Whole-breast Irradiation Group Research Articles

Comparative long-term oncological outcomes of intraoperative radiotherapy vs. whole-breast irradiation in early breast cancer: a single institute study.

Intraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breast-conserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings. Female patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed. A total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5cm for BC and 1.2cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030). At a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER- patients for IORT.

Patient-reported outcomes in N1 breast cancer: A phase III trial comparing whole-breast to whole-breast plus regional irradiation after taxane-based chemotherapy (KROG 1701).

577 Background: Recent randomized trials have highlighted the benefits of regional node irradiation (RNI) in high-risk node-positive or pN1 breast cancer, yet its impact in the context of modern taxane-based adjuvant chemotherapy remains unclear. In this multi-center phase III trial, we study to prove the hypothesis that there is no difference in terms of disease-free survival between standard whole-breast irradiation (WBI) with RNI and WBI alone in pN1 breast cancer patients receiving taxane-based adjuvant chemotherapy. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are now reported. Methods: The KROG 17-01 trial (NCT03269981), a prospective, multicenter, non-inferiority study, randomized patients with pN1 breast cancer after breast-conserving surgery and adjuvant taxane-containing chemotherapy to WBI or WBI+RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. PROs were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at follow-up intervals of 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. Linear mixed models were used to compare PROs between treatment arms. Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI). Overall, PRO domains improved over time (p<0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (p<0.05), and reported lower global health (p=0.090) and physical functioning (p=0.049) with borderline significance compared to the WBI group. At 3-6 months post-RT, WBI+RNI group also showed higher arm symptom scores (p=0.030). Apart from these specific timepoints, no significant differences were observed in other PRO domain scores, including arm and breast symptoms, between treatment arms. In addition, there was no significant differences in PRO domains according to RT techniques and fractionation, except for breast symptoms during RT, favoring hypofractionation and intensity-modulated RT. Conclusions: In patients with pN1 breast cancer treated with taxane-based adjuvant chemotherapy, adding RNI was associated with minor, transient declines in specific PRO domains. However, these differences were not clinically significant, indicating comparable overall patient experiences between the two treatment arms. Clinical trial information: NCT03269981 .

Adjuvant Hypofractionated Whole Breast Irradiation (WBI) vs. Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5Years Update of the HYPAB Trial

Therapeutical strategies in breast cancer are continuously updating. Recent researches assessed the possibility of irradiating only the surgical bed in selected patients (Partial Breast Irradiation, PBI). In 2014 we designed a study to evaluate toxicity and cosmesis of APBI using Volumetric Modulated Arc Therapy-Rapid Arc compared with hypofractionated whole breast irradiation (WBI). We present here the 5-years updated data. HYPAB was a single-institution randomized trial that recruited 172 patients from 2015 to 2018. Patients underwent conserving surgery and were randomized to either adjuvant WBI (40.5Gy/15 fractions with simultaneous boost to 48 Gy to tumoral bed) or APBI (30Gy/5 fractions), both delivered with VMAT-RA technique. Clinical evaluation was performed during the first visit, once a week during radiotherapy and during follow up. Cosmesis was assessed using the Harvard Scale for Breast Cosmesis. At the time of the analysis 161 patients were eligible, 53% in the WBI and 47% in the APBI group, with a median follow-up of 67 months. Most common late skin toxicities were G1 fibrosis (32%) and oedema (28%) and were higher in the WBI group; no G3 toxicities were observed. Cosmesis was rated poor in only 6 cases. 147 patients had no evidence of disease at the last follow-up, and no patients died of the disease. Mature results confirm the safety and efficacy of APBI in selected early stage breast cancer patients. Late toxicity is improved in the APBI arm at the cost of a slight increase in local relapse. Further studies are ongoing to better elucidate the use of APBI as a de-escalation approach.

Prospective Cohort Study to Evaluate Toxicity and Cosmesis between Interstitial APBI and Ultra-Hypo-Fractionated Whole Breast Irradiation in Patients with Early Breast Cancer

