http://hub.hku.hk/bitstream/10722/202753/1/Content.pdf

Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)60837-9.pdf

Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial

With the emergence of individualized medicine and the increasing amount and complexity of available medical data, a growing need exists for the development of clinical decision-support systems based on prediction models of treatment outcome. In radiation oncology, these models combine both predictive and prognostic data factors from clinical, imaging, molecular and other sources to achieve the highest accuracy to predict tumour response and follow-up event rates. In this Review, we provide an overview of the factors that are correlated with outcome-including survival, recurrence patterns and toxicity-in radiation oncology and discuss the methodology behind the development of prediction models, which is a multistage process. Even after initial development and clinical introduction, a truly useful predictive model will be continuously re-evaluated on different patient datasets from different regions to ensure its population-specific strength. In the future, validated decision-support systems will be fully integrated in the clinic, with data and knowledge being shared in a standardized, instant and global manner.

/pdf/predicting-outcomes-in-radiation-oncology-multifactorial-3gfq2rvwlt.pdf

Predicting outcomes in radiation oncology--multifactorial decision support systems

https://cris.maastrichtuniversity.nl/ws/files/36170460/Lambin_2017_Decision_Support_Systems.pdf

Decision support systems for personalized and participative radiation oncology

After breast-conserving radiation therapy most patients experience acute skin toxicity to some degree. This may impair patients’ quality of life, cause pain and discomfort. In this study, we investigated treatment and patient-related factors, including genetic polymorphisms, that can modify the risk for severe radiation-induced skin toxicity in breast cancer patients. We studied 377 patients treated at Ghent University Hospital and at ST.-Elisabeth Clinic and Maternity in Namur, with adjuvant intensity modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer. Women were treated in a prone or supine position with normofractionated (25 × 2 Gy) or hypofractionated (15 × 2.67 Gy) IMRT alone or in combination with other adjuvant therapies. Patient- and treatment-related factors and genetic markers in regulatory regions of radioresponsive genes and in LIG3, MLH1 and XRCC3 genes were considered as variables. Acute dermatitis was scored using the CTCAEv3.0 scoring system. Desquamation was scored separately on a 3-point scale (0-none, 1-dry, 2-moist). Two-hundred and twenty patients (58%) developed G2+ dermatitis whereas moist desquamation occurred in 56 patients (15%). Normofractionation (both p < 0.001), high body mass index (BMI) (p = 0.003 and p < 0.001), bra cup size ≥ D (p = 0.001 and p = 0.043) and concurrent hormone therapy (p = 0.001 and p = 0.037) were significantly associated with occurrence of acute dermatitis and moist desquamation, respectively. Additional factors associated with an increased risk of acute dermatitis were the genetic variation in MLH1 rs1800734 (p=0.008), smoking during RT (p = 0.010) and supine IMRT (p = 0.004). Patients receiving trastuzumab showed decreased risk of acute dermatitis (p < 0.001). The normofractionation schedule, supine IMRT, concomitant hormone treatment and patient related factors (high BMI, large breast, smoking during treatment and the genetic variation in MLH1 rs1800734) were associated with increased acute skin toxicity in patients receiving radiation therapy after breast-conserving surgery. Trastuzumab seemed to be protective.

https://biblio.ugent.be/publication/5848950/file/5849079.pdf

Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy.

Summary Background Letrozole radiosensitises breast cancer cells in vitro In clinical settings, no data exist for the combination of letrozole and radiotherapy We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting Methods This phase 2 randomised trial was undertaken in two centres in France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007 150 postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75) Randomisation was open label with a minimisation technique, stratified by investigational centres, chemotherapy (yes vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte apoptosis (≤16% vs >16%) Whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks In the case of supraclavicular and internal mammary node irradiation, the dose was 44–50 Gy Letrozole was administered orally once daily at a dose of 2·5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the sequential group) The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin Analyses were by intention to treat This study is registered with ClinicalTrialsgov, number NCT00208273 Findings All patients were analysed apart from one in the concurrent group who withdrew consent before any treatment During radiotherapy and within the first 12 weeks after radiotherapy, 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity The most common skin-related adverse event was dermatitis: four patients in the concurrent group and six in the sequential group had grade 3 acute skin dermatitis during radiotherapy At a median follow-up of 26 months (range 3–40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis) Interpretation Letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy Long-term follow-up is needed to investigate cardiac side-effects and cancer-specific outcomes Funding Novartis Oncology France

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(10)70013-9.pdf

Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial

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Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial