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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 × 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: A simultaneous integrated boost (SIB) leads to less acute toxicity. Less is known for late toxicity due to SIB. In this first and only randomized trial, two-years toxicity is analysed., Materials and Methods: Physician-assessed toxicity, using the LENT SOMA scale, and photographs, analysed with the BCCT.core software, was examined for 150 patients, randomized between SIB and sequential boost (SEB)., Results: Differences in physician-assessed two-years toxicity and photographic analysis between SIB and SEB are very small and not significant., Conclusion: There is no indication that a SIB leads to an excess in toxicity or worse cosmetic outcome at 2 years., Competing Interests: Conflict of interest This work was supported by the Cancer Plan Action 29 (project 015 and 008) by the Federal Public Service of Health, Food Chain Safety and Environment, Belgium and by grants of Stand up to Cancer (Flemish Cancer Society) and Foundation against Cancer (FAF-C/2016/854). Liv Veldeman holds a Clinical Mandate of Foundation against Cancer. None of the other auteurs have a conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In breast cancer patients, duration of illness and treatment have a negative impact on the quality of life. The duration of radiotherapy can be shortened by reducing the number of treatment fractions. In this study, the impact of an accelerated breast irradiation schedule in 5 fractions over 10 to 12 days on health-related quality of life (HRQoL) was investigated and compared to a standard hypofractionation schedule of 15 fractions., Methodology: The study population was composed of 530 patients treated in 15 fractions and 196 patients treated in 5 fractions. Patients were included in different trials evaluating HRQoL. Radiotherapy-related items of the EORTC QLQ-C30 and BR23 and Breast-Q questionnaires were evaluated by comparing baseline scores to scores at 2-4 weeks and 1 year after radiotherapy. Clinically important improvements and deteriorations of HRQoL were compared between the 2 radiation schedules., Results: Patients treated in 5 fractions show less deterioration of physical well-being 2-4 weeks after radiotherapy. One year after radiotherapy, the 5 fractions schedule results in more patients reporting a clinically important improvement in pain, arm and breast symptoms and future perspective., Conclusion: Radiotherapy in 5 fractions over 10-12 days results in more improvement and less deterioration of HRQoL than a 15 fractions schedule over 3 weeks., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose/objective: Health economic evaluations (HEE) are increasingly having an impact on policymakers, although the results greatly depend on the quality of the methodology used and on transparent reporting. The two main objectives of this study were to evaluate the quality of cost analyses of external beam radiotherapy (EBRT) and to assess the comprehensiveness and relevance of cost criteria defined in three validated quality-assessment instruments., Materials and Methods: The selection of articles was based on a previous systematic literature review of EBRT-costing studies retrieved from January 2004 to January 2015 (Period 1) in MEDLINE, Embase, and NHS-EED databases and completed in a second time period from January 2015 to November 2018 (Period 2). Three validated instruments to assess the methodology quality with the CHEC and the QHES, and the methodology with the CHEERS checklists were used. The quality was evaluated by both quantitative and qualitative analyses. The scoring robustness was examined with the Kendall coefficient of concordance and inter-class correlation coefficients., Results: In total, twenty-three articles were selected. The main geographic areas of cost analyses were Canada (n = 5), France (n = 4), and the USA (n = 4). The most commonly studied pathologies and technologies were prostate (n = 7) and head and neck cancer (n = 5) and IMRT (n = 8) and IGRT (n = 2), respectively. The mean instrument scores demonstrated a fair degree of methodological quality, with 69.7% for the CHEC, 73.6% for the QHES, as well as for the reporting quality, with 59.4% for CHEERS for Period 1 (74.4%, 71.5%, and 66.1%, respectively, for Period 2). An additional qualitative analysis per criterion revealed that certain items, essential for understanding the costing methodology and the results (e.g., the time horizon, discount rate, sensitivity analysis) were often only partially completed. Statistical analysis confirmed that the reviewers' scoring was consistent. The instruments identified the same top three articles, albeit with a degree of variation in the ranking., Conclusion: Qualitative and quantitative assessment of cost analyses in EBRT exhibits a fair level of study quality in terms of the methodology and reporting transparency. The impact of cost calculations on the final HEE result appears to be underestimated, and increased transparency of the data sources and the