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Background: Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly in many western countries due to Human papillomavirus (HPV) and tobacco smoking, with a considerable overlap. Immunotherapy directed at the PD1/PD-L1 axis have shown promise in head and neck cancer and other cancer types. PD-L1 expression may indicate a poorer prognosis, and at the same time indicate a possible benefit of anti-PD-L1 immunotherapeutic agents. The primary aim of this study was to establish the prognostic effect of PD-L1 expression after primary curative radiotherapy alone.Material and methods: A cohort of 303 OPSCC patients treated with primary, curative intended radiotherapy was established. PD-L1 expression was evaluated by immunohistochemistry on formalin fixed, paraffin embedded tissue sections. PD-L1 positivity was defined as a Combined Positive Score (CPS) ≥1, indicating staining of either tumor cells, lymphocytes or macrophages.Results: Median follow-up was 5.3 years. With 199 deaths, there was no difference in overall survival between patients with PD-L1+ and PD-L1- tumors (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.0 [0.71-1.4]). Also, locoregional failure was similar between the two groups (aHR 1.1 [CI: 0.68 - 1.7]). Tumors were PD-L1+ in 76% of cases, significantly more among HPV p16+ tumors (82% vs. 70%, p = .01). Interestingly, higher prevalence of PD-L1+ expression was seen in HPV p16+ patients with <10 pack-years of tobacco-smoking (93%) compared to HPV p16+ smokers (76%) or HPV p16-negative patients (70%) (p = .003).Conclusion: PD-L1 expression had no prognostic significance in OPSCC patients treated with primary radiotherapy alone. A substantial proportion of OPSCC tumors show PD-L1 overexpression, especially in HPV p16+ tumors in patients with little or no smoking history.
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Alphapapillomavirus , Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/radioterapia , Neoplasias Orofaríngeas/radioterapia , Infecciones por Papillomavirus/complicaciones , Fumar Tabaco/efectos adversos , Anciano , Antígeno B7-H1/análisis , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/mortalidad , Intervalos de Confianza , Femenino , Estudios de Seguimiento , Papillomavirus Humano 16 , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/química , Neoplasias Orofaríngeas/etiología , Neoplasias Orofaríngeas/mortalidad , Infecciones por Papillomavirus/metabolismo , Pronóstico , Fumar Tabaco/metabolismoRESUMEN
INTRODUCTION: A significant part of patients with head and neck squamous cell carcinoma (HNSCC) develop recurrent disease after curative radiotherapy. We aimed to analyze loco-regional recurrence pattern by identifying possible points of recurrence origin by three different methods in relation to treatment volumes. MATERIAL AND METHODS: A total of 455 patients completed IMRT-based treatment for HNSCC from 2006 to 2012. A total of 159 patients had remaining cancer after IMRT, developed loco-regional recurrence or distant disease during follow-up. Among those, 69 patients with loco-regional recurrences had affirmative CT or PET/CT scan. Possible points of origin (POs) of the recurrences were identified on scans by two independent observers, estimated as center of mass and as maximum surface distance. The recurrence position was analyzed in relation to high-dose treatment volume (CTV1) and 95% of prescription dose. RESULTS: In total, 104 loco-regional recurrences (54 in T-site and 50 in N-site) were identified in 69 patients. Median time to recurrence for the 69 patients was 10 months. No clinically relevant difference was found between the four POs, with standard deviation between POs in x, y and z axes of 3, 3 and 6 mm. For recurrences inside CTV1, 0-5 mm and 5-10 mm outside CTV1 the standard deviation of dose differences between the POs were 1, 1.4 and 1 Gy, respectively. 56% and 25% of T-site and N-site recurrences were inside CTV1, respectively. Coverage by 95% prescription dose to high-dose treatment volume was achieved in 78% of T-site and 39% of N-site recurrences. CONCLUSIONS: For recurrences identified by possible points of recurrence origin, no significant difference between observer-based or mathematically estimated methods was found. More than half of T-site recurrences were inside high-dose treatment volume, whereas N-site recurrences were mainly outside.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Recurrencia Local de Neoplasia/diagnóstico , Radioterapia de Intensidad Modulada/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/etiología , Pronóstico , Dosificación RadioterapéuticaRESUMEN
Background The study was performed to determine the epidemiological, clinical, and histopathological characteristics and prognosis of primary mucosal melanoma of the head and neck (MMHN) in Denmark. Material and methods This was a national retrospective multicenter study of patients diagnosed with MMHN between 1982 and 2012 in Denmark. Data were retrieved from national databases and patient records. Incidence trends were examined for the entire period. We prepared survival curves and performed univariate and multivariate analysis for the period 1992-2012 to identify possible prognostic factors. Results No significant trends in incidence were found in the study period. The three-year overall and disease-free survival rates for MMHN were 46.5% and 35.5%, respectively. Negative margins was an independent predictor of disease-free survival, and age below 65, absence of distant metastases, and low overall TNM stage were predictors of overall survival. Radiotherapy did not improve survival significantly. Recurrence rates were high, even for patients with negative margins. Conclusions MMHN remains a rare disease with a poor prognosis, particularly for patients aged over 65, those with distant metastasis, and those with advanced TNM stage. Importantly, the rate of recurrence is lowest in patients with negative margins.
