Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast.

PURPOSE: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. RESULTS: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). CONCLUSIONS: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer.

PURPOSE: To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). METHODS AND MATERIALS: At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane & Women's Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40 Gy in 15 fractions ('the 40 Gy/15# group') or 45 Gy in 30 fractions ('the 45 Gy/30# group'). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. RESULTS: Of 118 eligible patients, there were 38 patients in the 40 Gy/15# group and 41 patients in the 45 Gy/30# group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2-37 months) in the 40 Gy/15# group and 26 months (95% CI 1-48 months) in the 45 Gy/30# group. The 5-year overall survival rates were 20% and 25%, respectively (P = 0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P = 0.01) and whether salvage chemotherapy was given at the time of relapse (P = 0.057). CONCLUSIONS: Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival.

A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.

The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, ie, breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects. A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields. Patients were randomized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment. Weekly skin assessments were performed by nursing staff. Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment. Subjects with D cup or larger size breasts experienced significantly more erythema, regardless of treatment arm. For subjects who had undergone lymphocele drainage, the aloe vera group experienced significantly more pain than the aqueous cream group. Within the aqueous cream arm, smokers were significantly more likely to experience itching within the treatment field than were nonsmokers. Within the aloe vera arm, subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage. In this study, aloe vera gel did not significantly reduce radiation-induced skin side effects. Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy.