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Lymph node metastasis (LNM) from primary tumors of the central nervous system (CNS) is an infrequent condition, and classically it was thought that CNS tumors could not spread via the lymphatic route. Recent discoveries about this route of dissemination make its knowledge necessary for surgeons and pathologists to avoid delays in diagnosis and unnecessary treatments. The aim of this paper is to review the literature and to discuss the relevant pathogenetic mechanism and the cytologic features along with recommendations for surgical treatment of these cervical LNM. Using PRISMA guidelines, we conducted a systematic review of the literature published from 1944 to 2021, updating the comprehensive review published in 2010 by our group. Our review includes data of 143 articles obtaining 174 patients with LNM from a primary CNS tumor. The mean age of the patients was 31.9 years (range, 0.1-87) and there were 61 females (35.1%) and 103 males (59.2%), and in 10 cases (5.7%) the gender was not specified. The more frequent sites of distant metastasis were bones (23%), lungs (11.5%) and non-cervical lymph nodes (11%). Cervical LNM from CNS tumors is infrequent. Pathologic diagnosis can be obtained by fine-needle aspiration cytology in most cases, giving surgeons the option to plan the appropriate surgical treatment. Given the poor prognosis of these cases, the most conservative possible cervical dissection is usually the treatment of choice.

BACKGROUND: The prognostic importance of intraparotid lymph node metastasis (P+) in patients with primary parotid gland carcinoma is unclear. METHODS: Nineteen retrospective and noncomparative cohort studies, published between 1992 and 2020, met the inclusion criteria and included 2202 patients for this systematic review. RESULTS: The pooled prevalence of the P in adult patients in the unselected studies was 24.10% (95% confidence interval = 17.95-30.25). The number of P+ lymph nodes per patient was counted in only three studies and ranged from 1 to 11. The 5-year recurrence-free survival rate based on Kaplan-Meier analysis varied from 83% to 88% in P- patients compared to 36% to 54% in P+ patients. The average hazard ratio for tumor recurrence in patients with P+ compared to P- was 2.67 ± 0.58. CONCLUSIONS: P+ is an independent negative prognostic factor in primary parotid gland cancer and should be included into the treatment planning.

The oropharynx belongs to the upper aerodigestive tract including the base of tongue and vallecula, the posterior pharyngeal wall, the tonsillar region and lateral oropharyngeal walls, and the soft palate and uvula. Most oropharyngeal cancers are squamous cell carcinoma (OPSCC). Similar to other head and neck cancers, OPSCCs were traditionally more often diagnosed in heavy smokers/heavy drinkers with lower income, lower socioeconomical background and frequent comorbidities related to their lifestyle. However, the last two decades have witnessed an increase in the incidence of OPSCC related to the emergence of human papillomavirus (HPV) -positive tumours mainly observed in high-income countries. [...]

OBJECTIVES: The study investigated the association between hospital volume and observed survival of patients with a head and neck squamous cell carcinoma (HNSCC). METHODS: Overall, 9245 patients diagnosed with HNSCC between 2009 and 2014, were identified in the population-based Belgian Cancer Registry. This database was coupled with other databases providing information on diagnostic and therapeutic procedures, vital status, and comorbidities. The overall and relative survival probabilities were estimated using the Kaplan-Meier and the Ederer II methods, respectively. The relation between hospital volume and observed survival since diagnosis was then assessed using Cox proportional hazard models adjusted for potential confounders. RESULTS: The care for patients with HNSCC in Belgium was dispersed over more than 99 centres with half of the centres treating four or less patients with HNSCC per year. Survival probabilities were significantly better for patients treated in higher volume centres (>20 patients/year): the median survival of patients treated in these centres was 1.1 year longer (5.1 versus 4.0 years) than in lower volume centres. This association was confirmed in analyses taking the case-mix between hospitals into account: the hazard to die of any cause decreased on average with 0.4% per increase of one additionally treated patient. Beyond 20 assigned patients per year, there was no further decrease in the hazard to die. CONCLUSIONS: Statistically significant and clinically relevant improved survival probabilities were obtained in patients treated in higher volume centres (>20 patients/year) compared with their peers treated in lower volume centres. This supports the recommendation to concentrate the care for patients with HNSCC in reference centres.

BACKGROUND: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. METHODS: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. RESULTS: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). CONCLUSIONS: The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant.