Both interstitial multi-catheter brachytherapy based accelerated partial breast irradiation (APBI) and ultra-hypo-fractionated whole breast irradiation (WBI) with 5 fractions can complete treatment in a short time and result in lower treatment-related costs. Although data are available on their toxicity compared with conventional and hypo-fractionated regimens, there are few data directly comparing these two techniques. This prospective cohort study enrolled early breast cancer patients with negative ink margin, T1 or T2 stage, and tumor size of 3 cm or less, with 0 to 3 positive lymph nodes after adequate axillary dissection or negative sentinel lymph node biopsy (N0-1), regardless of receptor status (ER, PR, HER2neu). Of the total 31 patients, 15 received APBI with multi-catheter interstitial brachytherapy (35 Gy in10 fractions over 5 days with a minimum interval of 6 hours between fractions) and 16 patients received WBI (27 Gy in 5 fractions over 5 days) with either 3DCRT or VMAT technique. Acute toxicity was assessed using the RTOG toxicity grading and breast cosmesis was assessed using the Harvard breast cosmesis score. Toxicity and cosmesis were assessed immediately after treatment, after one month, and after three months of treatment. Results were compared between groups using the Mann Whitney U test. All patients completed a 3-month follow-up after completion of treatment. There was no statistically significant difference between the 2 groups in terms of highest grade toxicity (p = 0.97) and acute toxicity immediately after RT (p = 1.0) and after 1 month of RT (p = 0.91). However, at 3 months, more patients in the WBI group had a residual skin reaction than in the APBI group (p = 0.03). There was no statistically significant difference in breast cosmesis scores at any time point. 53.3%, 6.6% had grade 1 and 2 skin toxicities respectively immediately after RT in the APBI group and 62.5% of patients had grade 1 skin toxicity in WBI group. After 1 month 26.6%, 26.6% & 13.3% patients had grade 2, grade 1 and grade 3 toxicities respectively. In the WBI group, at 1 month, 50%, 18.7% and 12.5% patients had grade 1, 3 and 2 skin toxicities respectively. At 3 months, 42.8% and 7.1% of patients in the APBI group had grade 1 and grade 2 toxicities, respectively. In the WBI group, 78.5% and 7.1% of patients had grade 1 and 2 skin toxicities respectively. In this study, no difference in acute toxicity or breast cosmesis was demonstrated between APBI-based interstitial brachytherapy and ultra-hypo-fractionated WBI. Since both regimens can be administered within 5 days, the decision between them is challenging for both physicians and patients. This study can be considered hypothesis-generating and used for further planning of equivalence or noninferiority studies.

Whole Breast Irradiation in Comparison to Endocrine Therapy in Early Stage Breast Cancer-A Direct and Network Meta-Analysis of Published Randomized Trials.

Multiple randomized trials have established adjuvant endocrine therapy (ET) and whole breast irradiation (WBI) as the standard approach after breast-conserving surgery (BCS) in early-stage breast cancer. The omission of WBI has been studied in multiple trials and resulted in reduced local control with maintained survival rates and has therefore been adapted as a treatment option in selected patients in several guidelines. Omitting ET instead of WBI might also be a valuable option as both treatments have distinctly different side effect profiles. However, the clinical outcomes of BCS + ET vs. BCS + WBI have not been formally analyzed. We performed a systematic literature review searching for randomized trials comparing BCS + ET vs. BCS + WBI in low-risk breast cancer patients with publication dates after 2000. We excluded trials using any form of chemotherapy, regional nodal radiation and mastectomy. The meta-analysis was performed using a two-step process. First, we extracted all available published event rates and the effect sizes for overall and breast-cancer-specific survival (OS, BCSS), local (LR) and regional recurrence, disease-free survival, distant metastases-free interval, contralateral breast cancer, second cancer other than breast cancer and mastectomy-free interval as investigated endpoints and compared them in a network meta-analysis. Second, the published individual patient data from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) publications were used to allow a comparison of OS and BCSS. We identified three studies, including a direct comparison of BCS + ET vs. BCS + WBI (n = 1059) and nine studies randomizing overall 7207 patients additionally to BCS only and BCS + WBI + ET resulting in a four-arm comparison. In the network analysis, LR was significantly lower in the BCS + WBI group in comparison with the BCS + ET group (HR = 0.62; CI-95%: 0.42-0.92; p = 0.019). We did not find any differences in OS (HR = 0.93; CI-95%: 0.53-1.62; p = 0.785) and BCSS (OR = 1.04; CI-95%: 0.45-2.41; p = 0.928). Further, we found a lower distant metastasis-free interval, a higher rate of contralateral breast cancer and a reduced mastectomy-free interval in the BCS + WBI-arm. Using the EBCTCG data, OS and BCSS were not significantly different between BCS + ET and BCS + WBI after 10 years (OS: OR = 0.85; CI-95%: 0.59-1.22; p = 0.369) (BCSS: OR = 0.72; CI-95%: 0.38-1.36; p = 0.305). Evidence from direct and indirect comparison suggests that BCS + WBI might be an equivalent de-escalation strategy to BCS + ET in low-risk breast cancer. Adverse events and quality of life measures have to be further compared between these approaches.

Cosmetic Outcome and Toxicity After Stereotactic Accelerated Partial Breast Irradiation in Early Breast Cancer: A Prospective Observational Cohort Study

The aim of this work was to prospectively evaluate the toxicity and cosmetic outcomes of 5-fraction, stereotactic, accelerated partial breast irradiation (APBI). This prospective observational cohort study enrolled women who underwent APBI for invasive carcinoma or carcinoma in situ of the breast. APBI was delivered using a CyberKnife M6 robotic radiosurgery system at 30 Gy in 5 nonconsecutive, once-daily fractions. Women undergoing whole breast irradiation (WBI) were also enrolled for comparison. Patient-reported and physician-assessed adverse events were recorded. Breast fibrosis was measured using a tissue compliance meter, and breast cosmesis was assessed using BCCT.core (an automatic, computer-based software). Outcomes were collected until 24 months posttreatment according to the study protocol. In total, 204 patients (APBI, n=103; WBI, n=101) were enrolled. Regarding patient-reported outcomes, the APBI group reported significantly less skin dryness (6.9% vs 18.3%; P=.015), radiation skin reaction (9.9% vs 23.5%; P=.010), and breast hardness (8.0% vs 20.4%; P=.011) at 6 months than the WBI group. On physician assessment, the APBI group had significantly less dermatitis at 12 months (1.0% vs 7.2%; P=.027) than the WBI group. Any severe toxicities after APBI were rare in patient-reported outcomes (score ≥3, 3.0%) and physician assessments (grade ≥3, 2.0%). In the uninvolved quadrants, measured fibrosis in the APBI group was significantly lower than that in the WBI group at 6 (P=.001) and 12 (P=.029) months but not at 24 months. In the involved quadrant, measured fibrosis in the APBI group was not significantly different from that in the WBI group at any time. Cosmetic outcomes in the APBI group were mostly excellent or good (77.6%) at 24 months, and there was no significant cosmetic detriment from the baseline. Stereotactic APBI was associated with less fibrosis in the uninvolved breast quadrants than WBI. Patients showed minimal toxicity and no detrimental effects on cosmesis after APBI.

