Whole-breast Irradiation Research Articles

Early Outcome, Cosmetic Result and Tolerability of an IOERT-Boost Prior to Adjuvant Whole-Breast Irradiation.

Simple SummaryOur study with 139 breast cancer patients treated with intraoperative radiotherapy reports favorable data on the cosmetic outcome as well as the acute and early long-term side effects. Our oncologic control rates are comparable to the previous literature.Background/Aims: Due to its favorable dose distribution and targeting of the region at highest risk of recurrence due to direct visualization of tumor bed, intraoperative electron radiation therapy (IOERT) is used as part of a breast-conserving treatment approach. The aim of this study was to analyze tumor control and survival, as well as the toxicity profile, and cosmetic outcomes in patients irradiated with an IOERT boost for breast cancer. Materials and Methods: 139 Patients treated at our institution between January 2010 and January 2015 with a single boost dose of 10 Gy to the tumor bed during breast-conserving surgery followed by whole-breast irradiation were retrospectively analyzed. Results: 139 patients were included in this analysis. The median age was 54 years (range 28–83 years). The preferred surgical strategy was segmental resection with sentinel lymphonodectomy (66.5%) or axillary dissection (23.1%). Regarding adjuvant radiotherapy, the vast majority received 5 × 1.8 Gy to 50.4 Gy. At a median follow-up of 33.6 months, recurrence-free and overall survival were 95.5% and 94.9%, respectively. No patient developed an in-field recurrence. Seven patients (5.0%) died during the follow-up period, including two patients due to disease recurrence (non-in-field). High-grade (CTCAE > 2) perioperative adverse events attributable to IOERT included wound healing disorder (N = 1) and hematoma (N = 1). High-grade late adverse events (LENT-SOMA grade III) were reported only in one patient with fat necrosis. Low-grade late adverse events (LENT-SOMA grade I-II) included pain (18.0%), edema (10.5%), fibrosis (21%), telangiectasia (4.5%) and pigmentation change (23.0%). The mean breast retraction assessment score was 1.66 (0–6). Both patients and specialists rated the cosmetic result “excellent/good” in 84.8% and 87.9%, respectively. Conclusion: Our study reports favorable data on the cosmetic outcome as well as the acute and early long-term tolerability for patients treated with an IOERT boost. Our oncologic control rates are comparable to the previous literature. However, prospective investigations on the role of IOERT in comparison to other boost procedures would be desirable.

Dosimetric comparison of different intensity-modulated radiotherapy techniques for whole-breast irradiation of right-breast cancer

PurposeThis study compared the dosimetric parameters of field-in-field forward intensity-modulated radiotherapy (FIF-IMRT) and fixed-field inversely optimized intensity-modulated radiotherapy (FFIO-IMRT) for the whole-breast irradiation of patients undergoing right-breast lumpectomy. Material and methodsA total of 30 patients with pT1-2N0M0 right-breast invasive ductal carcinoma were enrolled in this study. Two different treatment plans, i.e., FIF-IMRT and FFIO-IMRT, were designed for each patient. The dosimetric parameters of the two treatment plans were compared including ipsilateral lung and heart, conformity index (CI), and the homogeneity index (HI) of the planning target volume (PTV). ResultsFixed-field inversely optimized intensity-modulated radiotherapy was found to significantly improve CI (83.302% vs. 60.146%) and HI (11.837% vs. 19.280%), and significantly reduced V25 (18.038% vs. 19.653%) and V30 (15.790% vs. 18.492%) of the ipsilateral lung. It also significantly increased V5 (69.791% vs. 32.615%) of the ipsilateral lung and V5 (61.579% vs. 3.829%), V10 (14.130% vs. 0.381%), V20 (1.843% vs. 0.051%), and Dmean (5.211Gy vs. 1.870Gy) of the heart. ConclusionRegardless of improving the conformity and homogeneity of PTV and reducing the ipsilateral lung irradiation volume at high doses, FFIO-IMRT significantly raised the ipsilateral lung irradiated volume at low doses, as well as the irradiation volume and mean radiation doses to the heart. This limits its use in patients with early-stage right breast cancer.

Definitive radiotherapy with stereotactic or IMRT boost with or without radiosensitization strategy for operable breast cancer patients who refuse surgery.

For breast cancer (BC) patients who refused surgery, we developed a definitive treatment employing modern sophisticated radiation techniques. Thirty-eight operable BC patients were treated by conventionally fractionated whole-breast (WB) radiotherapy in combination with stereotactic (for primary tumor) or intensity-modulated (for primary tumor with/without regional lymph nodes [LN]) radiotherapy (IMRT) boost. Standard doses were 50Gy/25 fractions, 21Gy/3 fractions and 20Gy/8 fractions, respectively, for the three radiation modalities. Disease stages were 0 (ductal carcinoma in situ [DCIS]) in seven patients, I in 12, II in 16 and III in three. In 26 patients, intratumoral hydrogen peroxide injection or hyperthermia with oral tegafur-gimeracil-oteracil potassium (S-1) was also used to sensitize the tumors to radiation. Hormonal and standard systemic therapy were administered in 25 and 13 patients, respectively. Complete and partial responses were obtained in 19 patients each; in patients with partial response, no further regrowth of the residual mass was observed, except for two patients who developed local recurrence. During a follow-up of 8-160months (median, 50months for living patients), two, one and two patients developed local relapse, sub-clavicular node metastasis and distant metastasis, respectively. The 5-year rates for overall, progression-free and local relapse-free survival were 97.2, 90.9 and 93.4%, respectively. Fourteen patients developed Grade 3 radiation dermatitis but all recovered after treatment. In 47%, the affected breast became better-rounded, and the nipple of the irradiated breast became higher by ≥1cm than the contralateral nipple. Our method might be a treatment option for operable BC patients.

Feasibility and Short-Term Toxicity of a Consecutively Delivered Five Fraction Stereotactic Body Radiation Therapy Regimen in Early-Stage Breast Cancer Patients Receiving Partial Breast Irradiation.

BackgroundFor appropriately selected patients with early-stage breast cancer (ESBC), accelerated partial breast irradiation (APBI) yields equivalent rates of ipsilateral breast tumor recurrence with mixed results in patient-rated cosmesis compared with whole-breast radiotherapy depending on the technique utilized. When utilizing external beam radiotherapy for APBI, techniques to reduce target margins and overall treatment volume are potentially important to decrease rates of long-term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is a promising technique to deliver APBI because of its increased accuracy and sparing of uninvolved breast tissue. We report the initial results of a prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of a daily five-fraction SBRT regimen for APBI.MethodsTwenty-three patients with ESBC after lumpectomy who met APBI suitability were enrolled. During lumpectomy, a bioabsorbable three-dimensional fixed array tissue marker (BioZorb™, Hologic, Marlborough, MA) was placed for enhanced visualization of the cavity boundaries. Clinical target volume (CTV) was defined as the delineable cavity plus a 1-cm isotropic expansion followed by a 3-mm isotropic planning target volume (PTV) expansion. Patients received 30 Gy delivered in five planned consecutive daily fractions in either prone or supine positioning depending on individual anatomy. Two patients completed the five-fraction treatments in 9-day interval and 11-day interval due to external circumstances. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans utilized 10-MV flattening filter–free beams delivered on a Varian Edge linear accelerator. Local control, toxicity, and nurse/patient-scored cosmesis at pre-treatment baseline, 1 month post-treatment, and at subsequent 6-month intervals were recorded.ResultsTwenty-three patients were accrued at the time of submission with median follow-up of 6 months. No patients experienced grade ≥3 acute toxicity. Of the 10 events reported probably related to SBRT, nine were grade 1 (n = 9/10, 90%). There was no evidence of difference, deterioration, or change in patient or nurse-scored cosmesis from baseline to 1 and 6 months post-treatment. One patient developed nodal failure shortly after APBI.ConclusionsAlthough longer follow-up is needed to assess long-term toxicity and local control, this study demonstrated a five-fraction SBRT regimen delivered over consecutive days is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering APBI in suitable women.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03643861, NCT03643861.

"Sequential Volumetric Modulated Arc Therapy (VMAT) Boost in Hy- brid Plan With Tangential Beams for Whole Breast Treatment: a Do- simetric Study "

"Purpose: Whole breast radiation therapy (WBRT) with a boost to the tumor bed following con-servative primary surgery in women with breast cancer (BC) plays a central role in reducing local recurrences and mortality. Volumetric modulated arc therapy (VMAT) technique has been shown to allow better dose conformation with low dose levels to organs at risk (OARs), compared to static fields three-dimensional Conformal Radiotherapy (3D-CRT). The aim of this study was to evaluate the feasibility and dosimetric advantages of sequential boost (SB), administered with VMAT tech-nique in hybrid plans with tangential beams for whole breast treatment. Material and methods: BC patients undergoing adjuvant RT from June to October 2020 were selected. ESTRO guidelines for the Clinical Target Volume (CTV) delineation were used. Total delivered dose was 60-66 Gy; 50 Gy in 2 Gy daily fractions for whole breast and 10-16 in 2 Gy daily fractions Gy to tumor bed was 10-16 Gy in 2 Gy daily fractions. Results: The analysis included 31 patients with BC treated with adjuvant RT following con-servative surgery. Hybrid treatment plans characterized by a 3D-CRT plan using tangential medi-olateral and lateromedial fields for the irradiation of the whole breast Planning Target Volume (PTV) and a sequential VMAT plan with 2 coplanar arches for boost PTV irradiation were gener-ated. Dosimetric analysis resulted in homogeneous target volumes coverage and OARs constraints compliance. As regarding to organs at risks (OARs), contralateral breast, ipsi- and contralateral lung and heart constraints values were analysed. Conclusions: In the frame BC RT, this dosimetric study showed that hybrid plans performed with 3D-CRT and VMAT techniques are feasible in terms of dosimetric outcomes. "

Comparison of Heart and Lung Doses According to Tumor Bed Boost Techniques in Early-Stage Left-Sided Breast Cancer: Simultaneous Integrated Boost versus Sequential Boost.