81-91, Objectives: The study investigated the association between hospital volume and observed survival of patients with a head and neck squamous cell carcinoma (HNSCC). Methods: Overall, 9245 patients diagnosed with HNSCC between 2009 and 2014, were identified in the population-based Belgian Cancer Registry. This database was coupled with other databases providing information on diagnostic and therapeutic procedures, vital status, and comorbidities. The overall and relative survival probabilities were estimated using the Kaplan-Meier and the Ederer II methods, respectively. The relation between hospital volume and observed survival since diagnosis was then assessed using Cox proportional hazard models adjusted for potential confounders.

INTRODUCTION: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. AREAS COVERED: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. EXPERT OPINION: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.

Introduction: The aim of this study was to assess the validity of a treatment strategy for T1N0 glottic squamous cell carcinoma. Methods: One hundred and seventeen patients were prospectively treated according to institutional guidelines. using 1) laser microsurgery (L) for exophytic tumor, limited to one vocal cord, without extension to the anterior commissure or the vocal process of the arytenoid cartilage, 2) radiotherapy (RT) for large or infiltrative tumor reaching the anterior commissure or the vocal process of the arytenoid cartilage, poor endoscopic exposure and cT1b or 3) partial laryngectomy (PL) for tumor infiltrating the anterior commissure. Ninety-five patients were treated with RT and 22 with surgery alone (S) [L:19; PL:3]. Results: The 5-year overall survival (OS) and disease-specific survival (DSS) were 81.5% and 97.1% (median follow-up: 73 months), respectively. There was no statistically significant difference in OS or DSS between patients treated with RT or S (logrank test: p ¼ 0.974 and 0.978). The 5-year ultimate local control rate reached 98.3%. The local control rate with larynx preservation was 94.9% with no difference between RT (94.7%) and S (95.5%) (c2: p¼ 0.891). Continued smoking after RT was significantly associated with a lower 5-year OS (77.9% versus 87%), [HR 3.458; p ¼ 0.043 (95%CI 1.010e11.837)]. Conclusions: For patients with T1 glottic carcinoma, and based on our previous studies, these data prospectively confirm the oncologic validity of an institutional treatment strategy. Continued smoking after RT correlated with poor OS.

In 1994 a decision analysis, based on the literature and utility ratings for outcome by a panel of experienced head and neck physicians, was presented which showed a threshold probability of occult metastases of 20% to recommend elective treatment of the neck. It was stated that recommendations for the management of the cN0 neck are not immutable and should be reconfigured to determine the optimal management based on different sets of underlying assumptions. Although much has changed and is published in the almost 25 years after its publication, up to date this figure is still mentioned in the context of decisions on treatment of the clinically negative (cN0) neck. Therefore, we critically reviewed the developments in diagnostics and therapy and modeling approaches in the context of decisions on treatment of the cN0 neck. However, the results of studies on treatment of the cN0 neck cannot be translated to other settings due to significant differences in relevant variables such as population, culture, diagnostic work-up, follow-up, costs, institutional preferences and other factors. Moreover, patients may have personal preferences and may weigh oncologic outcomes versus morbidity and quality of life differently. Therefore, instead of trying to establish “the” best strategy for the cN0 neck or “the” optimal cut-off point for elective neck treatment, the approach to optimize the management of the cN0 neck would be to develop and implement models and decision support systems that can serve to optimize choices depending on individual, institutional, population and other relevant variables.

Introduction: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.

Introduction: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.

