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BACKGROUND: Chemotherapy-induced toxicities frequently occur in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Low skeletal muscle mass (SMM) has been associated with a higher incidence of toxicities for several types of cancers and cytostatics. The aim of this study was to evaluate the association between skeletal muscle measures and chemotherapy-induced toxicity in a large cohort of NSCLC patients. METHODS: A multicentre prospective follow-up study (PGxLUNG, NTR number NL5373610015) in NSCLC patients was conducted. Included were patients diagnosed with NSCLC (stage II-IV) treated with first-line platinum-based (cisplatin or carboplatin) chemotherapy of whom pretreatment imaging was available. Skeletal muscle area (SMA) segmentation was performed on abdominal imaging at the level of the third lumbar vertebra (L3). SMA at the level of L3 was corrected for squared height (m2 ) to yield the lumbar skeletal muscle mass index (LSMI). Skeletal muscle density (SMD) was calculated as the mean Hounsfield Unit (HU) of the segmented SMA. SMM and SMD were categorized as low, intermediate, and high, based on LSMI and mean HU tertiles, respectively. Chemotherapy-induced toxicity was scored using CTCAE v4.03 and categorized into haematological (anaemia, leukocytopenia, neutropenia, and thrombocytopenia), non-haematological (nephrotoxicity, neurotoxicity, and esophagitis), and dose-limiting toxicity (DLT) (treatment switch, delay, de-escalation, discontinuation, or hospitalization). The relationship between SMM, SMD, and toxicities was assessed with logistic regression modelling taking into account potential confounders like gender and body mass index (BMI). RESULTS: In total, 297 patients (male n = 167, median age 64 years) were included. Haematological toxicity grade 3/4 was experienced in 36.6% (n = 108) of the patients, 24.6% (n = 73) experienced any non-haematological toxicity grade ≥2, and 55.6% (n = 165) any DLT. Multivariate logistic regression analysis showed that low SMM (ORadj 2.41, 95% CI 1.31-4.45, P = 0.005) and age at diagnosis >65 years (ORadj 1.76, 95% CI 1.07-2.90, P = 0.025) were statistically significantly associated with overall haematological toxicity grade 3/4. No statistically significant associations were found between low SMM or low SMD and non-haematological toxicities. Low SMM (ORadj 2.23, 95% CI 1.23-4.04, P = 0.008) and high SMD (ORadj 0.41, 95% CI 0.23-0.74, P = 0.003) were statistically significantly associated with a higher respectively lower risk of DLT. CONCLUSIONS: Non-small cell lung cancer patients with pretreatment low SMM are at significant higher risk for haematological toxicities grade 3/4 and DLT. NSCLC patients with high SMD are at significant lower risk for DLT. Further studies should be aimed to investigate whether platinum dosing based on skeletal muscle measurements and/or improvement of pretreatment SMM/SMD could reduce the risk of toxicity without compromising efficacy.

Contains fulltext : 251419.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Tumor hypoxia results in worse local control and patient survival. We performed a digital, single-cell-based analysis to compare two biomarkers for hypoxia (hypoxia-inducible factor 1-alpha [HIF-1alpha] and pimonidazole [PIMO]) and their effect on outcome in laryngeal cancer patients treated with accelerated radiotherapy with or without carbogen breathing and nicotinamide (AR versus ARCON). MATERIALS AND METHODS: Immunohistochemical staining was performed for HIF-1alpha and PIMO in consecutive sections of 44 laryngeal cancer patients randomized between AR and ARCON. HIF-1alpha expression and PIMO-binding were correlated using digital image analysis in QuPath. High-density areas for each biomarker were automatically annotated and staining overlap was analyzed. Kaplan-Meier survival analyses for local control, regional control and disease-free survival were performed to predict a response benefit of ARCON over AR alone for each biomarker. RESULTS: 106 Tissue fragments of 44 patients were analyzed. A weak, significant positive correlation was observed between HIF-1alpha and PIMO positivity on fragment level, but not on patient level. A moderate strength correlation (r = 0.705, p < 0.001) was observed between the number of high-density staining areas for both biomarkers. Staining overlap was poor. HIF-1alpha expression, PIMO-binding or a combination could not predict a response benefit of ARCON over AR. CONCLUSION: Digital image analysis to compare positive cell fractions and staining overlap between two hypoxia biomarkers using open-source software is feasible. Our results highlight that there are distinct differences between HIF-1alpha and PIMO as hypoxia biomarkers and therefore suggest co-existence of different forms of hypoxia within a single tumor.

Introduction Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorexia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients. Methods We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC. Results A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to enhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome. Conclusion Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients.

Background: Inevitably, the emergence of COVID-19 has impacted non-COVID care. Because timely diagnosis and treatment are essential, especially for patients with head and neck cancer (HNC) with fast-growing tumours in a functionally and aesthetically important area, we wished to quantify the impact of the COVID-19 pandemic on HNC care in the Netherlands. Material and Methods: This population-based study covered all, in total 8468, newly diagnosed primary HNC cases in the Netherlands in 2018, 2019 and 2020. We compared incidence, patient and tumour characteristics, primary treatment characteristics, and time-to-treatment in the first COVID-19 year 2020 with corresponding periods in 2018 and 2019 (i.e. pre-COVID). Results: The incidence of HNC was nearly 25% less during the first wave (n = 433) than in 2019 (n = 595) and 2018 (n = 598). In April and May 2020, the incidence of oral cavity and laryngeal carcinomas was significantly lower than in pre-COVID years. There were no shifts in tumour stage or alterations in initial treatment modalities. Regardless of the first treatment modality and specific period, the median number of days between first visit to a HNC centre and start of treatment was significantly shorter during the COVID-19 year (26–28 days) than pre-COVID (31–32 days, p < 0.001). Conclusion: The incidence of HNC during the Netherlands’ first COVID-19 wave was significantly lower than expected. The expected increase in incidence during the remainder of 2020 was not observed. Despite the overloaded healthcare system, the standard treatment for HNC patients could be delivered within a shorter time interval.

Wai Tong Ng,1,2 Barton But,2 Horace CW Choi,3 Remco de Bree,4 Anne WM Lee,1,2 Victor HF Lee,1,2 Fernando López,5,6 Antti A Mäkitie,7– 9 Juan P Rodrigo,5,6 Nabil F Saba,10 Raymond KY Tsang,11 Alfio Ferlito12 1Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; 3Department of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; 4Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Otolaryngology, Hospital Universitario Central de Asturias (HUCA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, 33011, Spain; 6Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Madrid, 28029, Spain; 7Department of Otorhinolaryngology - Head and Neck Surgery, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 8Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 9Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; 10Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA; 11Division of Otorhinolaryngology, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 12Coordinator of the International Head and Neck Scientific Group, Padua, ItalyCorrespondence: Barton ButDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of ChinaTel +852 2255 4352Fax +852 2872 6426Email bbut@hku.hkIntroduction: Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC.Methods: The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles.Results: A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented.Conclusion: There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon.Keywords: machine learning, neural network, deep learning, prognosis, diagnosis, auto contouring

Andrés Coca-Pelaz,1 Justin A Bishop,2 Nina Zidar,3 Abbas Agaimy,4 Eloisa Maria Mello Santiago Gebrim,5,6 Vanni Mondin,7 Oded Cohen,8 Primož Strojan,9 Alessandra Rinaldo,10 Ashok R Shaha,11 Remco de Bree,12 Marc Hamoir,13 Antti A Mäkitie,14 Luiz P Kowalski,15 Nabil F Saba,16 Alfio Ferlito17 1Department of Otolaryngology, Hospital Universitario Central de Asturias-University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, IUOPA, CIBERONC, Oviedo (Asturias), Spain; 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; 4Institute of Pathology, Friedrich Alexander University Erlangen-Nürnberg, University Hospital, Erlangen, Germany; 5Otorhinolaryngology Department, National Institute of Rehabilitation, Mexico City, Mexico; 6Radiology Department, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil; 7ENT Clinic, Policlinico Città di Udine, Udine, Italy; 8ARM - Center for Otolaryngology - Head and Neck Surgery and Oncology, Assuta Medical Center, Tel Aviv, Affiliated with Ben Gurion University, Beer Sheva, Israel; 9Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia; 10University of Udine School of Medicine, Udine, Italy; 11Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 12Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The NetherlAnds; 13Department of Head and Neck Surgery, UC Louvain, St Luc University Hospital and King Albert II Cancer Institute, Brussels, Belgium; 14Department of Otorhinolaryngology, Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 15Head and Neck Surgery and Otorhinolaryngology Department, A C Camargo Cancer Center and Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil; 16Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA; 17International Head and Neck Scientific Group, Padua, ItalyCorrespondence: Andrés Coca-Pelaz, Department of Otolaryngology, Hospital Universitario Central de Asturias-University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, IUOPA, CIBERONC, Avenida de Roma s/n, Oviedo (Asturias), 33011, Spain, Email acocapelaz@yahoo.esIntroduction: 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.Materials and Methods: 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.Results: 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%).Conclusion: 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.Keywords: brain tumors, central nervous system, extraneural metastasis, extracranial metastasis, cervical lymph node metastasis