methodologies is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: A series of health economic evaluations (HEE) has analysed the efficiency of new fractionation schedules and techniques for adjuvant breast radiotherapy. This overview assembles the available evidence and evaluates to what extent HEE-results can be compared., Methods: Based on a systematic literature review of HEEs from 1/1/2000 to 30/10/2016, all cost comparison (CC) and cost-effectiveness analyses (CEA) comparing different adjuvant breast radiotherapy approaches were analysed. Costs were extracted and converted to Euro 2016 and costs per QALY were summarized in cost-effectiveness planes., Results: Twenty-four publications are withheld, comparing different fractionation schedules and/or irradiation techniques or evaluating the value of adding radiotherapy. Normofractionation and intensity-modulated, interstitial or intraluminal techniques are important cost-drivers. Highest reimbursements are observed in the US, but may overestimate the real cost. Hypofractionation is cost-effective compared to normofractionation, the results of partial breast irradiation are less unequivocal. Intra-operative and external beam approaches seem the most cost-effective for favourable risk groups, but whole breast irradiation is superior in terms of health effect and omission of radiotherapy in terms of costs., Conclusion: Hypofractionation may be considered the most relevant comparator for new strategies in adjuvant breast radiotherapy, with omission of radiotherapy as an interesting alternative in the very favourable subcategories, especially for partial breast techniques. Although comparison of CC and CEA is hampered by the variability in clinical and economic settings, HEE-based evidence can guide decision-making to tailor-made strategies, allocating the optimal treatment in terms of effectiveness as well as efficiency to the right indication., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Evolving practice in adjuvant breast radiotherapy inevitably impacts healthcare budgets. This is reflected in a rise of health economic evaluations (HEE) in this domain. The available HEE literature was analysed qualitatively and quantitatively, using available instruments., Methods: HEEs published between 1/1/2000 and 31/10/2016 were retrieved through a systematic search in Medline, Cochrane and Embase. A quality-assessment using CHEERS (Consolidated Health Economic Evaluation Reporting Standards) was translated into a quantitative score and compared with Tufts Medical Centre CEA registry and Quality of Health Economic Studies (QHES) results., Results: Twenty cost-effectiveness analyses (CEA) and thirteen cost comparisons (CC) were analysed. In qualitative evaluation, valuation or justification of data sources, population heterogeneity and discussion on generalizability, in addition to declaration on funding, were often absent or incomplete. After quantification, the average CHEERS-scores were 74% (CI 66.9-81.1%) and 75.6% (CI 70.7-80.5%) for CEAs and CCs respectively. CEA-scores did not differ significantly from Tufts and QHES-scores., Conclusion: Quantitative CHEERS evaluation is feasible and yields comparable results to validated instruments. HEE in adjuvant breast radiotherapy is of acceptable quality, however, further efforts are needed to improve comprehensive reporting of all data, indispensable for assessing relevance, reliability and generalizability of results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: The safety of a simultaneous integrated boost (SIB) in combination with prone hypofractionated whole-breast irradiation (WBI) was investigated., Materials and Methods: 167 patients were randomized between WBI with a sequential boost (SeB) or SIB. All patients were treated in prone position to 40.05Gy in 15 fractions to the whole breast. In the control arm, a SeB of 10Gy in 4 fractions (negative surgical margins) or 14.88Gy in 6 fractions (transsection) was prescribed. In the experimental arm a SIB of 46.8 or 49.95Gy (negative and positive surgical margins, respectively) was prescribed., Results: Patient age was the only significantly different parameter between treatment arms with patients in the SIB arm being slightly older. In both arms, 6/83 patients developed moist desquamation. Grade 2/3 dermatitis was significantly more frequent in the SeB arm (38/83vs 24/83 patients, p=0.037). In the SIB and SeB arm, respectively, 36 patients (43%) and 51 patients (61%) developed pruritus (p=0.015). The incidence of oedema was lower in the SIB arm (59vs 68 patients), but not statistically significant (p=0.071)., Conclusions: The primary endpoint, moist desquamation, was not significantly different between treatment arms., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Deep inspiration breath hold in the prone position causes a caudal shift of the heart away from the nearly unmodified breast and internal mammary lymph node region, suggesting better heart protection for left-sided whole breast irradiation with or without regional nodal radiotherapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)