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4. No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity

Author

Barnett, Gillian C., Kerns, Sarah L., Dorling, Leila, Fachal, Laura, Aguado-Barrera, Miguel E., Martínez-Calvo, Laura, Jandu, Harkeran K., Welsh, Ceilidh, Tyrer, Jonathan, Coles, Charlotte E., Haviland, Joanne S., Parker, Christopher, Gómez-Caamaño, Antonio, Calvo-Crespo, Patricia, Sosa-Fajardo, Paloma, Burnet, Neil G., Summersgill, Holly, Webb, Adam, De Ruysscher, Dirk, Seibold, Petra, Chang-Claude, Jenny, Talbot, Christopher J., Rattay, Tim, Parliament, Matthew, De Ruyck, Kim, Rosenstein, Barry S., Pharoah, Paul D.P., Dunning, Alison M., Vega, Ana, and West, Catharine M.L.

Published
2022
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6. The European Particle Therapy Network (EPTN) consensus on the follow-up of adult patients with brain and skull base tumours treated with photon or proton irradiation

Author

De Roeck, Laurien, van der Weide, Hiska L., Eekers, Daniëlle B.P., Kramer, Miranda C., Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G., Calugaru, Valentin, Coremans, Ida E.M., Di Perri, Dario, Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L.B., Langendijk, Johannes A., Méndez Romero, Alejandra, Paulsen, Frank, Roelofs, Erik, de Ruysscher, Dirk, Timmermann, Beate, Vitek, Pavel, Weber, Damien C., Whitfield, Gillian A., Nyström, Petra Witt, Zindler, Jaap, Troost, Esther G.C., and Lambrecht, Maarten

Published
2022
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7. Update of the EPTN atlas for CT- and MR-based contouring in Neuro-Oncology

Author

Eekers, Daniëlle B.P., Di Perri, Dario, Roelofs, Erik, Postma, Alida, Dijkstra, Jeanette, Ajithkumar, Thankamma, Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G, Calugaru, Valentin, Compter, Inge, Coremans, Ida E.M., Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L.B., Lambrecht, Maarten, Romero, Alejandra Méndez, Paulsen, Frank, Timmermann, Beate, Vitek, Pavel, van der Weide, Hiske L, Whitfield, Gillian A, Nyström, Petra Witt, Zindler, Jaap, de Ruysscher, Dirk, Langendijk, Johannes, Weber, Damien C, and Troost, Esther G.C.

Published
2021
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11. Radiotherapy intensification for atypical and malignant meningiomas: A systematic review.

Author

Gaito, Simona, Goyal, Love, Rieu, Romelie, France, Anna, Burnet, Neil G, Barker, Claire, Pan, Shermaine, Colaco, Rovel J, Minniti, Giuseppe, Roncaroli, Federico, Smith, Ed, Aznar, Marianne, and Whitfield, Gillian

Subjects
LITERATURE reviews, RADIOTHERAPY, RANDOMIZED controlled trials, PROGRESSION-free survival, RESEARCH questions
Abstract

Background The outcomes of nonbenign (WHO Grades 2 and 3 [G2, G3]) meningiomas are suboptimal and radiotherapy (RT) dose intensification strategies have been investigated. The purpose of this review is to report on clinical practice and outcomes with particular attention to RT doses and techniques. Methods The PICO criteria (Population, Intervention, Comparison, and Outcomes) were used to frame the research question, directed at outlining the clinical outcomes in patients with G2−3 meningiomas treated with RT. The same search strategy was run in Embase and MEDLINE and, after deduplication, returned 1 807 records. These were manually screened for relevance and 25 were included. Results Tumor outcomes and toxicities are not uniformly reported in the selected studies since different endpoints and time points have been used by different authors. Many risk factors for worse outcomes are described, the most common being suboptimal RT. This includes no or delayed RT, low doses, and older techniques. A positive association between RT dose and progression-free survival (PFS) has been highlighted by analyzing the studies in this review (10/25) that report the same endpoint (5y-PFS). Conclusions This literature review has shown that standard practice RT leads to suboptimal tumor control rates in G2–3 meningiomas, with a significant proportion of disease recurring after a relatively short follow-up. Randomized controlled trials are needed in this setting to define the optimal RT approach. Given the increasing data to suggest a benefit of higher RT doses for high-risk meningiomas, novel RT technologies with highly conformal dose distributions are preferential to achieve optimal target coverage and organs at risk sparing. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Radiotherapy intensification for atypical and malignant meningiomas: A systematic review

