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Introduction: Federated learning has the potential to perfrom analysis on decentralised data; however, there are some obstacles to survival analyses as there is a risk of data leakage. This study demonstrates how to perform a stratified Cox regression survival analysis specifically designed to avoid data leakage using federated learning on larynx cancer patients from centres in three different countries. Methods: Data were obtained from 1821 larynx cancer patients treated with radiotherapy in three centres. Tumour volume was available for all 786 of the included patients. Parameter selection among eleven clinical and radiotherapy parameters were performed using best subset selection and cross-validation through the federated learning system, AusCAT. After parameter selection, β regression coefficients were estimated using bootstrap. Calibration plots were generated at 2 and 5-years survival, and inner and outer risk groups’ Kaplan-Meier curves were compared to the Cox model prediction. Results: The best performing Cox model included log(GTV), performance status, age, smoking, haemoglobin and N-classification; however, the simplest model with similar statistical prediction power included log(GTV) and performance status only. The Harrell C-indices for the simplest model were for Odense, Christie and Liverpool 0.75[0.71–0.78], 0.65[0.59–0.71], and 0.69[0.59–0.77], respectively. The values are slightly higher for the full model with C-index 0.77[0.74–0.80], 0.67[0.62–0.73] and 0.71[0.61–0.80], respectively. Smoking during treatment has the same hazard as a ten-years older nonsmoking patient. Conclusion: Without any patient-specific data leaving the hospitals, a stratified Cox regression model based on data from centres in three countries was developed without data leakage risks. The overall survival model is primarily driven by tumour volume and performance status.

Purpose: The aim of this study is to present incidence, histological subtypes, survival rates, and prognostic factors based on a national cohort of patients with salivary gland carcinoma.Methods: All Danish patients with submandibular gland carcinoma diagnosed from 1990 to 2015 (n = 206) were included and analyzed following histological re-evaluation. Data were collected by the Danish Head and Neck Cancer Group (DAHANCA). Overall, disease-specific and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression.Results: The study population consisted of 109 (53%) men and 97 (47%) women, median age 62 years (range 11-102). Adenoid cystic carcinoma was the most frequent subtype (50%). Tumour classification T1/T2 (75%) and N0 (78%) was most frequent. The mean crude incidence was 0.17/100,000/year. Most patients (n = 194, 94%) were treated with primary surgery, and 130 (67%) received postoperative radiotherapy. The 5- and 10-year survival rates were for overall survival 64% and 41%, disease-specific survival 74% and 61%, and recurrence-free survival 70% and 56%, respectively. Survival rates were higher for adenoid cystic carcinoma compared to other subtypes, but the difference was not significant in multivariate analysis. Recurrence occurred in 69 patients, and 37 (53.6%) of them had recurrence in a distant site. Advanced T-classification and regional lymph-node metastases had significant negative impact on survival rates.Conclusion: The incidence of submandibular gland carcinoma in Denmark was 0.17/100,000/year and stable during the time period. The most frequent subtype was adenoid cystic carcinoma. Half of the recurrences presented in a distant site, and multivariate analysis confirmed that advanced stage was independent negative prognostic factor for recurrence and survival. Purpose: The aim of this study is to present incidence, histological subtypes, survival rates, and prognostic factors based on a national cohort of patients with salivary gland carcinoma.Methods: All Danish patients with submandibular gland carcinoma diagnosed from 1990 to 2015 (n = 206) were included and analyzed following histological re-evaluation. Data were collected by the Danish Head and Neck Cancer Group (DAHANCA). Overall, disease-specific and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression.Results: The study population consisted of 109 (53%) men and 97 (47%) women, median age 62 years (range 11-102). Adenoid cystic carcinoma was the most frequent subtype (50%). Tumour classification T1/T2 (75%) and N0 (78%) was most frequent. The mean crude incidence was 0.17/100,000/year. Most patients (n = 194, 94%) were treated with primary surgery, and 130 (67%) received postoperative radiotherapy. The 5- and 10-year survival rates were for overall survival 64% and 41%, disease-specific survival 74% and 61%, and recurrence-free survival 70% and 56%, respectively. Survival rates were higher for adenoid cystic carcinoma compared to other subtypes, but the difference was not significant in multivariate analysis. Recurrence occurred in 69 patients, and 37 (53.6%) of them had recurrence in a distant site. Advanced T-classification and regional lymph-node metastases had significant negative impact on survival rates.Conclusion: The incidence of submandibular gland carcinoma in Denmark was 0.17/100,000/year and stable during the time period. The most frequent subtype was adenoid cystic carcinoma. Half of the recurrences presented in a distant site, and multivariate analysis confirmed that advanced stage was independent negative prognostic factor for recurrence and survival.

