External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial.

BACKGROUND: Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. METHODS: We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. FINDINGS: Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). INTERPRETATION: External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. FUNDING: Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

Predictors of adverse cosmetic outcome in the RAPID trial: an exploratory analysis.

PURPOSE: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. METHODS AND MATERIALS: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only. RESULTS: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. CONCLUSION: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.

Evaluation of dosimetric consequences of seroma contour variability in accelerated partial breast irradiation using a constructed representative seroma contour.

PURPOSE: Contouring variability of the seroma can have important implications in the planning and delivery of accelerated partial breast irradiation (APBI). This study aimed to quantify the dosimetric impact of these interobserver and intraobserver contouring variations by construction of a representative seroma contour (RSC). METHODS AND MATERIALS: Twenty-one patients with a seroma suitable for APBI underwent four computed tomography (CT) scans: one planning CT and three additional CTs on the first, third, and fifth days of treatment. Three radiation oncologists contoured the seroma on each CT scan. For 3 patients, oncologists repeated contouring twice to assess intraobserver variations. Seroma contour variability was quantified by construction of an RSC. In addition, the percent volume overlap (PVO) was calculated. Root-mean-square (RMS) differences in seroma volume, size, and center of mass position compared to those of the RSC were calculated. Treatment fields from the original plan were applied to the repeated CTs by using the same isocenter shifts as the original plan. The dosimetric impact of the contour variations was assessed using V(95) (volume receiving at least 95% of the prescribed dose) and equivalent uniform dose (EUD). RESULTS: Interobserver RMS volume differences were, on average, 5.6 times larger than intraobserver differences. The median interobserver RMS seroma volume difference was 1.48 cm(3). The median PVO was 51.6%. V(95) and EUD of the seroma contours were similar for all patients. The median RMS differences of the seroma V(95) and EUD were 0.01% (range, 0%-3.99%) and 0.05 Gy (range, 0-0.98 Gy). CONCLUSIONS: Construction of the RSC showed that interobserver variations were most responsible for contour variations of the seroma. Current planning margins provided adequate dose coverage of the seroma despite these contour variations.

Polyradiculopathy post-concomitant chemoradiation for carcinoma of the uterine cervix treated with pelvic and para-aortic fields.

BACKGROUND: It is becoming more common to include the para-aortic lymph nodes in the radiation fields of patients treated with concomitant weekly cisplatin for node-positive squamous cell carcinoma of the cervix. CASE: We report on two patients who developed unexpected subacute neurological toxicity with lower extremity paresis and paresthesis, beginning 1 and 4 months post-treatment. CONCLUSION: We believe this to be a rare side effect of chemoradiation. As the dose delivered to the spinal nerve roots was less than 37 Gy in 25 fractions, we believe that the extended fields and concomitant cisplatin had a synergistic effect on the nerves.