Adjuvant Whole Breast Radiotherapy Research Articles

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.

Adjuvant Radiotherapy Is Associated with an Increase in the Survival of Old (Aged over 80 Years) and Very Old (Aged over 90 Years) Women with Breast Cancer Receiving Breast-Conserving Surgery.

This study is the first to examine the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM) in old (aged ≥80 years) and very old (aged ≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving surgery. After propensity score matching, adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old and very old women with IDC compared with no use of adjuvant WBRT. Background: To date, no data on the effect of adjuvant whole-breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available for old (aged ≥80 years) and very old (≥90 years) women with breast invasive ductal carcinoma (IDC) receiving breast-conserving conservative surgery (BCS). Patients and Methods: We enrolled old (≥80 years old) and very old (≥90 years old) women with breast IDC who had received BCS followed by adjuvant WBRT or no adjuvant WBRT. We grouped them based on adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. To reduce the effects of potential confounders when comparing all-cause mortality between the groups, propensity score matching was performed. Results: Overall, 752 older women with IDC received BCS followed by adjuvant WBRT, and 752 with IDC received BCS with no adjuvant WBRT. In multivariable Cox regression analysis, the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) of all-cause death for adjuvant WBRT compared with no adjuvant WBRT in older women with IDC receiving BCS was 0.56 (0.44–0.70). The aHRs (95% CIs) of LRR and DM for adjuvant WBRT were 0.29 (0.19–0.45) and 0.45 (0.32–0.62), respectively, compared with no adjuvant WBRT. Conclusions: Adjuvant WBRT was associated with decreases in all-cause death, LRR, and DM in old (aged ≥80 years) and very old (aged ≥90 years) women with IDC compared with no adjuvant WBRT.

Abstract P3-19-03: Preliminary results of a feasibility study assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer

Abstract BACKGROUND: Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast irradiation (WBI) following lumpectomy for select patients. However, the challenges to post-operative APBI include targeting inaccuracy and the inability to measure tumor response to radiation. We hypothesized that preoperative APBI (pAPBI) could reliably target the tumor using MRI-guidance that is acquired prone in combination with our established prone breast radiation delivery. We developed methodology for prone CT simulation to establish radiation position, MRI acquisition in treatment position, registration of MRI-CT data for treatment planning, and treatment delivery with daily cone-beam CT using the same immobilization platform. This study aimed to assess the reproducibility, toxicity and local control associated with MRI/CT-directed prone pAPBI. METHODS: This was a prospective, single arm study enrolling patients &amp;gt;50 yo with clinical (c) Stage IA ER+/PR+/HER2- breast cancer intending lumpectomy. Axillary US and MRI imaging to confirm clinical node negative disease was required. A planning CT in the prone position was followed by MRI using the same prone immobilization platform. Rigid registration of MRI-CT data was used for radiation planning. pAPBI of 3850 cGy was delivered in 10 fractions BID with the same prone immobilization technique. Another MRI was obtained 4 weeks post-APBI to assess tumor response. The intensity, kinetics and volume of the lesion on MRI was quantitatively assessed and an experienced reader evaluated MRI volume and kinetic changes in the tumor post-APBI. Lumpectomy was performed 4-6 weeks after APBI. Simon 2 stage design required assessment after accrual of 19 patients for assessment of feasibility. RESULTS: Nineteen cStage IA ER+/PR+/HER2- breast cancer patients with a median age of 65 (range 51-78) were enrolled on the study, completed APBI, lumpectomy, and adjuvant AI. Median follow up was 3.4 years. Mean clinical tumor size was 1.1 cm ± 0.4 and mean path tumor size was 0.94 cm ± 0.6. There was complete pathologic response in 10.5% (n=2) and an additional 36.8% (n=7) were downstaged from clinical stage (measured by mammogram/US) to pathologic stage, resulting in a total response of 47.4% (n=9). Six (31.6%) patients had stable disease after APBI. Four (21.0%) were upstaged from clinical stage to pathological stage. Tumor response detected by MRI significantly correlated with tumor response based on clinical to pathologic stage (p=0.03). Cosmesis was rated as excellent/good in 89.5% (n=17) patients post-APBI. Cosmesis worsened to fair in 2 patients post-APBI, one of which required adjuvant WBI after focal triple negative breast cancer was detected on pathology. Three patients had positive macrometastatic lymph nodes on final pathology despite clinically negative nodes on imaging. One in-breast recurrence outside the RT field was detected by MRI at 14 months, resulting in a locoregional recurrence rate of 5.4% at 3.4 years. Another patient developed metastases at 20 months. CONCLUSIONS: Using the same prone platform, all patients successfully underwent CT simulation, MRI acquisition, and completed pAPBI. Nearly half of enrolled patients had a measurable tumor response to pAPBI based on MRI and pathologic response, confirming the accuracy and reproducibility of defining tumor targets with our MRI/CT-directed pAPBI approach. While this methodology for prone pAPBI resulted in good cosmesis and local control and remains a promising approach for select patients, the challenge of excluding patients with subclinical lymph node positive disease remains. Correlative studies will determine whether Ki-67 and OncotypeDx pre- and post-APBI can help predict response to pAPBI. Citation Format: Sasha Beyer, Tamara Smith, Ashley Sekhon, Jose Bazan, Sachin Jhawar, Erin Healy, Lai Wei, Vedat Yildiz, Mohamed Mohamed, Michael Knopp, Julia White. Preliminary results of a feasibility study assessing radiation response with MRI/CT directed preoperative accelerated partial breast irradiation in the prone position for hormone responsive early stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-03.

Comparison between the use of hypofractionated and conventionally fractionated radiotherapy in early breast cancer: A single-center real-world study in Taiwan

This study aimed to analyze the long-term outcomes of hypofractionated whole-breast irradiation (WBI) (HF-WBI) compared with those of conventionally fractionated WBI (CF-WBI) for early breast cancer treated with breast-conservation surgery (BCS) and adjuvant WBI in Taiwan. This study included patients treated at our institution between 2012 and 2016. All patients with early breast cancer received BCS (pT1-2, pN0, M0) and adjuvant WBI through one of two treatment schemes. Propensity score matching analysis was conducted to create comparable cohorts. The major result is ipsilateral breast tumor recurrence (IBTR) rates and overall survival rates. A total of 869 patients with early-stage breast cancer received adjuvant HF-WBI or CF-WBI were included. After matching, 718 patients were separated into two groups of the same number. With a median follow-up of 66 months, seven cases of IBTR were noted (three for CF, four for HF). There were no significant differences between the HF-WBI and CF-WBI groups in 5-year IBTR rates (0.9% vs 0.6%, P=0.3887, 95% CI [0.25-7.79]) and 5-year overall survival rates (98.1% vs 98.9%, P=0.4702, 95% CI [0.32-3.49]). In our institution, the use of HF-WBI increased significantly from 5% before 2012 (Q3) to 92% in 2016 (Q4). There was no significant difference in grade 1-2 toxicity between the two treatment groups. Fewer cases of grade 3 skin toxicity noted in the HF-WBI group (zero vs four events). HF-WBI had similar IBTR, OS and toxicity to CF-WBI.

Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery

Background: to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). Patients and Methods: we included 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). Results: in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44–0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24–0.71; p = 0.0017) and 0.37 (0.22–0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group. Conclusion: Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.

Surgical and Oncologic Outcomes With Intraoperative Radiation Therapy for Early Breast Cancer.

For selected patients with early-stage breast cancer (BC), intraoperative radiation therapy (IORT) has emerged as a convenient alternative to standard whole breast irradiation (WBI). We report a single institution experience with IORT in terms of oncologic outcomes, toxicities, and cosmesis. Clinicopathological and perioperative outcomes of patients who underwent IORT for early-stage BC at a public hospital from 2017 to 2020 were retrospectively retrieved. Toxicity was categorized to acute or chronic based on 6 months post-IORT cutoff. 85 patients underwent IORT and had complete data, aged 49-85 years (mean 62). Intraoperative radiation therapy added 23 minutes on average to the total operative time. Final stage was 0, I, and II in 40%, 58.9%, and 1.1% of patients, respectively. Mean tumor size was 0.8cm (range .1-2.1), with ductal histology comprising 94% of cases. Surgical margins were positive in 2 patients, and adjuvant WBI was required in 5 patients. After a median follow-up of 17 months (range 3-41), none of the patients had local recurrence and no mortality was recorded. Early wound complications included wound dehiscence (n = 1), seroma/hematoma (n = 15), and re-operation with loss of nipple-areola complex (n = 1). Chronic skin toxicities were reported in 10 (12%) patients and good or excellent cosmetic outcome was reported in 93% of patients. Utilizing IORT among low-risk early BC patients may be a safe and more convenient alternative to traditional WBI, with low toxicity rate, acceptable cosmetic results, and good oncologic outcomes at 17 months. Longer follow-up and further prospective controlled studies are needed to confirm these findings.

