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Given that most local relapses of breast cancer occur proximal to the original location of the primary, the delivery of additional radiation dose to breast tissue that contained the original primary cancer (known as a "boost") has been a standard of care for some decades. In the context of falling relapse rates, however, it is an appropriate time to re-evaluate the role of the boost. This article reviews the evolution of the radiotherapy boost in breast cancer, discussing who to boost and how to boost in the 2020s, and arguing that, in both cases, less is more. • Delivery of additional RT dose to breast tumour bed has a sound pathological basis. • Breast boost local relapse benefits vary according to clinicopathological risk factors. • Young age, high grade & triple negative phenotype are key eligibility criteria. • There is no survival benefit from a tumour bed boost in breast RT. • The boost target volume and treatment burden should be minimised. [ABSTRACT FROM AUTHOR]

Since its introduction more than a decade ago, intensity-modulated radiotherapy (IMRT) has spread to most radiotherapy departments worldwide for a wide range of indications. The technique has been rapidly implemented, despite an incomplete understanding of its advantages and weaknesses, the challenges of IMRT planning, delivery, and quality assurance, and the substantially increased cost compared with non-IMRT. Many publications discuss the theoretical advantages of IMRT dose distributions. However, the key question is whether the use of IMRT can be exploited to obtain a clinically relevant advantage over non-modulated external-beam radiation techniques. To investigate which level of evidence supports the routine use of IMRT for various disease sites, we did a review of clinical studies that reported on overall survival, disease-specific survival, quality of life, treatment-induced toxicity, or surrogate endpoints. This review shows evidence of reduced toxicity for various tumour sites by use of IMRT. The findings regarding local control and overall survival are generally inconclusive. [ABSTRACT FROM AUTHOR]

Introduction About 5% of cancer patients receiving radiation therapy (RT) exhibit severe normal tissue reactions. The prediction of late toxicity in cancer patients would enable individualized and optimized radiation dose prescription. In this study, four different candidate in vitro cellular radiosensitivity assays for prediction of late normal tissue reactions were evaluated in a retrospective matched case-control set-up of breast cancer patients. Materials and methods Breast cancer patients expressing severe radiation toxicity (12 cases) and no or minimal reactions (12 controls) with a follow-up of at least 3 years were selected for this study. Case and control patients were matched for therapy and patient related variables. After in vitro irradiation of patient blood samples, case and control radiation responses were compared for the following biological end points: radiation-induced CD8+ late apoptosis, residual DNA double strand breaks (DSB), G0 and G2+caf micronucleus assay. Results Despite a substantial overlap in standard deviations, all cellular assays showed a significant difference between cases and controls. Less radiation-induced apoptosis was observed in CD8+ lymphocytes of cases (14.45%) compared to the matched controls (30.64%) ( p < 0.01). The number of residual DNA DSB was higher in cases (9.92 foci/cell) compared to their matched controls (9.17 foci/cell) ( p < 0.01). The average dose response curve of the G0 MN assay for cases lies above the average dose response curve of the controls. Finally, a pairwise comparison of the G2+caf MN results showed a higher MN yield for cases (351 MN/1000BN) compared to controls (219 MN/1000BN) ( p < 0.01). Conclusion Current results suggest that intrinsic radiosensitivity is involved in the development of late radiotoxic effects. Larger prospective studies are warranted to validate the retrospective findings in order to use in vitro cellular assays in the future to predict late normal tissue radiosensitivity in clinical practice. [ABSTRACT FROM AUTHOR]

