المؤلفون: Naderi, Elnaz, Aguado-Barrera, Miguel E, Schack, Line M H, Dorling, Leila, Rattay, Tim, Fachal, Laura, Summersgill, Holly, Martínez-Calvo, Laura, Welsh, Ceilidh, Dudding, Tom, Odding, Yasmin, Varela-Pazos, Ana, Jena, Rajesh, Thomson, David J, Steenbakkers, Roel J H M, Dennis, Joe, Lobato-Busto, Ramón, Alsner, Jan, Ness, Andy, Nutting, Chris, Gómez-Caamaño, Antonio, Eriksen, Jesper G, Thomas, Steve J, Bates, Amy M, Webb, Adam J, Choudhury, Ananya, Rosenstein, Barry S, Taboada-Valladares, Begona, Herskind, Carsten, Azria, David, Dearnaley, David P, de Ruysscher, Dirk, Sperk, Elena, Hall, Emma, Stobart, Hilary, Chang-Claude, Jenny, De Ruyck, Kim, Veldeman, Liv, Altabas, Manuel, De Santis, Maria Carmen, Farcy-Jacquet, Marie-Pierre, Veldwijk, Marlon R, Sydes, Matthew R, Parliament, Matthew, Usmani, Nawaid, Burnet, Neil G, Seibold, Petra, Symonds, R Paul, Elliott, Rebecca M, Bultijnck, Renée, Kerns, S.L., Vanneste, Ben

المصدر: Naderi , E , Aguado-Barrera , M E , Schack , L M H , Dorling , L , Rattay , T , Fachal , L , Summersgill , H , Martínez-Calvo , L , Welsh , C , Dudding , T , Odding , Y , Varela-Pazos , A , Jena , R , Thomson , D J , Steenbakkers , R J H M , Dennis , J , Lobato-Busto , R , Alsner , J , Ness , A , Nutting , C , Gómez-Caamaño , A , Eriksen , J G , Thomas , S ....

مصطلحات موضوعية: GWAS, Radiogenomics, SNP-based heritability, acute radiation-induced toxicity

الوصف: BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung). METHODS: A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type. RESULTS: Shared SNP-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 SNPs with rSTATacute (5.0x10-8

العلاقة: https://cris.maastrichtuniversity.nl/en/publications/c91c501c-8567-4d35-bfe7-a72e7fb5d3d4Test

الإتاحة: https://doi.org/10.1093/jncics/pkad088Test
https://cris.maastrichtuniversity.nl/en/publications/c91c501c-8567-4d35-bfe7-a72e7fb5d3d4Test

المؤلفون: Heumann, Philipp, Aguado-Barrera, Miguel E., Avuzzi, Barbara, Azria, David, Briers, Erik, Bultijnck, Renée, Choudhury, Ananya, De Ruysscher, Dirk, Farcy-Jacquet, Marie-Pierre, Fonteyne, Valerie, Gómez Caamaño, Antonio, Helmbold, Irmgard, Johnson, Kerstie, Kerns, Sarah L., Lambrecht, Maarten, Lingard, Zoe, Rancati, Tiziana, Rosenstein, Barry S., Sperk, Elena, Paul Symonds, R., Talbot, Christopher, Valdagni, Riccardo, Vega, Ana, Veldeman, Liv, Ward, Tim, Webb, Adam, West, Catharine M., Chang-Claude, Jenny, Seibold, Petra

المصدر: RADIOTHERAPY AND ONCOLOGY ; ISSN: 0167-8140 ; ISSN: 1879-0887

مصطلحات موضوعية: Medicine and Health Sciences, Radiology, Nuclear Medicine and imaging, Oncology, Hematology, Radiotherapy, Prostate cancer, Patient -reported outcomes, Adverse events, Agreement