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

Lumpectomy followed by whole-breast radiation therapy (WBRT) provides a 50% recurrence rate-reduction in 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 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. We hypothesize that with the utilization of hypofractionation, there may be an increase in delivery of RT for these "good-risk" patients.The National Cancer Database was queried to identify women treated with lumpectomy for a < 2.5 cm, nuclear grade 1 or 2 DCIS of the breast from 2004-2016. Data regarding age, tumor size, endocrine therapy use, ER receptor status, margin status, race, insurance type and distance from the treatment center were collected. 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 no radiation. 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.A total of 13,313 patients met the eligibility criteria. Of those, 6,814 (51.2%) received adjuvant WBRT. On multivariable regression, patients whose tumors were ER- (OR 1.35, 95% CI 1.19-1.54, P < 0.001) and those who did not receive endocrine therapy (OR 2.34, 95% CI 1.94-2.95, P < 0.001) were more likely to receive WBRT. Factors less likely to receive WBRT included later year of diagnosis (OR 0.97, 95% CI 0.96-0.98, P < 0.001) increasing age over 50 (age 50-65 OR 0.84, P = 0.001; age > 65 OR 0.59, < 0.001), and distance of > 15.8 miles (OR 0.80, 95% CI 0.72-0.88, P < 0.001). 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.This 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 utilization in hypofractionation techniques. Overall, slightly more than half of these patients receive adjuvant RT.

High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial.

This study analyzes the potential of stromal platelet-derived growth factor receptor-beta (PDGFRb) expression as biomarker for radiotherapy (RT) benefit on ipsilateral breast events (IBE) in ductal carcinoma in situ (DCIS). Improved identification of DCIS patients refractory to adjuvant whole-breast RT is needed. Predictive biomarker studies in DCIS have focused on tumor cell features rather than the tumor-associated stroma, despite growing evidence of its influence on therapy efficiency. Samples from the Swedish randomized radiotherapy DCIS trial (SweDCIS) were subjected to IHC analysis for stromal PDGFRb expression. IBE incidence at 10 years after breast-conserving surgery was the primary endpoint. Interactions between marker and treatment were analyzed. PDGFRb score was predictive for RT benefit with regard to IBE (P interaction = 0.002 and P interaction = 0.008 adjusted multivariably). Patients of the PDGFRblow group had a strong benefit from RT regarding IBE risk [HR, 0.23; 95% confidence interval (CI), 0.12-0.45; P < 0.001] with an absolute risk reduction of 21% (cumulative risk 7% vs. 28%) at 10 years. No significant risk reduction by RT was observed for patients of the PDGFRbhigh group (HR, 0.83; 0.51-1.34; P = 0.444; cumulative risk 22% vs. 25%). The RT response-predictive effect of stromal PDGFRb was equally strong in analyses for in situ and invasive IBE when analyzed separately (in situ IBE: P = 0.029; invasive IBE: P = 0.044). Results suggest high stromal PDGFRb expression as a novel biomarker identifying DCIS patients who are refractory to standard whole-breast adjuvant RT. The data imply previously unrecognized fibroblast-mediated modulation of radiosensitivity of DCIS, which should be further explored from mechanistic and targeting perspectives.

Does Surgical Margin Width Remain a Challenge for Triple-Negative Breast Cancer? A Retrospective Analysis.