Background and Objectives: The boost dose to the tumor bed after whole breast irradiation (WBI) can be divided into sequential boost (SEQ) and simultaneous integrated boost (SIB). SIB using modern radiation therapy (RT) techniques, such as volumetric modulated arc therapy, allow the delivery of a highly conformal dose to the target volume and has a salient ability to spare at-risk organs. This study aimed to compare the radiation dose delivered to the heart and lungs according to boost technique and tumor bed location. Materials and Methods: RT planning data of 20 patients with early-stage left-sided breast cancer were used in this study. All patients were treated with volumetric modulated arc therapy after breast-conserving surgery with a sentinel lymph node biopsy. For each patient, two different plans, whole breast irradiation with simultaneous integrated boost (WBI-SIB) and sequential boost after WBI (WBI-SEQ), were generated. To compare the dose received by each organ at risk (OAR), dose-volume histogram data were analyzed. The mean dose (Dmean) and volume of each organ that received x Gy (Vx) were calculated and compared. Results: For the heart, the V10 was lower for the WBI-SIB plan than for the WBI-SEQ plan (5.223 ± 1.947% vs. 6.409 ± 2.545%, p = 0.008). For the left lung, the V5 was lower in the WBI-SIB plan than for the WBI-SEQ plan (27.385 ± 3.871% vs. 32.092 ± 3.545%, p < 0.001). The Dmean for the heart and left lung was lower for the WBI-SIB plan than for the WBI-SEQ plan (heart: 339.745 ± 46.889 cGy vs. 413.030 ± 52.456 cGy, p < 0.001; left lung: 550.445 ± 65.094 cGy vs. 602.270 ± 55.775 cGy, p < 0.001). Conclusions: The WBI-SIB plan delivered lower radiation doses to the heart and left lung than the WBI-SEQ plan in terms of Dmean and low-dose volume in hypofractionated RT of early-stage left-sided breast cancer patients. Furthermore, a large radiation dose per day may be advantageous, considering the radiobiologic aspects of breast cancer. Long-term follow-up data are needed to determine whether the dosimetric advantages of the WBI-SIB plan can lead to clinically improved patient outcomes and reduced late side effects.

Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy

The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer. We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea. The 786 patients in the pathologic complete response group (RpCR) had significantly longer local recurrence-free survival (LRFS) than the 1,949 patients in clear or close RM and non-pCR group (R0) and the 68 patients in involved RM and non-pCR group (R1) (vs. R0, p = 0.001; vs. R1, p = 0.049). Patients in R0 showed no benefit in LRFS compared to R1 on both log-rank test (HR = 1.20; 95% C.I., 0.49-2.93; p = 0.692) and Cox regression analysis (HR = 2.05; 95% C.I., 0.64-6.58; p = 0.227). Subgroup analysis according to tumor subtypes revealed that there was no significant difference in LRFS, distant metastasis-free survival, and recurrence-free survival between the R0 and R1 group. Additionally, among 286 patients with pCR with residual ductal carcinoma in situ (DCIS) alone, RM status was not significantly associated with LRFS. Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Methods of Esthetic Assessment after Adjuvant Whole-Breast Radiotherapy in Breast Cancer Patients: Evaluation of the BCCT.core Software and Patients' and Physicians' Assessment from the Randomized IMRT-MC2 Trial.

Simple SummaryTo validate the BCCT.core software, the present analysis compares the esthetics assessment by the software in relation to patients’ and physicians’ rating in breast cancer patients after surgery and adjuvant radiotherapy. Agreement rates of the different assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with all asymmetry indices, while for patients’ self-assessment, this general correlation was first seen after 2 years. Only a slight agreement between the BCCT.core software and the physicians’ or patients’ assessment was seen, while a moderate and substantial agreement was detected between the physicians’ and the patients’ assessments. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry seems to increase in importance.The present analysis compares the esthetics assessment by the BCCT.core software in relation to patients’ and physicians’ ratings, based on the IMRT-MC2 trial. Within this trial, breast cancer patients received breast-conserving surgery (BCS) and adjuvant radiotherapy. At the baseline, 6 weeks, and 2 years after radiotherapy, photos of the breasts were assessed by the software and patients’ and physicians’ assessments were performed. Agreement rates of the assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with asymmetry indices. Before and 6 weeks after radiotherapy, the patients’ self-assessment was only correlated with the lower breast contour (LBC) and upward nipple retraction (UNR), while after 2 years, there was also a correlation with other indices. Only a slight agreement between the BCCT.core software and the physicians’ or patients’ assessment was seen, while a moderate and substantial agreement was detected between the physicians’ and the patients’ assessment after 6 weeks and 2 years, respectively. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry appears to increase in importance.

Is kV Intraoperative Radiation Therapy an Acceptable Method for Partial Breast Irradiation?

Multiple large prospectively randomized trials of postoperative partial breast irradiation (PBI) have established it as a viable alternative to whole-breast irradiation for risk-adapted breast conserving management of early stage disease. An area of controversy remains regarding the relative efficacy, safety, and utility of intraoperative radiation therapy as a PBI technique. This is particularly true regarding the use of a 50 kV x-ray device, whereby the inherent dosimetry of the applicator results in a low dose of radiation to an exceedingly small volume of tissue. A critical analysis of the current clinical data would strongly support the view that intraoperative radiation therapy with a 50 kV x-ray device is associated with inferior outcomes compared with the variety of currently available modalities used for postoperative PBI.

Hypofractionation and Concomitant Boost in Ductal Carcinoma In Situ (DCIS): Analysis of a Prospective Case Series with Long-Term Follow-Up.

We previously reported on a cohort of breast cancer patients affected with ductal carcinoma in situ (DCIS) that were treated with breast conservative surgery and hypofractionated whole-breast radiotherapy with a concomitant boost to the lumpectomy cavity. We now report on the long-term results of the oncological and toxicity outcomes, at a median follow-up of 11.2 years. We also include an analysis of the predictive factors for local recurrence (LR). Eighty-two patients with long-term observation were considered for this report. All received hypofractionated post-operative radiotherapy with a concomitant boost (45 Gy/20 fractions to the whole breast and 50 Gy/20 fractions to the lumpectomy cavity). We report on LC rates at 5 and 10 years, overall survival (OS), and breast-cancer-specific survival (BCSS), employing the Kaplan–Meier method. Cox proportional regression analysis was used to determine the role of selected clinical parameters on the risk of local recurrence, by the univariate and multivariate models. After a median follow-up of 11.2 years (range 5–15 years), 9 pts (11%) developed LR. The LR rates at 5 years and 10 years were 2.4% and 8.2%, respectively. The 5- and 10-year overall survival rates were 98.8% and 91.6%, respectively. The 5- and 10-year breast-cancer-specific survival rates were 100.0% and 99.0%. Late skin and subcutaneous toxicities were generally mild, and cosmetic results were good–excellent for most patients. For the univariate regression analysis, ER positive status (HR; 95% CI, p = 0.021), PgR positive status (HR; 95% CI, p = 0.012), and the aggregate data of positive hormonal status (HR; 95% CI, p = 0.021) were inversely correlated to LR risk. Conversely, a high tumor grade (G3) was directly correlated with the risk of LR (HR; 95% CI, p = 0.048). For the multivariate regression analysis, a high tumor grade (G3) confirmed its negative impact on LR (HR 0.40; 95% CI 0.19–0.75, p = 0.047). Our long-term data demonstrate hypofractionated whole-breast radiotherapy with a concomitant boost to be feasable, effective, and tolerable. Our experience suggests positive hormonal status to be protective with respect to LR risk. A high tumor grade is a risk factor for LR.

Effect of neoadjuvant versus adjuvant chemotherapy on ipsilateral breast tumor recurrence after breast-conserving surgery and whole-breast irradiation.

604 Background: Early Breast Cancer Trialists’ Collaborative Group conducted a large meta-analysis and reported that patients who underwent neoadjuvant chemotherapy (NAC) had higher ipsilateral breast tumor recurrence (IBTR) rate than those with adjuvant chemotherapy. However, since the study was conducted with patients treated two decades ago, the results could not reflect the advance in treatments and IBTR rate was much higher than in recent studies, Thus, we investigated the association between chemotherapy settings and IBTR rates in breast cancer patients. Methods: We retrospectively reviewed the data of 5,307 patients who underwent breast conserving surgery followed by whole breast irradiation between January 2004 and December 2018 in a single institution. Patients who underwent mastectomy or omitted chemotherapy were excluded. Results: The 1,473 patients who underwent NAC showed significantly higher IBTR rate than the 3,564 patients who underwent adjuvant chemotherapy (10-year risk: 4.5% vs. 4.0%; log-rank p=0.045, hazard ratio 1.42 [95%CI,1.01-1.99]). The difference was more evident for patients with hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER2) negative tumor (unadjusted p=0.001, hazard ratio 2.27 [95%CI,1.37-3.74; adjusted p=0.002, hazard ratio 2.80 [95%CI,1.45-5.42]], and the statistical significance was still remained after 1:1 propensity score matching (p=0.026). In contrast, patients with other subtypes did not show significant differences between two groups. Conclusions: Patients who underwent NAC for HR+/HER2- tumors carry increased risk of IBTR than those who underwent adjuvant chemotherapy. Our observation supports the need for considering tumor subtypes in initial treatment. In addition, more intensive surveillance would be needed for patients with HR+/HER2- tumors after NAC.