34 p., ill., KEY MESSAGES. 1 -- SHORT REPORT. 3 -- 1. BACKGROUND 7 -- 1.1. QUALITY IMPROVEMENT INITIATIVES IN ONCOLOGY. 7 -- 1.2. HEAD AND NECK CANCER, A HETEROGENEOUS GROUP OF MALIGNANCIES AFFECTING VARIOUS SITES WITH DIFFERING PROGNOSES. 7 -- 1.3. SCOPE 7 -- 1.4. WHAT THIS STUDY AIMS AT AND DOES NOT AIM AT 7 -- 2. DATA AND METHODS. 8 -- 2.1. THE DATABASE - A LINKAGE BETWEEN THE BELGIAN CANCER REGISTRY AND ADMINISTRATIVE DATABASES. 8 -- 2.2. THE PATIENTS - DIAGNOSED IN 2009-2014, WITH EXCLUSION OF PATIENTS WITH MULTIPLE AND RECURRENT TUMOURS 9 -- 2.3. ASSIGNMENT OF PATIENTS TO A CENTRE OF DIAGNOSIS, A CENTRE OF MAIN TREATMENT AND A CENTRE OF FIRST TREATMENT 9 -- 2.4. CASE-MIX ADJUSTMENT 9 -- 2.5. IDENTIFICATION AND SELECTION OF POSSIBLE QUALITY INDICATORS 9 -- 2.6. VALIDATION STUDY AND SUBSEQUENT DATA CHECKS. 10 -- 2.7. STATISTICAL ANALYSES 10 -- 3. QUALITY OF CARE FOR PATIENTS WITH HEAD AND NECK SQUAMOUS CELL CARCINOMA 11 -- 3.1. A COHORT OF 9 245 HNSCC PATIENTS DIAGNOSED IN 2009-2014 11 -- 3.2. MAIN THERAPEUTIC PROCEDURES: RADIOTHERAPY AND SURGERY 13 -- 3.3. LARGE DISPERSION OF CARE IN BELGIUM. 13 -- 3.4. RESULTS FOR 12 QUALITY INDICATORS 14 -- 3.4.1. Diagnosis and staging 15 -- 3.4.2. Treatment 18 -- 3.4.3. Safety of care – 30-day mortality after treatment with curative intent 20 -- 3.4.4. Survival after the diagnosis of HNSCC 22 -- 3.5. ASSOCIATION BETWEEN HOSPITAL VOLUME AND SURVIVAL 22 -- 4. STRENGTHS AND LIMITATIONS 24 -- 5. CONCLUSIONS AND PERSPECTIVES FOR THE FUTURE 26 -- RECOMMENDATIONS 28 -- REFERENCES 31

28 p., ill., Le Centre fédéral d’expertise des soins de santé (KCE), le Registre du cancer et le Collège d'oncologie mènent depuis plusieurs années un travail de fond pour améliorer la qualité des soins aux patients atteints de cancer. La dernière étude en date porte sur les cancers de la tête et du cou. Un ensemble d'indicateurs de qualité et d'objectifs à atteindre a été défini avec l’aide d’experts de terrain, et les soins délivrés dans les hôpitaux belges ont ensuite été évalués sur cette base. Une fois de plus, le KCE a constaté que les chances de survie sont significativement plus élevées dans les hôpitaux qui traitent, par an, plus de 20 patients atteints de ce type de cancers, un seuil que seuls 23 hôpitaux atteignent (soit moins d’un quart des hôpitaux de notre pays). Le KCE recommande donc de centraliser le traitement de ces cancers dans les hôpitaux disposant de l'expertise nécessaire, comme cela vient d’être décidé pour la chirurgie des cancers de l'œsophage et du pancréas. Simultanément à la publication de cette étude, chaque hôpital évalué recevra un rapport de feedback du Registre du cancer, contenant ses propres résultats pour les différents indicateurs et sa situation par rapport aux autres hôpitaux (benchmarking) afin d’adopter des mesures pour améliorer la qualité des soins., MESSAGES CLÉS 2 -- SYNTHÈSE 4 -- 1. CONTEXTE. 7 -- 1.1. INITIATIVES POUR L’AMÉLIORATION DE LA QUALITÉ DES SOINS EN ONCOLOGIE 7 -- 1.2. CARACÉTRISTIQUES DES CANCERS DE LA TÊTE ET DU COU. 8 -- 1.3. OBJECTIF DE CETTE ÉTUDE. 8 -- 2. COMMENT AVONS-NOUS PROCÉDÉ ? 9 -- 2.1. COUPLAGE ENTRE LES DONNÉES DU REGISTRE DU CANCER ET D’AUTRES BASES DE DONNÉES ADMINISTRATIVES 9 -- 2.2. COLLABORATION ÉTROITE AVEC DES EXPERTS CLINIQUES 9 -- 2.3. PLUS DE 9 000 PATIENTS INCLUS ENTRE 2009 ET 2014 9 -- 2.4. PRISE EN COMPTE DES CARACTÉRISTIQUES DU PATIENT ET DE LA TUMEUR 10 -- 2.5. IDENTIFICATION ET SÉLECTION DES INDICATEURS DE QUALITÉ 10 -- 2.6. VALIDATION ET ANALYSES STATISTIQUES 10 -- 2.7. AVERTISSEMENT : LES DONNÉES ADMINISTRATIVES NÉCESSITENT UNE INTERPRÉTATION PRUDENTE 10 -- 3. QUALITÉ DES SOINS AUX PATIENTS ATTEINTS D’UN CANCER DE LA TÊTE ET DU COU 11 -- 3.1. ANALYSE DES DONNÉES DE PLUS DE 9 000 PATIENTS 11 -- 3.2. TRAITEMENT PRINCIPAL : RADIOTHÉRAPIE OU CHIRURGIE 11 -- 3.3. GRANDE DISPERSION DES SOINS 12 -- 3.4. RÉSULTATS POUR 12 INDICATEURS DE QUALITÉ 12 -- 3.4.1. Diagnostic et stadification de la tumeur 15 -- 3.4.2. Traitement 16 -- 3.4.3. Mortalité à 30 jours après un traitement curatif 17 -- 3.4.4. Survie après le diagnostic 17 -- 3.5. LIEN ENTRE LA SURVIE ET L’EXPÉRIENCE DE L’ÉQUIPE SOIGNANTE. 18 -- 3.6. CE QUE NOUS NE SAVONS PAS (ENCORE)… 20 -- 3.7. DÉCLARATION INSUFFISANTE AU REGISTRE DU CANCER 20 -- 4. CONCLUSION 21 -- RECOMMANDATIONS 22 -- RÉFÉRENCES 25