Background: Patients with pre-existing severe mental disorders are significantly less likely to receive guideline-recommended cancer treatment and seems to have a significantly lower rate of cancer survival compared to patients with cancer without mental disorders.Aim: To perform a systematic review on barriers at patient-, provider- and system-levels in cancer trajectories of patients with pre-existing severe mental disorders.Method: A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).Results: Nine eligible studies were identified. Barriers at patient-level included lack of self-care and ability to recognize physical symptoms and signs. Provider-level barriers included stigma from health care professionals on mental disorders, whereas system-level barriers included fragmented health care and consequences of this.Conclusion: This systematic review found that barriers at patient-, provider- and system-levels exist in cancer trajectories for patients with severe mental disorders, causing disparities in cancer care. Further research is needed to improve cancer trajectories for patients with severe mental disorder. Background: Patients with pre-existing severe mental disorders are significantly less likely to receive guideline-recommended cancer treatment and seems to have a significantly lower rate of cancer survival compared to patients with cancer without mental disorders.Aim: To perform a systematic review on barriers at patient-, provider- and system-levels in cancer trajectories of patients with pre-existing severe mental disorders.Method: A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).Results: Nine eligible studies were identified. Barriers at patient-level included lack of self-care and ability to recognize physical symptoms and signs. Provider-level barriers included stigma from health care professionals on mental disorders, whereas system-level barriers included fragmented health care and consequences of this.Conclusion: This systematic review found that barriers at patient-, provider- and system-levels exist in cancer trajectories for patients with severe mental disorders, causing disparities in cancer care. Further research is needed to improve cancer trajectories for patients with severe mental disorder.

Purpose: Risk of subclinical disease decreases with increasing distance from the GTV in head- and-neck squamous cell carcinoma (HNSCC). Depending on individual patient anatomy, OAR sparing could be improved by reducing target coverage in regions with low risk of subclinical spread. Using automated multi-criteria optimization, we investigate patient-specific optimal trade-offs between target periphery coverage and OAR sparing. Methods: VMAT plans for 39 HNSCC patients were retrospectively created following our clinical three-target-level protocol: high-risk (PTV1), intermediate-risk (PTV2, 5 mm expansion from PTV1), and elective (PTV3). A baseline plan fulfilling clinical constraints (D 99 % ≥95 % for all PTVs) was compared to three plans with reduced PTV2 coverage (goals: PTV2 D 99 % ≥90 % or 85 %, or no PTV2) at the outer edge of PTV2. Plans were compared on PTV D 99 %, OAR D mean, and NTCP (xerostomia/dysphagia). Results: Trade-offs between PTV2 coverage and OAR doses varied considerably between patients. For plans with PTV2 D 99 % -goal 90 %, median PTV2 D 99 % was 91.5 % resulting in xerostomia (≥grade 4) and dysphagia (≥grade 2) NTCP decrease of median [maximum] 1.9 % [5.3 %] and 1.1 % [4.1 %], respectively, compared to nominal PTV2 D 99 % -goal 95 %. For PTV2 D 99 % -goal 85 % median PTV D 99 % was 87 % with NTCP improvements of 4.6 % [9.9 %] and 1.5 % [5.4 %]. For no-margin plans, PTV2 D 99 % decreased to 83.3 % with NTCP reductions of 5.1 % [10.2 %] and 1.4 % [6.1 %]. Conclusion: Clinically relevant, patient-specific reductions in OARs and NTCP were observed at limited cost in target under-coverage at the outermost PTV edge. Given the observed inter-patient variations, individual evaluation is warranted to determine whether trade- offs would benefit a specific patient.

50% of patients with locally advanced HNSCC eventually present with disease recurrence or metastasis. Interaction of programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), allows tumour cells to evade immune attack by inhibiting T-cell activation. PD-1/PD-L1 checkpoint inhibitors block this immunosuppressive effect. This study aims to investigate the efficacy of anti-PD-1/PD-L1 agents for recurrent/metastatic (R/M) HNSCC in terms of survival, toxicity, and response. It will test the hypothesis that immunotherapy improves treatment outcomes for R/M HNSCC patients.Studies were identified through an electronic search of databases EMBASE and Medline. Data on survival, response and toxicity following PD-1/PD-L1 inhibition was extracted from included studies and compared. A subgroup meta-analysis compared these outcomes in PD-1/PD-L1 inhibition versus the standard of care (SOC).Thirteen studies (Based on the observed safety and efficacy, PD-1/PD-L1 checkpoint inhibition improves treatment outcomes for R/M HNSCC patients. PD-1/PD-L1 inhibitors significantly prolonged survival and reduced toxicity compared to the SOC, however further randomised trials are needed to investigate their role in HNSCC.

