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In recent years, there have been relevant advances in the use of surgery, radiation therapy, and chemotherapy for the treatment of malignant tumors of the head and neck. Extensive tumor resection and radical radiotherapy frequently result in altered form and function of orofacial structures that can severely impact the patient's quality of life. This study reports the benefits obtained with the injection of autologous fat to correct the deformities and improve functionality in a series of 40 patients who have been treated for head and neck cancer. Esthetic improvement was obtained in 77.5% of patients and functional improvement in 89.2%. In addition, there was a high degree of satisfaction regarding esthetic improvement and 92.5% of patients would recommend the procedure to other patients in the same situation. The injection of autologous fat is an effective procedure for the management of sequelae of head and neck cancer treatment. A single-center retrospective study was designed to assess the outcomes of autologous fat grafting for improving surgery- and radiotherapy-related sequelae in 40 patients with head and neck cancer. All patients underwent surgical resection of primary tumors and radiotherapy (50-70 Gy) and were followed over 12 months after fat grafting. Eligibility for fat grafting procedures included complete remission after at least 3 years of oncological treatment. The cervical and paramandibular regions were the most frequently treated areas. Injected fat volumes ranged between 7.5 and 120 mL (mean: 23 mL). Esthetic improvement was obtained in 77.5% of patients, being significant in 17.5%, and functional improvement in 89.2%, being significant in 29.7% of patients. Minor complications occurred in three patients. There was a high degree of satisfaction regarding esthetic improvement, global satisfaction, and 92.5% of patients would recommend the procedure. This study confirms the benefits of fat grafting as a volumetric correction reconstructive strategy with successful cosmetic and functional outcomes in patients suffering from sequelae after head and neck cancer treatment.

PURPOSE Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. METHODS Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment. RESULTS The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes. CONCLUSION With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.

Mucositis; Radiation toxicities; Simultaneous care Mucositis; Toxicitats per radiació; Atenció simultània Mucositis; Toxicidades por radiación; Atención simultánea Treatment of locally advanced head and neck carcinoma not amenable for surgical resection or resected with high-risk features is usually based on (chemo-)radiation treatment. Oral mucositis represents one of the main side effects of (chemo-)radiation, with an important impact on quality of life and causing approximately 20% of early interruption of treatment, leading to a suboptimal dose administered. Treatment and prevention of oral mucositis have a central role in the therapeutic pathways of head and neck cancer patients but remains quite challenging. Although extensive research is conducted to identify interventions for the management of mucositis, very few interventions had sufficient evidence to generate an international expert consensus. This may be partially explained by confounding factors that could influence the development and assessment of oral mucositis. Little is known about the confounding factors of oral mucositis, which, if not well balanced in an experimental study, could lead to non-solid results. The current paper aims to review the main oral mucositis confounding factors related to head and neck cancer patients. Open access funding provided by Università degli Studi di Brescia within the CRUI-CARE Agreement. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Epstein Barr virus; Prognosis; Response to treatment Virus de Epstein Barr; Pronóstico; Respuesta al tratamiento Virus d'Epstein Barr; Pronòstic; Resposta al tractament The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers. SEOM and SEAP acknowledge the financial support for this project in the form of unrestricted collaboration in the logistics from AstraZeneca.

Càncer de cap i coll; Radioteràpia; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Cáncer de cabeza y cuello; Terapia de radiación; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Head and Neck Cancer; Radiation Therapy; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Purpose Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. Methods and Materials A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. Results In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. Conclusions This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.

Head and neck cancer; Outcome measurement; Patient-centered care Cáncer de cabeza y cuello; Medición de resultados; Atención centrada en el paciente Càncer de cap i coll; Mesura del resultat; Atenció centrada en el pacient Purpose: A systematic, standardized collection of health outcomes during patient treatment and follow-up, relevant from the perspective of all stakeholders, is a crucial step toward effective and efficient disease management. This project aimed to define a standard set of health outcomes for patients with squamous cell carcinoma of the head and neck (SCCHN). Methods: The project was led and coordinated by a scientific committee (SC). It comprised: (1) a literature review (to identify variables used during SCCHN management); (2) 1st-SC meeting (to select the variables for presentation during nominal groups-NG); (3) five NG (n=42 experts) and four interviews with patients (to reach consensus on the variables for inclusion); and (4) final-SC meeting (to review the results of NG ensuring consensus on the variables where consensus was not reached). Results: Experts agreed to include the following variables in the standard set: treatment-related (treatment intent and type, response to treatment, treatment toxicity/complication, treatment completion), degree of health (performance status, patient-reported health status, pain, dysphonia, feeding and speech limitations, body image alteration, tracheotomy), survival (overall and progression-free survival, cause of death), nutritional (weight, nutritional intervention), other variables (smoking status, alcohol consumption, patient satisfaction with aftermath care, employment status), and case-mix variables (demographic, tumor-related, clinical and nutritional factors). Conclusions: This project may pave the way to standardizing the collection of health outcomes in SCCHN and promote the incorporation of patients’ perspective in its management. The information provided through the systematic compilation of this standard set may define strategies to achieve high-quality, patient-centered care. The project was sponsored by Bristol Myers Squibb.