Author

Gaito, Simona, primary, Goyal, Love, additional, Rieu, Romelie, additional, France, Anna, additional, Burnet, Neil G, additional, Barker, Claire, additional, Pan, Shermaine, additional, Colaco, Rovel J, additional, Minniti, Giuseppe, additional, Roncaroli, Federico, additional, Smith, Ed, additional, Aznar, Marianne, additional, and Whitfield, Gillian, additional

Published
2023
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14. Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus

Author

Lambrecht, Maarten, Eekers, Daniëlle B.P., Alapetite, Claire, Burnet, Neil G., Calugaru, Valentin, Coremans, Ida E.M., Fossati, Piero, Høyer, Morten, Langendijk, Johannes A., Méndez Romero, Alejandra, Paulsen, Frank, Perpar, Ana, Renard, Laurette, de Ruysscher, Dirk, Timmermann, Beate, Vitek, Pavel, Weber, Damien C., van der Weide, Hiske L., Whitfield, Gillian A., Wiggenraad, Ruud, Roelofs, Erik, Nyström, Petra Witt, and Troost, Esther G.C.

Published
2018
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15. The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology

Author

Eekers, Daniëlle BP, in 't Ven, Lieke, Roelofs, Erik, Postma, Alida, Alapetite, Claire, Burnet, Neil G., Calugaru, Valentin, Compter, Inge, Coremans, Ida E.M., Høyer, Morton, Lambrecht, Maarten, Nyström, Petra Witt, Méndez Romero, Alejandra, Paulsen, Frank, Perpar, Ana, de Ruysscher, Dirk, Renard, Laurette, Timmermann, Beate, Vitek, Pavel, Weber, Damien C., van der Weide, Hiske L., Whitfield, Gillian A., Wiggenraad, Ruud, and Troost, Esther G.C.

Published
2018
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19. Individual patient data meta-analysis shows a significant association between the ATM rs1801516 SNP and toxicity after radiotherapy in 5456 breast and prostate cancer patients

Author

Andreassen, Christian Nicolaj, Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, De Ruysscher, Dirk, Cesaretti, Jamie A., Barnett, Gillian C., Dunning, Alison M., Dorling, Leila, West, Catharine M.L., Burnet, Neil G., Elliott, Rebecca, Coles, Charlotte, Hall, Emma, Fachal, Laura, Vega, Ana, Gómez-Caamaño, Antonio, Talbot, Christopher J., Symonds, R. Paul, De Ruyck, Kim, Thierens, Hubert, Ost, Piet, Chang-Claude, Jenny, Seibold, Petra, Popanda, Odilia, Overgaard, Marie, Dearnaley, David, Sydes, Matthew R., Azria, David, Koch, Christine Anne, Parliament, Matthew, Blackshaw, Michael, Sia, Michael, Fuentes-Raspall, Maria J., Ramon y Cajal, Teresa, Barnadas, Agustin, Vesprini, Danny, Gutiérrez-Enríquez, Sara, Mollà, Meritxell, Díez, Orland, Yarnold, John R., Overgaard, Jens, Bentzen, Søren M., and Alsner, Jan

Published
2016
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21. Radiotherapy toxicity

Author

De Ruysscher, Dirk, Niedermann, Gabriele, Burnet, Neil G., Siva, Shankar, Lee, Anne W. M., and Hegi-Johnson, Fiona

Published
2019
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23. Sub-regional analysis of the parotid glands: model development for predicting late xerostomia with radiomics features in head and neck cancer patients

Author

Berger, Thomas, primary, Noble, David J., additional, Yang, Zhuolin, additional, Shelley, Leila EA., additional, McMullan, Thomas, additional, Bates, Amy, additional, Thomas, Simon, additional, Carruthers, Linda J., additional, Beckett, George, additional, Duffton, Aileen, additional, Paterson, Claire, additional, Jena, Raj, additional, McLaren, Duncan B., additional, Burnet, Neil G., additional, and Nailon, William H., additional