Introduction: The aim of this study was to investigate phase IV efficacy, of the PD-1 inhibitor nivolumab among an unselected and unbiased national cohort of recurrent/metastatic Head and Neck Squamous Cell Carcinoma (rmHNSCC) patients. Material and Methods: Inclusion criteria included histologically confirmed rmHNSCC and nivolumab as a second-line palliative treatment. Data were collected from patient files at the five Danish head and neck cancer centers and from the DAHANCA database. The iRECIST criteria were used for treatment evaluation. Endpoints were response rate (RR), overall survival (OS), and progression-free survival (PFS), calculated from the start of treatment to the date of event/censoring by the KM-method. Descriptive statistics were used to describe patients and treatment. Analyses were two-sided, with p

Prediction models are useful to design personalised treatment. However, safe and effective implementation relies on external validation. Retrospective data are available in many institutions, but sharing between institutions can be challenging due to patient data sensitivity and governance or legal barriers. This study validates a larynx cancer survival model performed using distributed learning without any sensitive data leaving the institution.Open-source distributed learning software based on a stratified Cox proportional hazard model was developed and used to validate the Egelmeer et al. MAASTRO survival model across two hospitals in two countries. The validation optimised a single scaling parameter multiplied by the original predicted prognostic index. All analyses and figures were based on the distributed system, ensuring no information leakage from the individual centres. All applied software is provided as freeware to facilitate distributed learning in other institutions.1745 patients received radiotherapy for larynx cancer in the two centres from Jan 2005 to Dec 2018. Limiting to a maximum of one missing value in the parameters of the survival model reduced the cohort to 1095 patients. The Harrell C-index was 0.74 (CI95%, 0.71-0.76) and 0.70 (0.66-0.75) for the two centres. However, the model needed a scaling update. In addition, it was found that survival predictions of patients undergoing hypofractionation were less precise.Open-source distributed learning software was able to validate, and suggest a minor update to the original survival model without central access to patient sensitive information. Even without the update, the original MAASTRO survival model of Egelmeer et al. performed reasonably well, providing similar results in this validation as in its original validation.

We aim to investigate the current state of brachytherapy (BT) training among the radiation oncology trainees in Europe. Material and methods: A 22-question online survey based on the one by the American Association of Radiation Oncology Residents (2017) with added queries pertinent to training in Europe was sent to 1450 residents in two iterations. These included site-specific training, volume of experience, barriers to training, institutional support, and preferences for further education. Responses to individual statements were given on a 1 to 5 Likert-type scale. The answers were reported by junior (≤3 years of training) and senior years of training (year of training 4/5/6 and junior staff). Descriptive statistics were used to describe frequencies. Results: Residents from 21 European countries participated, 445 (31%) responded. 205 (47%) were senior residents. 60% residents consider that performing BT independently at the end of residency is very or somewhat important. Confidence in joining a brachytherapy practice at the end of residency was high or somewhat high in 34% of senior residents. They reported as barriers to achieving independence in BT to be lack of appropriate didactic/procedural training from supervisors (47%) and decreased case load (31%). 68% reported their program lacks a formal BT curriculum and standardized training assessment. Conclusions: Residents in Europe, feel independent BT practice is very or somewhat important, but do not feel confident they will achieve this goal. To address this gap, efforts are needed to develop and implement a formal and comprehensive BT curriculum with easy access to trained instructors.

© 2022 The AuthorsSurvivors of head and neck cancer can experience long-term consequences of the cancer and subsequent treatments even after the cancer has resolved. Increasingly clinicians are aware of the social, psychological, financial, and emotional impacts of these cancers, in addition to the support required for the physical symptoms. This review provides recommendations on the long-term management and support required for survivors of head and neck cancer in the European healthcare setting.

Purpose To develop a European White Paper document on oropharyngeal dysphagia (OD) in head and neck cancer (HNC). There are wide variations in the management of OD associated with HNC across Europe. Methods Experts in the management of specific aspects of OD in HNC across Europe were delegated by their professional medical and multidisciplinary societies to contribute to this document. Evidence is based on systematic reviews, consensus-based position statements, and expert opinion. Results Twenty-four sections on HNC-specific OD topics. Conclusion This European White Paper summarizes current best practice on management of OD in HNC, providing recommendations to support patients and health professionals. The body of literature and its level of evidence on diagnostics and treatment for OD in HNC remain poor. This is in the context of an expected increase in the prevalence of OD due to HNC in the near future. Contributing factors to increased prevalence include aging of our European population (including HNC patients) and an increase in human papillomavirus (HPV) related cancer, despite the introduction of HPV vaccination in various countries. We recommend timely implementation of OD screening in HNC patients while emphasizing the need for robust scientific research on the treatment of OD in HNC. Meanwhile, its management remains a challenge for European professional associations and policymakers.

