Adjuvant Whole Breast Radiotherapy Research Articles

Breast cancer radiobiology: The renaissance of whole breast radiation fractionation (Review).

Breast cancer radiotherapy has evolved significantly, driven by decades of research into fractionation schedules aimed at optimizing treatment efficacy and minimizing toxicity. Initial trials such as NSABP B-06 and EBCTCG meta-analyses established the benefits of adjuvant whole-breast irradiation in reducing local recurrence and improving survival rates. The linear-quadratic (LQ) model provided a framework to understand tissue response to radiation, highlighting the importance of the α/β ratio in determining fractionation sensitivity. The present scoping review aimed to identify and describe hypofractionation regimens for whole breast radiotherapy and evaluate dose differences using the LQ model across proposed α/β ratios. A comprehensive PubMed search for clinical trials published since 2010 on hypo-fractionated regimens was performed. Studies discussing α/β ratios for breast cancer have been also searched. Data on dose, fractions and α/β ratios were collected, and biologically effective dose (BED) and equivalent dose in 2 Gy fractions were calculated. The coefficient of variation for BED varied with α/β ratios, showing the lowest variability for an α/β ratio of ~3 without tumor repopulation and increased with repopulation (BED-kT; k is a constant that depends on the repopulation rate of the tumor, and T is the total treatment time in days). Significant differences in BED variances were observed across α/β ratios (F-statistic 219.6, P<0.0001). START trials (P, A, and B) established α/β ratios of 3-4 Gy for breast cancer and normal tissues, confirming that hypofractionation is as effective as standard fractionation with potentially fewer late toxicities. Subsequent trials, such as FAST and FAST-Forward, demonstrated that ultra-hypofractionation is equivalent in tumor compared with conventional regimens. Further research is needed to gain a stronger understanding of radiobiological properties of breast cancer cells. Advances in radiotherapy technologies and the integration of biomarkers, radiomics and genomics are transforming treatment, moving towards precision medicine.

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.

Do Barrier Films Impact Long-Term Skin Toxicity following Whole-Breast Irradiation? Objective Follow-Up of Two Randomised Trials.

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37-73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI (p < 0.001) and a significant increase of cutis, subcutis, and oedema thickness (p < 0.001, p < 0.001, and p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use.

Physician- and Patient-Reported Outcomes of the MC1635 Phase 3 Trial of Ultrahypofractionated Versus Moderately Hypofractionated Adjuvant Radiation Therapy After Breast-Conserving Surgery

Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.

Practice of Tumor Bed Boost in Patients after Oncoplastic Breast-Conserving Surgery.

The practice of boost to the tumor bed after treatment with oncoplastic breast-conserving surgery (BCS) remains variable. Using a survey, the present study evaluated the current practice of tumor bed boost administered in women after oncoplastic BCS. Actively practicing radiation oncologists across India were sent a questionnaire on the practice of adjuvant whole-breast radiotherapy and tumor bed boost after oncoplastic BCS via email and encouraged to participate. Of the 54 radiation oncologists who participated, most (98.1%) used a linear accelerator for radiotherapy. Hypofractionation was preferred by 59.26%, standard fractionation by 7.41%, and the remaining selected the fractionation strategy based on various patient factors. In addition, 83.33% participants reported that they always planned tumor boost, 51.85% preferred photons for the boost, and 75.93% administered sequential boost. The most common dose for the boost was 12.5Gy in five fractions (40.74%). Most participants (77.78%) revealed that they used a combination of methods for identifying the tumor bed. With respect to clip placement, most surgeons (96%) at the participants' centers placed ≥ 4 clips at the tumor site, with both the base and margins being preferred by surgeons (81.48%) for placement. Finally, 12.96% participants revealed that the surgeons always involved them during surgical planning, whereas 7.4% participants reported that they always included the surgeons during radiotherapy planning, suggesting that radiation oncologists and oncoplastic surgeons do not involve each other during surgical and radiotherapy planning, possibly leading to suboptimal treatment. This may be attributed to the absence of guidelines regarding boost practices after oncoplastic BCS.

Tumor Bed Boost Radiotherapy in the Conservative Treatment of Breast Cancer: A Review of Intra-Operative Techniques and Outcomes.