Use of breast MRI to distinguish treatment failure versus new primary tumor following single fraction breast intraoperative radiotherapy for breast cancer (SF-IORT).

e12534 Background: Single-fraction, intraoperative radiation therapy (SF-IORT) can replace whole breast radiotherapy (WBT) in select patients after lumpectomy for breast cancer. By combining histology review with co-registration of breast MRI at diagnosis and following an in-breast tumor recurrence, we sought to characterize IBTR as: missed on initial MRI, treatment failure, or new primary tumor. This has important implications for both breast MRI and understanding the effectiveness of SF-IORT. Methods: We reviewed our IORT database for patients with IBTR. Three radiologists recorded findings on DCE-MRI, mammograms and ultrasound, pathology at initial diagnosis and IBTR, and time to IBTR. Results: 90 women received SF-IORT between 12/6/2002 - 4/10/2019. There were 6 IBTRs (average age at recurrence 63, range 49-71 years). For these 6 patients, initial diagnostic mammograms showed fatty (1), scattered (4) or extremely dense (1) breasts with suspicious masses (4), calcifications (1), or asymmetry (1), average size 1.4 cm: range 0.3 - 2.0 cm. On MRI, background parenchymal enhancement was minimal (2), mild (2), moderate (1), or marked (1), showing a mass (4), mass/distortion (1), or post-biopsy marker/no abnormal enhancement (1). Initial pathology showed 2 IDC, 3 IDC/DCIS, and 1 DCIS, (average size 1.7 cm, range 1.1 - 2.4 cm) with 6/6 ER +, 5/6 PR + and 6 HER2 negative. IDC Ki-67 ranged from 5-25%. 5/6 patients had sentinel lymph node biopsy (SLNB) with 1/5 having a positive SLN. 4/6 received endocrine therapy. One patient declined follow-up mammography. After IORT, IBTR (average size 1.4 cm, range 0.7 - 3.6 cm) was diagnosed by mammography (3), palpable breast lump (2), or palpable axillary lymph node (LN) (1) shown as mass (4), mass/calcifications (1), or abnormal LN (1). IBTR occurred post-SF-IORT an average of 141.7 months, range 88.3 to 195.8 months. 2/6 IBTR occurred near the biopsy cavity. Subsequent surgery included mastectomy (3), re-excision lumpectomy/RT (2), or axillary LN dissection/RT (1) showing 4 IDC, 1 IDC/DCIS, and 1 IDC /ILC (6/6 ER +; 3/6 PR positive; 2 PR weakly positive; and 5 HER2 negative, 1 HER2 equivocal). Ki-67 ranged from 1-70%. Conclusions: 6/90 (6.6%) patients had an IBTR an average of 141.7 months post SF-IORT with 2/6 near the biopsy cavity. Breast MRI reliably screens patients for SF-IORT. Co-registration of imaging can help distinguish true recurrences from new primary tumors.

Ethnic disparities in adverse events of radiotherapy for breast cancer: A scoping review.

e18502 Background: Ethnic disparities have been well-documented in the US as a contributor to poor outcomes following radiotherapy in ethnic minorities. The objective was to examine the intra-group and inter-group ethnic differences in adverse effects experienced by Asian breast cancer patients undergoing radiotherapy. Methods: A scoping review involving the Pubmed database was conducted. The search strategy included a combination of keywords and index terms related to Asians, breast cancer, CTCAE and treatment. Title, abstract and then full-text screening was performed by two reviewers. Primary research studies and systematic review articles involving female adults in peer-reviewed articles or grey literature records, of any design or date and published in English, were included. Descriptive statistics and charting was used to summarize the results. Results: Of 1765 abstracts retrieved and screened, 37 articles were ultimately included for analysis. The majority of the studies involved Japanese patients (40.5%) followed by Chinese patients (24.3%) with an average of 468 patients being studied per study (ranging from 1-4,869 patients). Only a single study was conducted in the US. 35.1% of studies reported ethnicity and 64.8% of studies reported Asian ethnic subgroups. Most patients underwent whole-breast irradiation (62.1%). 37.5% of studies involved patients with TNM stages I-III breast cancer. Most patients were postoperatively enrolled after BCS (59.4%).ER/PR status was reported in most studies (54.1%) with an average of 553 patients being positive for either hormone receptor and averages of 210 and 905 patients each in studies where numbers were reported individually. HER-2 status was reported in 48.7% of studies with an average of 28 positive HER-2 patients in each study. Most studies reported skin toxicity following radiotherapy (81.1%), commonly grade 1 or 2 (40.5% each) affecting an average of 46% of patients in each study. These dermatological adverse events were radiation dermatitis, hyperpigmentation, fibrosis, hypertrophic scarring or erythema. Conclusions: Ethnicity was under-reported in the studied literature involving breast cancer treatment. Strategies to improve reporting of ethnic subgroups in literature and to reduce psychosocial barriers to access and treatment with a specific focus on mitigating dermatological adverse events of radiotherapy in Asian breast cancer patients may improve overall outcomes in this group.

Does the Use of BioZorb® Result in Smaller Breast Seroma Volume?