Published
2023
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26. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity

Author

Barnett, Gillian C., Thompson, Deborah, Fachal, Laura, Kerns, Sarah, Talbot, Chris, Elliott, Rebecca M., Dorling, Leila, Coles, Charlotte E., Dearnaley, David P., Rosenstein, Barry S., Vega, Ana, Symonds, Paul, Yarnold, John, Baynes, Caroline, Michailidou, Kyriaki, Dennis, Joe, Tyrer, Jonathan P., Wilkinson, Jennifer S., Gómez-Caamaño, Antonio, Tanteles, George A., Platte, Radka, Mayes, Rebecca, Conroy, Don, Maranian, Mel, Luccarini, Craig, Gulliford, Sarah L., Sydes, Matthew R., Hall, Emma, Haviland, Joanne, Misra, Vivek, Titley, Jennifer, Bentzen, Søren M., Pharoah, Paul D.P., Burnet, Neil G., Dunning, Alison M., and West, Catharine M.L.

Published
2014
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28. No Association Between Polygenic Risk Scores for Cancer and Development of Radiation Therapy Toxicity

Author

Barnett, Gillian C, Kerns, Sarah L, Dorling, Leila, Fachal, Laura, Aguado-Barrera, Miguel E, Martínez-Calvo, Laura, Jandu, Harkeran K, Welsh, Ceilidh, Tyrer, Jonathan, Coles, Charlotte E, Haviland, Joanne S, Parker, Christopher, Gómez-Caamaño, Antonio, Calvo-Crespo, Patricia, Sosa-Fajardo, Paloma, Burnet, Neil G, Summersgill, Holly, Webb, Adam, De Ruysscher, Dirk, Seibold, Petra, Chang-Claude, Jenny, Talbot, Christopher J, Rattay, Tim, Parliament, Matthew, De Ruyck, Kim, Rosenstein, Barry S, Pharoah, Paul DP, Dunning, Alison M, Vega, Ana, West, Catharine ML, RGC and REQUITE Consortia, Coles, Charlotte [0000-0003-4473-8552], Pharoah, Paul [0000-0001-8494-732X], and Apollo - University of Cambridge Repository

Subjects
Male, Biological Products, Risk Factors, Humans, Prostatic Neoplasms, Breast Neoplasms, Genetic Predisposition to Disease, Radiation Injuries, Polymorphism, Single Nucleotide, Genome-Wide Association Study
Abstract

PURPOSE: Our aim was to test whether updated polygenic risk scores (PRS) for susceptibility to cancer affect risk of radiation therapy toxicity. METHODS AND MATERIALS: Analyses included 9,717 patients with breast (n=3,078), prostate (n=5,748) or lung (n=891) cancer from Radiogenomics and REQUITE Consortia cohorts. Patients underwent potentially curative radiation therapy and were assessed prospectively for toxicity. Germline genotyping involved genome-wide single nucleotide polymorphism (SNP) arrays with nontyped SNPs imputed. PRS for each cancer were generated by summing literature-identified cancer susceptibility risk alleles: 352 breast, 136 prostate, and 24 lung. Weighted PRS were generated using log odds ratio (ORs) for cancer susceptibility. Standardized total average toxicity (STAT) scores at 2 and 5 years (breast, prostate) or 6 to 12 months (lung) quantified toxicity. Primary analysis tested late STAT, secondary analyses investigated acute STAT, and individual endpoints and SNPs using multivariable regression. RESULTS: Increasing PRS did not increase risk of late toxicity in patients with breast (OR, 1.000; 95% confidence interval [CI], 0.997-1.002), prostate (OR, 0.99; 95% CI, 0.98-1.00; weighted PRS OR, 0.93; 95% CI, 0.83-1.03), or lung (OR, 0.93; 95% CI, 0.87-1.00; weighted PRS OR, 0.68; 95% CI, 0.45-1.03) cancer. Similar results were seen for acute toxicity. Secondary analyses identified rs138944387 associated with breast pain (OR, 3.05; 95% CI, 1.86-5.01; P = 1.09 × 10-5) and rs17513613 with breast edema (OR, 0.94; 95% CI, 0.92-0.97; P = 1.08 × 10-5). CONCLUSIONS: Patients with increased polygenic predisposition to breast, prostate, or lung cancer can safely undergo radiation therapy with no anticipated excess toxicity risk. Some individual SNPs increase the likelihood of a specific toxicity endpoint, warranting validation in independent cohorts and functional studies to elucidate biologic mechanisms.