Conservative surgery is the preferred treatment in the management of breast cancer followed by adjuvant whole-breast irradiation. Since the tumor bed is the main site of relapse, boost doses are conveniently administered according to risk factors for local relapse to increase the efficacy of the treatment. The benefit of a radiation boost is well established and it can be performed by several techniques like brachytherapy, external radiation or intraoperative radiotherapy. Greater precision in localizing the tumor cavity, immediacy and increased biological response are the main advantages of intraoperative boost irradiation. This modality of treatment can be performed by means of mobile electron accelerators or low-photon X-ray devices. There is a lot of research and some published series analyzing the results of the use of an intraoperative boost as an adjuvant treatment, after neoadjuvant systemic therapy and in combination with some reconstructive surgeries. This review discusses advantages of intraoperative radiotherapy and presents the main results of a boost in terms of local control, survival, tolerance and cosmesis.

Objective, Clinician- and Patient-Reported Evaluation of Late Toxicity Following Adjuvant Radiation for Early Breast Cancer: Long-Term Follow-Up Results of a Randomised Series.

Background and Purpose: This study aimed to differentially assess the frequency and severity of late radiation-induced toxicity following adjuvant whole-breast irradiation for early breast cancer with conventional fractionation (CF) and moderate hypofractionation (mHF). Materials and Methods: Patients recruited in a previous randomised controlled trial comparing acute toxicity between CF and mHF without disease recurrence were included in a post hoc analysis. Spectrophotometric and ultrasonographic examinations were performed for an objective evaluation and subsequent comparison of long-term skin toxicity. Furthermore, patient- and clinician-reported outcomes were recorded. Results: Sixty-four patients with a median age of 58 (37-81) years were included. The median follow-up was 57 (37-73) months. A total of 55% underwent CF and 45% mHF. A total of 52% received a sequential boost to the tumour bed. A significant decrease in mean L* (p = 0.011) and an increase in a* (p = 0.040) and b* values (p < 0.001) were observed, indicating hyperpigmentation. In comparison with the non-irradiated breast, there was a significant increase in both cutis (+14%; p < 0.001) and subcutis (+17%; p = 0.011) thickness, significantly more pronounced in CF patients (p = 0.049). In CF patients only, a sequential boost significantly increased the local cutis thickness and oedema compared to non-boost regions in the same breast (p = 0.001 and p < 0.001, respectively). Conclusions: mHF objectively resulted in reduced long-term skin toxicity compared to CF. A sequential boost increased the local fibrosis rate in CF, but not in mHF. This might explain the subjectively reported better cosmetic outcomes in patients receiving mHF and reinforces the rationale for favouring mHF as the standard of care.

Incidental Axillary Dose of Tomotherapy in Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer: A Dosimetrical Analysis.

Background and Objectives: Intensity-modulated radiation therapy (IMRT) is becoming a more common method of performing whole breast irradiation (WBI) for early breast cancer. This study aimed to examine the incidental dose to the axillary region using tomotherapy, a unique form of IMRT. Patients and Methods: This study included 30 patients with early-stage breast cancer who underwent adjuvant WBI using TomoDirect IMRT. A hypofractionation scheme of 42.4 Gy delivered in 16 fractions was prescribed. The plan comprised of two parallel-opposed beams, along with two additional beams positioned anteriorly at gantry angles of 20° and 40° from the medial beam. The incidental dose received at axillary levels I, II, and III was evaluated using several dose-volume parameters. Results: The study participants had a median age of 51 years, and 60% had left-sided breast cancer. The mean dose of the axilla for levels I, II, and III were 15.5 ± 4.8 Gy, 14.9 ± 4.2 Gy, and 1.5 ± 1.6 Gy, respectively. Adequate coverage of the axilla, defined as V95%[%], was achieved for 4.7 ± 3.9%, 4.8 ± 3.7%, and 0 ± 0% for levels I, II, and III, respectively. The results were compared with those of previously published studies, and the axillary mean dose and V95%[%] of TomoDirect IMRT were low, comparable to other IMRT techniques, and lower than those of traditional tangential therapy. Conclusions: While incidental axillary radiation during WBI has been proposed to assist in regional disease control, the TomoDirect plan was demonstrated to decrease this dose, and a hypofractionation scheme would further lower its biological effectiveness. Future clinical studies should incorporate dosimetrical analysis of incidental axillary dose, in order to facilitate hypofractionated IMRT planning with risk-adjusted axilla coverage in early breast cancer.

Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

V5 and High Sensitivity Cardiac Troponin T for Early Detection of Cardiac Toxicity During Left Breast Cancer Irradiation.

