Different meaning of the mean heart dose between 3D-CRT and IMRT for breast cancer radiotherapy

BackgroundPrevious studies in 2D and in 3D conformal radiotherapy concludes that the maximal heart distance and the mean heart dose (MHD) are considered predictive of late cardiac toxicities. As the use of inverse-planned intensity modulated radiation therapy (IMRT) is increasing worldwide, we hypothesized that this 3D MHD might not be representative of heart exposure after IMRT for breast cancer (BC).MethodsPatients with left-sided BC and unfavorable cardiac anatomy received IMRT. Their treatment plan was compared to a virtual treatment plan for 3D conformal radiotherapy with similar target volume coverage (study A). Then, a second 3D conformal treatment plan was generated to achieve equivalent individual MHD obtained by IMRT. Then the heart and left anterior descending (LAD) coronary artery exposures were analyzed (study B). Last, the relationship between MHD and the heart volume or LAD coronary artery volume receiving at least 30Gy, 40Gy and 45Gy in function of each additional 1Gy to the MHD was assessed (study C).ResultsA significant decrease of heart and LAD coronary artery exposure to high dose was observed with the IMRT compared with the 3D conformal radiotherapy plans that both ensured adequate target coverage (study A). The results of study B and C showed that 3D MHD was not representative of similar heart substructure exposure with IMRT, especially in the case of high dose exposure.ConclusionsThe mean heart dose is not a representative dosimetric parameter to assess heart exposure following IMRT. Equivalent MHD values following IMRT and 3DRT BC treatment do not represent the same dose distribution leading to extreme caution when using this parameter for IMRT plan validation

Treatment time and circadian genotype interact to influence radiotherapy side-effects. A prospective European validation study using the REQUITE cohort

Breast cancer; Circadian rhythm; RadiotherapyCáncer de mama; Ritmo circadiano; RadioterapiaCàncer de mama; Ritme circadià; RadioteràpiaBackground 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 normally.EU-FP7

Higher Toxicity with 42 Gy in 10 Fractions as a Total Dose for 3D-Conformal Accelerated Partial Breast Irradiation: Results from a Dose Escalation Phase II Trial

Objective: Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/5 days. Here, we report early results of the latest step compared with the 40 Gy dose level. Methods and materials: From October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12–26). All the patients were treated by APBI using a technique with 2 minitangents and an “enface” electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months. Results: Patients’ recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade ≥2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade ≥2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy. Conclusions: Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities