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Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.
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Países em Desenvolvimento , Neoplasias , Radioterapia (Especialidade) , Humanos , Países em Desenvolvimento/economia , Neoplasias/radioterapia , Radioterapia (Especialidade)/economia , Pesquisa Biomédica/economia , Radioterapia/economia , PobrezaRESUMO
BACKGROUND: Comprehensive cancer care requires effective collaboration by interprofessional healthcare teams. The need to develop educational initiatives to improve interprofessional collaboration is increasingly recognised. However, there is no agreement regarding the interprofessional competencies required for effective cancer care leading to much variation on the focus of research, planning and managing change. A scoping review was conducted to identify the current status of IPE in cancer care and to summarise the results of previous research in order to guide the development of interprofessional education in cancer care. METHODS: The JBI Scoping Review guidelines were used to guide the process of the review. A search of the available literature was conducted in CINAHL, MEDLINE (Ovid), PubMed, PsycInfo, Scopus databases from January 2012 to March 2023 to investigate IPE for health professional clinicians working in cancer care. RESULTS: Of the 825 initial references and 153 studies imported for screening, a total of 28 studies were included in the final review. From those studies, seven focused on the need for IPE and interprofessional competence for oncology healthcare professionals, four reviewed existing IPE programs and 17 described the development and evaluation of interprofessional education. Findings show variation and lack of concept definitions underpinning research in IPE in cancer care settings. Variation also exists in the range of research activities in IPE, most notably related to communication, teamwork and the development of interprofessional practice. The evaluation of impact of IPE is mainly focused on health care professionals' self-evaluation and general feedback. Impact on patient care was only evaluated in one study. CONCLUSIONS: Based on the results, interprofessional education research in the field of cancer care is limited in Europe. Thus, there is a significant increase in publications in the last five years. A more systematic focus on the theoretical framework and definition of concepts would be of value. Research and programme development should be based on a shared understanding on what constitutes the interprofessional competences and IPE. Programmes to develop interprofessional practice should be developed and implemented systematically with inclusion of validated assessment methods, and evaluated and improved regularly.
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Relações Interprofissionais , Neoplasias , Equipe de Assistência ao Paciente , Humanos , Neoplasias/terapia , Educação Interprofissional , Oncologia/educação , Pessoal de Saúde/educação , Comportamento CooperativoRESUMO
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.
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Transtornos Mentais , Neoplasias , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Atenção à Saúde , Pessoal de Saúde , Neoplasias/terapiaRESUMO
INTRODUCTION: The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19. MATERIALS AND METHODS: We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel. RESULTS: HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected.Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7). CONCLUSION: In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas/patologia , Imuno-Histoquímica , Prognóstico , Papillomavirus Humano , DNA , Inibidor p16 de Quinase Dependente de CiclinaRESUMO
BACKGROUND: Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. METHODS AND MATERIALS: A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. RESULTS: Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation.Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. CONCLUSION: The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a 'data processor', meaning that it is a tool for other research projects to use rather than a research project in and of itself.
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Radioterapia (Especialidade) , Radioterapia , Humanos , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. MATERIALS AND METHODS: The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. RESULTS: The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 - 0.90] and 0.68 [0.51 - 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 - 1.1] mm and 1.9 mm [1.5 - 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in ΔNTCP. CONCLUSIONS: The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the ΔNTCP calculations could be discerned.
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Inteligência Artificial , Neoplasias de Cabeça e Pescoço , Humanos , Órgãos em Risco , Prótons , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
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.
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Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Salivares , Masculino , Humanos , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/terapia , Prognóstico , Glândula Submandibular , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/terapia , Taxa de Sobrevida , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologiaRESUMO
We compare outcomes in two large-scale contemporaneously treated HPV-positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16-confirmed HPV+ OPC treated between 2007 and 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-category and N-category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM-8T-categories (T1-T2: 77% vs 56%), N-categories (N0-N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P < .001). PMH used standard-fractionation CRT in 69% (481) while 31% (220) received hypofractionated 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 < .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.
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Quimiorradioterapia/métodos , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologiaRESUMO
PURPOSE: A two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT. MATERIALS AND METHODS: The analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site. RESULTS: We found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48-2.41; ppooled = 4.34 × 10-16). CONCLUSION: This first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted.