Published
2022
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31. The European Particle Therapy Network (EPTN) consensus on the follow-up of adult patients with brain and skull base tumours treated with photon or proton irradiation.

Author

UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de radiothérapie oncologique, De Roeck, Laurien, van der Weide, Hiska L, Eekers, Daniëlle B P, Kramer, Miranda C, Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G, Calugaru, Valentin, Coremans, Ida E M, Di Perri, Dario, Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L B, Langendijk, Johannes A, Romero, Alejandra Méndez, Paulsen, Frank, Roelofs, Erik, de Ruysscher, Dirk, Timmermann, Beate, Vitek, Pavel, Weber, Damien C, Whitfield, Gillian A, Nyström, Petra Witt, Zindler, Jaap, Troost, Esther G C, Lambrecht, Maarten, work package 1 of the taskforce “European Particle Therapy Network” of ESTRO, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de radiothérapie oncologique, De Roeck, Laurien, van der Weide, Hiska L, Eekers, Daniëlle B P, Kramer, Miranda C, Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G, Calugaru, Valentin, Coremans, Ida E M, Di Perri, Dario, Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L B, Langendijk, Johannes A, Romero, Alejandra Méndez, Paulsen, Frank, Roelofs, Erik, de Ruysscher, Dirk, Timmermann, Beate, Vitek, Pavel, Weber, Damien C, Whitfield, Gillian A, Nyström, Petra Witt, Zindler, Jaap, Troost, Esther G C, Lambrecht, Maarten, and work package 1 of the taskforce “European Particle Therapy Network” of ESTRO

Abstract

Treatment-related toxicity after irradiation of brain tumours has been underreported in the literature. Furthermore, there is considerable heterogeneity on how and when toxicity is evaluated. The aim of this European Particle Network (EPTN) collaborative project is to develop recommendations for uniform follow-up and toxicity scoring of adult brain tumour patients treated with radiotherapy. A Delphi method-based consensus was reached among 24 international radiation-oncology experts in the field of neuro-oncology concerning the toxicity endpoints, evaluation methods and time points. In this paper, we present a basic framework for consistent toxicity scoring and follow-up, using multiple levels of recommendation. Level I includes all recommendations that are considered minimum of care, whereas level II and III are optional evaluations in the advanced clinical or research setting, respectively. Per outcome domain, the clinical endpoints and evaluation methods per level are listed. Where relevant, the organ at risk threshold doses for recommended referral to specific organ specialists are defined. These consensus-based recommendations for follow-up will enable the collection of uniform toxicity data of brain tumour patients treated with radiotherapy. With adoptation of this standard, collaboration will be facilitated and we can further propel the research field of radiation-induced toxicities relevant for these patients. An online tool to implement this guideline in clinical practice is provided at www.cancerdata.org.

Published
2022

32. Advances in radiotherapy

Author

Ahmad, Saif S, Duke, Simon, Jena, Rajesh, Williams, Michael V, and Burnet, Neil G

Published
2012

36. Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: a prospective analysis study

Author

Barnett, Gillian C, Coles, Charlotte E, Elliott, Rebecca M, Baynes, Caroline, Luccarini, Craig, Conroy, Don, Wilkinson, Jennifer S, Tyrer, Jonathan, Misra, Vivek, Platte, Radka, Gulliford, Sarah L, Sydes, Matthew R, Hall, Emma, Bentzen, Søren M, Dearnaley, David P, Burnet, Neil G, Pharoah, Paul DP, Dunning, Alison M, and West, Catharine ML

Published
2012
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37. Current practice in proton therapy delivery in adult cancer patients across Europe