28 p., ill., In België nemen het Federaal Kenniscentrum voor de Gezondheidszorg (KCE), het Kankerregister en het College voor Oncologie al een aantal jaren initiatieven om de zorgkwaliteit voor kankerpatiënten te verbeteren. Deze keer werd de zorg voor mensen met hoofd- en halskanker onder de loep genomen. Het KCE stelde samen met klinische experten een set van kwaliteitsindicatoren en te behalen doelstellingen op, en evalueerde aan de hand daarvan de zorg die in de Belgische ziekenhuizen wordt aangeboden. Opnieuw stelde het KCE vast dat de kans op overleving significant groter is in ziekenhuizen die jaarlijks meer dan 20 patiënten met hoofd- en halskanker verzorgen. In België halen 23 ziekenhuizen (of minder dan één vierde van de ziekenhuizen) deze drempel. Het KCE beveelt daarom aan om de zorg voor deze patiënten te centraliseren in ziekenhuizen met de nodige expertise, zoals dit onlangs ook gebeurde voor slokdarm- en pancreaskankerchirurgie. Op het moment van deze publicatie ontvangt elk betrokken ziekenhuis een feedbackrapport van het Kankerregister met daarin zijn resultaten en situering t.o.v. de andere ziekenhuizen (benchmarking), zodat verbetertrajecten kunnen opgestart worden., KERN BOODSCHAPPEN 2 -- SYNTHESE 4 -- 1. ACHTERGROND 7 -- 1.1. INITIATIEVEN VOOR KWALITEITSVERBETERING IN DE ONCOLOGIE 7 -- 1.2. KENMERKEN VAN HOOFD- EN HALSKANKER 8 -- 1.3. DOELSTELLING VAN DEZE STUDIE 8 -- 2. HOE GINGEN WE TE WERK? 9 -- 2.1. EEN KOPPELING TUSSEN DE GEGEVENS VAN HET KANKERREGISTER EN ANDERE ADMINISTRATIEVE DATABANKEN 9 -- 2.2. NAUWE SAMENWERKING MET KLINISCHE EXPERTEN 9 -- 2.3. MEER DAN 9 000 PATIËNTEN BESTUDEERD, GEDIAGNOSTICEERD IN 2009-2014 9 -- 2.4. REKENING HOUDEN MET PATIËNT- EN TUMORKENMERKEN 10 -- 2.5. IDENTIFICATIE EN SELECTIE VAN KWALITEITSINDICATOREN 10 -- 2.6. VALIDATIE EN STATISTISCHE ANALYSES 10 -- 2.7. KANTTEKENING: ADMINISTRATIEVE DATA VRAGEN EEN VOORZICHTIGE INTERPRETATIE 10 -- 3. KWALITEIT VAN ZORG VOOR PATIËNTEN MET HOOFD-EN HALSKANKER 11 -- 3.1. ANALYSE VAN DE GEGEVENS VAN MEER DAN 9 000 PATIËNTEN 11 -- 3.2. VOORAL RADIOTHERAPIE EN CHIRURGIE 11 -- 3.3. GROTE ZORGSPREIDING 11 -- 3.4. RESULTATEN VOOR 12 KWALITEITSINDICATOREN 12 -- 3.4.1. Diagnose en stadiëring van de tumor 14 -- 3.4.2. Behandeling 16 -- 3.4.3. Mortaliteit op 30 dagen na een curatieve behandeling 17 -- 3.4.4. Overleving na de diagnose 17 -- 3.5. VERBAND TUSSEN OVERLEVING EN ERVARING VAN ZORGTEAM 17 -- 3.6. WAT WE (NOG) NIET WETEN…. 19 -- 3.7. ONVOLDOENDE RAPPORTERING AAN HET KANKERREGISTER 20 -- 4. CONCLUSIE 21 -- AANBEVELINGEN 22 -- REFERENTIES 25

