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.

Prognostic Assessment of Interim F18-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer Treated With Chemoradiation With or Without Surgery.

Purpose This study aimed to evaluate if the F18-fluorodeoxyglucose positron emission tomography (F18-FDG PET) response after two weeks of chemoradiation for locoregionally advanced esophageal cancer (staged Tumor (T) 3 and/or Nodes (N)+ Metastases (M) 0) was linked to the pathologic response for patients undergoing surgery, to disease-free survival (DFS) or overall survival (OS). Materials and Methods Between March 2006 and September 2017, 40 patients were prospectively enrolled in our study, gave written consent, and had PET scans performed before treatment and after two weeks of chemoradiation. One patient did not undergo his two-week PET without informing study coordinators and was excluded from analyses. Results The median age at diagnosis was 62 years. Seventy-two percent of patients had N+ disease. Median OS for the entire group was 24 months. Five-year overall survival was 17%. Survival curves for patients with no PET response, minor PET response, or good PET response overlapped and were not statistically different. For the 25 patients who underwent surgery, the positive predictive value (PPV) of the PET response relative to the pathologic response was 75% and the negative predictive value (NPV) was 62%. In study patients, the crude recurrence rate was 68% and there was no correlation between PET response and DFS. Conclusion In our study, interim PET response after two weeks of chemoradiation for locoregionally advanced esophageal cancer was not predictive of outcome or pathologic response. Based on our data and current literature, interim PET should not be used to alter treatment (whether to escalate neo-adjuvant treatment or omit surgery).

In a Heartbeat: An Assessment of Dynamic Dose Variation to Cardiac Structures Using Dual Source Computed Tomography.

PURPOSE: To assess radiation dose variation to the left anterior descending artery (LAD), left main coronary artery (LMCA), left ventricle (LV), and whole heart (WH) during the cardiac cycle using dual source computed tomography (DSCT). METHODS AND MATERIALS: The present prospective study included patients with left-side breast cancer planned to undergo tangential radiation therapy. An electrocardiogram-synchronized contrast-injected DSCT scan was obtained with the patient in the treatment position, in deep-inspiration breath-hold, using retrospective sequential acquisition. The WH, LV, LMCA, and proximal, middle, and distal LAD segments were contoured on each phase of the cardiac cycle. The maximum, minimum, and mean Hausdorff distance between each structure and the tangential fields was assessed in ventricular systole and diastole. Four-dimensional dose-volume histograms were used to compare the systolic and diastolic dosimetric data. RESULTS: Ten patients were enrolled. The average maximum, minimum, and mean Hausdorff distance variation from systole to diastole was ≤4 mm for the LV and LMCA and ≤3 mm for the WH and LAD segments. WH maximum dose and volume receiving 5 Gy were decreased in systole compared with diastole (42.9 Gy versus 44.5 Gy, P = .03, and 21.7 cm3 versus 27.7 cm3, P = .01), but the mean dose remained similar throughout the cycle. The maximum and mean dose to the distal LAD was 21.2 Gy versus 26.6 Gy (P = .005) and 8.6 Gy versus 13.2 Gy (P = .006) in systole versus diastole, respectively. The maximum and mean dose to the middle LAD was 18.4 Gy versus 25.1 Gy (P = .005) and 8.5 Gy versus 10.2 Gy in systole versus diastole (P = .005). The maximum dose to the LV was lower in systole than in diastole (21.5 Gy vs 26.7 Gy; P = .005). CONCLUSIONS: In addition to deep-inspiration breath-hold, systolic irradiation is associated with a reduction in dose to the LAD, LV, and WH. In addition to its potential use in radiation planning for cardiac gating, DSCT imaging can be used to help define a planning organ at risk volume for clinically important cardiac substructures.

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.

Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma.

PURPOSE: To evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT). METHODS: From 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires. RESULTS: Five-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients. CONCLUSIONS: Short split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity.

Endocavitary radiation therapy for rectal adenocarcinoma: 10-year results.

Local control, survival, and toxicity in patients treated with endocavitary radiation therapy for rectal cancer were evaluated. Thirty-five patients received a total of 20 to 155 Gy in 1 to 5 fractions with 50 kV x-rays through a treatment proctoscope. Twenty-nine of the 35 patients were treated with curative intent. Median follow-up was 102 months. Local control was achieved in 23 of the 29 patients treated curatively and in 3 of the 6 treated palliatively. Local control for patients treated curatively was 76% at 10 years. No local failures occurred after 21 months. For patients treated curatively, survival was 65% at 5 years and 42% at 10 years. Toxicity within 90 days after treatment was observed in 77% of the patients. Toxicity occurring more than 90 days after treatment was observed in 80%, but only 1 patient needed a colostomy, which was for a perforation after the biopsy of a benign ulcer. In conclusion, radiation therapy resulted in a local control rate of 76% at 10 years in curatively treated patients. Although most patients experience toxicity from this treatment, loss of sphincter function is rare.