Significance of Hypofractionated Radiotherapy in Postoperative Irradiation for Breast Cancer: An Asian Multi-institutional Prospective Study

AimsThere is a need for the adequate distribution of healthcare resources in Southeast Asia. Many countries in the region have more patients with advanced breast cancer who are eligible for postmastectomy radiotherapy (PMRT). Therefore, it is critical that hypofractionated PMRT is effective in most of these patients. This study investigated the significance of postoperative hypofractionated radiotherapy in patients with breast cancer, including advanced breast cancer, in these countries. Materials and methodsEighteen facilities in 10 Asian countries participated in this prospective, interventional, single-arm study. The study included two independent regimens: hypofractionated whole-breast irradiation (WBI) for patients who had undergone breast-conserving surgery and hypofractionated PMRT for patients who had undergone total mastectomy at a dose of 43.2 Gy in 16 fractions. In the hypofractionated WBI group, patients with high-grade factors received additional 8.1 Gy boost irradiation sessions for the tumour bed in three fractions. ResultsBetween February 2013 and October 2019, 227 and 222 patients were enrolled in the hypofractionated WBI and hypofractionated PMRT groups, respectively. The median follow-up periods in the hypofractionated WBI and hypofractionated PMRT groups were 61 and 60 months, respectively. The 5-year locoregional control rates were 98.9% (95% confidence interval 97.4–100.0) and 96.3% (95% confidence interval 93.2–99.4) in the hypofractionated WBI and hypofractionated PMRT groups, respectively. Regarding adverse events, grade 3 acute dermatitis was observed in 2.2% and 4.9% of patients in the hypofractionated WBI and hypofractionated PMRT groups, respectively. However, no other adverse events were observed. ConclusionAlthough further follow-up is required, hypofractionated radiotherapy regimens for postoperative patients with breast cancer in East and Southeast Asian countries are effective and safe. In particular, the proven efficacy of hypofractionated PMRT indicates that more patients with advanced breast cancer can receive appropriate care in these countries. Hypofractionated WBI and hypofractionated PMRT are reasonable approaches that can contain cancer care costs in these countries. Long-term observation is required to validate our findings.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival

Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P=.02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P=.02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Evaluation of Early Cosmetic Outcome and Toxicity after 5-Fraction Stereotactic Partial Breast Irradiation in Early-Stage Breast Cancer: A Prospective Cohort Study

<h3>Purpose/Objective(s)</h3> Partial breast irradiation (PBI) is a promising approach to minimize the patient burden by reducing irradiated volumes with accelerated schedules. Stereotactic-PBI (S-PBI) using a robotic stereotactic radiation system is a less invasive modality. However, prospective data are limited regarding the course of breast fibrosis and cosmesis as objective measures. We prospectively evaluated early toxicity and cosmetic outcome in women undergoing 5-fraction S-PBI. <h3>Materials/Methods</h3> Women undergoing S-PBI for invasive carcinoma and/or carcinoma in situ were prospectively enrolled. S-PBI was delivered with a robotic radiosurgery system with a dose of 30 Gy in 5 fractions. Simultaneously, women who were not a candidate for PBI, but were undergoing whole breast irradiation (WBI) were also enrolled for comparison. Patient-reported and physician-assessed adverse events were noted. Breast fibrosis was measured with a tissue compliance meter. Cosmesis was assessed with automatic computer-based software, BCCT.core. <h3>Results</h3> In total, 204 patients (n = 103, S-PBI; n = 101, WBI) were included, of whom 197 (97%) and 133 (65%) completed a 12-month and 24-month evaluation, respectively. The amount of fibrosis in uninvolved quadrants decreased over time following S-PBI for 12 months. In contrast, this finding peaked at 6 months and further decreased at 12 months in the WBI group. The amount of fibrosis of uninvolved quadrants at 6 months was significantly lower in the S-PBI group than in the WBI group (<i>P = 0.002</i>), while that of involved quadrants or scar sites was not significantly different between groups. In the S-PBI group, patient-reported grade 3–4 events were 3% at 6 months and 0% at 12 months. Physician-assessed grade 3–4 events were 2% at 6 months and 0% at 12 months. Moreover, in the S-PBI group, most cosmetic outcomes were excellent or good (82%) at 24 months, and there was no significant cosmetic detriment from baseline (<i>P = 0.353</i>). <h3>Conclusion</h3> Patients who underwent S-PBI presented with less fibrosis affecting their uninvolved breast quadrants than those who underwent WBI. Patients showed minimal toxicity with no detrimental effect on cosmesis after S-PBI. Longer-term follow-up is ongoing and necessary.