الوصف: Introduction: Previous studies showed that healthcare professionals and patients had only moderate to low agreement on their assessment of treatment-related symptoms. We aimed to determine the levels of agreement in a large cohort of prostate cancer patients. Methods: Analyses were made of data from 1,756 prostate cancer patients treated with external beam radiotherapy (RT) and/or brachytherapy in Europe and the USA and recruited into the prospective mul-ticentre observational REQUITE study. Eleven pelvic symptoms at the end of RT were compared after translating patient-reported outcomes (PROs) into CTCAE-based healthcare professional ratings. Gwet's AC2 agreement coefficient and 95% confidence intervals were calculated for each symptom. To compare severity of grading between patients and healthcare professionals, percent agreement and deviations for each symptom were graphically depicted. Stratified and sensitivity analyses were conducted to identify potential influencing factors and to assess heterogeneity and robustness of results.Results: The agreement for the 11 pelvic symptoms varied from very good (AC2 > 0.8: haematuria, rectal bleeding, management of sphincter control) to poor agreement (AC2 <= 0.2: proctitis and urinary urgency). Fatigue had a negative impact on the agreement. Patients tended to grade symptoms more severely than healthcare professionals. Information on sexual dysfunction was missing more frequently in healthcare professional assessment than PROs. Conclusion: Agreement was better for observable than subjective symptoms, with patients usually grad-ing symptoms more severely than healthcare professionals. Our findings emphasize that PROs should complement symptom assessment by healthcare professionals and be taken into consideration for clin-ical decision-making to incorporate the patient perspective.(c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 176 (2022) 109426 This is an open access article under the CC BY-NC-ND license ...

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/01GSA3TCNNBEGMM6V29JTV82NPTest; http://hdl.handle.net/1854/LU-01GSA3TCNNBEGMM6V29JTV82NPTest; http://doi.org/10.1016/j.radonc.2022.11.015Test; https://biblio.ugent.be/publication/01GSA3TCNNBEGMM6V29JTV82NP/file/01GV3ES7SYPCDYS3C83JQD4M6ETest

الإتاحة: https://doi.org/10.1016/j.radonc.2022.11.015Test
https://biblio.ugent.be/publication/01GSA3TCNNBEGMM6V29JTV82NPTest
http://hdl.handle.net/1854/LU-01GSA3TCNNBEGMM6V29JTV82NPTest
https://biblio.ugent.be/publication/01GSA3TCNNBEGMM6V29JTV82NP/file/01GV3ES7SYPCDYS3C83JQD4M6ETest

المؤلفون: Jandu, Harkeran K., Veal, Colin D., Fachal, Laura, Luccarini, Craig, Aguado-Barrera, Miguel E., Altabas, Manuel, Azria, David, Baten, Adinda, Bourgier, Celine, Bultijnck, Renée, Colciago, Riccardo R., Farcy-Jacquet, Marie-Pierre, Chang-Claude, Jenny, Choudhury, Ananya, Dunning, Alison, Elliott, Rebecca M., Green, Sheryl, Gutiérrez-Enríquez, Sara, Herskind, Carsten, Lambrecht, Maarten, Monten, Christel, Rancati, Tiziana, Reyes, Victoria, Rosenstein, Barry S., De Ruysscher, Dirk, Carmen De Santis, Maria, Seibold, Petra, Sperk, Elena, Veldwijk, Marlon, Paul Symonds, R., Stobart, Hilary, Taboada-Valladares, Begoña, Vega, Ana, Veldeman, Liv, Webb, Adam J., Weltens, Caroline, West, Catharine M., Rattay, Tim, Talbot, Christopher J., Consortium, REQUITE

المصدر: RADIOTHERAPY AND ONCOLOGY ; ISSN: 0167-8140 ; ISSN: 1879-0887

مصطلحات موضوعية: Medicine and Health Sciences, Radiology, Nuclear Medicine and imaging, Oncology, Hematology, Breast Cancer, Radiotherapy, Radiotherapy side effects, Chronic toxicity, Genome-wide association study, Radiogenomics

الوصف: Background 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 x 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 x 10-8), breastoedema grade > 2 with rs12657177 (p = 1. 12 x 10-10), rs75912034 (p = 1.12 x 10-10), rs145328458 (p = 1.06 x 10-9) and rs61966612 (p = 1.23 x 10- 9), induration grade > 2 with rs77311050 (p = 2.54 x 10-8) and rs34063419 (p = 1.21 x 10-8), and arm lymphoedema grade > 1 with rs643644 (p = 3.54 x 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. (c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 187 (2023) 1-10 This is an open access article under the CC BY license ...