Background and Objectives: Local and distant relapse (LR, DR) in breast cancer vary according to its molecular subtypes, with triple-negative breast cancer (TNBC) being the most aggressive. The surgical resection margin width (SRMW) for breast-conserving surgery (BCS) has been intensely debated, especially for the aforementioned subtype. The aim of this study was to examine the impact of SRMW on LR following BCS in TNBC patients. Materials and Methods: We conducted a retrospective study including all patients with TNBC for whom BCS was performed between 2005 and 2014. Results: Final analysis included a total of 92 patients, with a median tumor size of 2.5 cm (range 0–5 cm) and no distant metastasis at the time of diagnosis. A total of 87 patients had received neoadjuvant and/or adjuvant chemotherapy, and all patients had received adjuvant whole-breast radiotherapy. After a median follow-up of 110.7 months (95% CI, 95.23–126.166), there were 5 local recurrences and 8 regional/distant recurrences with an overall LR rate of 5.4%. The risk of LR and DR was similar between groups of patients with several SRMW cut-off values. Conclusions: Our study supports a safe “no ink on tumor” approach for TNBC patients treated with BCS.

Abstract OT-04-03: Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial

Abstract Background Main weaknesses of neoadjuvant chemotherapy (NACT) to avoid axillary dissection (ALND) in patients with clinically node-positive breast cancer are frequent failure of achieving nodal pathologic complete response (pCR) and administration of chemotherapy even though not indicated otherwise in many cases. Tailored axillary surgery (TAS) was designed to selectively remove positive nodes and omit ALND in patients with clinically node-positive breast cancer either in the upfront surgery setting or in case of residual nodal disease after neoadjuvant therapy, which distinguishes this trial from all others ongoing and published. Trial design In this international, multi-center, phase-III, non-inferiority randomized controlled trial, including 61 study sites from six countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS only followed by regional nodal irradiation including the full axilla. TAS consists of selective removal of the sentinel lymph nodes (SLNs) and all palpably suspicious findings, thereby tailoring the extent of axillary surgery to the extent of axillary disease, followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. All patients undergo adjuvant whole-breast irradiation after breast conserving surgery and chest wall irradiation after mastectomy. Inclusion of internal mammary nodes is recommended irrespective of treatment arm. ClinicalTrials.gov Identifier: NCT03513614. Inclusion criteria - Clinically node-positive breast cancer (all molecular subtypes allowed) - Node-positivity palpable or detectable only by imaging at time of initial diagnosis - Newly diagnosed or isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT. - In case of prior neoadjuvant treatment: residual disease (including residual ITCs) confirmed by pathology at the time of surgery - Clipping of sampled axillary lymph node Exclusion criteria - Absence of clip in the specimen radiography - Palpable disease left behind in the axilla after TAS - No SLN identified in the axilla Specific aims To test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival (DFS) of clinically node-positive breast cancer patients. Secondary objective is to test if quality of life is significantly better with TAS and axillary radiotherapy compared to ALND. Statistical methods With type I error 5% and power 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio (HR) of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm), including one interim analysis for efficacy/futility after 20% of the required events have occurred. The sample size needed is 1500 patients (750 per arm). The HR and one-sided 95% confidence interval will be calculated using a Cox regression model based on the per-protocol set. Present accrual and target accrual The trial was activated on 31 July 2018 and the first patient was randomized on 07 August 2018. As of 03 July 2020, 291 patients have been randomized. Accrual is currently running according to protocol and is planned until end of 2023 with the primary endpoint analysis expected in 2029. Contact information Prof. Dr. Walter Paul Weber, University Hospital Basel; Tel: +41 61 328 61 49; Walter.Weber@usb.ch Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihály Újhelyi, Christian Kurzeder, Loïc Lelièvre, Christoph Tausch, Daniel Egle, Jörg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial [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 OT-04-03.

Cardiac Dose Control and Optimization Strategy for Left Breast Cancer Radiotherapy With Non-Uniform VMAT Technology.