Aims: Curative-intent radiotherapy (RT) or chemoradiation (CRT) of squamous cell carcinoma of the head and neck (HNSCC) produces high survival rates, but is associated with substantial toxicity. However, there are no commonly accepted quality metrics for early mortality in radiation oncology. To assess the applicability of early mortality as a clinical quality indicator, this study investigated the temporal distribution, risk factors and trends of 90- and 180-day overall and non-cancer mortality in a nationwide cohort of HNSCC patients treated with RT/CRT. Materials and methods: Information on all HNSCC patients treated with curative-intent RT/CRT in Denmark between 2000 and 2017 was obtained from the national Danish Head and Neck Cancer Group clinical database. Deaths in patients with residual or recurrent disease after RT/CRT were classified as cancer-related. Possible risk factors were investigated using logistic regression analysis. Results: Data from 11 419 patients were extracted. In total, 90- and 180-day mortality risks were 3.1% and 7.1%, respectively. There was a uniform temporal distribution of 180-day mortality. In multivariable analysis, increasing age, stage, performance status, earlier treatment year and hypopharyngeal cancer were significantly associated with an increased risk (P < 0.05). Risk factor estimates were comparable for 90- versus 180-day mortality as well as for overall versus non-cancer mortality. Between 2000 and 2017 there was a significant decrease in 180-day mortality, which was driven by a reduction in cancer-related events. Conclusion: The distribution of 180-day overall and non-cancer mortality did not indicate a well-defined early high-risk period. Moreover, risk factor estimates were highly similar across risk periods and groups. Taken together, our findings question the applicability of early mortality as a standard metric for treatment-associated toxicity.

The definition of tumor involved volumes in patients with head and neck cancer poses great challenges with the increasing use of highly conformal radiotherapy techniques eg, volumetric modulated arc therapy and intensity modulated proton therapy. The risk of underdosing the tumor might increase unless great care is taken in the process. The information gained from imaging is increasing with both PET and MRI becoming readily available for the definition of targets. The information gained from these techniques is indeed multidimensional as one often acquire data on eg, metabolism, diffusion, and hypoxia together with anatomical and structural information. Nevertheless, much work remains to fully exploit the available information on a patient-specific level. Multimodality target definition in radiotherapy is a chain of processes that must be individually scrutinized, optimized and quality assured. Any uncertainties or errors in image acquisition, reconstruction, interpretation, and delineation are systematic errors and hence will potentially have a detrimental effect on the entire radiotherapy treatment and hence; the chance of cure or the risk of unnecessary side effects. Common guidelines and procedures create a common minimum standard and ground for evaluation and development. In Denmark, the treatment of head and neck cancer is organized within the multidisciplinary Danish Head and Neck Cancer Group (DAHANCA). The radiotherapy quality assurance group of DAHANCA organized a workshop in January 2020 with participants from oncology, radiology, and nuclear medicine from all centers in Denmark, treating patients with head and neck cancer. The participants agreed on a national guideline on imaging for target delineation in head and neck cancer radiotherapy, which has been approved by the DAHANCA group. The guidelines are available in the Supplementary. The use of multimodality imaging is being recommended for the planning of all radical treatments with a macroscopic tumor. 2-[18F]FDG-PET/CT should be available, preferable in the treatment position. The recommended MRI sequences are T1, T2 with and without fat suppression, and T1 with contrast enhancement, preferable in the treatment position. The interpretation of clinical information, including thorough physical examination as well as imaging, should be done in a multidisciplinary setting with an oncologist, radiologist, and nuclear medicine specialist.

