Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group

Breast cancer; Hypofractionation; RadiotherapyCàncer de mama; Hipofraccionament; RadioteràpiaCáncer de mama; Hipofraccionamiento; RadioterapiaIntroduction Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. Materials and methods Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. Results Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. Conclusion Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

A gender- based approach to the current situation of Spanish dentists

To determine the perception of Spanish dentists about the situation of the profession nowadays and how the changes occurred in dental workforce (in number and gender of the past twenty years) have affected their personal and professional lives, under a g

Gamma passing rates of daily EPID transit images correlate to PTV coverage for breast cancer IMRT treatment plans

The use of the transit image obtained with the electronic portal-imaging device (EPID) is becoming an extended method to perform in-vivodosimetry. The transit images acquired during each fraction can be comparedwith a predicted image, if available, or with a baseline image, usually theobtained in the first fraction.This work aims to study the dosimetric impact of thefailing fractions and to evaluate the appropriateness of using a baseline imagein breast plans.Material and methods:Twenty breast patients treated in a Halcyon were ret-rospectively selected. For each patient and fraction, the treatment plan wascalculated over the daily CBCT image.For each fraction,the differences respectto the treatment plan values of OARs and PTV dosimetric parameters wereanalyzed:¿Dmean,¿D95%,¿D98%,¿D2%,¿V36Gy,¿V38.5Gy, and¿V43.5Gy.Daily fractions were ranked according to the differences found in the dosimet-ric parameters between the treatment plan and the daily CBCT to establish thebest fraction.The daily transit images acquired in every fraction were comparedto the first fraction using the global gamma index with the Portal Dosime-try tool. The comparison was repeated using the best fraction image as abaseline.We assessed the correlation of the dosimetric differences obtained from theCBCT images-based treatment plans with the gamma index passing ratesobtained using first fraction and best fraction as baseline.Results:Average values of -11.6% [-21.4%, -3.3%] and -3.2% [-1.0%, -10.3%]for the¿PTVD98% and¿PTVD95% per every 10% decrease in the passingrate were found, respectively.When using the best fraction as baseline patients were detected with failingfractions that were not detected with the first fraction as baseline.Conclusion:The gamma passing rates of daily transit images correlate withthe coverage loss parameters in breast IMRT plans. Using first fraction imageas baseline can lead to the non-detectability of failing fractionsPeer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

Multimodality imaging fusion to guide stereotactic radioablation for refractory complex ventricular tachycardia

Hypertrophic cardiomyopathy; Multimodality imaging; Stereotactic radioablationMiocardiopatía hipertrófica; Imágenes multimodales; Radioablación estereotácticaMiocardiopatia hipertròfica; Imatges multimodals; Radioablació estereotàctic

Development and Optimization of a Machine-Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort

Breast Radiation Therapy; Machine-Learning Prediction; Acute DesquamationRaditeràpia de mama; Predicció d'aprenentatge automàtic; Descamació agudaRadioterapia de mama; Predicción de aprendizaje automático; Descamación agudaPurpose Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Methods and Materials Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. Results One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the “hero” model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. Conclusions ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan

Effect of Two Immediate Dentin Sealing Approaches on Bond Strength of Lava™ CAD/CAM Indirect Restoration

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of the University of Granada (Spain) (protocol code #1005/CEIH/2019 approved on 13 January 2020).Informed consent was obtained from all subjects involved in the studyThe objective of this work was to compare the micro-tensile bond strength (mu TBS) of CAD/CAM (Computer-Aided Design/ Computer-Aided Manufacturing) specimens cemented with different pairing of adhesives and resin-cements using two Immediate Dentin Dealing (IDS) approaches in comparison with Delay Dentin Sealing (DDS). Coronal dentin from 108 molars were divided into nine groups (n = 12) depending on the adhesive/resin-cement (A-C) assigned. Lava (TM) Ultimate (4 x 10 x 10 mm) was cemented according to different strategies: IDS1(cementation after dentin sealing), DDS (dentin sealing and cementation at 2-weeks), IDS2 (immediate dentin sealing and cementation at 2-weeks). Samples were sectioned and tested until failure to determine the mu TBS. Failure mode was categorized as dentin/cement (DC), at Lava (TM) Ultimate/cement (LC) and hybrid (H). Kruskal-Wallis and Mann-Whitney U tests and influence of the type of failure on the mu TBS by survival analysis with competing risk was explored. Mostly, mu TBS values were equal or higher in IDS2 than DDS. In general, A-Cs that showed higher mu TBS, have high percentages of LC failure. Survival analysis with competing risk between DC + H and LC values showed that some A-Cs would significantly increase the mu TBS values for IDS2. A-Cs with the highest adhesion values showed a high percentage of fractures at the LC interface, suggesting that the adhesion at the adhesive/dentin interface would be higher

Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer

Càncer de mama; Toxicitat crònica; RadiogenòmicaBreast cancer; Chronic toxicity; RadiogenomicsCáncer de mama; Toxicidad crónica; RadiogenómicaBackground and purpose Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. Materials and Methods A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited across 18 European and US centres into the prospective REQUITE cohort study. Toxicity data (CTCAE v4.0) were collected at baseline, end of radiotherapy, and annual follow-up. A total of 7,097,340 SNPs were tested for association with the residuals of toxicity endpoints, adjusted for clinical, treatment co-variates and population substructure. Results Quantile-quantile plots showed more associations with toxicity above the p < 5 × 10-5 level than expected by chance. Eight SNPs reached genome-wide significance. Nipple retraction grade ≥ 2 was associated with the rs188287402 variant (p = 2.80 × 10-8), breast oedema grade ≥ 2 with rs12657177 (p = 1.12 × 10-10), rs75912034 (p = 1.12 × 10-10), rs145328458 (p = 1.06 × 10-9) and rs61966612 (p = 1.23 × 10-9), induration grade ≥ 2 with rs77311050 (p = 2.54 × 10-8) and rs34063419 (p = 1.21 × 10-8), and arm lymphoedema grade ≥ 1 with rs643644 (p = 3.54 × 10-8). Heritability estimates across significant endpoints ranged from 25% to 39%. Our study did not replicate previously reported SNPs associated with breast radiation toxicity at the pre-specified significance level. Conclusions This GWAS for long-term breast radiation toxicity provides further evidence for significant association of common SNPs with distinct toxicity endpoints.REQUITE received funding from the European Union's Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 601826. We thank all patients who participated in the REQUITE study and all the *members of the REQUITE project consortium in: Belgium: Ghent University Hospital; KU Leuven. France: ICM Montpellier, CHU Nîmes (Department of Radiation Oncology, CHU Nîmes, Nîmes, France). Germany: Zentrum für Strahlentherapie Freiburg (Dr. Petra Stegmaier); Städtisches Klinikum Karlsruhe (Dr. Bernhard Neu); ViDia Christliche Kliniken Karlsruhe (Prof. Johannes Claßen); Klinikum der Stadt Ludwigshafen GmbH (PD Dr. Thomas Schnabel); Universitätsklinikum Mannheim: Anette Kipke, Stefanie Kolb, Anke Keller and Christiane Zimmermann; Strahlentherapie Speyer (Dr. Jörg Schäfer). The researchers at DKFZ also thank Anusha Müller, Irmgard Helmbold, Thomas Heger, and Sabine Behrens. Petra Seibold was supported by ERA PerMed JCT2018 funding (ERAPERMED2018-244, BMBF #01KU1912) and BfS funding (#3619S42261). Italy: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Candiolo Cancer Institute – FPO, IRCCS. Tiziana Rancati was partially funded by Fondazione Italo Monzino. Spain: Barcelona: Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus; VHIO acknowledge the Cellex Foundation for providing research facilities and the CERCA Programme/Generalitat de Catalunya for institutional support. Sara Gutiérrez-Enríquez is supported by ERAPerMed JTC2018 funding (ERAPERMED2018-244 and SLT011/18/00005) and the Government of Catalonia (2021SGR01112). Santiago: Complexo Hospitalario Universitario de Santiago. Ana Vega is supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (PI22/00589, PI19/01424, PI16/00046, PI13/ 02030, PI10/00164; INT20/00071, INT17/00133, INT16/00154, INT15/00070), through the Autonomous Government of Galicia (Consolidation and structuring program: IN607B), by ERAPerMed JTC2018 funding (ERAPERMED2018-244) and by the AECC (PRYES211091VEGA). UK: University Hospitals of Leicester NHS Trust: Theresa Beaver, Sara Barrows, Monika Kaushik, Frances Kenny, Jaroslaw Krupa, Kelly V Lambert, Simon M Pilgrim, Sheila Shokuhi, Kalliope Valassidou, Kiran Kancherla, Kufre Sampson, Ahmed Osman and Kaitlin Walker. Harkeran K Jandu is supported by the Wellcome Trust Genetic Epidemiology and Public Health Genomics Doctoral Training Partnership (Grant Number: 218505/Z/19/Z). Tim Rattay was funded by a National Institute of Health Research (NIHR) Clinical Lectureship (CL 2017-11-002). He was previously funded by an NIHR Doctoral Research Fellowship (DRF 2014-07-079). This publication presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. University of Manchester: Catharine West and Rebecca Elliott are supported by the NIHR Manchester Biomedical Research Centre and Catharine West is supported by Cancer Research UK (C1094/A18504, C147/A25254). USA: Mount Sinai Hospital, New York