Purpose: A novel in-house technology “Non-Uniform VMAT (NU-VMAT)” was developed for automated cardiac dose reduction and treatment planning optimization in the left breast radiotherapy. Methods: The NU-VMAT model based on IGM (gantry MLC Movement coefficient index) was established to optimize the volumetric modulated arc therapy (VMAT) MLC movement and modulation intensity in certain gantry angles. The ESAPI embedded in Eclipse® was employed to connect TPS and the optimization program via I/O relevant DICOM RT files. The adjuvant whole-breast radiotherapy of 14 patients with left breast cancer was replanned using our NU-VMAT technology in comparison with VMAT and IMRT technology. Dosimetric parameters including D1%, D99%, and Dmean of PTV, V5, V10, and V20 of ipisilateral lung, V5, D20, D30, and Dmean of heart, monitor units (MUs), and delivery time derived from IMRT, VMAT, and NU-VMAT plans were evaluated for plan quality and delivery efficiency. The quality assurance (QA) was conducted using both point-dose and planar-dose measurements for all treatment plans. Results: The IGM−NU−VMAT curves with plan optimization (range from 50% to 147%) were converged more significantly than IGM-VMAT curves (range from 0% to 297%). The dose distribution requirements of the target and normal tissues could be met using IMRT, VMAT, or NU-VMAT; the lowest Dmean was achieved in NU-VMAT plans (5.38 ± 0.46 Gy vs 5.63 ± 0.61 Gy in IMRT and 7.95 ± 0.52 Gy in VMAT plans). Statistically significant differences were found in terms of delivery time and MU when comparing IMRT with VMAT and NU-VMAT plans (P < .05). In comparison with IMRT plans, the MU and delivery time in NU-VMAT plans dramatically decreased by 69.8% and 28.4%, respectively. Moreover, NU-VMAT plans showed a high gamma passing rate (96.5% ± 1.11) in plane dose verification and minimal dose difference (2.4% ± 0.19) in point absolute dose verification. Conclusion: Our non-uniform VMAT facilitated the treatment strategy optimization for left breast cancer radiotherapy with dosimetric advantage in cardiac dose reduction and delivery efficiency in comparison with the conventional VMAT and IMRT.

Risk Factors for Lymphedema After Breast Conservation Therapy and Oncoplastic Reduction.

Lymphedema is a known complication after the surgical management of breast cancer, yet the incidence is poorly defined after breast conserving therapy and oncoplastic reduction. The primary aim of this study was to define lymphedema incidence in this population. Furthermore, we sought to correlate demographic factors, surgical approach, and complementary treatment modalities with incidence. Data were collected retrospectively on patients who underwent breast conserving therapy at our institution from 2012 to 2015 with greater than 1 year of follow-up. Patients were excluded if they underwent breast surgery before treatment, completion mastectomy, delayed breast reconstruction, or delayed breast reduction. Five hundred and eighty-four patients met study criteria with a 11% lymphedema rate. Patients developing lymphedema had higher preoperative body mass index (P = 0.02), larger breast mass resection volume (P < 0.01), higher rate of axillary dissection (P < 0.01), increased rate of adjuvant whole-breast radiation (P = 0.03), supraclavicular radiation (P < 0.01), axillary radiation (P < 0.01), and neoadjuvant medical therapy (P < 0.01). Multivariate analysis showed breast specimen mass, axillary radiation, and neoadjuvant medical therapy, which were associated with lymphedema (P < 0.05). There was no difference in lymphedema incidence between partial mastectomy and oncoplastic reduction cohorts with independent multivariate analyses for each showing axillary radiation and neoadjuvant medical therapy were significantly associated with lymphedema (P < 0.05), although breast specimen mass was not. Elevated preoperative body mass index, radiation, axillary dissection, and neoadjuvant medical therapy are associated with an increased risk of lymphedema after breast conserving surgery. Oncoplastic reconstruction is not a risk factor for lymphedema.

Quantitative Analysis of the Treatment Set Up Reliability of a Prone Breast Boost for Early Stage Breast Cancer