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Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/terapia , Melanoma/epidemiología , Melanoma/terapia , Anciano , Dinamarca/epidemiología , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Membrana Mucosa/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/mortalidad , Estudios RetrospectivosRESUMEN
Treatment planning is time-consuming and the outcome depends on the person performing the optimization. A system that automates treatment planning could potentially reduce the manual time required for optimization and could also provide a method to reduce the variation between persons performing radiation dose planning (dosimetrist) and potentially improve the overall plan quality. This study evaluates the performance of the Auto-Planning module that has recently become clinically available in the Pinnacle3 radiation therapy treatment planning system. Twenty-six clinically delivered head and neck treatment plans were reoptimized with the Auto-Planning module. Comparison of the two types of treatment plans were performed using DVH metrics and a blinded clinical evaluation by two senior radiation oncologists using a scale from one to six. Both evaluations investigated dose coverage of target and dose to healthy tissues. Auto-Planning was able to produce clinically acceptable treatment plans in all 26 cases. Target coverages in the two types of plans were similar, but automatically generated plans had less irradiation of healthy tissue. In 94% of the evaluations, the autoplans scored at least as high as the previously delivered clinical plans. For all patients, the Auto-Planning tool produced clinically acceptable head and neck treatment plans without any manual intervention, except for the initial target and OAR delineations. The main benefit of the method is the likely improvement in the overall treatment quality since consistent, high-quality plans are generated which even can be further optimized, if necessary. This makes it possible for the dosimetrist to focus more time on difficult dose planning goals and to spend less time on the more tedious parts of the planning process.
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Algoritmos , Simulación por Computador , Neoplasias de Cabeza y Cuello/radioterapia , Órganos en Riesgo/efectos de la radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Automatización , Humanos , Dosificación RadioterapéuticaRESUMEN
INTRODUCTION: Multidisciplinary and multi-professional collaboration is vital in providing better outcomes for patients The aim of the INTERACT-EUROPE Project (Wide Ranging Cooperation and Cutting Edge Innovation As A Response To Cancer Training Needs) was to develop an inter-specialty curriculum. A pilot project will enable a pioneer cohort to acquire a sample of the competencies needed. METHODS: A scoping review, qualitative and quantitative surveys were undertaken. The quantitative survey results are reported here. Respondents, including members of education boards, curriculum committees, trainee committees of European specialist societies and the ECO Patient Advisory Committee, were asked to score 127 proposed competencies on a 7-point Likert scale as to their value in achieving the aims of the curriculum. Results were discussed and competencies developed at two stakeholder meetings. A consultative document, shared with stakeholders and available online, requested views regarding the other components of the curriculum. RESULTS: Eleven competencies were revised, three omitted and three added. The competencies were organised according to the CanMEDS framework with 13 Entrustable Professional Activities, 23 competencies and 127 enabling competencies covering all roles in the framework. Recommendations regarding the infrastructure, organisational aspects, eligibility of trainees and training centres, programme contents, assessment and evaluation were developed using the replies to the consultative document. CONCLUSIONS: An Inter-specialty Cancer Training Programme Curriculum and a pilot programme with virtual and face-to-face components have been developed with the aim of improving the care of people affected by cancer.