Simple Summary Drug resistance is the principal limiting factor to achieving good survival rates in patients with cancer. The identification of potential biomarkers for diagnosis and prognostic prediction, as well as the design of new molecular-targeted treatments, will be essential to improving head and neck squamous cell carcinoma (HNSCC) patient outcomes. In this sense, the sensitization of resistant cells and cancer stem cells (CSCs) represents a major challenge in cancer therapy. We conducted a proteomic study involving cisplatin-resistance and CSCs with the aim to unravel the molecular and cellular mechanisms by which tumor cells acquire resistance to chemotherapy. Syntenin-1 (SDCBP) was identified as an important protein involved in the chemoresistance and stemness of HNSCC tumors. Abstract To characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance.

Anticossos; Immunoteràpia; Càncer de cap i coll Anticuerpos; Inmunoterapia; Cáncer de cabeza y cuello Antibodies; Immunotherapy; Head and neck cancer Background Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study ( NCT02207530 ) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC. Patients and methods Immunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS). Results Among evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9–24.4); 29.4% (95% CI, 15.1–47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5–21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9–3.7) and 7.1 months (95% CI, 4.9–9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5–22.1) and 33.6% (95% CI, 24.8–42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up. Conclusion Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients. This study was supported by AstraZeneca.

Càncer de cèl·lules escatoses de cap i coll; Tractament en platí; Pacients adults Cáncer de células escamosas de cabeza y cuello; Tratamiento en platino; Pacientes adultos Cancer of scaly cells of head and neck; Platinum treatment; Adult patients El càncer de cap i coll (CCC) és una patologia heterogènia que agrupa als càncers de la cavitat nasal, sinus paranasals, oïda, glàndules salivars, cavitat oral, nasofaringe, orofaringe, hipofaringe i laringe. La histologia epidermoide o escatosa és la més freqüent (90% dels casos) i les seves localitzacions més freqüents són cavitat oral, orofaringe, hipofaringe i laringe. Els principals factors de risc relacionats amb el CCC són el consum de tabac i alcohol. També s'ha relacionat amb la infecció del virus del papil·loma humà subtipus 16 (VPH-16), en el cas de CCC d'orofaringe, constituint un factor pronòstic. Head and neck cancer (HCC) is a heterogeneous pathology that groups the cancers of the nasal cavity, sinuses, ear, salivary glands, oral cavity, nasopharynx, oropharynx, hypopharynx and larynx. Epidermoid or scratchy histology is the most frequent (90% of cases) and its most frequent locations are oral cavity, oropharynx, hypopharynx and larynx. The main risk factors related to the HCC are the consumption of tobacco and alcohol. Also it has been related to the infection of the human papilloma virus subtype 16 (HPV-16), in the case of HCC of oropharynx, constituting a prognostic factor El cáncer de cabeza y cuello (CCC) es una patología heterogénea que agrupa a los cánceres de la cavidad nasal, senos paranasales, oído, glándulas salivares, cavidad oral, nasofaringe, orofaringe, hipofaringe y laringe. La histología epidermoide o escamosa es la más frecuente (90% de los casos) y sus localizaciones más frecuentes son cavidad oral, orofaringe, hipofaringe y laringe. Los principales factores de riesgo relacionados con el CCC son el consumo de tabaco y alcohol. También se ha relacionado con la infección del virus del papiloma humano subtipo 16 (VPH-16), en el caso de CCC de orofaringe, constituyendo un factor pronóstico.

Tractament mèdic; Tractament amb irradiació; Càncer de cap i coll; Carcinoma de nasofaringe Tratamiento médico; Tratamiento con irradiación; Cáncer de cabeza y cuello; Carcinoma de nasofaringe Medical treatment; Irradiation treatment; Head and neck cancer; Nasopharyngeal carcinoma L’anomenat càncer de cap i coll engloba un grup de tumors malignes localitzats en diverses zones de les vies aerodigestives superiors: sins paranasals, nasofaringe, orofaringe (amígdala, paladar tou, base de la llengua), hipofaringe, laringe, cavitat oral (mucosa oral, geniva, paladar dur, llengua i terra de la boca) i glàndules salivals. L'objectiu d'aquest document és - Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi per al tractament del càncer d’orofaringe, hipofaringe, laringe i nasofaringe. - Disminuir la variabilitat terapèutica entre els pacients tractats en els diversos centres d’aquesta institució. - Implementar els resultats de la terapèutica en els pacients amb càncer de càvum, orofaringe, hipofaringe o laringe tractats d’acord amb les recomanacions d’aquesta guia.