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Neoplasias de Cabeça e Pescoço , Mucosite , Radioterapia (Especialidade) , Estudo de Associação Genômica Ampla , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/radioterapia , HumanosRESUMO
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 < .05 considered significant. RESULTS: A total of 146 patients were identified in the period 2017-2020. They had a RR of 14%, median OS of 10.2 months [95% CI: 8.2-12.2] and median PFS of 3.1 months [95% CI: 2.3-4.2]. Patient age (≥ 70 years) or comorbidity did not significantly affect outcome. WHO performance status (PS) =1 was associated with an increased risk of death (HR: 2.1 [95% CI: 1.2-4.0], p = .02) and progression (HR: 1.9 [95% CI: 1.2-3.2], p = .01). Concomitant glucocorticoid-treatment during immunotherapy (≥ 50% of treatment time) appeared important for risk of death (HR: 6.4 [95% CI: 2.3-17.8], p < .001) and risk of progression (HR: 4.8 [95% CI: 1.8-12.5], p = .001). PD-L1 expression ≥ 20% was associated with a lowered risk of progression (HR: 0.5 [95% CI: 0.3-0.7], p = .001), but not lowered risk of death. CONCLUSION: In this unselected national cohort, outcome of second-line treatment reflects data from the registration studies. Furthermore, the results suggest that immunotherapy should be used with great care in treatment of rmHNSCC in patients with poor performance.
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Neoplasias de Cabeça e Pescoço , Nivolumabe , Idoso , Estudos de Coortes , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
The ESO-ESSO-ESTRO Multidisciplinary Course in Oncology is intended to fill the gap of the undergraduate fragmented oncology education, to provide insight into all theoretical and practical aspects of oncology, and to encourage future professional choices towards an oncology discipline. Students are exposed to (a) preclinical cancer topics; (b) natural history of the disease; (c) laboratory diagnostic tests; (d) medical, radiation, surgical, and palliative treatment; and (e) direct or through multidisciplinary patients' approach. Students are obliged to attend (i) all theoretical lectures, (ii) clinical case presentations, (iii) laboratories and ward visits, and (iv) to prepare and present a specific project under supervision. Participation is limited to 24 medical students who are selected through a competitive application process. Between 2016 and 2019, 96 students from 29 countries have attended. Data analysis derived from a given questionnaire demonstrates that most of the participants have declared that (1) they have achieved their expectations and objectives, (2) they have highly rated both clinical and non-clinical teaching oncological topics, and (3) they have been stimulated in developing a professional career in the field of oncology.
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Educação de Graduação em Medicina , Neoplasias , Estudantes de Medicina , Currículo , Humanos , Estudos Interdisciplinares , Oncologia/educação , Neoplasias/terapia , Cuidados PaliativosRESUMO
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.
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Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Infecções por Papillomavirus/epidemiologia , Sepse/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Quimiorradioterapia/efeitos adversos , Bases de Dados Factuais , Dinamarca/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radioterapia/efeitos adversos , Sistema de Registros , Fatores de Risco , Sepse/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Análise de SobrevidaRESUMO
INTRODUCTION: 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. MATERIAL AND METHODS: 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). RESULTS: Thirteen studies (n = 1798) were included in this review. Overall survival following PD-1/PD-L1 checkpoint inhibition ranged from 6 to 13 months. The most common treatment-related adverse events (TRAEs) were fatigue, hypothyroidism and nausea; Grade ≥3 TRAEs occurred in 13% of patients. Meta-analysis of RCTs showed that anti-PD-1/PD-L1 agents improved survival and reduced toxicity compared to the SOC. This was demonstrated by a 37% lower risk of death (OR = 0.63, 95% CI = 0.51-0.78, I2 = 18%, p ≤ 0.0001) and a 77% lower risk of any-grade TRAEs (OR = 0.23, 95% CI = 0.18-0.29, I2 = 90%, p ≤ 0.00001) with immunotherapy versus SOC. DISCUSSION: 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.