A propensity score-matched analysis of breast-conserving surgery plus whole-breast irradiation versus mastectomy in breast cancer.

Recent observations regarding long-term outcomes among patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS) plus whole-breast irradiation (WBI) or mastectomy are from a small number of registry-based studies. Therefore, these findings may overestimate differences in survival between the two groups, compared with randomized controlled trials conducted in the 1980s. The aim of this study is to compare long-term outcomes and clinicopathologic characteristics between patients treated with BCS + WBI or mastectomy for BC. We performed a propensity score-matched analysis in a cohort of 9710 patients aged < 70years who underwent BCS + WBI or mastectomy without external radiotherapy for a first primary BC (pT1-2, N0-3a) at the European Institute of Oncology between 2000 and 2008. Patients were matched by propensity score. Median follow-up was 8.4years (interquartile range 6.5-10.2). The cumulative incidence of axillary lymph node recurrence at 10years was lower in the BCS + WBI group [2.4% (95% CI, 1.7-3.3%)] than in the mastectomy group [4.4% (95% CI, 3.5-5.5%)] (P = .0005), and the cumulative incidence of contralateral BC was higher in the BCS + WBI group [3.9% (95% CI, 2.8-5.1%)] than in the mastectomy group [2.5% (95% CI, 1.7-3.4%)] (P = .01). Among the 366 patients with HER2 subtype BC, BCS + WBI was associated with a fivefold higher risk [hazard ratio 4.97 (95% CI, 2.28-10.8)] of ipsilateral breast tumor recurrence (IBTR), compared with mastectomy (P < .0001); however, among patients with other BC subtypes, the rates of IBTR were not statistically significantly different. Patients with HER2 subtype BC (T1-2, N0-3) who underwent BCS + WBI had a statistically significantly higher risk of IBTR than patients who underwent mastectomy. Survival was not statistically significantly different between the groups.

Comparison of Prognosis Between Breast Conserving Therapy and Mastectomy in Early Breast Cancer: A Propensity Score Matching Analysis

The survival benefit of breast conserving therapy (BCT) over mastectomy has been shown in recent studies. The aim of the present study is to further explore oncologic outcomes between BCT and mastectomy in modern era.Continuous patients diagnosed with stage pT1-2, pN0-1, M0 breast cancer between 2009 and 2015 in one hospital were retrospectively reviewed. Recurrence patterns were evaluated among whole breast irradiation (WBI), mastectomy-alone, WBI with RNI and PMRT. Two separate comparisons of survival outcomes were performed using 1:1 propensity score matching (PSM): WBI versus mastectomy-alone, WBI with RNI versus PMRT (including RNI).2429 patients were enrolled in this analysis. The median follow up was 72 months (range, 54 to 94 months). Compared with those treated with mastectomy, patients who received BCT were younger (P<0.001) and with smaller tumors (P = 0.000). In addition, patients with BCT were more likely to receive RNI (OR, 2.579; P = 0.001). Nonetheless, there were no differences in chemotherapy regimens between patients who received BCT and those who underwent mastectomy (OR, 1.396; P = 0.062). For first recurrence, WBI patients demonstrated the lowest rate of distant metastases (3.1%), followed by mastectomy (4.1%), WBI with RNI (7.6%), PMRT (8.3%) (P = 0.007). Besides, WBI had the lowest rate of lung, liver and brain metastases (P = 0.047). There were no significant differences in terms of locoregional recurrence (P = 0.155) or contralateral breast cancer (P = 0.807) as first recurrence. After PSM, 904 patients (452 in the WBI group and 452 in the mastectomy-alone group) and 188 patients (94 in the WBI with RNI group and 94 in the PMRT group) were included for further analysis, respectively. There was no difference between WBI group and mastectomy-alone group in terms of overall survival (OS), breast cancer specific survival (BCSS), disease free survival (DFS), distant metastasis free survival (DMFS) and regional recurrence free survival (RRFS). No significant difference of local recurrence free survival (LRFS) was found between WBI and mastectomy. In subgroup analysis, patients with grade I/II tumor had a superior DMFS over mastectomy alone (P = 0.005). The 10-year RRFS was significantly higher in patients who underwent WBI with RNI versus PMRT (100% vs 90.3%, P = 0.025). In patients≥40 years and with grade I/II tumor (n = 76), WBI with RNI group had better DFS (P = 0.035) and DMFS (P = 0.035) over PMRT.In the whole cohort, there exist differences in recurrence patterns, while no differences in overall survival between WBI and mastectomy-alone group or WBI with RNI and PMRT group. However, WBI patients did show superior DMFS in patients with grade I/II tumor over mastectomy alone. WBI with RNI group had a higher RRFS rates compared with PMRT. Patients ≥ 40 years and with grade I/II tumor had better DFS and DMFS following WBI with RNI compared with PMRT. BCT is recommended to be therapeutic choice of priority in early breast cancer.

Prognosis of patients with axillary lymph node metastases from occult breast cancer: analysis of multicenter data.