We compare outcomes in two large-scale contemporaneously-treated HPV-positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemo-radiotherapy (RT/CRT). p16-confirmed HPV+ OPC treated between 2007-2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted-hazard-ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack-years, T- and N-category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM-8 T-categories (T1-2:77% vs 56%), N-categories (N0-N1: 77% vs 67%), and stages (stage I: 63% vs 44% (all P < 0.001). PMH used standard-fractionation CRT in 69% (481) while 31% (220) received hypo-fractionated or moderately-accelerated RT-alone. All DAHANCA patients were treated with moderately-accelerated RT; 96% (1129) received Nimorazole (NIM) and 73% (856) concurrent weekly Cisplatin. DAHANCA had shorter overall-treatment-time (P < 0.001), lower gross tumor (66-68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow-up was 4.8 years. DAHANCA had higher 5-year LRF (13% vs 7%, aHR = 0.47 [0.34-0.67]), comparable DM (7% vs 12%, aHR = 1.32 [0.95-1.82]), but better OS (85% vs 80%, aHR = 1.30 [1.01-1.68]). CRT patients had a lower risk of LRF (aHR 0.56 [0.39-0.82]), DM (aHR 0.70 [0.50-1.00]) and death (aHR 0.39 [0.29-0.52]) vs RT-alone. We observed exemplary outcomes for two large-scale trans-Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de-intensification of treatment for this disease. This article is protected by copyright. All rights reserved.

Purpose: To study the associations between development of moderate to severe skin rash, clinical outcome, and single nucleotide polymorphisms (SNPs) in candidate genes in head and neck cancer patients from the DAHANCA 19 trial receiving the EGFR-inhibitor zalutumumab concurrently with radiation treatment. Material and methods: 310 patients were included from the zalutumumab-arm of the DAHANCA 19 study. Nine SNPs in the candidate genes EGFR, EGF, AREG, FCGR2A, FCGR3A, and CCND1 were successfully determined in 294 patients. Clinical endpoints were moderate to severe skin rash within the first 3 weeks of treatment, loco-regional failure (LRF), disease-specific survival (DSS), and overall survival (OS). Results: During the first 3 weeks of treatment, 86% of the patients experienced any grade of rash and 17% experienced a moderate to severe rash. Development of moderate to severe rash was not associated with LRF or DSS but was associated with improved OS, HR 0.40 (95% CI: 0.19–0.82). The effect was similar for patients with p16-negative or p16-positive tumors (p = .90). After adjustment for comorbidity and performance status, the minor alleles of SNPs rs9996584 and rs13104811 located near the AREG gene were significantly associated with increased risk of moderate to severe rash with per-allele odds ratios of 1.61 (1.01–2.54) and 1.56 (1.00–2.44). SNP rs11942466 located close to rs9996584 had a borderline significant association, and none of the other SNPS were significantly associated with risk of skin rash. Conclusions: Moderate to severe skin rash after zalutumumab during radiation treatment was associated with improved OS, independent of HPV/p16-status. Genetic variants in AREG (member of the EGF family) may be associated with increased risk of skin rash.

Cancer care; Curriculum; Surgical oncology Cuidado del cancer; Plan de estudios; Oncología quirúrgica Cura del càncer; Pla d'estudis; Oncologia quirúrgica Introduction Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology. Material and methods The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts. Results The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology. Conclusions As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients.

INTRODUCTION: In 2017 it was decided to revise the European Core Curriculum for Radiation Oncology/Radiotherapy to produce a 4th edition. The aims of the ESTRO curriculum are to develop comparable standards for training across Europe and to facilitate free movement of specialists across borders. It is also hoped that it will improve the level of training across Europe and will make the non-medical expert roles more explicit.MATERIALS AND METHODS: A wide range of stakeholders including National Society representatives, trainees, recently appointed specialists, members of the European Union Medical Specialists Radiotherapy section, an RTT, a radiobiologist, a physicist and lay members from ESTRO staff developed and commented on iterations of the curriculum.RESULTS: The 4th edition is based on the CanMEDS 2015 framework and identifies 14 Entrustable Professional Activities (EPAs) and the competencies required to perform these. The manager role is replaced by competencies related to leadership. The levels of proficiency required for tumour sites is defined as levels of EPAs.CONCLUSIONS: It is hoped that the inclusive method of developing the 4th edition has resulted in a document that will have utility in the wide range of environments in which radiation oncology is practised in Europe.