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/01H8HSXR14CP6Z8FACN7R156MHTest; http://hdl.handle.net/1854/LU-01H8HSXR14CP6Z8FACN7R156MHTest; http://doi.org/10.1016/j.radonc.2023.109806Test; https://biblio.ugent.be/publication/01H8HSXR14CP6Z8FACN7R156MH/file/01H8HT15C7M0GHHT5FYSQC6C7FTest

الإتاحة: https://doi.org/10.1016/j.radonc.2023.109806Test
https://biblio.ugent.be/publication/01H8HSXR14CP6Z8FACN7R156MHTest
http://hdl.handle.net/1854/LU-01H8HSXR14CP6Z8FACN7R156MHTest
https://biblio.ugent.be/publication/01H8HSXR14CP6Z8FACN7R156MH/file/01H8HT15C7M0GHHT5FYSQC6C7FTest

المؤلفون: Rosas, Juan C., Aguado‐Barrera, Miguel E., Azria, David, Briers, Erik, Elliott, Rebecca, Farcy‐Jacquet, Marie‐Pierre, Giraldo, Alexandra, Gutiérrez‐Enríquez, Sara, Rancati, Tiziana, Rattay, Tim, Reyes, Victoria, Rosenstein, Barry, De Ruysscher, Dirk, Sperk, Elena, Stobart, Hilary, Talbot, Christopher, Vega, Ana, Taboada‐Valladares, Begoña, Veldeman, Liv, Ward, Tim, Webb, Adam, West, Catharine, Chang‐Claude, Jenny, Seibold, Petra, the REQUITE Consortium, missing

المصدر: INTERNATIONAL JOURNAL OF CANCER ; ISSN: 0020-7136 ; ISSN: 1097-0215

مصطلحات موضوعية: Medicine and Health Sciences, Cancer Research, Oncology, radiotherapy, longitudinal trajectories, fatigue, determinants, breast cancer

الوصف: Fatigue is common in breast-cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long-term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI-20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post-RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI-20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P < .05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI-20 fatigue dimensions (ORGeneralFatigue = 3.81, P < .001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/01H93F704QS24TPQBSZPCJ7HWCTest; http://hdl.handle.net/1854/LU-01H93F704QS24TPQBSZPCJ7HWCTest; http://doi.org/10.1002/ijc.34640Test; https://biblio.ugent.be/publication/01H93F704QS24TPQBSZPCJ7HWC/file/01H93FBSJ8ADS3W6X61W0GC7TTTest

الإتاحة: https://doi.org/10.1002/ijc.34640Test
https://biblio.ugent.be/publication/01H93F704QS24TPQBSZPCJ7HWCTest
http://hdl.handle.net/1854/LU-01H93F704QS24TPQBSZPCJ7HWCTest
https://biblio.ugent.be/publication/01H93F704QS24TPQBSZPCJ7HWC/file/01H93FBSJ8ADS3W6X61W0GC7TTTest

المؤلفون: Joseph, Nuradh, Cicchetti, Alessandro, McWilliam, Alan, Webb, Adam, Seibold, Petra, Fiorino, Claudio, Cozzarini, Cesare, Veldeman, Liv, Bultijnck, Renée, Fonteyne, Valérie, Talbot, Christopher J, Symonds, Paul R, Johnson, Kerstie, Rattay, Tim, Lambrecht, Maarten, Haustermans, Karin, De Meerleer, Gert, Elliott, Rebecca M, Sperk, Elena, Herskind, Carsten, Veldwijk, Marlon, Avuzzi, Barbara, Giandini, Tommaso, Valdagni, Riccardo, Azria, David, Jacquet, Marie-Pierre Farcy, Charissoux, Marie, Vega, Ana, Aguado-Barrera, Miguel E, Gómez-Caamaño, Antonio, Franco, Pierfrancesco, Garibaldi, Elisabetta, Girelli, Giuseppe, Iotti, Cinzia, Vavassori, Vittotorio, Chang-Claude, Jenny, West, Catharine M L, Rancati, Tiziana, Choudhury, Ananya