313 p., ill., TABLE OF CONTENTS.1 -- LIST OF FIGURES 5 -- LIST OF TABLES.8 -- LIST OF ABBREVIATIONS .19 --  SCIENTIFIC REPORT 22 -- 1 INTRODUCTION.22 -- 1.1 HEAD AND NECK CANCER IN BELGIUM22 -- 1.2 DISPERSION OF CARE IN BELGIUM 23 -- 1.3 MEASURING QUALITY 24 -- 2 OBJECTIVES, SCOPE & TERMINOLOGY .25 -- 2.1 WHAT THIS STUDY AIMS AT AND DOES NOT AIM AT .25 -- 2.2 PRECEDING STEPS 26 -- 2.3 SCOPE.26 -- 2.4 TARGET AUDIENCE 26 -- 2.5 TERMINOLOGY 26 -- 3 METHODOLOGY27 -- 3.1 STEP 1: IDENTIFICATION OF THE TARGET POPULATION: DATA SELECTION AND LINKAGE OF DATABASES.27 -- 3.1.1 Selection of the study population in the Belgian Cancer Registry database .27 -- 3.1.2 Linkage with health insurance data.29 -- 3.1.3 Linkage with hospital discharge data.30 -- 3.1.4 Vital status30 -- 3.2 STEP 2: IDENTIFICATION AND SELECTION OF POSSIBLE QUALITY INDICATORS .30 -- 3.2.1 Identification of possible quality indicators 30 -- 3.2.2 Selection process and results 31 -- 3.2.3 Measurability of selected quality indicators 32 -- 3.2.4 Final selection of quality indicators to be fully elaborated32 -- 3.3 STEP 3: OPERATIONALIZATION OF INDICATORS 34 -- 3.3.1 Technical fiches 34 -- 3.3.2 Defining diagnostic and therapeutic procedures based on health insurance data.34 -- 3.3.3 Defining the treatment scheme of the patient 38 -- 3.3.4 Statistical analyses 38 -- 3.3.5 Case-mix adjustment .41 -- 3.4 STEP 4: ASSIGNMENT OF EACH PATIENT TO ONE CENTRE.45 -- 3.5 STEP 5: VALIDATION OF DIAGNOSTIC AND THERAPEUTIC DATA .46 -- 3.5.1 Introduction and methodology 46 -- 3.5.2 Validation of the algorithm to assign patients to one treatment hospital .47 -- 3.5.3 Validation of patient and tumour characteristics and of diagnostic and therapeutic procedures as identified in the health insurance data linked to cancer registry data .48 -- 3.6 STEP 6: MEASUREMENT OF QUALITY INDICATORS, AT NATIONAL LEVEL AND BY CENTRE.50 -- 3.7 STEP 7: INTERPRETATION OF RESULTS.50 -- 4 CHARACTERISTICS OF THE STUDY SAMPLE .50 -- 4.1 BASELINE DEMOGRAPHICS