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Competencia Clínica , Neoplasias , Humanos , Proyectos Piloto , Curriculum , Europa (Continente) , Neoplasias/terapiaRESUMEN
BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). METHODS: A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12â042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV-formerly SNP)-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was higher for prostate (17%, SE = 0.07), head and neck (27%, SE = 0.09), and breast (16%, SE = 0.09) cancers. We identified 130 suggestive associated SNVs with rSTATacute (5.0 × 10â8 < P < 1.0 × 10â5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size â0.17; P = 1.7 × 10â7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified 'RNA splicing via endonucleolytic cleavage and ligation' (P = 5.1 × 10â6, P = .079 corrected) as the top gene set associated with rSTATacute among all patients. In silico gene expression analysis showed that the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed P = .004 corrected; sun exposed P = .026 corrected). CONCLUSIONS: There is shared SNV-based heritability for acute radiation-induced toxicity across and within individual cancer sites. Future meta-genome-wide association studies among large radiation therapy patient cohorts are worthwhile to identify the common causal variants for acute radiotoxicity across cancer types.
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Estudio de Asociación del Genoma Completo , Neoplasias , Masculino , Humanos , Neoplasias/genética , Neoplasias/radioterapia , Mama , Predisposición Genética a la EnfermedadRESUMEN
Purpose: Effective leadership across all areas of radiation oncology (RO) is vital to fully realise the benefits of radiation therapy in cancer care. We report outcomes of a novel interdisciplinary leadership program designed for RO professionals under a global joint society initiative. Methods: The Foundations of Leadership in RO (FLiRO) program was designed for aspiring RO leaders. Initially delivered in a blended learning format, it was adapted to fully virtual in 2021. It comprised a webinar tutorial, on-line modules and homework followed by 'live' in-person/virtual workshops over an approximately 6-week period. Topics included personal awareness, effective teamwork, quality improvement skills, leading change and conflict management. An immediate post-program online survey was performed using Likert scales to measure self-reported educational value, interaction with others and the likely application of learning to practice. Open comments were invited. Results: 170 participants from 36 countries and 6 continents took part from 2018 to 2021 (99 doctors, 36 physicists, 32 radiation therapists/RTTs and 3 others). 141 (83%) participants responded to the post-program survey. Average weightings for responders' views on whether pre-determined learning objectives were met ranged from 4.30 to 4.61 on a 5-point scale (1 = 'not met at all' and 5 = completely met). For the question addressing potential value of learning for application to their workplace, 124 of 130 (95%) of responders indicated that FLIRO would be 'very useful' or 'extremely useful'. Conclusion: Initial evaluation of the FLiRO program supports its continuation and expansion with ongoing evolution based on emerging evidence around leadership education and participant feedback.
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Background: During the last decade, radiotherapy using MR Linac has gone from research to clinical implementation for different cancer locations. For head and neck cancer (HNC), target delineation based only on MR images is not yet standard, and the utilisation of MRI instead of PET/CT in radiotherapy planning is not well established. We aimed to analyse the inter-observer variation (IOV) in delineating GTV (gross tumour volume) on MR images only for patients with HNC. Material/methods: 32 HNC patients from two independent departments were included. Four clinical oncologists from Denmark and four radiation oncologists from Australia had independently contoured primary tumour GTVs (GTV-T) and nodal GTVs (GTV-N) on T2-weighted MR images obtained at the time of treatment planning. Observers were provided with sets of images, delineation guidelines and patient synopsis. Simultaneous truth and performance level estimation (STAPLE) reference volumes were generated for each structure using all observer contours. The IOV was assessed using the DICE Similarity Coefficient (DSC) and mean absolute surface distance (MASD). Results: 32 GTV-Ts and 68 GTV-Ns were contoured per observer. The median MASD for GTV-Ts and GTV-Ns across all patients was 0.17 cm (range 0.08-0.39 cm) and 0.07 cm (range 0.04-0.33 cm), respectively. Median DSC relative to a STAPLE volume for GTV-Ts and GTV-Ns across all patients were 0.73 and 0.76, respectively. A significant correlation was seen between median DSCs and median volumes of GTV-Ts (Spearman correlation coefficient 0.76, p < 0.001) and of GTV-Ns (Spearman correlation coefficient 0.55, p < 0.001). Conclusion: Contouring GTVs in patients with HNC on MRI showed that the median IOV for GTV-T and GTV-N was below 2 mm, based on observes from two separate radiation departments. However, there are still specific regions in tumours that are difficult to resolve as either malignant tissue or oedema that potentially could be improved by further training in MR-only delineation.
