IMPORTANCE The most appropriate dose-fractionation for whole breast irradiation (WBI) remains uncertain. OBJECTIVE To assess acute and six-month toxicity and quality of life (QoL) with conventionally fractionated WBI (CF-WBI) versus hypofractionated WBI (HF-WBI). DESIGN Unblinded randomized trial of CF-WBI (n=149; 50 Gy/25 fractions + boost [10–14 Gy/5–7 fractions]) versus HF-WBI (n=138; 42.56 Gy/16 fractions + boost [10–12.5 Gy/4–5 fractions]). SETTING Community-based and academic cancer centers. PARTICIPANTS 287 women age ≥ 40 years with stage 0–II breast cancer treated with breast-conserving surgery for whom whole breast irradiation without addition of a third field was recommended. 76% (n=217) were overweight or obese. Patients were enrolled from February 2011 through February 2014. INTERVENTION(S) FOR CLINICAL TRIALS CF-WBI versus HF-WBI. MAIN OUTCOME MEASURES Physician-reported acute and six-month toxicities using NCICTCv4.0 and patient-reported QoL using the FACT-B version 4. All analyses were intention-to-treat, with outcomes compared using chi-square, Cochran-Armitage test, and ordinal logistic regression. Patients were followed for a minimum of 6 months. RESULTS Treatment arms were well-matched for baseline characteristics including FACT-B total score (P=0.46) and individual QoL items such as lack of energy (P=0.86) and trouble meeting family needs (P=0.54). Maximal physician-reported acute dermatitis (P<0.001), pruritus (P<0.001), breast pain (P=0.001), hyperpigmentation (P=0.002), and fatigue (P=0.02) during radiation were lower in patients randomized to HF-WBI. Overall grade ≥2 acute toxicity was less with HF-WBI vs. CF-WBI (47% vs. 78%; P<0.001). Six months after radiation, physicians reported less fatigue in patients randomized to HF-WBI (P=0.01), and patients randomized to HF-WBI reported less lack of energy (P<0.001) and less trouble meeting family needs (P=0.01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (OR 0.39, 95% CI 0.24–0.63) and trouble meeting family needs (OR 0.34, 95% CI 0.16–0.75). CONCLUSIONS AND RELEVANCE HF-WBI appears to yield less acute toxicity than CF-WBI, as well as less fatigue and trouble meeting family needs six months after completing radiation. These findings should be communicated to patients as part of shared decision-making. TRIAL REGISTRATION NCT01266642 (https://clinicaltrials.gov/ct2/show/NCT01266642)

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Evidence on the comparative effectiveness and safety of charged-particle radiation therapy in cancer is needed to assess the benefits, risks, and costs of treatment alternatives.

Successful retreatment of patients in whom the initial GKS treatment fails is feasible. Patients who respond initially may be at a higher risk of retreatment-related complications. There appears to be a dose-response relationship for both pain control and development of new side effects. It is important to counsel and treat patients individually based on this dose-response relationship.

Given the potential morbidity of whole brain radiation therapy (WBRT), there has been an increasing trend to defer WBRT and deliver Gamma Knife stereotactic radiosurgery (GKS) to cerebral metastatic lesions. We analyzed our experience delivering GKS to the tumor cavity following surgical resection of brain metastases and compared our results to patients receiving WBRT after surgical resection of a metastatic lesion. We performed a retrospective review of patients undergoing surgical resection of at least one brain metastasis between December 1999 and December 2008. Both univariate and multivariate Cox proportional hazards regression were utilized to analyze the influence of various prognostic factors on survival. Twenty-five patients had a metastatic lesion resected followed by adjuvant GKS to the resection cavity while another 18 had surgical resection followed by WBRT. Aside from a disparity in gender distribution (72% of GKS patients were female while women only constituted 28% of the WBRT group), no significant differences existed between groups. The median survival for patients receiving GKS was 15.00 months as compared to 6.81 months among those receiving WBRT (P = 0.08). Univariate Cox regression analysis identified the number of metastases (HR 1.65, 95% CI 1.07-2.54, P = 0.02) and regional recurrence (RR 5.23, 95% CI 1.78-15.38, P = 0.003) as poor prognostic factors. Multivariate regression analysis showed that regional recurrence (HR 5.17, 95% CI 1.69-15.78, P = 0.004) was again strongly associated with worse survival. Although limited by the retrospective nature of our study and lack of some clinical measures, patients undergoing GKS to the resection cavity had a trend towards longer median survival.