Aprovechamiento de recursos naturales y culturales con fines turísticos. Caso de estudio comuna San Jacinto del Pindo, en la provincia de Pastaza (Ecuador)

Tourism is an activity of sustained growth in the world, it offers opportunities for economic welfare and development, as confirmed by the World Tourism Organization, which reports a 7% growth during 2017, surpassing 1,300 million international arrivals, of which approximately 1'600,000 visitors arrived in Ecuador. The study included an inventory of the tourism potential of the San Jacinto del Pindo commune, in the province of Pastaza, through field visits, participatory workshops and the use of information sheets on situational diagnosis and tourism characterization. Its real situation was determined by the existence of tourist facilities, infrastructure, offer, and governance in the territory. Tourism resources were identified, as established by the Inventory Methodology of the Tourism Ministry of Ecuador, which allowed for their recognition, registration, classification, and ranking. This study was carried out in collaboration with the Autonomous Decentralized Government of the province of Pastaza and students of the tourism program of the Amazon State University as part of community service activities. The participatory execution of this research allowed to reach results that are valid contributions for the construction of territorial development and planning strategies from the conception of the collective work of the communities and the institutions of the public sector.El turismo es una actividad de crecimiento sostenido en el mundo, ofrece oportunidades de bienestar económico y desarrollo, así lo confirma la Organización Mundial del Turismo, que refiere un crecimiento del 7% durante el 2017, superando 1.300 millones de llegadas internacionales, de los cuales arribaron al Ecuador alrededor de 1´600.000 visitantes. El estudio contempló un inventario del potencial turístico de la comuna San Jacinto del Pindo, en la provincia de Pastaza, por medio de visitas de campo, talleres participativos y utilización de fichas de diagnóstico situacional y de caracterización turística, se determinó su situación real, la existencia de planta turística, infraestructura, oferta y la gobernanza en el territorio. Se identificaron los recursos turísticos, conforme lo establece la Metodología de inventario del Ministerio de Turismo del Ecuador, lo cual permitió su reconocimiento, registro, clasificación y jerarquización. Este estudio se llevó a cabo en colaboración con el Gobierno Autónomo Descentralizado de la provincia de Pastaza y estudiantes de la carrera de Turismo de la Universidad Estatal Amazónica como parte de las actividades de servicio comunitario. La ejecución de forma participativa de esta investigación permitió alcanzar resultados que constituyen aportes válidos para la construcción de estrategias de desarrollo y planificación territorial desde la concepción del trabajo colectivo de las comunidades y las instituciones del sector público