PurposeThis study was conducted to evaluate prognosis of patients with level I/II axillary lymph node metastases from occult breast cancer (OBC). Materials and MethodsData of 53 patients with OBC who received axillary lymph node dissection (ALND) positive/negative (+/–) breast-conserving surgery between 2001 and 2013 were retrospectively collected at seven hospitals in Korea. The median number of positive lymph nodes (+LNs) was 2. Seventeen patients (32.1%) had >3 +LNs. A total of 48 patients (90.6%) received radiotherapy. Extents of radiotherapy were as follows: whole-breast (WB; n = 11), regional lymph node (RLN; n = 2), and WB plus RLN (n = 35).ResultsThe median follow-up time was 85 months. Recurrence was found in four patients: two in the breast, one in RLN, and one in the breast and RLN. The 5-year and 7-year disease-free survival (DFS) rates were 96.1% and 93.5%, respectively. Molecular subtype and receipt of breast radiotherapy were significantly associated with DFS. Patients with estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative (ER-/PR-/HER2-) subtype had significantly lower 7-year DFS than those with non-ER-/PR-/HER2- tumor (76.9% vs. 100.0%; p = 0.03). Whole breast irradiation (WBI) was significantly associated with a higher 7-year DFS rate (94.7% for WBI group vs. 83.3% for non-WBI group; p = 0.01). Other factors including patient’s age, number of +LNs, taxane chemotherapy, and RLN irradiation were not associated with DFS. ConclusionPatients with OBC achieved favorable outcome after ALND and breast-targeting treatment. Molecular subtype and receipt of WBI was significant factors for DFS.

Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial

In the randomised, phase 3 equivalence trial on electron intraoperative radiotherapy (ELIOT), accelerated partial breast irradiation (APBI) with the use of intraoperative radiotherapy was associated with a higher rate of ipsilateral breast tumour recurrence (IBTR) than whole-breast irradiation (WBI) in patients with early-stage breast cancer. Here, we aimed to examine the planned long-term recurrence and survival outcomes from the ELIOT trial. This single-centre, randomised, phase 3 equivalence trial was done at the European Institute of Oncology (Milan, Italy). Eligible women, aged 48-75 years with a clinical diagnosis of a unicentric breast carcinoma with an ultrasound diameter not exceeding 25 mm, clinically negative axillary lymph nodes, and who were suitable for breast-conserving surgery, were randomly assigned (1:1) via a web-based system, with a random permuted block design (block size of 16) and stratified by clinical tumour size, to receive post-operative WBI with conventional fractionation (50 Gy given as 25 fractions of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial was open label and no-one was masked to treatment group assignment. The primary endpoint was the occurrence of IBTR. The trial was designed assuming a 5-year IBTR rate of 3% in the WBI group and equivalence of the two groups, if the 5-year IBTR rate in the ELIOT group did not exceed a 2·5 times excess, corresponding to 7·5%. Overall survival was the secondary endpoint. The main analysis was done by intention to treat. The cumulative incidence of IBTR events and overall survival were assessed at 5, 10, and 15 years of follow-up. This trial is registered with ClinicalTrials.gov, NCT01849133. Between Nov 20, 2000, and Dec 27, 2007, 1305 women were enrolled and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a median follow-up of 12·4 years (IQR 9·7-14·7), 86 (7%) patients developed IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62, 95% CI 2·68-7·95, p<0·0001). In the ELIOT group, the 5-year IBTR rate was 4·2% (95% CI 2·8-5·9), the 10-year rate was 8·1% (6·1-10·3), and the 15-year rate was 12·6% (9·8-15·9). In the WBI group, the 5-year IBTR rate was 0·5% (95% CI 0·1-1·3), the 10-year rate was 1·1% (0·5-2·2), and the 15-year rate was 2·4% (1·4-4·0). At final follow-up on March 11, 2019, 193 (15%) women had died from any cause, with no difference between the two groups (98 deaths in the ELIOT group vs 95 in the WBI group; HR 1·03, 95% CI 0·77-1·36, p=0·85). In the ELIOT group, the overall survival rate was 96·8% (95% CI 95·1-97·9) at 5 years, 90·7% (88·2-92·7) at 10 years, and 83·4% (79·7-86·4) at 15 years; and in the WBI group, the overall survival rate was 96·8% (95·1-97·9) at 5 years, 92·7% (90·4-94·4) at 10 years, and 82·4% (78·5-85·6) at 15 years. We did not collect long-term data on adverse events. The long-term results of this trial confirmed the higher rate of IBTR in the ELIOT group than in the WBI group, without any differences in overall survival. ELIOT should be offered to selected patients at low-risk of IBTR. Italian Association for Cancer Research, Jacqueline Seroussi Memorial Foundation for Cancer Research, Umberto Veronesi Foundation, American Italian Cancer Foundation, The Lombardy Region, and Italian Ministry of Health.

Abstract GS2-04: A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01)

Abstract Background: Wholebreast irradiation (WBI) after breast conserving surgery for DCIS reduces therisk of local recurrence including invasive recurrence. The objective of BIG3-07/TROG 07.01 is to test radiation dose escalation to the tumor bed (tumorbed boost) and fractionation sensitivity of whole breast irradiation (WBI) inpatients with non-low risk DCIS treated with breast conserving therapy. Methods: BIG3-07/TROG 07.01 is an international, multicenter, randomized, controlled, phase 3 trial. Eligible women were ≥18 years ofage with completely resected non-low risk DCIS defined as age &amp;lt;50 years orage ≥50 years plus at least one of the risk factors for local recurrence (palpable tumor,multifocal disease, tumor size ≥ 1.5cm, intermediate or high nuclear grade, central necrosis, comedo histologyand/or surgical margin &amp;lt;10 mm). Patients were randomized to have tumor bedboost (16 Gy in 8 daily fractions) or no boost following conventional WBI (50Gy in 25 daily fractions) or hypofractionated WBI (42.5 Gy in 16 dailyfractions) in one of three randomization categories selected by centers priorto study activation. Randomization A was a 4-arm randomization of no boost vs. boostfollowing conventional WBI vs. hypofractionated WBI. Patients in RandomizationB and Randomization C were assigned no boost or boost following conventional WBIand hypofractionated WBI, respectively. The primary endpoint was time to localrecurrence, analyzed by intention to treat. The trial was designed to detect a3% difference in 5-year free-from- local recurrence rates between the no boostand boost groups (93% vs 96%; hazard ratio, 0.56) with 90% power and 2-sidedalpha level of 5%. The primary effect of boost was assessed on all randomizedpatients. The secondary effect of WBI dose-fractionation and the interactionbetween boost and WBI dose-fractionation were assessed on patients in RandomizationA and additionally on all patients. Results: BetweenJune 2007 and June 2014, 1608 patients were randomized to have no boost (805patients) or boost (803 patients) after WBI. Conventional WBI was given in 831 patients(no boost in 416 patients; boost in 415 patients). Hypofractionated WBI wasgiven in 777 patients (no boost in 389 patients; boost in 388 patients). Adjuvantendocrine therapy was planned in 106 patients (13%) in the no boost group and105 patients (13%) in the boost group. Median follow-up was 6.6 years. The 5-yearfree-from- local recurrence rates were 93% in the no boost group and 97% in theboost group (hazard ratio, 0.47; 95% confidence interval [CI], 0.31 to 0.72;P&amp;lt;0.001). Forty-four percent and 45% of LRs were invasive in the no boostgroup and boost group, respectively. The effect of boost did not vary significantlyby age, tumor size, nuclear grade, surgical margin or endocrine therapy. Therewere no significant differences in the 5-year free-from- local recurrence ratesbetween the conventional WBI group and hypofractionated WBI group inRandomization A (94% vs. 94%, P=0.84) and in all randomized patients (95% vs.95%, P=0.89). The test for interaction between boost and dose-fractionation wasnot significant in Randomization A or in all randomized patients (both P=0.89).The rates of grade ≥2 breastpain (12% vs. 16%, P=0.84) and skin and subcutaneous tissue fibrosis (6% vs.15%, P=0.14) did not differ significantly between the groups. Conclusions: Inwomen with non-low risk DCIS treatedwith breast conserving surgery, the addition of tumor bed boost followingconventional or hypofractionated WBI reduced local recurrence rates. There wasno difference in local recurrence rates between conventional WBI andhypofractionated WBI. (Registered with ClinicalTrials.gov, NCT00470236.) Citation Format: Boon Hui Chua, Emma Link, Ian Kunkler, Ivo Olivotto, Antonia Helen Westenberg, Timothy Whelan, Guenther Gruber, Breast International Group (BIG)-aisbl, Trans Tasman Radiation Oncology Group, Scottish Cancer Trials Breast Group, Canadian Cancer Trials Group, European Organization for Research and Treatment of Cancer, International Breast Cancer Study Group, Cancer Trials Ireland. A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-04.

Breast Cancer: Toxicity, QoL and Economy after External Beam APBI

Accelerated partial breast irradiation (APBI) is increasingly available approach in adjuvant RT of selected group of the early-stage breast cancer. Accumulating data are showing non-inferiority of both interstitial brachytherapy and external beam radiotherapy via stereotactic body radiotherapy (SBRT). The aim of this single institutional prospective randomized study is to compare the SBRT_APBI with accelerated whole breast irradiation (WBI). The main objective is to evaluate feasibility, safety, tolerance and cosmetic effects of SBRT. Patients with early breast carcinoma after partial mastectomy were screened for eligibility: age ˃ 50, NST histology, size ≤ 2 cm, negative margins ≥ 2 mm, no lymphovascular invasion, ER positive, BRCA negative. Randomization to: surgery bed SBRT (5x 6Gy) and accelerated WBI with tumor bed boost (15x 2.67Gy + 5x 2Gy). 4DCT-based planning, deep inspiration breath hold, daily pre-treatment positioning by cone-beam CT and volumetric arc therapy dose delivery were utilized. Quality of life (QoL) was evaluated by official translation of EORTC questionnaires (QLQ-C30 and QLQ-BR23). Cosmetics and toxicity were evaluated subjectively and objectively using questionnaires, CTCAE criteria and chest photodocumentation. Economy burden was evaluated at the end of radiotherapy by a 4-point graded scale. In this pilot report we present results of first 30/84 planned patients. Both groups (15 patients in each) were well balanced according to baseline characteristics. Median age 66 years, 66 % invasive ductal carcinoma, 70 % grade 1, median tumor size 9 mm. In SBRT group median PTV volume 52 ccm, minimum PTV dose median 29 Gy, maximum PTV dose median 32 Gy. 6 patients with no dermatitis, 9 patients with grade 1 dermatitis in SBRT group and 8 patients with grade 1, six with grade 2 and one with grade 3 skin toxicity in WBI group at the end of therapy. Significantly less skin sensitivity, dryness, pigmentation and fatigue in SBRT arm comparing to control arm. No differences between groups with respect to acute skin toxicity after 1 and 3 months. No significant difference in questionnaires evaluation. Cosmetic results as well as economic analysis favor SBRT technique. Description of two most common VMAT techniques with evaluation of dose coverage of the target and surrounding tissues parameters will be part of poster presentation. Feasibility, toxicity, cosmetic and financial influence of two radiotherapeutic regiments - the SBRT surgery bed radiotherapy and accelerated whole breast irradiation with the boost to tumor bed were compared. SBRT technique is less toxic and easier feasible approach for adjuvant treatment of selected early-stage breast cancer patients. We add to increase level of evidence for establishment of SBRT in indicated patients into daily clinical practice of APBI.