المساهمون: Joseph, Nuradh, Cicchetti, Alessandro, Mcwilliam, Alan, Webb, Adam, Seibold, Petra, Fiorino, Claudio, Cozzarini, Cesare, Veldeman, Liv, Bultijnck, Renée, Fonteyne, Valérie, Talbot, Christopher J, Symonds, Paul R, Johnson, Kerstie, Rattay, Tim, Lambrecht, Maarten, Haustermans, Karin, De Meerleer, Gert, Elliott, Rebecca M, Sperk, Elena, Herskind, Carsten, Veldwijk, Marlon, Avuzzi, Barbara, Giandini, Tommaso, Valdagni, Riccardo, Azria, David, Jacquet, Marie-Pierre Farcy, Charissoux, Marie, Vega, Ana, Aguado-Barrera, Miguel E, Gómez-Caamaño, Antonio, Franco, Pierfrancesco, Garibaldi, Elisabetta, Girelli, Giuseppe, Iotti, Cinzia, Vavassori, Vittotorio, Chang-Claude, Jenny, West, Catharine M L, Rancati, Tiziana, Choudhury, Ananya

مصطلحات موضوعية: fatigue, functional lo, integral dose, prostate cancer, radiotherapy - adverse effects

الوصف: IntroductionWe hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT). MethodsThe study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in >= 2 (WS2) or >= 3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis. ResultsIn REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L center dot Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L center dot Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58, ConclusionIncreasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36387203; info:eu-repo/semantics/altIdentifier/wos/WOS:000882506100001; volume:12; firstpage:1; lastpage:14; numberofpages:14; journal:FRONTIERS IN ONCOLOGY; https://hdl.handle.net/11579/149002Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85141666278

الإتاحة: https://doi.org/10.3389/fonc.2022.937934Test
https://hdl.handle.net/11579/149002Test

المؤلفون: Rosas, Juan C., Aguado-Barrera, Miguel E., Azria, David, Briers, Erik, Elliott, Rebecca, Farcy-Jacquet, Marie Pierre, Giraldo, Alexandra, Gutiérrez-Enríquez, Sara, Rancati, Tiziana, Rattay, Tim, Reyes, Victoria, Rosenstein, Barry, De Ruysscher, Dirk, Sperk, Elena, Stobart, Hilary, Talbot, Christopher, Vega, Ana, Taboada-Valladares, Begoña, Veldeman, Liv, Ward, Tim, Webb, Adam, West, Catharine, Chang-Claude, Jenny, Seibold, Petra

المصدر: Rosas , J C , Aguado-Barrera , M E , Azria , D , Briers , E , Elliott , R , Farcy-Jacquet , M P , Giraldo , A , Gutiérrez-Enríquez , S , Rancati , T , Rattay , T , Reyes , V , Rosenstein , B , De Ruysscher , D , Sperk , E , Stobart , H , Talbot , C , Vega , A , Taboada-Valladares , B , Veldeman , L , Ward , T , Webb , A , West , C , Chang-Claude , J & Seibold , P ....

العلاقة: https://cris.maastrichtuniversity.nl/en/publications/f6073f04-ada0-4ae6-aab7-95ff799ea974Test

الإتاحة: https://doi.org/10.1002/ijc.34772Test
https://cris.maastrichtuniversity.nl/en/publications/f6073f04-ada0-4ae6-aab7-95ff799ea974Test

المؤلفون: Naderi, Elnaz, Aguado-Barrera, Miguel E, Schack, Line MH, Dorling, Leila, Rattay, Tim, Fachal, Laura, Summersgill, Holly, Martínez-Calvo, Laura, Welsh, Ceilidh, Dudding, Tom, Odding, Yasmin, Varela-Pazos, Ana, Jena, Rajesh, Thomson, David J, Steenbakkers, Roel JHM, Dennis, Joe, Lobato-Busto, Ramón, Alsner, Jan, Ness, Andy, Nutting, Chris, Gómez-Caamaño, Antonio, Eriksen, Jesper G, Thomas, Steve J, Bates, Amy M, Webb, Adam J, Choudhury, Ananya, Rosenstein, Barry S, Taboada-Valladares, Begona, Herskind, Carsten, Azria, David, Dearnaley, David P, de Ruysscher, Dirk, Sperk, Elena, Hall, Emma, Stobart, Hilary, Chang-Claude, Jenny, De Ruyck, Kim, Veldeman, Liv, Altabas, Manuel, De Santis, Maria Carmen, Farcy-Jacquet, Marie-Pierre, Veldwijk, Marlon R, Sydes, Matthew R, Parliament, Matthew, Usmani, Nawaid, Burnet, Neil G, Seibold, Petra, Symonds, R Paul, Elliott, Rebecca M, Bultijnck, Renée, Gutiérrez-Enríquez, Sara, Mollà, Meritxell, Gulliford, Sarah L, Green, Sheryl, Rancati, Tiziana, Reyes, Victoria, Carballo, Ana, Peleteiro, Paula, Sosa-Fajardo, Paloma, Parker, Chris, Fonteyne, Valérie, Johnson, Kerstie, Lambrecht, Maarten, Vanneste, Ben, Valdagni, Riccardo, Giraldo, Alexandra, Ramos, Mónica, Diergaarde, Brenda, Liu, Geoffrey, Leal, Suzanne M, Chua, Melvin LK, Pring, Miranda, Overgaard, Jens, Cascallar-Caneda, Luis M, Duprez, Fréderic, Talbot, Christopher J, Barnett, Gillian C, Dunning, Alison M, Vega, Ana, Andreassen, Christian Nicolaj, Langendijk, Johannes A, West, Catharine ML, Alizadeh, Behrooz Z, Kerns, Sarah L, Radiogenomics Consortium

