Adjuvant hypofractionated radiotherapy with simultaneous integrated boost after breast-conserving surgery: results of a prospective trial.

PURPOSE: We report results of a multicenter prospective single-arm phase II trial (ARO-2013-04, NCT01948726) of moderately accelerated hypofractionated radiotherapy with a simultaneous integrated boost (SIB) in patients with breast cancer receiving adjuvant radiotherapy after breast-conserving surgery. METHODS: The eligibility criteria included unifocal breast cancer with an indication for adjuvant radiotherapy to the whole breast and boost radiotherapy to the tumor bed. The whole breast received a dose of 40 Gy and the tumor bed a total dose of 48 Gy in 16 fractions of 2.5 and 3 Gy, respectively. Radiotherapy could be given either as 3D conformal RT (3D-CRT) or as intensity-modulated radiotherapy (IMRT). The study was designed as a prospective single-arm trial to evaluate the acute toxicity of the treatment regimen. The study hypothesis was that the frequency of acute skin reaction grade ≥2 would be 20% or less. RESULTS: From November 2013 through July 2014, 149 patients were recruited from 12 participating centers. Six patients were excluded, leaving 143 patients for analysis. Eighty-four patients (58.7%) were treated with 3D-CRT and 59 (41.3%) with IMRT. Adherence to the treatment protocol was high. The rate of grade ≥2 skin toxicity was 14.7% (95% confidence interval 9.8-21.4%). The most frequent grade 3 toxicity (11%) was hot flashes. CONCLUSION: This study demonstrated low toxicity of and high treatment adherence to hypofractionated adjuvant radiotherapy with SIB in a multicenter prospective trial, although the primary hypothesis was not met.

Hypofractionation with simultaneous integrated boost after breast-conserving surgery: Long term results of two phase-II trials.

PURPOSE: To analyze long-term results of two multicenter prospective single-arm trials (ARO-2010-01 and ARO-2013-04) investigating adjuvant hypofractionated radiotherapy (HF) with simultaneous integrated boost (SIB) after breast-conserving surgery (BCS). METHODS: Eligible patients had histopathologically confirmed unifocal breast cancer planned for whole breast irradiation plus boost radiotherapy to the tumor bed. In both studies, a total dose of 40 Gy was applied to the whole breast and of 48 Gy to the tumor bed in 16 fractions of 2.5 and 3.0 Gy. Radiotherapy could be given either as three-dimensional conformal radiotherapy (3D-CRT) or as intensity-modulated radiotherapy (IMRT). The primary study objectives were feasibility and security within an observation period of six months. The current investigation focuses on long-term efficacy and toxicities. RESULTS: Between 2011 and 2014, both trials enrolled 300 patients in total. Data from 274 of these patients could be used for the current analysis. The median follow-up time was 60 months and the 5-year disease-free survival 92.1%. Three patients suffered a local recurrence (after 36-72 months) while a regional recurrence occurred in one patient (after 17 months). The 5-year local control rate in the breast was 99.6%. 63.5% of all patients did not report any late radiation-related toxicity, 28.5% reported grade 1 and 7.3% grade 2 toxicities. The highest late toxicity was grade 3 in 2 women (0.7%, telangiectasia and lymphedema of the breast). CONCLUSION: Our analysis demonstrates favorable efficacy and low rates of long-term side effects of HF with SIB after BCS. Randomized controlled phase III trials are ongoing.

Cardiac Toxicity after Radiotherapy for Breast Cancer: Myths and Facts.

Radiotherapy is an important component in the multidisciplinary treatment of breast cancer. In recent years, the cardiac risks of radiation have been discussed several times. This problem has long been known and resolved from the radiotherapeutic point of view. The current data is briefly described here.

Is standard breast-conserving therapy (BCT) in elderly breast cancer patients justified? A prospective measurement of acute toxicity according CTC-classification.

