Cosmetic Results and Side Effects of Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Low-Risk Invasive Carcinoma of the Breast: The Randomized Phase III IRMA Trial.

PURPOSE: The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. METHODS: We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. RESULTS: Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities. CONCLUSION: External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

Breast-conserving therapy for primary Ductal Carcinoma in Situ in The Netherlands: A multi-center study and population-based analysis.

OBJECTIVE: The aim of this study was to analyse the efficacy of breast-conserving therapy (BCT) for women with primary DCIS in a population-based setting. METHODS: Data were used from five Radiotherapy centres in The Netherlands from 2000 to 2010, all treated with BCT. Of all the cases, 59.2% received a boost of radiotherapy after their whole breast irradiation (WBI), irrespective of margin status. RESULTS: A total of 1248 cases with primary DCIS were analysed. The 10-years LRFS was 92.9%. Age ≤50 years and a positive margin were significantly related to local relapse free survival (LRFS). Having a boost had no impact on LRFS, showing a nearly equal recurrence pattern in patients with and without a boost. Separate analyses were done on patients who had received and not received a boost of radiotherapy after WBI. We noted 9.1% contra-lateral breast tumours. The 10-years disease specific survival (DSS) rate was 99.0%. CONCLUSIONS: DCIS of the breast and treated with BCT results in excellent LRFS and DSS. Primary surgical lumpectomy with negative margins followed by WBI seems to be the treatment of choice in DCIS treated with BCS with respect to IBTR.

Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial.

PURPOSE: To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC) survivors. PATIENTS AND METHODS: In the PORTEC-2 trial, 427 patients with stage I high-intermediate-risk EC were randomly allocated to EBRT or VBT. The 7- and 10-year HRQL questionnaires consisted of EORTC QLQ-C30; subscales for bowel and bladder symptoms; the Impact of Cancer Questionnaire; and 14 questions on comorbidities, walking aids, and incontinence pads. Analysis was done using linear mixed models for subscales and (ordinal) logistic regression with random effects for single items. A two-sided P value <.01 was considered statistically significant. RESULTS: Longitudinal HRQL analysis showed persisting higher rates of bowel symptoms with EBRT, without significant differences in global health or any of the functioning scales. At 7 years, clinically relevant fecal leakage was reported by 10.6% in the EBRT group, versus 1.8% for VBT (P=.03), diarrhea by 8.4% versus 0.9% (P=.04), limitations due to bowel symptoms by 10.5% versus 1.8% (P=.001), and bowel urgency by 23.3% versus 6.6% (P<.001). Urinary urgency was reported by 39.3% of EBRT patients, 25.5% for VBT, P=.05. No difference in sexual activity was seen between treatment arms. Long-term impact of cancer scores was higher among the patients who had an EC recurrence or second cancer. CONCLUSIONS: More than 7 years after treatment, EBRT patients reported more bowel symptoms with impact on daily activities, and a trend for more urinary symptoms, without impact on overall quality of life or difference in cancer survivorship issues.

Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data.

BACKGROUND: The PORTEC-2 trial showed efficacy and reduced side-effects of vaginal brachytherapy (VBT) compared with external beam pelvic radiotherapy (EBRT) for patients with high-intermediate risk endometrial cancer. The current analysis was done to evaluate long-term health related quality of life (HRQL), and compare HRQL of patients to an age-matched norm population. METHODS: Patients were randomly allocated to EBRT (n=214) or VBT (n=213). HRQL was assessed using EORTC QLQ-C30 and subscales from PR25 and OV28 (bladder, bowel, sexual symptoms); and compared to norm data. FINDINGS: Median follow-up was 65 months; 348 (81%) patients were evaluable for HRQL (EBRT n=166, VBT n=182). At baseline, patient functioning was at lowest level, increasing during and after radiotherapy to reach a plateau after 12 months, within range of scores of the norm population. VBT patients reported better social functioning (p=0.005) and lower symptom scores for diarrhoea, faecal leakage, need to stay close to a toilet and limitation in daily activities due to bowel symptoms (p⩽0.001), compared to EBRT. There were no differences in sexual functioning or symptoms between the treatment groups; however, sexual functioning was lower and sexual symptoms more frequent in both treatment groups compared to the norm population. INTERPRETATION: Patients who received EBRT reported clinically relevant higher levels of bowel symptoms and related limitations in daily activities with lower social functioning, 5 years after treatment. VBT provides a better HRQL, which remained similar to that of an age-matched norm population, except for sexual symptoms which were more frequent in both treatment groups.

Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only.

Objective. The aim of this study is to look at possible differences in outcome between serosa and adnexal involvement stage IIIA endometrial carcinoma. Methods. 67 patients with stage IIIA endometrial carcinoma were included, 46 with adnexal involvement and 21 with serosa. A central histopathological review was performed. Results. The 7-year locoregional failure rate was (LRFR) 2.2% for adnexal involvement and 16.0% for involvement of the serosa (P = .0522). The 7-year distant metastasis-free survival was 72.7% for adnexal involvement and 58.7% for serosa (P = .3994). The 7-year disease-specific survival (DSS) was 71.8% for patients with adnexal involvement and 75.4% for patients with serosa. Conclusion. Endometrial carcinoma stage IIIA with involvement of the adnexa or serosa showed to have a comparable disease-specific survival. Locoregional control was worse for serosa involvement compared to adnexa.

Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial.

PURPOSE Studies on quality of life (QOL) among women with endometrial cancer have shown that patients who undergo pelvic radiotherapy report lower role functioning and more diarrhea and fatigue. In the Post Operative Radiation Therapy in Endometrial Cancer (PORTEC) trial, patients with endometrial carcinoma were randomly assigned to receive external-beam radiotherapy (EBRT) or vaginal brachytherapy (VBT). QOL was evaluated by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and subscales from the prostate cancer module, PR-25, and the ovarian cancer module, OV-28. PATIENTS AND METHODS PORTEC-2 accrued 427 patients between 2002 and 2006, of whom 214 were randomly assigned to EBRT, and 213 were randomly assigned to VBT. Three-hundred forty-eight patients (81%) were evaluable for QOL. QOL outcomes were analyzed at a median follow-up of 2 years. Results At baseline after surgery, patient functioning was at the lowest level, and it increased during and after radiotherapy to reach a plateau after 12 months. Patients in the VBT group reported better social functioning (P < .002) and lower symptom scores for diarrhea, fecal leakage, the need to stay close to the toilet, and limitation in daily activities because of bowel symptoms (P < .001). At baseline, 15% of patients were sexually active; this increased significantly to 39% during the first year (P < .001). Sexual functioning and symptoms did not differ between the treatment groups. CONCLUSION Patients who received EBRT reported significantly higher levels of diarrhea and bowel symptoms. This resulted in a higher need to remain close to a toilet and, as a consequence, more limitation of daily activities because of bowel symptoms and decreased social functioning. Vaginal brachytherapy provides a better QOL, and should be the preferred treatment from a QOL perspective.

Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial.

PURPOSE: Stage IC, grade 3 endometrial cancer is regarded as a high-risk category. Stage IC, grade 3 patients were not eligible for the randomized Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial, but were registered and received postoperative radiotherapy. PATIENTS AND METHODS: The PORTEC trial included 715 patients with stage IC, grade 1 or 2, and stage IB, grade 2 or 3 endometrial cancer. Patients were randomly assigned after surgery to receive pelvic radiotherapy (RT) or no further treatment. A total of 104 patients with stage IC, grade 3 endometrial cancer were registered, of whom 99 could be evaluated. Patterns of relapse and survival were compared with PORTEC patients receiving RT. Median follow-up was 83 months. RESULTS: The actuarial 5-year rates of locoregional relapse were 1% to 3% for PORTEC patients who received RT, compared with 14% for stage IC, grade 3 patients. Five-year distant metastases rates were 3% to 8% for grade 1 and 2 tumors; 20% for stage IB, grade 3 tumors; and 31% for stage IC, grade 3 tumors. Overall survival rates were 83% to 85% for grades 1 and 2; 74% for stage IB, grade 3; and 58% for stage IC, grade 3 patients (P <.001). In multivariate analysis grade 3 was the most important adverse prognostic factor for relapse and death as a result of endometrial cancer (hazard ratios, 5.4 and 5.5; P <.0001). CONCLUSION: Patients with stage IC, grade 3 endometrial carcinoma are at high risk of early distant spread and endometrial carcinoma-related death. Novel strategies for adjuvant therapy should be explored to improve survival for this patient group.