To evaluate the impact of BioZorb®, a 3D-bioabsorbable marker, on the tumor-bed boost volume and dosimetric parameters in adaptive boost planning for breast cancer. Records were reviewed for 51 breast-cancer patients who underwent breast-conserving surgery and adjuvant whole-breast irradiation between January 2017 and October 2018. Changes in lumpectomy boost volume (LBV), doses to organs at risk, toxicity and cosmesis were compared between patients with and without BioZorb® Chi-square test and paired and independent t-tests were used for comparisons of variables. Median follow-up was 35.5 months. Mean LBV on initial CT (LBV1; 32.2 vs. 33.8 cc, p=0.74) and on boost computed tomography (CT) (LBV2; 25.3 vs. 24.8 cc, p=0.87) were similar with and without BioZorb® The mean decrease from LBV1 to LBV2 was 9.0 cc and 6.8 cc with and without BioZorb®, respectively (p=0.42). LBV1 was significantly positively correlated with a 20% reduction in LBV (p=0.02). Mean heart and lung doses on adaptive boost planning CT were slightly lower compared to initial planning CT in both groups. Acute breast pain was reported in 18/51 patients, 9 of whom had BioZorb® (p=0.24). Grade-2 pain was reported in 5/51 patients, 3 of whom had BioZorb® (p=0.11). Excellent or good cosmesis was reported in 36/41 patients. Fair cosmesis was reported in 5/41 patients, of whom 2 had BioZorb® (p=0.64). BioZorb® placement does not impact the tumor-bed boost volume nor the variation of seroma volume within the period of treatment. More data and longer follow-up are needed to identify a measurable clinical impact of BioZorb® placement.

Target Volume Coverage and Organ at Risk Doses for Left-sided Whole-breast Irradiation With or Without Internal Mammary Chain Irradiation: A Comparison Between Three Techniques Representing the Past and the Present

AimsThe 15-year results of the EORTC 229922-10925 phase III trial showed a significant reduction in breast cancer mortality and breast cancer recurrences after internal mammary chain (IMC) and medio-supraclavicular irradiation. Unexpectedly, cardiac death was not increased, and the incidence of cardiac events did not differ between left- and right-sided cases, although target volume coverages and organ at risk doses were unknown. Therefore, a planning study was carried out comparing the past and the present, to eventually enable, thereafter, an increased therapeutic ratio of IMC irradiation. Materials and methodsA planning study was carried out on target volume coverage and organ at risk doses for whole-breast irradiation (WBI) ± IMC comparing the results between two-dimensional radiotherapy (free-breathing), hybrid intensity-modulated radiotherapy (IMRT; breath-hold) and robust intensity-modulated proton therapy (IMPT; free-breathing) for 10 left-sided breast cancer cases. Two-dimensional radiotherapy consisted of two tangential wedged photon breast fields and mixed electron/photon beams for the IMC. Hybrid IMRT included two tangential photon breast fields (70%) complemented with IMRT (30%). IMPT plans were created using multi-field robust optimisation (5 mm set-up and 3% range uncertainties) with two (WBI) or three (WBI + IMC) beams. ResultsTarget volume dose objectives were met for hybrid IMRT and IMPT. For two-dimensional radiotherapy, target coverage was 97% and 83% for breast and IMC, respectively. The mean heart dose for WBI only was <2 Gy for all techniques. For WBI + IMC, heart doses (mean heart dose, mean left anterior descending region, volume of the heart receiving 5 Gy (V5) were significantly higher for two-dimensional radiotherapy when compared with contemporary techniques. The V5 left anterior descending region reduced from 100% (two-dimensional radiotherapy) to 70% and 20% for hybrid IMRT and IMPT, respectively. Conclusion: Contemporary radiotherapy techniques result in improved target volume coverage and significantly decreased heart doses for WBI + IMC radiotherapy. Hence, nowadays an increased therapeutic ratio of elective IMC irradiation may be anticipated.

Long-term oncological outcomes of hypofractionated versus conventional fractionated whole breast irradiation with simultaneous integrated boost in early-stage breast cancer.

PurposeFor patients with early breast cancer who undergo breast-conserving surgery, adjuvant whole breast irradiation (WBI) with simultaneous integrated boost (SIB) results in lower radiotherapy fractions. Published studies have shown that both conventional fraction with SIB (C-SIB) and hypofractionation with SIB (H-SIB) seem to be safe and feasible. In this study, we sought to compare the oncologic outcomes between C-SIB and H-SIB in early-stage breast cancer.Materials and MethodsStage I–II breast cancer patients who received adjuvant WBI with SIB between January 2008 and December 2017 were retrospectively reviewed. The radiation dose in the C-SIB group was 50 Gy and 65 Gy in 25 daily fractions, while in the H-SIB group, it was 43.2 Gy and 52.8 Gy in 16 daily fractions to the whole breast and tumor bed, respectively.ResultsA total of 188 patients, 103 in the C-SIB group and 85 in the H-SIB group, were included. With a median follow-up time of 87 months, 7-year locoregional control of C-SIB was comparable to H-SIB (95.8% vs. 97.4%, p = 0.964). The 7-year distant metastasis-free survival rates of C-SIB and H-SIB were 89.9% and 95.9% (p = 0.111), while the 7-year disease-free survival rates were 84.2% and 95.4%, respectively (p = 0.176). In multivariate analysis, there was no significant prognostic factor associated with better overall survival. ConclusionH-SIB provided comparable locoregional control to C-SIB. With the advantage of a shorter radiotherapy course, H-SIB could be a favorable option for WBI in early-stage breast cancer.