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine, usually benign, tumors. Currently, the only reliable criterion of malignancy is the presence of metastases. Objective: The aim of this study was to identify genes associated with malignancy in PPGLs. Design: Transcriptomic profiling was performed on 40 benign and 11 malignant PPGLs. Genes showing a significantly different expression between benign and malignant PPGLs with a ratio ≥4 were confirmed and tested in an independent series by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed for the validated genes on 109 benign and 32 malignant PPGLs. Functional assays were performed with hPheo1 cells. Setting: This study was conducted at the Department of Pathology of the Erasmus MC University Medical Center Rotterdam Human Molecular Genetics laboratory of the de Duve Institute, University of Louvain. Patients: PPGL samples from 179 patients, diagnosed between 1972 and 2015, were included. Main outcome measures: Associations between gene expression and malignancy were tested using supervised clustering approaches. Results: Ten differentially expressed genes were selected based on messenger RNA (mRNA) expression array data. Contactin 4 (CNTN4) was overexpressed in malignant vs benign tumors [4.62-fold; false discovery rate (FDR), 0.001]. Overexpression at the mRNA level was confirmed using qRT-PCR (2.90-fold, P = 0.02; validation set: 4.26-fold, P = 0.005). Consistent findings were obtained in The Cancer Genome Atlas cohort (2.7-fold; FDR, 0.02). CNTN4 protein was more frequently expressed in malignant than in benign PPGLs by immunohistochemistry (58% vs 17%; P = 0.002). Survival after 7 days of culture under starvation conditions was significantly enhanced in hPheo1 cells transfected with CNTN4 complementary DNA. Conclusion: CNTN4 expression is consistently associated with malignant behavior in PPGLs.

Roennegaard et al. from Odense University Hospital, Denmark report their institutional experience, as tertiary cancer centre, on a nation-based head and neck cancer (HNC) fast-track programme, taking care of patients from the general practitioner (GP) suspicion of HNC to the start of initial treatment when the diagnosis of cancer is confirmed [1]. The decision to launch such a programme was made when it was observed during the 1990s that survival rates for HNC patients were worse in Denmark than in the other Scandinavian countries [2], [3]. Long waiting time from initial cancer symptoms to the start of treatment was considered as the main reason for the poor outcome of patients in Denmark. Studies have clearly shown disease progression during waiting time [4], [5]. [...]

PURPOSE: Quality assurance is much more difficult to achieve in surgical oncology than in medical oncology and radiotherapy where doses are standardized and toxicities are well-classified. To better define what is required in surgery, we analyzed recent articles addressing the point in head and neck surgery. RESULTS: The surgical report should match with the pathological description of the resected specimen with accurate delineation of the margins, number and level(s) of lymph nodes (capsular rupture if any). Complications (minor and major) should be standardized and meticulously recorded; as well as comorbidities and patient status. The acuity of the procedure should be defined by metrics collected in check-lists. Age > 60 years, male gender, tumor site and T4 stage, neck dissection(s), flap reconstruction, alcohol and tobacco consumption, are acknowledged risk factors for more complications and longer hospital stay (or readmission). NEEDS: Randomized controlled trials should be designed adopting the consolidated standards of reporting trials (CONSORT). Training young head and neck surgeons should encompass formation in designing, conducting and interpreting clinical trials.

PURPOSE: Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Grégoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy. METHOD: For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus. RESULTS: This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively. CONCLUSION: Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi-institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma.

Carotid blowout syndrome (CBS) refers to rupture of the carotid artery and is an uncommon complication of head and neck cancer that can be rapidly fatal without prompt diagnosis and intervention. CBS develops when a damaged arterial wall cannot sustain its integrity against the patient’s blood pressure, mainly in patients who have undergone surgical procedures and radiotherapy due to cancer of the head and neck, or have been reirradiated for a recurrent or second primary tumor in the neck. Among patients irradiated prior to surgery, CBS is usually a result of wound breakdown, pharyngocutaneous fistula and infection. This complication has often been fatal in the past, but at the present time, early diagnosis and modern technology applied to its management have decreased morbidity and mortality rates. In addition to analysis of the causes and consequences of CBS, the purpose of this paper is to critically review methods for early diagnosis of this complication and establish individualized treatment based on endovascular procedures for each patient.