Author

Tambas, Makbule, primary, van der Laan, Hans Paul, additional, Steenbakkers, Roel J.H.M., additional, Doyen, Jerome, additional, Timmermann, Beate, additional, Orlandi, Ester, additional, Hoyer, Morten, additional, Haustermans, Karin, additional, Georg, Petra, additional, Burnet, Neil G, additional, Gregoire, Vincent, additional, Calugaru, Valentin, additional, Troost, Esther G.C., additional, Hoebers, Frank, additional, Calvo, Felipe A., additional, Widder, Joachim, additional, Eberle, Fabian, additional, van Vulpen, Marco, additional, Maingon, Philippe, additional, Skóra, Tomasz, additional, Weber, Damien C., additional, Bergfeldt, Kjell, additional, Kubes, Jiri, additional, and Langendijk, Johannes A., additional

Published
2022
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38. The suitability of micronuclei as markers of relative biological effect

Author

Heaven, Charlotte J, primary, Wanstall, Hannah C, additional, Henthorn, Nicholas T, additional, Warmenhoven, John-William, additional, Ingram, Samuel P, additional, Chadwick, Amy L, additional, Santina, Elham, additional, Honeychurch, Jamie, additional, Schmidt, Christine K, additional, Kirkby, Karen J, additional, Kirkby, Norman F, additional, Burnet, Neil G, additional, and Merchant, Michael J, additional

Published
2022
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41. Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy?

Author

Sørensen, Brita S., primary, Pawelke, Jörg, additional, Bauer, Julia, additional, Burnet, Neil G., additional, Dasu, Alexandru, additional, Høyer, Morten, additional, Karger, Christian P., additional, Krause, Mechthild, additional, Schwarz, Marco, additional, Underwood, Tracy S.A., additional, Wagenaar, Dirk, additional, Whitfield, Gillian A., additional, and Lühr, Armin, additional

Published
2021
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43. Update of the EPTN atlas for CT- and MR-based contouring in Neuro-Oncology.

Author

UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de radiothérapie oncologique, Eekers, Daniëlle B P, Di Perri, Dario, Roelofs, Erik, Postma, Alida, Dijkstra, Jeanette, Ajithkumar, Thankamma, Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G, Calugaru, Valentin, Compter, Inge, Coremans, Ida E M, Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L B, Lambrecht, Maarten, Romero, Alejandra Méndez, Paulsen, Frank, Timmermann, Beate, Vitek, Pavel, van der Weide, Hiske L, Whitfield, Gillian A, Nyström, Petra Witt, Zindler, Jaap, de Ruysscher, Dirk, Langendijk, Johannes, Weber, Damien C, Troost, Esther G C, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de radiothérapie oncologique, Eekers, Daniëlle B P, Di Perri, Dario, Roelofs, Erik, Postma, Alida, Dijkstra, Jeanette, Ajithkumar, Thankamma, Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G, Calugaru, Valentin, Compter, Inge, Coremans, Ida E M, Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L B, Lambrecht, Maarten, Romero, Alejandra Méndez, Paulsen, Frank, Timmermann, Beate, Vitek, Pavel, van der Weide, Hiske L, Whitfield, Gillian A, Nyström, Petra Witt, Zindler, Jaap, de Ruysscher, Dirk, Langendijk, Johannes, Weber, Damien C, and Troost, Esther G C

Abstract

To update the digital online atlas for organs at risk (OARs) delineation in neuro-oncology based on high-quality computed tomography (CT) and magnetic resonance (MR) imaging with new OARs. In this planned update of the neurological contouring atlas published in 2018, ten new clinically relevant OARs were included, after thorough discussion between experienced neuro-radiation oncologists (RTOs) representing 30 European radiotherapy-oncology institutes. Inclusion was based on daily practice and research requirements. Consensus was reached for the delineation after critical review. Contouring was performed on registered CT with intravenous (IV) contrast (soft tissue & bone window setting) and 3 Tesla (T) MRI (T1 with gadolinium & T2 FLAIR) images of one patient (1 mm slices). For illustration purposes, delineation on a 7 T MRI without IV contrast from a healthy volunteer was added. OARs were delineated by three experienced RTOs and a neuroradiologist based on the relevant literature. The presented update of the neurological contouring atlas was reviewed and approved by 28 experts in the field. The atlas is available online and includes in total 25 OARs relevant to neuro-oncology, contoured on CT and MRI T1 and FLAIR (3 T & 7 T). Three-dimensional (3D) rendered films are also available online. In order to further decrease inter- and intra-observer OAR delineation variability in the field of neuro-oncology, we propose the use of this contouring atlas in photon and particle therapy, in clinical practice and in the research setting. The updated atlas is freely available on www.cancerdata.org.