Efficient method for whole-breast irradiation therapy using Halcyon linear accelerators.

BackgroundThe Halcyon is a linear accelerator‐based treatment machine designed for a high‐throughput simplified workflow. The machine features a compact jawless design, dual‐layer multileaf collimators, and a single 6‐MV flattening filter‐free (FFF) beam. However, the machine's 6‐MV FFF beam may restrict its applicability to conventional techniques, such as field‐in‐field (FiF) radiotherapy, for breast cancer treatment. This study developed a practical and efficient hybrid method for imaging, planning, and irradiation procedures for whole‐breast irradiation using Halcyon linear accelerators.Materials and methodsThe proposed method involves five major steps: (1) field arrangement, (2) planning target volume (PTV) generation and evaluation, (3) basal plan generation, (4) inverse planning intensity–modulated radiation therapy plan generation, and (5) plan evaluation and irradiation. The PTV is generated using isodose curves plotted on the basis of tangential fields, which are applied to create a basal plan. Subsequently, a basal‐dose‐compensation approach is applied to further optimize the treatment plan. This efficient workflow necessitates executing only one onboard cone‐beam computed tomography procedure. This study included 10 patients with early‐stage breast cancer who were treated at our center. The performance of the proposed method was evaluated by comparing its corresponding irradiation time and dose statistics with those derived for a dynamically flattened beam‐based FiF (DFB‐FiF) method.ResultsAll plans were normalized to ensure that 98% of the prescribed dose covered 95% of the PTV. On average, the global maximum doses in the proposed and DFB‐FiF methods were lower than 106%. The homogeneity index for right‐sided (left‐sided) breast cancer was 0.053 (0.056) in the proposed method and 0.073 (0.076) in the DFB‐FiF method. The dose statistics of normal tissues, including the contralateral breast, heart, and lungs, were comparable between the methods. However, the irradiation time per monitor unit in the proposed method was approximately five times faster than that in the DFB‐FiF method, but the planning time and complexity were similar between the methods.ConclusionsThis study developed and evaluated an efficient and practical hybrid method for whole‐breast irradiation using the Halcyon. This method can significantly reduce the irradiation time, while providing comparable dose statistics to the DFB‐FiF method.

Dosimetric Planning Comparison for Left-Sided Breast Cancer Radiotherapy: The Clinical Feasibility of Four-Dimensional-Computed Tomography-Based Treatment Planning Optimization.

Background: Adjuvant whole-breast radiotherapy (RT) is a significant part of the standard of care treatment after breast cancer (BC) conserving surgery. Modern techniques including intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) have constituted to better target coverage and critical organs sparing. However, BC survivors are at risk of developing radiation-induced cardiac toxicity. Hence, deep-inspiration breath-hold (DIBH) techniques have been implemented at many centers to further reduce cardiac exposure but require compliance. 4D-CT robust optimization can account for heart intrafractional motion per breathing phase. The optimization has been explored in cardiac sparing of breast IMRT compared to DIBH in a small sample size but has not been evaluated in substructures sparing, nor in VMAT. To provide patients who are not compliant to breath-hold with an optimal treatment approach, various heart sparing techniques need to be evaluated for statistical significance and clinical feasibility.Aim: This retrospective study aimed to provide an extensive dosimetric heart sparing comparison of free-breathing, 4D-CT-based treatment planning, including robust optimization with DIBH-based treatment planning. Combinations of forward and inverse IMRT and VMAT are also considered.Methods: Fifteen early stage left-sided BC standard treatment plans were selected. Breast, lung, left anterior descending artery (LAD), left ventricle (LV), and the whole heart were contoured on each 4D-CT phase and DIBH CT dataset. Each treatment plan was optimized using forward/inverse IMRT and VMAT on the following CT datasets: DIBH, average 4D-CT, and the complete 4D-CT dataset needed for robust optimization. Dose-volume histograms were used to compare V5GyHeart, mean heart dose, mean and max LAD dose, mean LV dose, and V50%Lung.Results: All RT techniques assessed including 4D robust optimization were clinically feasible. Statistically significant differences in mean heart, LAD and LV dose, max LAD dose, and V5GyHeart (p < 0.01) but no difference in V50%Lung (p = 0.29) were found between different techniques. IMRT DIBH achieved the optimal cardiac and substructure sparing among treatment plans. 4D robust IMRT had significantly greater mean heart and LV dose than DIBH IMRT (p ≤ 0.01), except LAD dose. Among free-breathing methods, no difference in all cardiac and substructure dose parameters was observed (p > 0.2) in comparing forward and inverse IMRT with average 4D-CT, inverse average 4D-CT, and 4D robust with IMRT, and between average 4D-CT VMAT and 4D robust VMAT. Only V5GyHeart and mean LV dose were significantly greater in 4D robust VMAT (p < 0.01) compared to DIBH VMAT. Mean heart and LV doses were significantly reduced (p < 0.01) in DIBH IMRT compared to DIBH VMAT. Moreover, mean heart and LV dose, V5GyHeart were significantly reduced in inverse IMRT average 4D-CT compared to average 4D-CT VMAT (p < 0.02) and in 4D robust IMRT compared to 4D robust VMAT (p < 0.04).Conclusion: This study demonstrated the clinical feasibility of 4D robust optimization in limiting the cardiac and substructures dose during free-breathing RT with both IMRT/VMAT for patients who are not compliant with breath-hold RT. However, this study also presents that 4D robust optimization can reduce LAD dose but not fully outperform DIBH or conventional 4D-CT-based planning with IMRT/VMAT in heart sparing in treating early staged left-sided BC patients.