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BACKGROUND AND PURPOSE: We aimed to the genetic components and susceptibility variants associated with acute radiation-induced toxicities (RITs) in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We performed the largest meta-GWAS of seven European cohorts (n = 4,042). Patients were scored weekly during radiotherapy for acute RITs including dysphagia, mucositis, and xerostomia. We analyzed the effect of variants on the average burden (measured as area under curve, AUC) per each RIT, and standardized total average acute toxicity (STATacute) score using a multivariate linear regression. We tested suggestive variants (p < 1.0x10-5) in discovery set (three cohorts; n = 2,640) in a replication set (four cohorts; n = 1,402). We meta-analysed all cohorts to calculate RITs specific SNP-based heritability, and effect of polygenic risk scores (PRSs), and genetic correlations among RITS. RESULTS: From 393 suggestive SNPs identified in discovery set; 37 were nominally significant (preplication < 0.05) in replication set, but none reached genome-wide significance (pcombined < 5 × 10-8). In-silico functional analyses identified "3'-5'-exoribonuclease activity" (FDR = 1.6e-10) for dysphagia, "inositol phosphate-mediated signalling" for mucositis (FDR = 2.20e-09), and "drug catabolic process" for STATacute (FDR = 3.57e-12) as the most enriched pathways by the RIT specific suggestive genes. The SNP-based heritability (±standard error) was 29 ± 0.08 % for dysphagia, 9 ± 0.12 % (mucositis) and 27 ± 0.09 % (STATacute). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STATacute. PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STATacute (0.4 %). CONCLUSION: In HNC patients, acute RITs are modestly heritable, sharing 10 % genetic susceptibility, when PRS explains < 3 % of their variance. We identified numerus suggestive SNPs, which remain to be replicated in larger studies.
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Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Mucositis , Traumatismos por Radiación , Humanos , Estudio de Asociación del Genoma Completo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/complicaciones , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
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.
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Neoplasias de Cabeza y Cuello , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Radiofármacos , Planificación de la Radioterapia Asistida por Computador , Tomografía Computarizada por Rayos XRESUMEN
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.
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Neoplasias , Oncología por Radiación , Competencia Clínica , Curriculum , Europa (Continente) , Humanos , Oncología por Radiación/educaciónRESUMEN
OBJECTIVE: To investigate whether a 18F-FDG PET/CT (PET/CT)-based diagnostic strategy adds decisive new information compared to conventional imaging in the evaluation of salivary gland tumours and the detection of cervical lymph node metastases, distant metastases, and synchronous cancer in patients with salivary gland carcinoma. METHODS: The study was a blinded prospective cohort study. Data were collected consecutively through almost 3 years. All patients underwent conventional imaging-magnetic resonance imaging (MRI) and chest X-ray (CXR)-in addition to PET/CT prior to surgery. Final diagnosis was obtained by histopathology. MRI/CXR and PET/CT were interpreted separately by experienced radiologists and nuclear medicine physicians. Interpretation included evaluation of tumour site, cervical lymph node metastases, distant metastases, and synchronous cancer. RESULTS: Ninety-one patients were included in the study. Thirty-three patients had primary salivary gland carcinoma and eight had cervical lymph node metastases. With PET/CT, the sensitivity was 92% and specificity 29% regarding tumour site. With MRI/CXR, the sensitivity and specificity were 90% and 26%, respectively. Regarding cervical lymph node metastases in patients with salivary gland carcinoma, the sensitivity with PET/CT was 100% and with MRI/CXR 50%. PET/CT diagnosed distant metastases in five patients, while MRI/CXR detected these in two patients. Finally, PET/CT diagnosed two synchronous cancers, whereas MRI/CXR did not detect any synchronous cancers. CONCLUSIONS: Compared with MRI/CXR PET/CT did not improve discrimination of benign from malignant salivary gland lesions. However, PET/CT may be advantageous in primary staging and in the detection of distant metastases and synchronous cancers.