Adjuvant whole-breast radiation and a tumor bed boost for early-stage breast cancer can be delivered in the supine or prone position. Delivering the boost in the prone position has the advantage of removing the supine simulation CT and the capability of obtaining the total treatment dose distribution. However, the reliability of daily prone boost set up is largely unknown, and imaging is used for treatment verification. Here we evaluate the reliability of a daily clinical setup protocol for a prone mini-tangent boost, using daily cone beam CT (CBCT) to verify the adequacy of target coverage. We retrospectively reviewed 13 patients treated with a prone mini-tangent boost. The target (CTV) was the tumor bed without further expansion. Distance from CTV to block edge was 1.5cm. The boost prescription was 10Gy in 5 fractions. Coverage goals were the treating physician’s discretion, However, in all cases the planned dose to 90% of the CTV (D90) > 90% of prescription. Patients were positioned daily using a clinical setup with visual verification. Port films were taken to verify day 1 setup and when there was concern about the daily clinical setup. A CBCT was then acquired. If needed, additional shifts were made based on the CBCT, often followed by port films. Retrospectively, the simulation CT was independently registered to the daily CBCTs by a physician, and a daily tumor bed contour was generated. The treatment plan was transferred to the daily CBCT and delivered dose was calculated. To assess the reliability of clinical setup prior to CBCT acquisition, we assessed how often the daily D90 was < 90% of prescription dose (D90 < 90%) and how often the daily volume receiving full prescription dose (V100daily) did not receive the planned V100 (V100plan) by > 10% (V100plan-V100daily > 10%). Twelve patients with full imaging details were analyzed. Of 60 analyzable daily fractions, D90 < 90% for 3/60 fractions (5%), and V100plan-V100daily > 10% for 11/60 fractions (18%). Post-CBCT shifts were made for 1 fraction with D90 < 90% and for 2 fractions with V100plan-V100daily > 10%. Fractions for which coverage did not meet reliability metrics most commonly involved superficial tumor beds that extended into the region of subcutaneous dose build-up. In all such cases, allowing a portion of the target to receive less than prescription dose was deemed acceptable by the treating physician. We found that a daily clinical treatment setup for a prone boost was reliable in most cases. Addition of a CBCT was helpful to identify clinical setup variability. Treatment of a superficial tumor bed may be more sensitive to small variations in daily treatment setup due to the dose gradient across the target. When superficial target coverage is critical, supine boost positioning may be considered.

A Prospective Analysis of Quality of Life in Patients Undergoing Whole Breast Irradiation

The impact of Whole Breast Irradiation (WBI) on Quality of Life (QoL) outcomes is unclear, especially in developing countries, therefore a prospective, observational, cohort study was conducted to gain insight into this aspect of patient care. 74 women with stage I-III breast cancer and treated with breast-conserving surgery followed by adjuvant systemic therapy, were prospectively enrolled in this study, after ethics committee approval. CT based target delineation was performed according to RTOG guidelines. The entire breast comprised the PTV, which was prescribed either 46–50 Gy in 23-25 fractions or 40–42.5Gy in 15-16 fractions, as per physician preference. All patients were treated with Forward-Optimized IMRT, following which they received a boost to the lumpectomy cavity (10 Gy in 4 fractions). QoL assessment was performed using the self-administered FACT-B questionnaire (in English or patient's native language). All FACT-B subscales [Physical (PWB), Emotional (EWB), Social (SWB) and Functional (FWB) well-being, as well as Breast Cancer-Specific Subscale (BCSS)] were assessed. The assessments were performed before starting radiotherapy, at the end of every week during radiotherapy, and at 3 and 6 months after radiotherapy. Repeated measures ANOVA was performed to determine any statistically significant differences throughout radiotherapy delivery. A comparison between baseline and every time-point henceforth was performed using the paired t-test. For the entire cohort and across all subscales, scores at 3 and 6 months were higher compared to baseline scores (p < 0.001 for all comparisons). During radiotherapy delivery, PWB, FWB and BCSS scores increased during the first week of treatment, followed by a gradual decline towards end-of-treatment, whereas SWB and EWB gradually improved (p < 0.001 for all comparisons). FACT-B score improved for first 2 weeks followed by a gradual decline towards end-of-treatment. There is a significant QoL reduction in all patients undergoing adjuvant WBI irrespective of fractionation regimen. However, QoL returned to baseline after completion of WBI.Abstract 2498; TableMean scores with standard deviations for all assessed QoL subscales. (*Week 5 & 6 assessment was performed for patients undergoing conventionally fractionated WBI)SubscalesBaselineWk 1Wk 2Wk 3Wk 4Wk 5 *Wk 6 *3 mo.6 mo.PWB9.5 ± 1.015.3 ± 2.814.2 ± 3.212.1 ± 3.49.6 ± 3.17.1 ± 3.66.1 ± 3.321.0 ± 2.915.1 ± 3.7SWB19.3 ± 1.420.8 ± 5.221.3 ± 5.122.2 ± 4.822.7 ± 4.922.8 ± 4.923.0 ± 4.825.7 ± 2.725.6 ± 3.9FWB12.5 ± 1.015 ± 5.314.1 ± 5.313.5 ± 5.512.5 ± 1.010.7 ± 5.49.8 ± 5.320.8 ± 4.517.0 ± 4.6EWB15 ± 2.815.1 ± 2.315.2 ± 2.415.4 ± 2.615.4 ± 4.815.6 ± 4.616.0 ± 4.518.7 ± 4.218.7 ± 4.1BCSS10 ± 1.421.2 ± 2.818.6 ± 3.315.6 ± 3.912.8 ± 3.910.6 ± 3.78.9 ± 3.724.4 ± 2.818.2 ± 4.8FACT-B66.4 ± 3.787.4 ± 11.383.4 ± 11.378.6 ± 12.372.5 ± 14.766.8 ± 14.663.8 ± 14.1110.5 ± 10.494.4 ± 15.4 Open table in a new tab