Quality improvement of care for patients with head and neck cancer remains a constant objective for the multidisciplinary team of physicians managing these patients. The purpose of quality assurance (QA) for head and neck surgical oncology and surgical trials however differs. While QA for the general head and neck patient aims to improve global outcome through structural changes of health-care systems, QA for surgical trials pursues the goal to help providing meaningful results from a clinical trial through the definition of structure, process and outcome measures within the trial. Establishing a QA program for surgical trials is challenging largely due to the variation in the execution of surgical techniques. Within this article, we describe the surgical QA program, which was developed for the phase III European Organisation for Research and Treatment of Cancer (EORTC) 1420 study, a trial assessing swallowing function after transoral surgery compared with radiation therapy. We propose based on our experience to further develop surgical QA for surgical clinical trials by introducing two separate components, one adaptable and one non-adaptable. The adaptable is tailored to the scientific question and specific procedure; the non-adaptable consists of minimal structural requirements of the clinical unit to participate in surgical trials at EORTC as well as guidelines and incentives for protocol adherence based on our experience in EORTC 24954. Finally, we strongly believe that surgical QA designed for clinical trials may serve as a basis for the development of QA surgical guidelines in clinical practice., SCOPUS: re.j, DecretOANoAutActif, info:eu-repo/semantics/published

Purpose: Quality assurance is much more difficult to achieve in surgical oncology than in medical oncology and radiotherapy where doses are standardized and toxicities are well-classified. To better define what is required in surgery, we analyzed recent articles addressing the point in head and neck surgery. Results: The surgical report should match with the pathological description of the resected specimen with accurate delineation of the margins, number and level(s) of lymph nodes (capsular rupture if any). Complications (minor and major) should be standardized and meticulously recorded; as well as comorbidities and patient status. The acuity of the procedure should be defined by metrics collected in check-lists. Age > 60 years, male gender, tumor site and T4 stage, neck dissection(s), flap reconstruction, alcohol and tobacco consumption, are acknowledged risk factors for more complications and longer hospital stay (or readmission). Needs: Randomized controlled trials should be designed adopting the consolidated standards of reporting trials (CONSORT). Training young head and neck surgeons should encompass formation in designing, conducting and interpreting clinical trials., SCOPUS: ar.j, info:eu-repo/semantics/published

OBJECTIVE: Salvage surgery in recurrent SCCHN is associated with poor outcomes. This study aimed to better identify suitable surgical candidates and those at high risk of new recurrence. MATERIALS AND METHODS: Single-center retrospective analysis of 109 patients undergoing salvage surgery for recurrent SCCHN. Univariate and multivariate analyses were used to identify prognostic factors affecting disease-free survival (DFS). RESULTS: The following factors showed a significant impact on DFS: Disease-free interval >6months [HR 0.53; p=0.04], age>70years [HR 0.26; p=0.03], primary chemoradiotherapy [HR 2.39; p<0.01] compared to radiotherapy, oropharynx [HR 5.46; p<0.01] and hypopharynx [HR 3.92; p=<0.01] sites, compared to larynx, initial stage III [HR 7.10; p<0.01] and stage IV [HR 4.13; p<0.01], compared to stage I, locoregional recurrence [HR 4.57; p<0.01], compared to local recurrence. Univariate analysis also identified significant postoperative predictors of poor DFS including flap reconstruction [HR 3.44; p<0.01], postoperative complications [HR 2.09; p=0.01], positive margins [HR 3.64; p<0.01] and close margins [HR 3.83; p<0.01]. On multivariate analysis, oropharynx site [HR 3.98; p<0.01], initial stage III [HR 5.93; p<0.01] and locoregional recurrence [HR 2.93; p=0.04] were independent preoperative prognostic factors for DFS. Positive margins [HR 2.32; p=0.04], close margins [HR 2.94; p=0.02], extracapsular spread (ECS) [HR 4.04; p=0.03] and postoperative complications [HR 3.64; p<0.01] were independent postoperative prognostic factors. CONCLUSIONS: Patients with advanced primary nonlaryngeal tumor and locoregional recurrence have limited success with salvage surgery. Because patients with positive margins and ECS are at high risk of relapse, adjuvant treatment should be discussed.

Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.

Introduction The authors modified an adult jet ventilation injector (Hunsaker Mon-Jet Ventilation Tube®) to be able to provide transglottal high-frequency jet ventilation (HFJV) in small children undergoing laryngeal procedures with CO2 laser. Methods and material Retrospective review of the anesthetic records of all children younger than 2 years undergoing transglottal HFJV for CO2 laser laryngeal procedures using this modified adult injector between 2006 and 2013. Results Nine children (5 boys, 4 girls) were identified who underwent a total of 20 procedures. Mean age was 7.4 ± 6.9 months, and mean weight was 6 ± 2.8 kg. No complications were observed with the use of HFJV or this modified injector. Conclusion In experienced hands, this modified injector ensures excellent visibility and field access to the surgeon as well as adequate ventilation during laryngeal laser surgery in infants.