BACKGROUND: Breast conserving therapy (BCT) is an accepted treatment for early-stage breast cancer. This study aimed to measure prospectively acute radiation-related toxicity and to create a comprehensive data base for long-term temporal analyses of 3D conformal adjuvant radiotherapy. The specific aspect of age has been neglected by traditional research. Therefore, the impact of age on acute BCT toxicity should be also specifically addressed. METHODS: Toxicity was measured in 109 patients at initiation (t1), during radiotherapy (t2-t7), and 6 weeks after treatment completion (t8) using a new topographic module. Organ systems were recorded in 15 scales and scored according to symptom intensity (grade 0-5) based on CTC (Common Toxicity Criteria) -classification. Radiotherapy was virtually CT-based planned and applied with 6-MeV-photons. Mean total dose was 60.1 Gy. Patients were stratified by age in 3 Groups: <50, 50-60, and >60 years. RESULTS: Registered toxicity was generally low. Mean overall-grade climbed from 0.29-0.40 (t1-t7), and dropped to 0.23 (t8). Univariate analyses revealed slightly higher toxicity in older (> 60 years) versus young patients (< 50 years) in 2 scales only: breast-symmetry (p = 0.033), and arm function (p = 0.007). However, in the scale "appetite" toxicity was higher in younger (< 50 years) versus older (> 60 years) patients (p = 0.039). Toxicity differences in all other scales were not significant. Between older (> 60 years) and midaged patients (50-60 years) no significant differences in toxicity were found. This was also true for the comparison between young (< 50 years) versus midaged patient groups (50-60 years). CONCLUSION: The treatment concept of BCT for breast cancer is generally well tolerated. The toxicity-measurement with the new topographic module is feasible. Not modified standard treatment for BC should be performed in elderly women.

[Perspectives of radiation therapy in benign diseases]. / Perspektiven der Strahlentherapie gutartiger Erkrankungen.

PURPOSE: The numbers of patients with nonmalignant diseases referred for radiation therapy had to be evaluated for the last 4 years. PATIENTS AND METHODS: In the years 2002, 2004, and 2005 radiation therapy was performed in 61, 40, and 26 patients, respectively. Regularly, more women than men were treated, median age annually was 57, 54, and 55 years, respectively (Table 1). The radiotherapy scheme was not modified within the evaluated period. RESULTS: The proportion of nonmalignant diseases among all patients treated decreased from 4.7% in 2002 to 3.3% in 2004 and 2.2% in 2005, respectively. A shift was noticed toward the treatment of four main diseases (endocrine orbitopathy, prevention of heterotopic ossification, meningeoma, tendinitis, Table 2). The number of referring physicians decreased from 19 to six. CONCLUSION: Due to administrative restrictions for treatment in hospitals, budget restrictions in private practices and lasting, insufficient revenues for radiotherapy in nonmalignant diseases, radiation therapy for the entire group of benign diseases is endangered.

Significant negative impact of adjuvant chemotherapy on health-related quality of life (HR-QoL) in women with breast cancer treated by conserving surgery and postoperative 3-D radiotherapy. A prospective measurement.

PURPOSE: To prospectively assess health-related quality of life (HR-QoL) in women after conserving surgery for breast cancer during/after postoperative 3-D radiotherapy. PATIENTS AND METHODS: 109 consecutively treated patients were analyzed. HR-QoL was assessed at initiation (t1), end (t2), and 6 weeks after radiotherapy (t3) using the EORTC modules QLQ-C30/BR23. Patients were divided into three therapy groups. Group I comprised 41 patients (radiotherapy and adjuvant chemotherapy), group II 45 patients (radiotherapy and adjuvant hormonal therapy), and group III 23 patients (radiotherapy alone). Reliability was tested. Scale means were calculated. Univariate (ANOVA) and multivariate (MANCOVA) analyses were performed. RESULTS: Reliability testing revealed mean Cronbach's alpha> 0.70 at all measurement points. ANOVA/MANCOVA statistics revealed significantly better HR-QoL for patients in group II versus I. Patients receiving radiotherapy alone (group III) showed the best results in HR-QoL. However, scale mean differences between groups II and III were not significant. CONCLUSION: HR-QoL measurement using EORTC instruments during/after radiotherapy is reliable. Adjuvant chemotherapy significantly lowered HR-QoL versus hormones or radiotherapy alone. Chemotherapy patients did not recover longitudinally (from t1 to t3).