Comparison Between Accelerated Partial Breast Irradiation and Whole Breast Irradiation: APBI IMRT Florence Retrospective Analysis of Subjective, Objective and Patient-reported Cosmetic Outcomes

Accelerated partial breast irradiation (APBI) represents a valid alternative to whole breast irradiation (WBI) in selected low risk patients with early stage breast cancer. The long-term analysis of the APBI-IMRT Florence randomized phase 3 trial showed no significant difference in terms of both local and distant disease control and survival outcomes. Acute/late toxicity and cosmesis evaluations were significantly in favor of the APBI arm. The aim of this analysis is to compare the agreement between objective and subjective patient-reported outcome measures (PROMs) of cosmesis assessment. From June 2019 to January 2020, 95 women previously enrolled in the APBI-IMRT Florence trial accepted to undergo photographic assessment. Late skin toxicity was assessed following the RTOG/EORTC late Radiation Morbidity Scoring questionnaire. Digital photographs were assessed (objective method) using the BCCT.core software v.31 (Breast Cancer Conservative Treatment. Cosmetic Results). Breast cosmetic outcomes scored both by physician and patient (subjective methods) were recorded using the Harvard Breast Cosmesis Grading Scale. At median follow up of 11 years (IQR 10.5-11.6 years), we evaluated 95 patients (51 APBI, 44 WBI). Late skin toxicity rates (any grade) were significantly in favor of the APBI group of patients (36.4% vs 6%; p = 0.0003). Also, cosmetic assessment was significantly in favor of the APBI group both evaluated by physician (excellent-good [EG] 98% vs 90%, p<0.0001; fair-poor [FP] 2% vs 10%, p = 0.0455) and patient (EG 86% vs 70%, p<0.0001; FP 14% vs 30%, p<0.0001). The BCCT.core cosmetic assessment showed significantly improved outcomes in the APBI group (EG 65% vs FP 35%) as compared to WBI group (EG 52% vs FP 48%; p = 0.0001). We observed a good agreement between BCCT.core objective evaluation and both patients (p = 0.19) and physicians PROMs (p = 0.17). Patients treated with APBI showed significant improved late toxicity and cosmetic outcomes. There is a significative agreement between patients/physician PROMs and BCCT.core. This score has proven to be a feasible tool in breast cancer clinical practice.

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial

Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. National Cancer Institute, US Department of Health and Human Services.

APBI (Accelerated Partial-Breast Irradiation) Versus WBI (Whole-Breast Irradiation) Delivered with the Same Dose Fractionation: A Propensity Score Matched Analysis of Two Prospective Studied Cohorts

The recent updates of the RAPID and RTOG 0413 trials have led to renewed interest in the question of APBI versus WBI outcomes. On the other hand, IMPORT-LOW, which was the only APBI randomized study strictly testing treatment volume without the confounding effect of dose-time factors, reported non-inferiority of APBI with fewer late toxicities. In this study, we report our institutional experience comparing two matched prospective cohorts of breast cancer patients treated with the same dose-fractionation using APBI or WBI. Two phase II trials using the same dose fractionation of 4995 cGy in 15 fractions enrolled early stage breast cancer patients at our institution between 2008 and 2017; one utilizing APBI and the other utilizing WBI. A total of 184 patients were enrolled in both trials (34 on the APBI and 150 on the WBI). Patients who received regional nodal irradiation or who were treated prone on the WBI trial were excluded. We then performed a propensity score 1:1 match between the two cohorts using age, histology, breast volume, and seroma volume. Outcomes of interest included loco-regional control, acute and late toxicity, and cosmesis. Cosmesis was scored using the Harvard Cosmesis Scale; toxicities were recorded using CTCAE version 4.03. A total of 68 patients were matched. All patients had T1-T2, N0 disease with negative margins. Median follow up was 62.5 months [6-96] for the WBI patients versus 92.5 months [23-119] for the APBI patients. Median time to final cosmetic evaluation was 24.5 months [6-67] in the WBI cohort versus 90 months [9-119] in the APBI cohort. In accordance with the propensity score match, breast size mean (1400 cc vs 1600 cc; p =0.15), seroma size mean (37 cc vs 49 cc, p=0.27) and mean age (58 vs 60, p=0.17) were similar in the two groups. Ipsilateral breast recurrence rates were similar between the two groups (2/34, 5.9%) in the APBI versus (3/34, 8.8%) in the WBI, p= 1.0. In the WBI group, 1 patient had distant metastasis 6 years after treatment and 1 patient had a contralateral breast recurrence (CBR). In the APBI group, 4 patients had CBR. At final cosmetic evaluation, 91.2% in each cohort had excellent/good cosmesis, 5.9% in each cohort had fair cosmesis and 2.9% (1 patient in each cohort) had poor cosmesis, p = 0.92. In the WBI cohort, 11/34 patients had grade 2 or 3 acute toxicities (32.4%) versus 2/34 in the APBI group (5.9%), p= 0.01. In the WBI cohort, 12/34 patients had grade 2 or 3 late toxicities (35.3%) versus 7 in the APBI group (20.6%), p= 0.28. Clinical outcomes, toxicity profiles and cosmetic results were similar in patients treated with APBI or WBI, with significantly fewer grade 2–3 acute side effects after APBI. Our results are in agreement with the IMPORT-LOW outcomes and suggest that with similar fractionation schemes APBI and whole breast are associated with similar outcomes.