Purpose The adoption of hypofractionated whole-breast irradiation (HF-WBI) remains low, in part because of concerns regarding its safety when used with a tumor bed boost or in patients who have received chemotherapy or have large breast size. To address this, we conducted a randomized, multicenter trial to compare conventionally fractionated whole-breast irradiation (CF-WBI; 50 Gy/25 fx + 10 to 14 Gy/5 to 7 fx) with HF-WBI (42.56 Gy/16 fx + 10 to 12.5 Gy/4 to 5 fx). Patients and Methods From 2011 to 2014, 287 women with stage 0 to II breast cancer were randomly assigned to CF-WBI or HF-WBI, stratified by chemotherapy, margin status, cosmesis, and breast size. The trial was designed to test the hypothesis that HF-WBI is not inferior to CF-WBI with regard to the proportion of patients with adverse cosmetic outcome 3 years after radiation, assessed using the Breast Cancer Treatment Outcomes Scale. Secondary outcomes included photographically assessed cosmesis scored by a three-physician panel and local recurrence-free survival. Analyses were intention to treat. Results A total of 286 patients received the protocol-specified radiation dose, 30% received chemotherapy, and 36.9% had large breast size. Baseline characteristics were well balanced. Median follow-up was 4.1 years. Three-year adverse cosmetic outcome was 5.4% lower with HF-WBI ( Pnoninferiority = .002; absolute risks were 8.2% [n = 8] with HF-WBI v 13.6% [n = 15] with CF-WBI). For those treated with chemotherapy, adverse cosmetic outcome was higher by 4.1% (90% upper confidence limit, 15.0%) with HF-WBI than with CF-WBI; for large breast size, adverse cosmetic outcome was 18.6% lower (90% upper confidence limit, −8.0%) with HF-WBI. Poor or fair photographically assessed cosmesis was noted in 28.8% of CF-WBI patients and 35.4% of HF-WBI patients ( P = .31). Three-year local recurrence-free survival was 99% with both HF-WBI and CF-WBI ( P = .37). Conclusion Three years after WBI followed by a tumor bed boost, outcomes with hypofractionation and conventional fractionation are similar. Tumor bed boost, chemotherapy, and larger breast size do not seem to be strong contraindications to HF-WBI.

PurposeChronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic.Patients and methodsThe Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic.ResultsThe objective of this paper was to outline the methodology of this study.ConclusionThe establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic.

Protein hydrolysates produced by hydrochloric acid hydrolysis were analysed for 3-chloropropane-1,2-diol and its enantiomers. It was found that (R)-3-chloropropane-1,2-diol and (S)-3-chloropropane-1,2-diol were present in the hydrolysates in equimolar concentrations. Model experiments with glycerol, triolein and soy lecithin heated with hydrochloric acid in solution showed that these materials were precursors of 3-chloropropane-1,2-diol and 2-chloropropane-1,3-diol and, as expected, yielded racemic 3-chloropropane-1,2-diol. Yields of 3-chloropropane-1,2-diols decreased in the order triolein > lecithin > glycerol. The mechanisms of 3-chloropropane-1,2-diol enantiomers formation during the production of protein hydrolysates are presented and discussed as well as the reaction pathways of their decomposition in alkaline media via the corresponding intermediates, (R)-and (S)-glycidol, respectively. Both epoxides are hydrolysed to glycerol and form a variety of products with hydrolysate constituents.