مصطلحات موضوعية: Male, Humans, Genome-Wide Association Study, Neoplasms, Breast, Genetic Predisposition to Disease

الوصف: Acknowledgements: The study sponsors were not involved in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. We thank all patients who participated in the study and the participating clinic staff for their contribution to data collection. This publication presents data from the Head and Neck 5000 study. The study was a component of independent research funded by the NIHR under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Core funding was also provided through awards from Above and Beyond, University Hospitals Bristol and Weston Research Capability Funding, and the NIHR Senior Investigator award to Professor Andy Ness. Genotyping was funded by World Cancer Research Fund Pilot Grant (grant No. 2018/1792), Above and Beyond, Wellcome Trust Research Training Fellowship (201237/Z/16/Z), and Cancer Research UK Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant No. C18281/A19169). The VHIO authors acknowledge the Cellex Foundation for providing research equipment and facilities and thank CERCA Program/Generalitat de Catalunya for institutional support. ; Funder: National Institute for Health Research; DOI: https://doi.org/10.13039/501100000272Test ; Funder: The Taylor Family Foundation ; Funder: Cancer Research UK; DOI: https://doi.org/10.13039/501100000289Test ; Funder: National Medical Research Council; DOI: https://doi.org/10.13039/501100001349Test ; 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 12 042 patients. Acute standardized total average ...

وصف الملف: application/pdf; text/xml; application/zip

العلاقة: https://www.repository.cam.ac.uk/handle/1810/362879Test

الإتاحة: https://www.repository.cam.ac.uk/handle/1810/362879Test

المؤلفون: Webb, Adam J., Harper, Emily, Rattay, Tim, Aguado-Barrera, Miguel E., Azria, David, Bourgier, Celine, Brengues, Muriel, Briers, Erik, Bultijnck, Renée, Chang-Claude, Jenny, Choudhury, Ananya, Cicchetti, Alessandro, De Ruysscher, Dirk, De Santis, Maria Carmen, Dunning, Alison M., Elliott, Rebecca M., Fachal, Laura, Gómez-Caamaño, Antonio, Gutiérrez-Enríquez, Sara, Johnson, Kerstie, Lobato-Busto, Ramón, Kerns, Sarah L., Post, Giselle, Rancati, Tiziana, Reyes, Victoria, Rosenstein, Barry S., Seibold, Petra, Seoane, Alejandro, Sosa-Fajardo, Paloma, Sperk, Elena, Taboada-Valladares, Begoña, Valdagni, Riccardo, Vega, Ana, Veldeman, Liv, Ward, Tim, West, Catharine M., Symonds, R. Paul, Talbot, Christopher J.

المصدر: Webb , A J , Harper , E , the REQUITE Consortium , Rattay , T , Aguado-Barrera , M E , Azria , D , Bourgier , C , Brengues , M , Briers , E , Bultijnck , R , Chang-Claude , J , Choudhury , A , Cicchetti , A , De Ruysscher , D , De Santis , M C , Dunning , A M , Elliott , R M , Fachal , L , Gómez-Caamaño , A , Gutiérrez-Enríquez , S , Johnson , K , Lobato-Busto , R , Kerns , S L ....

مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being

الوصف: Background: Circadian rhythm impacts broad biological processes, including response to cancer treatment. Evidence conflicts on whether treatment time affects risk of radiotherapy side-effects, likely because of differing time analyses and target tissues. We previously showed interactive effects of time and genotypes of circadian genes on late toxicity after breast radiotherapy and aimed to validate those results in a multi-centre cohort. Methods: Clinical and genotype data from 1690 REQUITE breast cancer patients were used with erythema (acute; n=340) and breast atrophy (two years post-radiotherapy; n=514) as primary endpoints. Local datetimes per fraction were converted into solar times as predictors. Genetic chronotype markers were included in logistic regressions to identify primary endpoint predictors. Findings: Significant predictors for erythema included BMI, radiation dose and PER3 genotype (OR 1.27(95%CI 1.03-1.56); P < 0.03). Effect of treatment time effect on acute toxicity was inconclusive, with no interaction between time and genotype. For late toxicity (breast atrophy), predictors included BMI, radiation dose, surgery type, treatment time and SNPs in CLOCK (OR 0.62 (95%CI 0.4-0.9); P < 0.01), PER3 (OR 0.65 (95%CI 0.44-0.97); P < 0.04) and RASD1 (OR 0.56 (95%CI 0.35-0.89); P < 0.02). There was a statistically significant interaction between time and genotypes of circadian rhythm genes (CLOCK OR 1.13 (95%CI 1.03-1.23), P < 0.01; PER3 OR 1.1 (95%CI 1.01-1.2), P < 0.04; RASD1 OR 1.15 (95%CI 1.04-1.28), P < 0.008), with peak time for toxicity determined by genotype. Interpretation: Late atrophy can be mitigated by selecting optimal treatment time according to circadian genotypes (e.g. treat PER3 rs2087947C/C genotypes in mornings; T/T in afternoons). We predict triple-homozygous patients (14%) reduce chance of atrophy from 70% to 33% by treating in mornings as opposed to mid-afternoon. Future clinical trials could stratify patients treated at optimal times compared to those scheduled ...

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/b738738b-28e4-42dd-a739-351b286ce1deTest

الإتاحة: https://doi.org/10.1016/j.ebiom.2022.104269Test
https://pure.eur.nl/en/publications/b738738b-28e4-42dd-a739-351b286ce1deTest
https://pure.eur.nl/ws/files/86717088/Treatment_time_and_circadian_genotype_interact_to_influence_radiotherapy_side_effects._A_prospective_European_validation_study_using_the_REQUITE_cohort.pdfTest
http://www.scopus.com/inward/record.url?scp=85138088248&partnerID=8YFLogxKTest

المؤلفون: Aldraimli, Mahmoud, Osman, Sarah, Grishchuck, Diana, Ingram, Samuel, Lyon, Robert, Mistry, Anil, Oliveira, Jorge, Samuel, Robert, Shelley, Leila E A, Soria, Daniele, Dwek, Miriam V, Aguado-Barrera, Miguel E, Azria, David, Chang-Claude, Jenny, Dunning, Alison, Giraldo, Alexandra, Green, Sheryl, Gutiérrez-Enríquez, Sara, Herskind, Carsten, van Hulle, Hans, Lambrecht, Maarten, Lozza, Laura, Rancati, Tiziana, Reyes, Victoria, Rosenstein, Barry S, de Ruysscher, Dirk, de Santis, Maria C, Seibold, Petra, Sperk, Elena, Symonds, R Paul, Stobart, Hilary, Taboada-Valadares, Begoña, Talbot, Christopher J, Vakaet, Vincent J L, Vega, Ana, Veldeman, Liv, Veldwijk, Marlon R, Webb, Adam, Weltens, Caroline, West, Catharine M, Chaussalet, Thierry J, Rattay, Tim, REQUITE consortium

الوصف: 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. 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. 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. 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. [Abstract copyright: © 2022 The Authors.]

وصف الملف: application/pdf

العلاقة: https://westminsterresearch.westminster.ac.uk/download/124d26335f374437415c2f634865bb0c569a020b3544d31a8e3bea98302c4bec/2554521/PIIS2452109421002487.pdfTest; https://doi.org/10.1016/j.adro.2021.100890Test; https://doi.org/S2452-1094Test(21)00248-7; Aldraimli, Mahmoud, Osman, Sarah, Grishchuck, Diana, Ingram, Samuel, Lyon, Robert, Mistry, Anil, Oliveira, Jorge, Samuel, Robert, Shelley, Leila E A, Soria, Daniele, Dwek, Miriam V, Aguado-Barrera, Miguel E, Azria, David, Chang-Claude, Jenny, Dunning, Alison, Giraldo, Alexandra, Green, Sheryl, Gutiérrez-Enríquez, Sara, Herskind, Carsten, van Hulle, Hans, Lambrecht, Maarten, Lozza, Laura, Rancati, Tiziana, Reyes, Victoria, Rosenstein, Barry S, de Ruysscher, Dirk, de Santis, Maria C, Seibold, Petra, Sperk, Elena, Symonds, R Paul, Stobart, Hilary, Taboada-Valadares, Begoña, Talbot, Christopher J, Vakaet, Vincent J L, Vega, Ana, Veldeman, Liv, Veldwijk, Marlon R, Webb, Adam, Weltens, Caroline, West, Catharine M, Chaussalet, Thierry J, Rattay, Tim and REQUITE consortium 2022. Development and Optimization of a Machine-Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort. Advances in radiation oncology. 7 (3) 100890. https://doi.org/10.1016/j.adro.2021.100890Test

الإتاحة: https://doi.org/10.1016/j.adro.2021.100890Test
https://westminsterresearch.westminster.ac.uk/item/vx020/development-and-optimization-of-a-machine-learning-prediction-model-for-acute-desquamation-after-breast-radiation-therapy-in-the-multicenter-requite-cohortTest
https://westminsterresearch.westminster.ac.uk/download/124d26335f374437415c2f634865bb0c569a020b3544d31a8e3bea98302c4bec/2554521/PIIS2452109421002487.pdfTest

المؤلفون: Naderi, Elnaz, Schack, Line M.H., Welsh, Ceilidh, Sim, Adelene Y.L., Aguado-Barrera, Miguel E., Dudding, Tom, Summersgil, Holly, Martínez-Calvo, Laura, Ong, Enya H.W., Odding, Yasmin, Varela-Pazos, Ana, Steenbakkers, Roel J.H.M., Crijns, Anne P.G., Jena, Rajesh, Pring, Miranda, Dennis, Joe, Lobato-Busto, Ramón, Alsner, Jan, Ness, Andy, Nutting, Christopher, Thomson, David J., Gómez-Caamaño, Antonio, Eriksen, Jesper G., Thomas, Steve J., Bates, Amy M., Overgaard, Jens, Cascallar-Caneda, Luis M., Duprez, Fréderic, Barnett, Gillian C., Dorling, Leila, Chua, Melvin L.K., Vega, Ana, West, Catharine M.L., Langendijk, Johannes A., Nicolaj Andreassen, Christian, Alizadeh, Behrooz Z.

المصدر: Radiogenomics Consortium , Naderi , E , Schack , L M H , Welsh , C , Sim , A Y L , Aguado-Barrera , M E , Dudding , T , Summersgil , H , Martínez-Calvo , L , Ong , E H W , Odding , Y , Varela-Pazos , A , Steenbakkers , R J H M , Crijns , A P G , Jena , R , Pring , M , Dennis , J , Lobato-Busto , R , Alsner , J , Ness , A , Nutting , C , Thomson , D J ....

مصطلحات موضوعية: Head and neck cancer, Meta-GWAS, Polygenic risk score, Radiation-induced acute toxicity, SNP-based heritability

الوصف: 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 (STAT acute ) 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 (p replication < 0.05) in replication set, but none reached genome-wide significance (p combined < 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 STAT acute (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 % (STAT acute ). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STAT acute . PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STAT acute (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.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/0b8488c0-6529-46a9-84ae-3c11e8311cd7Test

الإتاحة: https://doi.org/10.1016/j.radonc.2022.09.016Test
https://hdl.handle.net/11370/0b8488c0-6529-46a9-84ae-3c11e8311cd7Test
https://research.rug.nl/en/publications/0b8488c0-6529-46a9-84ae-3c11e8311cd7Test
https://pure.rug.nl/ws/files/252045407/1_s2.0_S0167814022044863_main.pdfTest