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Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Manual delineation of gross tumor volume (GTV) is essential for radiotherapy treatment planning, but it is time-consuming and suffers inter-observer variability (IOV). In clinics, CT, PET, and MRI are used to inform delineation accuracy due to their different complementary characteristics. This study aimed to investigate deep learning to assist GTV delineation in head and neck squamous cell carcinoma (HNSCC) by comparing various modality combinations. MATERIALS AND METHODS: This retrospective study had 153 patients with multiple sites of HNSCC including their planning CT, PET, and MRI (T1-weighted and T2-weighted). Clinical delineations of gross tumor volume (GTV-T) and involved lymph nodes (GTV-N) were collected as the ground truth. The dataset was randomly divided into 92 patients for training, 31 for validation, and 30 for testing. We applied a residual 3 D UNet as the deep learning architecture. We independently trained the UNet with four different modality combinations (CT-PET-MRI, CT-MRI, CT-PET, and PET-MRI). Additionally, analogical to post-processing, an average fusion of three bi-modality combinations (CT-PET, CT-MRI, and PET-MRI) was produced as an ensemble. Segmentation accuracy was evaluated on the test set, using Dice similarity coefficient (Dice), Hausdorff Distance 95 percentile (HD95), and Mean Surface Distance (MSD). RESULTS: All imaging combinations including PET provided similar average scores in range of Dice: 0.72-0.74, HD95: 8.8-9.5 mm, MSD: 2.6-2.8 mm. Only CT-MRI had a lower score with Dice: 0.58, HD95: 12.9 mm, MSD: 3.7 mm. The average of three bi-modality combinations reached Dice: 0.74, HD95: 7.9 mm, MSD: 2.4 mm. CONCLUSION: Multimodal deep learning-based auto segmentation of HNSCC GTV was demonstrated and inclusion of the PET image was shown to be crucial. Training on combined MRI, PET, and CT data provided limited improvements over CT-PET and PET-MRI. However, when combining three bimodal trained networks into an ensemble, promising improvements were shown.
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Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
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.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Laringe , Carcinoma de Células Escamosas/epidemiologia , Humanos , Faringe , Prognóstico , Estudos RetrospectivosRESUMO
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.
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Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/patologia , Criança , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
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.
Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Envelhecimento , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Europa (Continente)/epidemiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , PapillomaviridaeRESUMO
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.
Assuntos
Transtornos de Deglutição/tratamento farmacológico , Derivados da Hipromelose/administração & dosagem , Lubrificantes/administração & dosagem , Lesões por Radiação/tratamento farmacológico , Xerostomia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer , Transtornos de Deglutição/etiologia , Estudos de Viabilidade , Feminino , Géis , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Lesões por Radiação/etiologia , Saliva , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Resultado do Tratamento , Xerostomia/etiologiaRESUMO
Background: The study aimed to evaluate Hyperfractionated, Accelerated Radiotherapy (HART) with nimorazole for patients with head and neck squamous cell carcinoma (HNSCC) using loco-regional failure (LRF), overall survival (OS), early and late morbidity as endpoints. Material and methods: From February 2007 to January 2018, 295 patients with unresected HNSCC, T1-T4, N0-N3, M0, were treated with HART prescribed as 76 Gy in 56 fractions (fx), 10 fx weekly. IMRT was used in >90% of patients. No chemotherapy was given. Patients were prospectively registered in the DAHANCA database. Results: The median age was 64 years, 75% of patients were males. Primary sites were larynx (25%), pharynx (64%) and oral cavity (11%). In total, 59% were stage III-IV (UICC 2002). Of the 150 oropharyngeal cancer (OPC) patients, 42% were p16+. The proportion of patients receiving HART as planned was 97%. The median follow-up time was 66 months. Three-year actuarial LRF was 19% and OS was 66%. LRF was significantly higher for stage III-IV patients compared to stage I-II (25% vs. 11%, HR 2.12 [1.21-3.74]). The site-specific LRF rates were: for larynx 22% [12-32], hypopharynx 30% [16-45], non-p16+ oropharynx 15% [8-23], p16+ oropharynx 7% [1-13] and oral cavity 35% [18-53]. During therapy, 51% reported severe dysphagia and 60% required feeding tubes. The peak incidence of late, severe dysphagia and xerostomia was 21% and 9%, respectively. A comparison to historical data from previous DAHANCA trials showed that tumor control and morbidity are comparable to treatment with acceleration and/or chemo-radiation. Conclusions: HART represents an attractive approach for patients with HNSCC where treatment intensification is indicated.