Background: In head and neck cancer, distant metastases may be present at diagnosis (M1) or occur after treatment (DM). It is unknown whether M1 and DM follow the same clinical development and share prognosis, as population-based studies regarding outcomes are scarce. Therefore, we investigated the incidence, location of metastases and overall survival of patients with M1 and DM. Materials and methods: Patients diagnosed with squamous cell carcinoma of the pharynx and larynx in Denmark 2008–2017 were identified in the Danish Head and Neck Cancer Group (DAHANCA) database. We identified 7300 patients, of whom 197 (3%) had M1 and 498 (8%) developed DM during follow-up. Results: The 5-year cumulative incidence of DM was 8%. 1- and 2-year overall survival for DM (27% and 13%) vs. M1 (28% and 9%) were equally poor. There was no significant difference in location of metastases for M1 and DM and the most frequently involved organs were lungs, bone, lymph nodes and liver, in descending order. In oropharyngeal squamous cell carcinomas, the location of metastases did not differ by p16-status. For p16-positive patients, 21% of DM occurred later than three years of follow-up compared to 7% of p16-negative patients. Conclusion: Incidence, location of metastases and prognosis of primary metastatic (M1) or post-treatment metastatic (DM) disease in pharyngeal and laryngeal squamous cell carcinoma are similar in this register-based study.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) undergoing radiotherapy (RT) or chemoradiation (CRT) may become immunocompromised. In this population-based study, we aimed to investigate the risk factors, microbiological aetiologies, prognosis and impact on early non-cancer mortality of bloodstream infections (BSIs) after RT/CRT.METHODS: Patients with HNSCC of the pharynx, larynx and oral cavity treated with curative-intent RT/CRT in Denmark between 2010 and 2017 and subsequent BSI episodes occurring within 18 months of RT/CRT initiation were identified in national registries.RESULTS: We included 5674 patients and observed 238 BSIs. Increasing age, stage and performance status were significantly associated with an elevated BSI risk, while sex, smoking and high-grade mucositis were not. Human papillomavirus-positive oropharyngeal cancer patients had a decreased risk. Staphylococcus aureus accounted for 34% of episodes occurring during the first 3 months. The 30-day post-BSI mortality rate was 26% (95% confidence interval: 19-32) and BSIs were involved in 10% of early non-cancer deaths.CONCLUSION: The risk of BSI development is associated with several patient- and disease-related factors and BSIs contribute considerably to early non-cancer mortality. Empiric antibiotic treatment regimens should prioritise coverage for S. aureus when treating suspected systemic infection in this population.

BACKGROUND: The aim was to identify prognostic factors and test three prognostic scoring models that predicted the risk of recurrence in patients with parotid gland carcinoma.METHODS: All Danish patients with parotid gland carcinoma, treated with curative intent, from 1990 to 2015 (n = 726) were included. Potential prognostic factors were evaluated using Cox regression and competing risk analyses. The concordance of each prognostic model was estimated using Harrel's C index.RESULTS: The study population consisted of 344 men and 382 women, with a median age of 63 years. Age above 60 years, high grade histology, T3/T4 tumor, regional lymph node metastases, and involved surgical margins were all associated with a significant reduction in recurrence-free survival. The prognostic model that agreed best with actual outcomes had a C-index of 0.76.CONCLUSION: Prognostic scoring models may improve individualized follow-up strategies after curatively intended treatment for patients with parotid gland carcinoma.

Purpose: Salivary gland carcinoma is a rare disease and studies on epidemiology and outcome require data collection over many years. The aim of this study is to present an update of incidence rates, anatomical sites, histological subtypes, and survival rates based on the Danish national cohort of salivary gland carcinoma patients. Methods: Data from all Danish patients with salivary gland carcinoma diagnosed from 1990 to 2015 (n = 1601) were included and analyzed following histological reevaluation and reclassification. Overall, disease-specific, and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. Results: The study population consisted of 769 men and 832 women, median age 62 years (range 6–102). The most frequent anatomic site was the parotid gland (51.8%). Adenoid cystic carcinoma was the most common subtype (24.7%). The majority had tumor classification T1/T2 (65.3%). The mean crude incidence was 1.2/100.000/year with an increase of 1.5% per year. There was no increase in age-adjusted incidence. The 5-, 10-, and 20-year survival rates were for overall survival 68, 52, and 35%, for disease-specific survival, 77, 69, and 64%, and for recurrence-free survival, 75, 64, and 51%, respectively. Age, high-grade histological subtype, advanced T-classification, cervical lymph node metastases, vascular invasion, and involved surgical margins had significantly negative impact on survival rates. Conclusion: The age-adjusted incidence has been stable for a period of 26 years. Multivariate analysis confirmed that histological grade, advanced stage, involved surgical margins and vascular invasion are independent negative prognostic factors. Survival rates were stationary compared to earlier reports.

