) (p = 0.38). Late grade III/IV salivary gland and laryngeal toxicity occurred in 10.3% versus 9.8% and 6.8% versus 11.8% of patients receiving cisplatin-radiotherapy versus cetuximab, respectively. CONCLUSIONS: No significant difference in LEDFS was observed between the two arms. TPF-ICT followed by conventional chemoradiotherapy or cetuximab was feasible, and long-term toxicity was not statistically different between the two arms. LEDFS appears as a relevant end-point.

Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial.

PURPOSE: Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. PATIENTS AND METHODS: The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. RESULTS: Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). CONCLUSION: Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

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.

Long-term quality of life and psycho-social outcomes after oropharyngeal cancer surgery and radial forearm free-flap reconstruction: A GETTEC prospective multicentric study.

OBJECTIVE: To assess long-term quality of life (QoL) and psycho-social outcomes, and to determine their predictive factors after oropharyngeal cancer (OPC) surgery and radial forearm free-flap (RFFF) reconstruction. METHODS: Patients who had undergone OPC surgery and RFFF reconstruction who were still alive and disease-free at least 1 year after surgery were enrolled in this prospective multicentric study. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Core (QLQ-C30) and Head and Neck Cancer (QLQ-H&N35) QoL questionnaires, the Voice Handicap Index (VHI-10) questionnaire and the Hospital Anxiety and Depression Scale (HADS). The level of dysphagia was evaluated using the Dysphagia Handicap Index (DHI) and the Dysphagia Outcomes and Severity Scale (DOSS). Predictive factors of these clinical outcomes were determined in univariate and multivariate analysis. RESULTS: A total of 58 patients were included in this study. Long-term QoL and functioning scales scores were well-preserved (all superior to 70%). Main persistent symptoms were fatigue, reduced sexuality and oral function-related disorders (swallowing, teeth, salivary and mouth-opening problems). HADS anxiety and depression scores were 7.2 and 5.4, respectively. Twenty-one (36%) patients presented an anxiodepressive disorder (HADS global score ≥ 15). Among the 21 patients who were still working before surgery, 11 (52%) had returned to work at the time of our study. The HADS global score (p < 0.001) was the main predictor of QoL, VHI-10 and DOSS scores. CONCLUSIONS: Psychological distress is the main determinant of long-term QoL and is therefore of critical importance in the multidisciplinary management of OPC patients.

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.

Shear Wave Elastography in Thyroid Nodules with Indeterminate Cytology: Results of a Prospective Bicentric Study.

BACKGROUND: The clinical management of thyroid nodules with indeterminate cytology (IC) remains challenging. The role of shear wave elastography (SWE) in this setting is controversial. The aim of the study was to assess the performances of SWE in terms of prediction of malignancy, reproducibility, and combined analysis with ultrasound (US) examination in thyroid nodules with IC. METHODS: This prospective study was conducted in two referral centers. Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda class III-V) for which surgery had been recommended. Patients underwent a standardized US evaluation combined with a SWE exam followed by surgery. SWE parameters included mean (meanEI; kPa) and max (maxEI) elasticity values, and ratio (meanEI nodule/parenchyma). RESULTS: One hundred and thirty-one nodules (median size 30 mm) in 131 patients were studied. IC was class III in 28%, class IV in 64%, and class V in 8% of cases. After surgery, 21 (16%) nodules were malignant, including nine papillary thyroid cancers (PTC), six follicular thyroid cancers, five poorly differentiated carcinomas, and one large B-cell lymphoma. SWE parameters were similar in benign and malignant nodules, including meanEI (20.2 vs. 19.6 kPa), maxEI (34.3 vs. 32.5 kPa), and ratio (1.57 vs. 1.38). In malignant nodules, meanEI, maxEI, and ratio were higher in the classic PTC variants (n = 4) than in the other PTC variants (n = 5; p < 0.02) and in non-PTC tumors (n = 12; p < 0.005). Intra- and inter-observer coefficients of variations for meanEI in nodules were 23% and 26%, respectively. The French Thyroid Imaging Reporting and Data System score, the American Thyroid Association US classification, and the EU-Thyroid Imaging Reporting and Data System were not associated with malignancy. CONCLUSIONS: Despite high elasticity values in classic PTC variants, conventional SWE indexes failed to discriminate between benign and malignant tumors in thyroid nodules with IC.

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.

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

BACKGROUND: False-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. OBJECTIVES: We 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. CONCLUSION: These 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.

Trends in net survival from head and neck cancer in six European Latin countries: results from the SUDCAN population-based study.

The aim of the SUDCAN collaborative study was to compare the trends in 1- and 5-year net survival and the trends in the dynamics of the excess mortality rates in head and neck cancers between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland). The data were extracted from the EUROCARE-5 database. First, the net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain and Switzerland and from 2000 to 2004 in Belgium and Portugal. The analyses were carried out using a flexible excess rate modelling. There were significant differences between countries in 5-year age-standardized net survivals over the 2000-2004 period, ranging from 33 to 34% in France and Portugal from 42 to 44% in Switzerland and Italy, respectively. The age-standardized net survival improved considerably from 1992 to 2004 in Italy, Spain and Switzerland, but not in France because of lack of improvement in the elderly. The increase in net survival was linked to a decrease in the excess mortality rate up to 3-4 years after diagnosis. The net survival from head and neck cancers improved over the study period, but significant differences were still observed in 2004. Differences in sex ratio and anatomical distribution contributed only partially towards these disparities. Differences in stage at diagnosis, time to treatment and/or proportion of human papillomavirus-related cases are also probably involved in the survival disparities observed. Overall, the prognosis of these tumours remains poor.

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.

Endoscopic nasal versus open approach for the management of sinonasal adenocarcinoma: A pooled-analysis of 1826 patients.

BACKGROUND: Surgical resection represents the gold standard for the treatment of sinonasal malignancies. This study reviewed the published outcomes on endoscopic surgery or endoscopic-assisted surgery versus open approach for the management of sinonasal adenocarcinomas. METHODS: PubMed, EMBASE, the Cochrane Library, and CENTRAL electronic databases were searched for English language articles on endoscopic surgery, endoscopic-assisted surgery, and open approach for sinonasal adenocarcinomas. Each article was examined for patient data and outcomes for analysis. RESULTS: Thirty-nine articles including 1826 patients were used for the analysis. The endoscopic surgery and endoscopic-assisted surgery showed low rates of major complications (6.6% and 25.9%, respectively) compared to open approaches (36.4%; p < .01). The incidence of local failure was lower in the endoscopic surgery group as compared with open approach patients (17.8% vs 38.5%; p < .01, respectively). The multivariate Cox regression model showed a worst overall survival related to advanced T classification and open approach. CONCLUSION: From the existing body of data, there is growing evidence that endoscopic nasal resection is a safe surgical option in the management of sinonasal adenocarcinomas. © 2015 Wiley Periodicals, Head Neck 38: E2267-E2274, 2016.

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.

[Oropharyngeal cancer]. / 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%.

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.

Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study.

PURPOSE: To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP). PATIENTS AND METHODS: Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2) each on day 1 and fluorouracil 750 mg/m(2) per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m(2) per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m(2) loading dose and 250 mg/m(2) per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months. RESULTS: Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only. CONCLUSION: There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.