The high sensitivity cardiac troponin T (Hs-cTnT) is a myocardial damage biomarker that could have a predictive value in patients who undergo radiotherapy for left sided breast cancer. The aim of this study was to evaluate the early effect of left whole breast radiotherapy (WB-RT) on serum Hs-cTnT levels and its correlation with pre-existing factors. The study was conducted from December 2017 to May 2018. Forty-five patients with early stage left-sided breast cancer who received adjuvant breast hypofractionated RT without prior chemotherapy were included. Serum levels of Hs-cTnT were obtained before, weekly during RT, and within one week after the end of treatment. Considering the physiological variations of serum levels, an increase in Hs-cTnT (∆Hs-cTnT) of more than 30% from the baseline value was chosen as a threshold. The main cardiovascular risk factors were recorded. Dose volume histograms (DVHs) were used to provide a quantitative analysis for the whole heart, left ventricle, and left anterior descending artery (LAD). Twelve of 45 patients (26.6%) showed a ∆Hs-cTnT ≥30%. The maximum Hs-cTnT level was recorded in the last week of treatment. ∆Hs-cTnT was strongly associated with heart V5 (p=0.05) and hypertension (p=0.05). Multivariate analysis confirmed the importance of the heart V5 and correlated with ∆Hs-cTnT. The increase in Hs-cTnT serum levels during adjuvant WB-RT suggested a correlation with the cardiac radiation dose in chemotherapy-naive breast cancer patients. A longer follow-up is needed to correlate Hs-cTnT values with cardiac events.

Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial

PurposeThe natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. Methods1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. ResultsMedian follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77). ConclusionsThe risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer.

Adjuvant Therapy in Breast Cancer Patients With Microscopic Residual Disease

IntroductionSurgical resection is the gold standard for early-stage breast cancer. Positive surgical margins are associated with poor outcome. Endocrine therapy (ET) is recommended as primary systemic treatment for hormone receptor positive (HR+) breast cancer after surgery. We hypothesized that chemoenocrine therapy (CET) would not be associated with improved survival relative to ET for patients with positive margins. Materials and methodsThe National Cancer Database was queried for pathologic stage I HR + HER2-breast cancer patients treated with partial mastectomy and adjuvant whole-breast irradiation between 2004 and 2017. The adjuvant treatment approaches to positive surgical margins were investigated and compared. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression. ResultsAmong 228,453 patients, a positive surgical margin (microscopic residual disease, R1) was identified in 3561 (1.6%) patients. Compared with complete resections, positive margin was associated with inferior overall survival (hazard ratio [HR] = 1.276, P = 0.003). Among the R1 patients, 78.7% received ET only, 11.7% received CET, 1.2% received chemotherapy only, and 8.5% received no systemic therapy. After controlling for patient, facility, and tumor characteristics, ET provided greatest survival benefit (relative to no therapy, HR = 0.378, P < 0.001) followed by CET (HR = 0.446, P = 0.020). Compared with ET alone, CET is not associated with additional overall survival benefit (HR = 1.179, P = 0.595). ConclusionsCET appeared not to be associated with an improved overall survival in early stage HR + HER2-breast cancer with microscopic residual disease relative to ET. Positive surgical margins therefore are probably not a relevant clinical factor for adjuvant chemotherapy decision-making.

Machine-learning prediction model for acute skin toxicity after breast radiation therapy using spectrophotometry.

Radiation-induced skin toxicity is a common and distressing side effect of breast radiation therapy (RT). We investigated the use of quantitative spectrophotometric markers as input parameters in supervised machine learning models to develop a predictive model for acute radiation toxicity. One hundred twenty-nine patients treated for adjuvant whole-breast radiotherapy were evaluated. Two spectrophotometer variables, i.e. the melanin (IM) and erythema (IE) indices, were used to quantitatively assess the skin physical changes. Measurements were performed at 4-time intervals: before RT, at the end of RT and 1 and 6 months after the end of RT. Together with clinical covariates, melanin and erythema indices were correlated with skin toxicity, evaluated using the Radiation Therapy Oncology Group (RTOG) guidelines. Binary group classes were labeled according to a RTOG cut-off score of ≥ 2. The patient's dataset was randomly split into a training and testing set used for model development/validation and testing (75%/25% split). A 5-times repeated holdout cross-validation was performed. Three supervised machine learning models, including support vector machine (SVM), classification and regression tree analysis (CART) and logistic regression (LR), were employed for modeling and skin toxicity prediction purposes. Thirty-four (26.4%) patients presented with adverse skin effects (RTOG ≥2) at the end of treatment. The two spectrophotometric variables at the beginning of RT (IM,T0 and IE,T0), together with the volumes of breast (PTV2) and boost surgical cavity (PTV1), the body mass index (BMI) and the dose fractionation scheme (FRAC) were found significantly associated with the RTOG score groups (p<0.05) in univariate analysis. The diagnostic performances measured by the area-under-curve (AUC) were 0.816, 0.734, 0.714, 0.691 and 0.664 for IM, IE, PTV2, PTV1 and BMI, respectively. Classification performances reported precision, recall and F1-values greater than 0.8 for all models. The SVM classifier using the RBF kernel had the best performance, with accuracy, precision, recall and F-score equal to 89.8%, 88.7%, 98.6% and 93.3%, respectively. CART analysis classified patients with IM,T0 ≥ 99 to be associated with RTOG ≥ 2 toxicity; subsequently, PTV1 and PTV2 played a significant role in increasing the classification rate. The CART model provided a very high diagnostic performance of AUC=0.959. Spectrophotometry is an objective and reliable tool able to assess radiation induced skin tissue injury. Using a machine learning approach, we were able to predict grade RTOG ≥2 skin toxicity in patients undergoing breast RT. This approach may prove useful for treatment management aiming to improve patient quality of life.