BACKGROUND: Elective neck dissection (END) in patients with salivary gland carcinoma is controversial and there are no universally accepted guidelines.METHODS: Patients were identified from the Danish Head and Neck Cancer Group. Between 2006 and 2015, 259 patients with primary salivary gland carcinoma were treated with END. Variables potentially associated with regional metastases were analyzed using logistic regression. Neck recurrence-free survival was calculated using the Kaplan-Meier method.RESULTS: Occult metastases were found in 36 of the patients treated with END (14%) and were particularly frequent among patients with T3/T4 tumors and high-grade histology tumors. In multivariate analyses, high-grade histology and vascular invasion were associated with occult metastases.CONCLUSION: We recommend END of levels II and III for patients with high-grade or unknown histological grade tumors, and for T3/T4 tumors. Levels I, II, and III should be included in END in patients with submandibular, sublingual, or minor salivary gland carcinomas.

Background and purpose: Global curricula exist across medical specialties however, the factors which influence their implementation are not well understood. The purpose of this study is to report the perceived factors that impact the implementation of the ESTRO Core Curriculum.Methods: An anonymous, 37-item, survey was designed and distributed to the Presidents of the National Societies who have endorsed the ESTRO Core Curriculum (n = 29). The survey addressed perceptions about implementation factors related to context, process and curriculum change. The data was summarized using descriptive statistics.Results: Twenty-six (90%) National Societies completed the survey. One respondent perceived that the values of the training system of their country would be incompatible with the proposed ESTRO Core Curriculum. The most common contextual barriers to implementation was a lack of support from the government (57%), a lack of internal organizational support (35%) and a 'poor fit' between the ESTRO Core Curriculum and the broader political and economic context (35%). Perceived implementation process barriers included insufficient numbers of faculty (44%), poor coordination between the government and training institutions (48%), and a lack of an influential person leading the implementation (44%). Two barriers related to curriculum change were a lack of funding and lack of assessment tools.Conclusions: The content and values espoused in the ESTRO Core Curriculum are endorsed across diverse geopolitical and sociocultural regions. Barriers to curricular implementation are identified at the organizational and systems level and include insufficient teaching faculty, lack of coordination and the need for influential leadership. (c) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 147 (2020) 118-122

PURPOSE/OBJECTIVE: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis.MATERIALS/METHODS: Mucosal toxicity scores were prospectively recorded for 802 consecutive Head and Neck (H&N) cancer patients and dichotomised into non-severe event (grade 0-2) and severe event (grade 3+) groups. Two different model approaches were utilised to evaluate the robustness of the models. These used LASSO and Best Subset selection combined with 10-fold cross-validation performed on two-thirds of the patient cohort using principal component analysis of DVHs. The remaining one-third of the patients were used for validation. Model performance was tested through calibration plot and model performance metrics.RESULTS: The main predicted risk factors were treatment acceleration and the first two principal dose components, which reflect the mean dose and the balance between high and low doses to the oral cavity. For the LASSO model, gender and current smoker status were also included in the model. The AUC values of the two models on the validation cohort were 0.797 (95%CI: 0.741-0.857) and 0.808 (95%CI: 0.749-0.859), respectively. The two models predicted very similar risk values with an internal Pearson coefficient of 0.954, indicating their robustness.CONCLUSIONS: Robust prediction models of the risk of severe mucositis have been developed based on information from the entire dose distribution for a large cohort of patients consisting of all patients treated H&N for within our institution over a five year period.

Dysphagia is a significant late morbidity following treatment with radiotherapy (RT) for head and neck squamous cell carcinomas (HNSCC). The purpose of this feasibility study was to test a gel-based saliva substitute to reduce the subjective assessment of dysphagia while eating food items varying in size and texture. Eligible study subjects treated with curative intended RT and suffering from dysphagia and xerostomia were recruited from the outpatient clinic during a two-month period. Nineteen subjects consented to participation and completed the EORTC QLQ-H&N35 questionnaire and three test meals. A Numeric Rating Scale (NRS) was used for subjective assessment of dysphagia during all test meals. All data on patient, tumor, and treatment characteristics were obtained from the Danish Head and Neck Cancer (DAHANCA) database. NRS data suggested reduction of dysphagia after application of the oral gel. The swallowing dysfunctions, discomfort while swallowing (p = 0.008), stuck food items (p = 0.02), and multiple attempts of clearing the throat (p = 0.05), improved significantly for soft and regular items. Both small- and large-sized food items were tested. EORTC QLQ-H&N35 showed improvement regarding eating problems (p = 0.03) and social eating (p = 0.02). No episodes of food aspiration were recorded during the test meals. Late dysphagia reduces QOL and is an important morbidity following RT. In this feasibility study, the oral gel was able to reduce dysphagia while eating soft and selected regular food items. Eating-related EORTC QLQ-H&N35 items also improved, indicating a beneficial reduction in dysphagia after application of the oral gel. Electronic supplementary material The online version of this article (10.1007/s00455-019-10018-9) contains supplementary material, which is available to authorized users.