Define a multifactorial risk prediction model for RT-induced fibrosis and investigate the benefit of a personalized approach for breast cancer (BC) patients (pts) treated with whole breast RT. In a previous study, we confirmed the predictive role of 30 SNPs from the literature and built an interaction aware Polygenic Risk Score (PRS, following the methods from Franco RO 2021) for Late Fibrosis (FG2+) on a cohort of 1500 pts from the REQUITE EU/USA prospective observational study. The PRS weights the radiosensitive (RS) and radioresistant (RR) genetic components and can be included in NTCP models. In a subgroup from the same cohort (390 pts), we have also confirmed an NTCP model based on biologically Equivalent Uniform Dose (BEUD) from PTV DVHs for pts treated at 40-50 Gy and no RT boost. Here, we combine PRS and BEUD into a sigmoid model allowing PRS to modulate BEUD50 (BEUD leading to 50% FG2+), i.e., we permitted a personalized BEUD50. We can also consider this as translating the PRS into a personalized equivalent BEUD, which is added/subtracted to the treatment BEUD. We evaluated model performances through ROC-AUC, calibration plot and Precision-Recall AUC. A total of 381 pts had complete dosimetric/genetic data, prescribed dose 40-50 Gy, and no fibrotic alteration at RT start. We scored FG2+ in 87 pts (23%). PRS ranged from -13 (more RR pts) to 7 (more RS), and a unit in PRS corresponds to 5.3 Gy BEUD or 3 Gy in EQ EUD2 Gy. Table 1 summarizes model performances, with details for subgroups below/above the quartiles I/III of the BEUD distribution. The PRS-only model correctly describes the toxicity rates in the whole population (calibration slope/offset = 0/1). Still, it overestimates/underestimates the absolute risks in the low/high dose ranges. The integrated model improves AUC-ROC and AUC-PRC by 5% and 10% and guarantees a better calibration in pts receiving low/high BEUD to the PTV. We developed a multifactorial model for FG2+ based on two previously validated models and reported the improvement against single-factor models. The BEUD+PRS model is suitable for assisting clinicians in managing early-stage BC pts. The number of fractions or the daily dose could be reduced for RS pts. The integrated model resulted in a possible quantitative tool for driving the planning decision process. Also, it showed a better performance in the high BEUD region, suggesting the potential value of its extension toward RT including boost or ultra hypofractionation. We are testing this extension in the whole REQUITE cohort. [ABSTRACT FROM AUTHOR]

Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesized that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity. Data from 1681 men with prostate cancer were available from the multicenter perspective REQUITE study. Germline DNA was genotyped using a sequencing platform and imputed using the 1000 Genomes Project Phase 3. PRS and weighted-PRS (wPRS) were calculated for RA (101 SNPs) and analyzed as continuous variables and using a >95th percentile cut-off. Univariable and multivariable linear regression models analyzed relationships with: 1) acute and late standardized total averaged toxicity (STAT) scores; and 2) individual toxicity end points. Acute toxicity was defined as max reported toxicity within 90 days of RT (14 rectal, bladder and bowel endpoints) and late toxicity defined as max reported after 90 days for 5 endpoints. Multivariable analyses included: age, diabetes, previous surgery, hormone therapy and prescribed dose (converted to biologically equivalent dose). Residuals from multivariable linear regression models for acute and late STAT were calculated (rSTAT). Individual SNP gene doses were analyzed using linear regression against rSTAT to identify individual SNPs associated with worse reported toxicity. Bonferroni correction accounted for multiple testing with p<0.0005 considered significant. Men with >95th percentile PRS had a significantly worse STAT acute (p=0.02 in multivariable analysis). Age, previous surgery and hormones were also associated with worse STAT acute. For individual acute toxicity end points, hematuria (p=0.05) and dysuria (p=0.003) were higher in patients with >95th percentile PRS. PRS (p=0.02) and wPRS (p=0.03) were associated with worse STAT late on multivariable analysis. Patients with >95th percentile PRS also had worse STAT late on multivariable analysis (p=0.008). Age, previous surgery, hormones and dose were also associated with worse late STAT. For individual late toxicity endpoints, hematuria (p=0.01) and urinary frequency (p=0.006) showed a significant association with wPRS. Analysis of individual SNP gene doses against rSTAT acute identified an association with rs138193887 (p=0.0005) located in ATM , a gene linked with radiosensitivity. Men with prostate cancer and a high PRS for RA have an increased risk of acute and late toxicities after radiotherapy. Analysis of individual toxicity endpoints have identified bladder toxicities as most strongly associated with the RA PRS. Results will be validated in further cohorts, but suggest an actionable target for further bladder sparing for these men. [ABSTRACT FROM AUTHOR]

Purpose To quantify the influence on heart dose metrics of prone left-sided whole-breast irradiation in an end-inspiratory phase (Pr IN ) versus an end-expiratory phase (Pr EX ). Patients and methods Twenty patients underwent CT-simulation in Pr IN and Pr EX . Dynamic intensity-modulated radiotherapy was planned for whole-breast irradiation with a median prescription dose of 40.05 Gy in 15 fractions and maximal sparing of the organs at risk. Dose–volume parameters were analyzed for heart, left anterior descending coronary artery, ipsilateral lung and both breasts. Results Pr IN consistently reduced ( P < 0.001) heart and left anterior descending coronary artery dose metrics compared to Pr EX . Population averages for maximum and mean heart dose were 6.2 Gy and 1.3 Gy for Pr IN versus 21.4 Gy and 2.5 Gy for Pr EX , respectively. Moreover, a maximum heart dose less than 10 Gy was achieved in 80% of patients for Pr IN . Target dose distribution, ipsilateral lung and contralateral breast sparing by radiation dose were similar for both procedures. Conclusions Inspiratory gating consistently reduced heart dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for prone left-sided whole-breast irradiation. [ABSTRACT FROM AUTHOR]