NRG RTOG 1005: A Phase III Trial of Hypo Fractionated Whole Breast Irradiation with Concurrent Boost vs. Conventional Whole Breast Irradiation Plus Sequential Boost Following Lumpectomy for High Risk Early-Stage Breast Cancer

<h3>Purpose/Objective(s)</h3> Randomized trials support a supplemental radiation dose (Boost) to the lumpectomy (L) cavity region after whole breast irradiation (WBI), providing a 20-30% relative reduction of in-breast recurrence (IBR); with the disadvantage that it extends treatment duration ⁓ 1 week. Hypofractionated WBI (H-WBI) in ≤ 3 weeks is used after L to deliver adjuvant WBI with acceptable toxicity and comparable IBR as conventional WBI (C-WBI) 50 Gy in 2 Gy fractions (F). NRG RTOG 1005 sought to determine whether a boost delivered concomitantly with H-WBI over 15 F is non-inferior for IBR compared to boost delivered sequentially after C-WBI in patients (pts) considered at High Risk of IBR. <h3>Materials/Methods</h3> Protocol-specified High Risk pts post L with stages 0, I & II breast cancer were randomized to C-WBI 50 Gy in 25 F or 42.7 Gy in 16 F plus sequential boost of 12 Gy in 6 F or 14 Gy in 7 F (Arm I) or H-WBI 40 Gy in 15 F plus concomitant boost of 8 Gy in 15 F of 0.53 Gy per day (Arm II). Radiation was target based 3-dimensional conformal radiation therapy (3DCRT) or intensity modulated radiation therapy (IMRT) and quality review (QA) was required. Stratification was by age (<50 vs ≥ 50), adjuvant chemotherapy (Y vs N), ER status (+ vs -) and histologic grade (1, 2 v 3). The primary endpoint is IBR. Assuming Arm I 5‐year IBR of 1.59%, 90% CI upper bound hazard ratio (HR) of 2.12 and 1‐sided significance level = 0.05, 2150 pts with at least 46 IBR events provide >80% power to conclude non‐inferiority. IBR was analyzed comparing the cause-specific hazards. Adverse Events (AE) were graded with NCI CTCAE v4. Physician-reported NRG-RTOG Global Cosmetic Score (GCS) was grouped as excellent/good vs fair/poor, and arms compared with chi-square. <h3>Results</h3> 2262 of 2354 randomized pts were eligible (Arm I n=1124; Arm II n=1138). Median age 55 years, 34% Stage II, 52% grade 3, 30% ER-, 17% close/+ margins consistent with a "High Risk" population. Radiation was 3DCRT 81%, IMRT 19%, and the QA was per protocol 81% and 88% on Arm I vs II, respectively. With a median follow-up of 7.3 years and 56 IBR events, the 5 and 7-year IBR were 2.0% and 2.2% on Arm I and 1.9% and 2.6% on Arm II. The non-inferiority comparison (Arm I reference level) resulted in a HR (90% CI): 1.32 (0.84, 2.05) and p = 0.039, thus meeting non-inferiority. No differences in AEs noted between arms, with low rates of ≥ grade 3 treatment-related AEs, 3.3% vs 3.5% for Arm I vs II, respectively (p=0.79). No difference in 3-year excellent/good cosmesis by arm: 86% for Arm I vs 84% Arm II (p=0.61). <h3>Conclusion</h3> Concomitant boost with H-WBI results in non-inferior IBR compared to sequential boost after C-WBI in high-risk cases and reduces overall treatment time. Using target based 3DCRT or IMRT, there are no differences in toxicity or cosmetic outcome for concomitant v sequential boost or the WBI fractionation regimen.