Prospective Comparison of Hypofractionated Versus Normofractionated Intensity-Modulated Radiotherapy in Breast Cancer: Late Toxicity Results of the Non-Inferiority KOSIMA Trial (ARO2010-3).

PurposeTo compare the late toxicity profile of hypofractionation and normofractionation for whole-breast radiotherapy in breast cancer (BC) patients after conserving surgery.MethodsSixty-year-old or older patients with pTis-pT3, pN0-pN1a, M0 BC were recruited and stratified to hypofractionated (arm R-HF) or normofractionated (arm L-NF) intensity-modulated radiotherapy (IMRT), for right- and left-sided BC, respectively, in this single-center, non-randomized, non-inferiority trial. A boost was allowed if indicated. The primary outcome was the cumulative percentage of patients developing grade III fibrosis, grade I telangiectasia, and/or grade II hyperpigmentation after 2 years, with a pre-specified non-inferiority margin of 15% increase from an expected 2-year toxicity rate of 20%.ResultsThe Median follow-up was 4.93 (0.57–8.65) years for R-HF and 5.02 (0.65–8.72) years for L-NF (p=0.236). The median age was 68 (60–83 and 60–80) years, respectively. In total, 226 patients were recruited (107 for R-HF and 119 for L-NF), with 100 and 117 patients suitable for assessment, respectively. A boost was delivered in 51% and 53% of each arm, respectively. Median PTV volumes were 1013.6 (273–2805) cm3 (R-HF) and 1058.28 (315–2709) cm3 (L-NF, p=0.591). The 2-year primary endpoint rate was 6.1% (95% CI 1.3-11.7, n=5 of 82) and 13.3% (95% CI 7-20.2, n=14 of 105), respectively (absolute difference -7.2%, one-sided 95% CI ∞ to -0.26, favoring R-HF). No local recurrence-free- or overall-survival differences were found.ConclusionIn this prospective non-randomized study, hypofractionation did not have higher toxicity than normofractionated whole-breast IMRT.

Favorable safety profile of moderate hypofractionated over normofractionated radiotherapy in breast cancer patients: a multicentric prospective real-life data farming analysis

BackgroundModerately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients.Materials and methodsProspective data from breast cancer patients, treated with locoregional radiotherapy were collected between November 2015 and February 2020 in 3 comprehensive cancer centers. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used to compare HFRT and NFRT. Furthermore, risk factors of dermatitis were identified in a sub-study (622 patients) by multivariate logistic regression analysis.ResultsIn total, 3518 T0-4 N0-3 mostly M0 (85.8%) breast cancer patients with a median age of 60.7 (24–96 years old) were analyzed. Acute grade 2–3 dermatitis, grade 1–3 breast oedema, and grade 1–2 hyperpigmentation were less frequent with HFRT versus NFRT: respectively 8.9% versus 35.1% (Chi-2 = 373.7; p < 0.001), 29.0% versus 37.0% (Chi-2 = 23.1; p < 0.001) and 27.0% versus 55.8% (Chi-2 = 279.2; p < 0.001). Fewer patients experienced pain with HFRT versus NFRT: 33.4% versus 53.7% respectively (Chi-2 = 137.1; p < 0.001). Factors such as high BMI (OR = 2.30 [95% CI, 1.28–4.26], p < 0.01), large breast size (OR = 1.88 [95% CI, 1.07–3.28], p < 0.01) and lumpectomy over mastectomy (OR = 0.52 [95% CI, 0.27–0.97], p < 0.05) were associated with greater risk factors of grade 2–3 dermatitis in multivariate analysis regardless of NFRT or HFRT.ConclusionThe results of this study suggests that breast HFRT may be a better option even for patients with a high BMI or large breast size. Acute toxicity was low to mild, and lower with HFRT compared to NFRT. Results from real-life data were robust, and support the use of HFRT beyond randomized study populations. Long-term real-life data awaits further investigation.