INTRODUCTION: The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins.MATERIALS AND METHODS: In total, 1576 patients completing radical primary IMRT for larynx, pharynx, oral cavity HNSCC in three centers in Denmark between 2006 and 2012 were included. CT-verified LRs were analyzed as possible points of recurrence origin and compared between groups of small (0-2.5 mm), larger (>2.5 mm), and anatomical GTV-CTV1 margins. The recurrence point's position relative to the GTV and 95% prescription dose was evaluated. Overall local control rate was evaluated using Cox uni- and multi-variate analysis.RESULTS: After a median follow-up of 41 months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7 mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface (p = 0.4) or the dose to LRs (p = 0.2) was detected between the groups. A difference in LC was found univariate between the centers (p = 0.03), but not in multivariate analysis (p = 0.4).CONCLUSIONS: No relation was found between the recurrences' distributions as function of the margins used at three centers. In multivariate analysis, local control was not influenced by the centers.

Introduction Clinical oncologists are physicians with the competencies to manage cancer patients through the entire disease pathway combining the competencies of radiation and medical oncologists. The 4th edition of the European Society for Radiotherapy and Oncology Core Curriculum for Radiation Oncology/Radiotherapy (ESTRO curriculum) has received wide support by the clinical oncology community. The aim was to develop a clinical oncology module that could be combined with the ESTRO curriculum to enable clinical oncology trainees to follow a single curriculum. Materials and methods A range of stakeholders including National Society representatives, an oncologist from a low- middle-income country, and a recently appointed specialist, developed and commented on iterations of the curriculum. Further modifications were made by the ESTRO Education Council. Results The module is based on the CanMEDS 2015 framework and identifies 20 enabling competencies in the Medical Expert role that are required in addition to the ESTRO curriculum for the training of clinical oncologists. Recommendations are made for the levels of Entrustable Professional Activities (EPAs) to be attained by the end of training. Conclusions The Clinical Oncology module, when combined with the ESTRO curriculum, covers the entire cancer pathway rather than being modality specific. It is hoped it will aid in the development of comparable standards of training in clinical oncology across Europe and may also have utility in low- and middle-income countries as well as providing a single curriculum for trainees.

Background: Radiotherapy plays an important role in the treatment of pharyngo-laryngeal and oral cavity head and neck squamous cell carcinoma (HNSCC) either as single modality, in combination with concomitant chemotherapy or epithermal growth factor inhibitor, or as adjuvant treatment after curative surgery. Various biological factors have been shown to impact on tumour response to radiotherapy, and among them tumour hypoxia. Aim: This article reviews the clinical data on measurement of tumour hypoxia and summarizes the various options to counteract it, with a special emphasis on the use of hypoxic cell radiosensitizers, radiation dose escalation, and the proper selection of patients who may benefit from such therapeutic interventions. Results: It has been shown that up to 25% of HNSCC express pO2 value below 2.5 mm Hg, and modification of tumour hypoxia has been demonstrated to improve loco-regional control and overall survival. In particular, the concomitant use of nimorazole, a hypoxic cell radiosensitizer, has been demonstrated in a seminal DAHANCA trial to significantly improve outcome in patients with head and neck SCC. More recently, among the patients included into this trial, a 15-gene hypoxia classifier indicated that only those patients with hypoxic tumours benefited from the combined radiotherapy and nimorazole treatment. Conclusions: An ongoing trial is validating both the use of nimorazole and the gene classifier for patients treated with concomitant chemo-radiotherapy.

The massive global shortfall in radiotherapy equipment and human resources in developing countries is an enormous challenge for international efforts in cancer control. This lack of access to treatment has been long-standing, but there is now a growing consensus about the urgent need to prioritize solutions to this problem and that a global strategy is required for them to be successful. An essential element of making radiotherapy universally accessible is a coordinated approach to clinical training and practice. This has been recently recognized by many university departments and clinical training programs. However, formalized training and career promotion tracks in global health within radiation oncology have been slow to emerge, thereby limiting the sustained involvement of students and faculty, and restricting opportunities for leadership in this space. We examine here potential structures and benefits of formalized global health training in radiation oncology. We explore how defining specific competencies in this area can help trainees and practitioners integrate their activities in global health within their existing roles as clinicians, educators, or scientists. This would also help create a new global health track for academic advancement, which could focus on such domains as implementation science, health service, and advocacy. We discuss how effective mentorship models, international partnerships, and institutional twinning arrangements support this work and explore how new resources and funding models might be used to further develop and expand radiation oncology services globally.