Patterns of Care and Utilization of Radiation for Women With Good-Risk Ductal Carcinoma In Situ: A National Cancer Database Analysis.

Purpose/objective(s)Lumpectomy followed by whole-breast radiation therapy (WBRT) provides a 50% recurrence rate reduction in ductal carcinoma in situ (DCIS) patients when compared to lumpectomy alone. Certain factors increase the risk of recurrence, including higher nuclear grade, large size, age less than 50, and close margins. RTOG 9804 demonstrated a reduction in local failure after WBRT with the use of adjuvant radiation in women with "good-risk disease" (mammographically detected, measuring less than or equal to 2.5 cm, with a predominant nuclear grade of 1 or 2, and a margin of greater than or equal to 1 cm, or a negative re-excision). The purpose of this study is to retrospectively identify the patterns of care in women with low-risk DCIS utilizing the National Cancer Database (NCDB). We hypothesize that with the utilization of hypofractionation, there may be an increase in the delivery of RT for these "good-risk" patients.Materials/methodsThe National Cancer Database was queried to identify women treated with lumpectomy for <2.5 cm, nuclear grade 1 or 2 DCIS of the breast from 2004 to 2016. Data were collected regarding age, tumor size, endocrine therapy use, ER receptor status, race, insurance type, and distance from the treatment center. The distance was stratified into quartiles consisting of 0-3.9, 4-8, 8.1-15.8, and > 15.8 miles, respectively. Radiation fractionation was collected and categorized as hypofractionation, standard fractionation, or other if fractionation could not be ascertained. Clinical and patient-related factors were compared between patients who received radiation and those who received no radiation. The frequency distributions between categorical variables were compared using the Chi-square test. Multivariable logistic regression was used to identify covariables that impacted the receipt of radiation.ResultsThe eligibility criteria were met by a total of 12,846 patients. Of those, 6,600 (51.4%) received adjuvant WBRT. On multivariable regression, patients whose tumors were ER (OR 1.24, P<0.001) and those who had not received endocrine therapy (OR 2.24, P<0.001) were more likely to receive WBRT. Factors less likely to receive WBRT included increasing age over 50 (age 50-65 OR 0.83, P<0.001; age>65 OR 0.58, P<0.001), and distance of >15.8 miles (OR 0.78, P<0.001). The fractionation technique was categorized as standard or hypofractionated in 52.2% of patients. Of those, the use of hypofractionation increased from 0.4% in 2004 to 8.9% in 2010 and to 53.8% in 2016.ConclusionThis NCDB analysis demonstrated that patients who meet the RTOG 9804 criteria for "good-risk" DCIS are less likely to receive RT as time progresses despite an increase in the utilization of hypofractionation techniques. Overall, slightly more than half of these patients receive adjuvant RT.

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.

Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy Is Effective in Luminal Breast Cancer Patients Aged 60 Years and Older.

Adjuvant whole breast irradiation (AWBI) improves local control and survival in breast cancer patients after breast-conserving surgery. Between 2010 and 2017, 823 patients ≥ 60 years with ER-positive, Her-2 negative, clinically N0 breast cancer underwent breast-conserving surgery (BCS) at the West Pomeranian Oncology Center. Intraoperative radiotherapy (IORT) with kV photons was applied to 199 (24.2%) patients according to the IORT protocol, and AWBI only was applied to 624 (75.8%). IORT patients in cases with lymph node metastasis, lobular type presence, extensive in situ components, lymphatic vessel invasion, or resection margin < 2 mm, additionally underwent AWBI. Median follow-up was 74 months. There were two (1%) breast relapses in the IORT protocol group and one (0.2%) in the AWBI-only group. In each group, one axillary lymph node relapse was diagnosed (0.5% and 0.2%, respectively). There were two local relapses in the IORT-only group, and they were treated further with BCS and AWBI. Although locoregional relapse-free survival differed between the AWBI-only and IORT protocol groups (98.5% vs. 99.7%, p = 0.048), the local control, distant metastasis-free survival, and breast cancer-specific survival were similar. IORT is a reasonable option to avoid AWBI in ER-positive, Her-2 negative, cN0 women with breast cancer aged ≥ 60 years.

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.

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.

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.