Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy.The EORTC "boost no boost" trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up.Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III "boost no boost" trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years.No further treatment or 16-Gy boost, after BCS and 50-Gy WBI.Time to ipsilateral breast tumor recurrence (IBTR) as first event.The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age (P < .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P = .001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95% CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P < .001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P < .001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P < .001) in high-risk patients (≤50 years with DCIS present).The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately.clinicaltrials.gov Identifier: NCT02295033.
Optimization of radiation therapy for head and neck tumors requires the combination of several facets of radiation biology and physics. The aim is to achieve optimum tumor control while reducing normal tissue damage. Techniques have been developed to determine tumor radiosensitivity and growth characteristics. Their use as predictive assays of treatment response is gaining importance. As the range of therapeutic options (particularly altered fractionation regimens) increases, it is hoped that the ability to individually tailor patients' treatment will result in improved rates of tumor control and an improved therapeutic ratio. Optimization of treatment delivery based on three-dimensional treatment planning offers the opportunity for dose escalation studies and limitation of normal tissue morbidity. The combination of chemotherapy and radiotherapy continues to be investigated, although major advances using this strategy are unlikely.
<p>Supplementary Table 1 - Genes positively and negatively associated with radiation sensitivity in breast cancer cell lines. Supplementary Table 2 - Genes positively and negatively associated with radiation sensitivity in breast cancer cell lines after training in the clinical dataset with associated outcomes. Supplementary Table 3 - Univariate and Multivariable analysis results for locoregional recurrence in the training and validation datasets for all available clinical and pathologic variable in these datasets.</p>
<p>Complete details on cell culture, qRT-PCR, si- and shRNA, clonogenic survival, xenograft, flow cytometry, microarray, and statistical experiments and analyses</p>