Published
2021

45. Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy

Author

Kerns, Sarah L, Fachal, Laura, Dorling, Leila, Barnett, Gillian C, Baran, Andrea, Peterson, Derick R, Hollenberg, Michelle, Hao, Ke, Narzo, Antonio Di, Ahsen, Mehmet Eren, Pandey, Gaurav, Bentzen, Søren M, Janelsins, Michelle, Elliott, Rebecca M, Pharoah, Paul D P, Burnet, Neil G, Dearnaley, David P, Gulliford, Sarah L, Hall, Emma, Sydes, Matthew R, Aguado-Barrera, Miguel E, Gómez-Caamaño, Antonio, Carballo, Ana M, Peleteiro, Paula, Lobato-Busto, Ramón, Stock, Richard, Stone, Nelson N, Ostrer, Harry, Usmani, Nawaid, Singhal, Sandeep, Tsuji, Hiroshi, Imai, Takashi, Saito, Shiro, Eeles, Rosalind, DeRuyck, Kim, Parliament, Matthew, Dunning, Alison M, Vega, Ana, Rosenstein, Barry S, West, Catharine M L, Wilson, Leila [0000-0003-1214-8080], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], and Apollo - University of Cambridge Repository

Subjects
Urologic Diseases, 0604 Genetics, Aging, Biomedical, Prevention, Prostate Cancer, Human Genome, Articles, Clinical Medicine and Science, Clinical Research, Genetics, 2.1 Biological and endogenous factors, 1112 Oncology and Carcinogenesis, Patient Safety, Cancer, Biotechnology
Abstract

Background A total of 10%–20% of patients develop long-term toxicity following radiotherapy for prostate cancer. Identification of common genetic variants associated with susceptibility to radiotoxicity might improve risk prediction and inform functional mechanistic studies. Methods We conducted an individual patient data meta-analysis of six genome-wide association studies (n = 3871) in men of European ancestry who underwent radiotherapy for prostate cancer. Radiotoxicities (increased urinary frequency, decreased urinary stream, hematuria, rectal bleeding) were graded prospectively. We used grouped relative risk models to test associations with approximately 6 million genotyped or imputed variants (time to first grade 2 or higher toxicity event). Variants with two-sided Pmeta less than 5 × 10−8 were considered statistically significant. Bayesian false discovery probability provided an additional measure of confidence. Statistically significant variants were evaluated in three Japanese cohorts (n = 962). All statistical tests were two-sided. Results Meta-analysis of the European ancestry cohorts identified three genomic signals: single nucleotide polymorphism rs17055178 with rectal bleeding (Pmeta = 6.2 × 10−10), rs10969913 with decreased urinary stream (Pmeta = 2.9 × 10−10), and rs11122573 with hematuria (Pmeta = 1.8 × 10−8). Fine-scale mapping of these three regions was used to identify another independent signal (rs147121532) associated with hematuria (Pconditional = 4.7 × 10−6). Credible causal variants at these four signals lie in gene-regulatory regions, some modulating expression of nearby genes. Previously identified variants showed consistent associations (rs17599026 with increased urinary frequency, rs7720298 with decreased urinary stream, rs1801516 with overall toxicity) in new cohorts. rs10969913 and rs17599026 had similar effects in the photon-treated Japanese cohorts. Conclusions This study increases the understanding of the architecture of common genetic variants affecting radiotoxicity, points to novel radio-pathogenic mechanisms, and develops risk models for testing in clinical studies. Further multinational radiogenomics studies in larger cohorts are worthwhile.

Published
2020

50. Neuro-oncology in pregnancy

Author

Harris, Fiona, primary, Jefferies, Sarah J., additional, Jena, Rajesh, additional, Burton, Katherine E., additional, Muffett, Lorraine, additional, and Burnet, Neil G., additional

Published
2012
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