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Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de las Glándulas Salivales/patología , Adulto JovenRESUMEN
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.
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Curriculum , Educación de Postgrado en Medicina/normas , Oncología por Radiación/educación , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Europa (Continente) , Unión Europea , Humanos , Oncología por Radiación/normasRESUMEN
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 (0-2.5â¯mm), larger (>2.5â¯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 41â¯months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7â¯mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface (pâ¯=â¯0.4) or the dose to LRs (pâ¯=â¯0.2) was detected between the groups. A difference in LC was found univariate between the centers (pâ¯=â¯0.03), but not in multivariate analysis (pâ¯=â¯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.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Carcinoma de Células Escamosas/patología , Relación Dosis-Respuesta en la Radiación , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
PURPOSE: To assess safety, tolerability, pharmacokinetics and clinical activity of HuMax-EGFr in patients with SCCHN. PATIENTS AND METHODS: Twenty-eight patients with SCCHN were enrolled. The study comprised a single-dose escalation part for assessment of safety issues followed by a repeat dose extension including 4 weekly infusions at the same doses. Efficacy and metabolic response were evaluated according to RECIST by CT and FDG-PET. RESULTS: Most frequently reported adverse event was rash. All but one event were CTC grade 1 or 2 and a dose-dependent relationship was indicated. Duration of skin reactions varied from few days to 2 months. No DLTs were observed and MTD was not reached. In the two highest dose groups, 7 of 11 patients obtained a PR or SD and 9 patients obtained metabolic PR or SD. CONCLUSIONS: HuMax-EGFr can be safely administered in doses up to 8 mg/kg, and preliminary data on tumour response are encouraging.
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Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Células Escamosas/terapia , Receptores ErbB/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/terapia , Anciano , Anticuerpos Monoclonales/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Selección de Profesión , Países en Desarrollo , Salud Global , Accesibilidad a los Servicios de Salud , Oncología por Radiación/educación , Humanos , Oncología por Radiación/instrumentaciónRESUMEN
BACKGROUND AND PURPOSE: The need for radiation oncologists and other radiation oncology (RO) professionals to lead quality improvement activities and contribute to shaping the future of our specialty is self-evident. Leadership knowledge, skills and behaviours, like other competencies, can be learned (Blumenthal et al., 2012). The objective of this study was to define a globally applicable competency set specific to radiation oncology for the CanMEDS Leader Role (Frank et al., 2015). METHODS: A modified Delphi consensus process delivering two rounds of on-line surveys was used. Participants included trainees, radiation/clinical oncologists and other RO team members (radiation therapists, physicists, and nurses), professional educators and patients. RESULTS: 72 of 95 (76%) invitees from nine countries completed the Round 1 (R1) survey. Of the 72 respondents to RI, 70 completed Round 2 (R2) (97%). In R1, 35 items were deemed for 'inclusion' and 21 for 'exclusion', leaving 41 'undetermined'. After review of items, informed by participant comments, 14 competencies from the 'inclusion' group went into the final curriculum; 12 from the 'undetermined' group went to R2. In R2, 6 items reached consensus for inclusion. CONCLUSION: This process resulted in 20 RO Leader Role competencies with apparent global applicability. This is the first step towards developing learning, teaching and assessment tools for this important area of training.