Clinical observation of early-stage breast cancer after breast-conserving surgery with hypofractionated radiotherapy

Objective To observe the long-term effect, adverse reaction and cosmetic outcome of early-stage breast cancer with hypofractionated whole-breast irradiation (HF-WBI) after breast-conserving surgery. Methods A total of 206 patients with stage 0-Ⅱ breast cancer after breast-conserving surgery were included in Shandong Cancer Hospital Affiliated to Shandong University from May 2014 to August 2017. According to radiotherapy fraction, patients were divided into HF-WBI group and conventional whole-breast irradiation (CF-WBI) group. In HF-WBI group, 116 patients received whole-breast radiation to 42.56 Gy in 16 fractions followed by tumor bed boost of 9 Gy in 3 fractions or 10 Gy in 5 fractions. In CF-WBI group, 90 patients received whole breast radiation to 50 Gy in 25 fractions followed by tumor bed boost of 10 Gy in 5 fractions. The 2-year local recurrence rate, 2-year mortality rate, acute adverse reaction, late adverse reaction and cosmetic outcome of the two groups were analyzed. Results The 2-year local recurrence rates of HF-WBI group and CF-WBI group were 0.86% (1/116) and 2.22% (2/90) respectively, and there was no significant difference between the two groups (χ2=0.049, P=0.824). The 2-year mortality rates of the two groups were 0.86% (1/116) and 0 (0/90) respectively, and there was no significant difference (P>0.999). There were 108 cases (93.1%) in HF-WBI group and 84 cases (93.3%) in CF-WBI group with grade 0-1 acute dermatitis, and 8 cases (6.9%) and 6 cases (6.7%) with grade 2-3 respectively, with no statistically significant difference (χ2=0.004, P=0.948). There were 97 cases (83.6%) in HF-WBI group and 79 cases (87.8%) in CF-WBI group with grade 0-1 bone marrow suppression, and 19 cases (16.4%) and 11 cases (12.2%) with grade 2-4 respectively, with no statistically significant difference (χ2=0.704, P=0.401). In the two groups, there were 1 case (0.9%) and 3 cases (3.3%) with grade 1-2 radiation pneumonitis, and 115 cases (99.1%) and 87 cases (96.7%) with no radiation pneumonitis respectively, and the difference was not statistically significant (χ2=1.626, P=0.202). There was 1 case (0.9%, 1.1%) with grade 1 breast edema in each group, and 115 cases (99.1%) and 89 cases (98.9%) did not occur breast edema, with no statistically significant difference (χ2=0.033, P=0.857). In the late adverse reactions, there were 5 cases (4.3%) and 3 cases (3.3%) with skin pigmentation in HF-WBI group and CF-WBI group respectively. There were 2 cases (1.7%, 2.2%) with grade 1 subcutaneous tissue fibrosis in each group, and there were 1 case (0.8%) and 2 cases (2.2%) with grade 1 pulmonary fibrosis respectively. The differences between the two groups were not statistically significant (χ2=0.000, P>0.999; χ2=0.000, P>0.999; χ2=0.049, P=0.824). The 6-month, 1-year and 2-year cosmetic outcome good rates in HF-WBI and CF-WBI group were 96.5% (111/115) and 93.3% (84/90), 92.1% (105/114) and 90.0% (81/90), 91.4% (53/58) and 87.2% (41/47) respectively. The differences between the two groups were not statistically significant (χ2=0.526, P=0.468; χ2=0.277, P=0.599; χ2=0.476, P=0.490). The whole course of radiotherapy time in HF-WBI group was 25 days or 29 days, which was significantly shorter than the 40 days of CF-WBI group. Conclusion HF-WBI after breast-conserving surgery has the similar long-term effect, acute and late adverse reaction and cosmetic outcome compared with CF-WBI, and the treatment time is significantly shorter. It can be further promoted as the optimal adjuvant radiotherapy for early-stage breast cancer after breast-conserving surgery. Key words: Breast neoplasms; Radiotherapy; Treatment outcome

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial

Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. German Cancer Aid.