Papillary thyroid cancer (PTC) is the commonest endocrine malignancy, though no precursor lesion has been identified yet. Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in areas showing cytological features of PTC within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. Our study suggests that the progress of malignancy can be tracked by assessing expression of proliferative proteins like Ki67, pHH3 and cyclin D1, and that apoptosis inhibition by bcl-2 protein can further amplify the role of these proteins in tumour progression. Different mutations in the mitogen-activated protein kinase (MAPK) pathway play distinct roles in the growth and invasion of thyroid cancer cells. We have outlined a possible role of MAPK in the development of PTC, especially that of extracellular regulated kinases (ERK) and p38. MAPK activation may be linked to cyclin D1 expression., (MED - Sciences médicales) -- UCL, 2016

Objective: To review reports of adenoid cystic carcinomas arising in the head and neck area outside of the major salivary glands, in order to enhance the care of patients with these unusual neoplasms. Methods: An international team of head and neck surgeons, pathologists, oncologists and radiation oncologists was assembled to explore the published experience and their own working experience of the diagnosis and treatment of adenoid cystic carcinomas arising in the vicinity of the sinonasal tract, nasopharynx, lacrimal glands and external auditory canal. Results: The behaviour of adenoid cystic carcinoma arising in head and neck sites exclusive of the major salivary glands parallels that of tumours with a similar histology arising in the major salivary glands - these are relentless, progressive tumours, associated with high rates of mortality. Of 774 patients reviewed, at least 41 (5.3 per cent) developed documented regional node metastases. Conclusion: The relatively low overall incidence of nodal metastases in adenoid cystic carcinomas arising in the head and neck region outside of the major salivary glands suggests that routine elective regional lymph node dissection might not be indicated in most patients with these tumours. Copyright © JLO (1984) Limited 2016.

Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended.

The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0-14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.

Despite advances in treatment modalities, the management of hypopharyngeal squamous cell carcinoma (SCC) remains diffi cult. Most patients have advanced locoregional disease at the time of diagnosis. Treatment selection favors laryngeal preservation approaches either surgically or non- surgically to improve the quality of life without compromising locoregional control and survival. For patients with early disease, conservation surgery and primary radiotherapy are equally effective therapeutic options. For patient with advanced locoregional disease, a conservative treatment combining chemotherapy and radiotherapy should be favored. Total laryngopharyngectomy (TLP) remains indicated in tumors not suitable for conservative nonsurgical approaches and for salvage. Despite a good locoregional control rate, most patients succumb to distant metastases, intercurrent diseases, or second primaries. Future developments should be connected with treatments with a better toxicity profi le than chemotherapy aimed to decrease the rate of late distant recurrences and the occurrence of second primaries. Targeted agents could be nicely incorporated into the standard regimen to either improve effi cacy and/or decrease treatment toxicity. Ongoing studies investigating the combination of targeted agent administration during or after induction chemotherapy or with concomitant chemoradiation regimens will help to better defi ne the respective role of chemotherapy and targeted agents in the multimodal treatment of this disease. In addition, efforts to identify predictive biomarkers that could help to better select the patients who will benefi t of a specifi c treatment modality are of crucial importance.

Chapter 35: head and neck cancer. Oxford textbook of oncology (Oxford medicine online).

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.

Prophylactic neck dissection (PND) for papillary thyroid carcinoma (PTC) is controversial. Our aim was to assess current levels of evidence (LE) according to the Oxford Centre for Evidence-based Medicine (http://www.cebm.net/?O=1025) regarding the oncologic benefits of PND. Data were analyzed via MEDLINE keywords: PTC, differentiated thyroid carcinoma, PND, central lymph node metastases, central compartment, recurrence-free survival. There was conflicting evidence regarding the rate of reoperation for recurrence, with some studies showing a lower rate after PND with increased recurrence-free survival and a higher rate of undetectable pre- and post-ablation thyroglobulin levels (LE 4), whereas other studies did not show a difference (LE 4). Only one study (LE 4) showed improved disease-specific survival with PND. PND may improve recurrence-free survival, although this is supported by only a low LE. Current recommendations can only be based on low-level evidence.