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Curriculum , Técnica Delphi , Oncología por Radiación/educación , Competencia Clínica , Consenso , Femenino , Humanos , Liderazgo , MasculinoRESUMEN
BACKGROUND: Treatment plans for head and neck (H&N) cancer are highly complex due to multiple dose prescription levels and numerous organs at risk (OARs) close to the target. The plan quality is inter-planner dependent since it is dependent on the skills and experience of the dosimetrist. This study presents a blinded prospective clinical comparison of automatic (AU) and manually (MA) generated H&N VMAT plans made for clinical use. METHODS: MA and AU plans were generated for 30 consecutive patients in Pinnacle3 using the IMRT optimisation module and the new Autoplan module, respectively. The plan quality was blindedly compared by three senior oncologists and the best plan was selected for treatment of the patient. Planning time was measured as the active operator time used. The plan quality was analysed with DVH metrics and the dose delivery accuracy validated on the ArcCheck phantom. RESULTS: For twenty-nine out of the thirty patients the AU plan was chosen for treatment. Target doses were more homogenous with the AU plans and the OAR doses were significantly reduced, between 0.5 and 6.5 Gy. The average operator time spent on creating a manual plan was 64 min which was halved by Autoplan. The AU plans were more modulated as illustrated by an increase in MUs, which might cause the slightly lower pass rate of 97.7% in the ArcCheck measurements. CONCLUSIONS: Target doses were similar between MA and AU plan, while AU plans spared all OAR considerably better than the MA plans.
RESUMEN
BACKGROUND AND PURPOSE: Reduction of the overall treatment time of radiotherapy has increased locoregional control and disease specific survival in squamous cell carcinomas of the head and neck (HNSCC), but the response is heterogeneous. EGFr is often overexpressed in HNSCC and has been related to the repopulation taking place during radiotherapy. The aim of the current study was to address the influence of EGFr and histopathological differentiation when the overall treatment time of radiotherapy was moderately reduced. PATIENTS AND METHODS: Eight hundred and three patients with representative pretreatment tissue samples from the randomized DAHANCA 6 and 7 study of 5 vs. 6 fx/wk of radiotherapy. EGFr was visualized using immunohistochemistry and separated into high and low expression before correlation with clinical data. RESULTS: Tumors with high EGFr (84%) responded better to moderately accelerated radiotherapy, than carcinomas with low EGFr, using locoregional control as endpoint and a similar pattern was seen, stratifying by well/moderate vs. poor tumor differentiation. Therefore, a combined parameter was constructed showing a more prominent separation of response: tumors with high EGFr and well/moderate differentiation did benefit from moderate acceleration of treatment regarding locoregional control, HR 0.54 (0.37-0.78), whereas such an effect was not seen in tumors with low EGFr and/or poor differentiation, HR 0.8 (0.51-1.25). These results reflected the disease specific survival as well and were confirmed in multivariable analyses. CONCLUSIONS: Moderately accelerated fractionation is superior to conventional treatment in HNSCC but the response is heterogeneous and may be predicted by high expression of EGFr and well/moderate tumor differentiation.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Receptores ErbB/fisiología , Neoplasias de Cabeza y Cuello/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Transformación Celular Neoplásica , Receptores ErbB/biosíntesis , Femenino , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Representatives from countries and regions world-wide who have implemented modern competency-based radiation- or clinical oncology curricula for training medical specialists, met to determine the feasibility and value of an ongoing international collaboration. In this forum, educational leaders from the ESTRO School, encompassing many European countries adopting the ESTRO Core Curriculum, and clinician educators from Canada, Denmark, the United Kingdom, Australia and New Zealand considered the training and educational arrangements within their jurisdictions, identifying similarities and challenges between programs. Common areas of educational interest and need were defined, which included development of new competency statements and assessment tools, and the application of the latter. The group concluded that such an international cooperation, which might expand to include others with similar goals, would provide a valuable vehicle to ensure training program currency, through sharing of resources and expertise, and enhance high quality radiation oncology education. Potential projects for the Global Radiation Oncology Collaboration in Education (GRaCE) were agreed upon, as was a strategy designed to maintain momentum. This paper describes the rationale for establishing this collaboration, presents a comparative view of training in the jurisdictions represented, and reports early goals and priorities.