Once-weekly hypofractionated whole-breast radiotherapy after breast-conserving surgery in older patients: A potential alternative treatment schedule to daily 3-week hypofractionation

Background The purpose of this study was to retrospectively report clinical outcomes on a consecutive series of older early breast cancer patients treated with once-weekly adjuvant whole-breast radiation therapy (WBRT) after breast-conserving surgery (BCS). Patients and Methods A total of 291 patients (298 breasts) were treated with WBRT between 2007 and 2013. Patients were given 6 to 6.5 Gy in 5 weekly fractions (total dose, 32.5-30 Gy) over 5 weeks. Clinical end points were local control (LC), disease-free (DFS), cancer-specific (CSS), and overall survival (OS), and acute and late toxicity and cosmesis. Prognostic clinical variables were assessed with respect to DFS. Results Median follow-up was 46.5 months (range, 12-84 months). The 3- and 5-year LC rates were 99.5% (95% confidence interval [CI], 96.4-99.9) and 98% (95% CI, 91.1-99.6). The 3- and 5-year CSS and OS were 97.7% (95% CI, 94.5-99.1), 95.3% (95% CI, 90.5-97.7), 94.4% (95% CI, 90.4-96.7), and 83.6% (95% CI, 76.1-88.9), respectively. Maximum detected acute skin toxicity was Grade (G) 0 in 71.8% of patients, G1 in 22.6%, G2 in 4.8%, G3 in 1%, and G4 in 0.3%. Treatment interruption occurred in 2 patients because of severe skin reactions. Late skin toxicity consisted of G1 fibrosis in 31.5% of patients, G2 in 4.2%, and G3 in 3.5%. Grade 1 edema was observed in 7% of patients, G2 in 4.2%, and G3 in 1.4%. G1 telangiectasia occurred in 1.8% and G3 in 0.7%. G1 hyperpigmentation was found in 4.6% of patients, G2 in 2.4%, and G1 atrophy was detected in 2.1%. Pain was observed as G1 in 13%, G2 in 1.8%, and G3 in 0.4%. Cosmetic results were good to excellent in 86.4% and fair to poor in 13.6%. Conclusion Once-weekly hypofractionated WBRT (30-32-5 Gy in 5 fractions), delivered with standard tangential fields with the patient in the supine position seems feasible and effective for a selected population of primarily old breast cancer patients with predominantly low-risk features. This schedule might allow fragile patients to receive adjuvant WBRT after BCS, increasing radiotherapy accessibility and utilization

The young mouse heart is composed of myocytes heterogeneous in age and function

The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16 and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16-positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16-negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential (AP) duration and ICaL play in potentiating Ca cycling and the mechanical behavior of young myocytes or in decreasing Ca transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K current Ito which was influenced by the different expression of the K channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function. © 2007 American Heart Association, Inc