A Review of Intraoperative Radiotherapy After Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer: From Bench to Bedside

Adjuvant whole-breast irradiation with a boost to the tumor bed is the standard of treatment after breast-conserving surgery. Boost dose can be delivered either intraoperatively or externally. The purpose of this study is to review the literature regarding intraoperative radiation therapy (IORT) after neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer (LABC). The present study is a review of English-language articles regarding IORT after NACT in patients with LABC published between 1998 and 2020. For this, the databases of PubMed, Medline, Web of Science, EBSCO, IEEE, Scopus, and Springer were searched. The results of the studies were combined using the random-effects model in the meta-analysis. In patients with LABC who have received NACT, our review demonstrated encouraging results for boost IORT in terms of toxicity (0% in Spaich et al.’s single-arm study) and local control (96% in Homaei Shandiz et al.’s single-arm study). In comparison to the external beam irradiation boost (EBIB), IORT was noninferior in local control (98.5 vs 88.1%, p-value 0.2 in Fastner et al.’s study) and superior in overall survival (HR = 0.19, p = 0.016 in Kolberg et al.’s study). IORT (electron or photon) after NACT in patients with LABC is a safe procedure with comparable efficacy to EBIB. Highly accurate dose prescription, evasion of the proliferative cytokine cascade, and elimination of the effects of geometric and temporal miss all lead to this conclusion that boost IORT may be superior to EBIB.

Acute toxicity of normofractionated intensity modulated radiotherapy with simultaneous integrated boost compared to three-dimensional conformal radiotherapy with sequential boost in the adjuvant treatment of breast cancer

BackgroundIntensity-modulated radiotherapy (IMRT) improves dose homogeneity and late toxicity compared to simple tangential techniques in adjuvant whole-breast radiotherapy for patients with breast cancer. Simultaneous-integrated boost (SIB) radiotherapy shortens the overall treatment time and improves dose homogeneity. However, prospective randomized trials regarding IMRT with SIB for adjuvant radiotherapy in breast cancer are lacking.MethodsThe IMRT-MC2 (MINT) trial is a phase III prospective randomized controlled trial comparing IMRT with SIB (Arm A: whole breast 28 × 1.8 Gy, Boost 28 × 2.3 Gy) to 3D-conformal radiotherapy with a sequential boost (Arm B: whole breast 28 × 1.8 Gy, boost 8 × 2 Gy) in patients with breast cancer after BCS. Indication for boost radiotherapy was defined as age < 70 years or age > 70 years with presence of additional risk factors. This is a retrospective analysis of acute toxicity at one of two trial sites.ResultsFive hundred two patients were randomized, of which 446 patients were eligible for this analysis. There was no statistically significant difference in terms of any grade radiation dermatitis between the two treatment arms at the end of treatment (p = 0.26). However, radiation dermatitis grade 2/3 (29.1% vs. 20.1 and 3.5% vs. 2.3%) occurred significantly more often in Arm A (p = 0.02). Breast/chest wall pain at the first follow-up visit was significantly more common in patients treated on Arm B (p = 0.02).ConclusionsTreatment on both arms was well tolerated, however there were some differences regarding radiodermatitis and breast pain. Further analyses are ongoing.Trial registrationclinicaltrials.gov, NCT01322854, registered 24th March 2011.

Identifying Risk Factors for Regional Recurrence in Early-Stage Breast Cancer with pT1-2 and Negative Sentinel Lymph Node Biopsy.

BackgroundDue to the low rate of regional recurrence (RR) in early-stage breast cancer with pT1-2 and negative sentinel lymph node biopsy (SLNB), no regional therapy is suggested for them. However, whether there is a subset of patients who were with high risk of regional failure and may benefit from regional treatment is still unknown. The current study was designed to identify the patients with high risk of RR, thereby providing clues for enhanced regional therapy.MethodsWe analyzed a total of 1124 breast cancer patients with pT1-2N0 from May 2004 to Dec 2014. All the patients were treated with breast-conservation surgery (BCS) and adjuvant whole-breast radiotherapy. The regional recurrence-free survival (RRFS), local regional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were assessed by using the Kaplan–Meier method. Cox proportional hazards regression was performed to detect factors in predicting the RRFS.ResultsIn multivariable analysis, both T stage and molecular type were significant predictors of RRFS. Patients with T2 stage had a lower RRFS than those with T1stage. Triple-negative patients were more likely to suffer regional failure than the patients with other molecular types. The two predictors were then employed to divide all the patients into three groups based on the risk level of RR. Patients with both T2 and triple-negative molecular type had the lower RRFS, LRRFS, DFS and OS than the patients with one or no risk factor.ConclusionFor early-stage breast cancer patients with negative SLNB, those who were with both T2 stage and triple-negative molecular type had a high rate of RR and enhance regional therapy may be needed for them.

1-week hypofractionated adjuvant whole-breast radiotherapy: towards a new standard?

Hypofractionated radiotherapy delivers a higher dose (>2 Gy) per fraction than conventional radiotherapy, reducing overall treatment duration and associated costs. In women with early stage breast cancer, moderate hypofractionated (eg, 40–42·5 Gy per 15–16 fractions in 3–3·2 weeks) adjuvant whole-breast radiotherapy was shown to be non-inferior in terms of long-term tumour control and toxicities than the conventional schedule (50 Gy in 2 Gy daily fractions over 5 weeks).1,2 Subsequently, moderate hypofractionation has become the preferred dose-fractionation scheme for many patients.

The actual benefit of intraoperative radiation therapy using 50kV x-rays in early breast cancer: A retrospective study of 676 patients.

This French study reports the 5-year results of partial-breast irradiation using intraoperative radiation therapy (IORT) with 50kV x-rays, in select early breast cancer patients. We report a retrospective analysis of 676 consecutive early breast cancer patients treated between November 2011 and December 2015 by partial-breast irradiation using the INTRABEAM® system. Patients were highly selected based on the ASTRO and GEC-ESTRO criteria and underwent breast-conservative surgery and IORT, completed with additional whole-breast irradiation (WBI) when unexpected unfavorable prognostic factors were found at the final pathology report. Patients' outcomes relative to local and distant control, overall and breast cancer-specific survival, and toxicity are presented, as well as rates of additional WBI. Additional WBI was mandatory in one third of patients (31%), mainly due to lymph node involvement and extensive intraductal component. With a median follow-up time of 54months, the 5-year local recurrence rate was 1.7% [95%CI: 0.9-3.3]; the median time to local recurrence was 23months; ipsilateral breast recurrences mainly occurred in the same quadrant (7/11); in the restricted population, meeting all predefined criteria and treated with IORT alone (406 patients), the local recurrence rate was 1.5% [95%CI: 0.6-3.6]. Five-year distant tumor control was 98.6% [95%CI: 97.2-99.3], and the median time to distant recurrence was 22months. Five-year overall survival was 96.5% [95%CI: 94.2-97.8], and 5-year breast cancer-specific survival was 98.9% [95%CI: 97.6-99.7]. In patients treated with IORT alone, there was no grade 3 toxicity, only four grade 3 (mainly fibrosis) affected patients treated with IORT and WBI. Grade 1-2 toxicity rates were 14% and 34.4% in patients treated with IORT alone and IORT plus WBI, respectively. Partial-breast irradiation using IORT by a 50 kV photon device is safe and well-tolerated in select patients with early breast cancer and is a valuable option in patients reluctant for adjuvant WBI.

Quantifying the Mitigating Effects of Whole-Breast Radiotherapy and Systemic Treatments on Regional Recurrence Incidence Among Breast Cancer Patients

BackgroundDespite the potential for residual lymph node metastases after a negative or positive sentinel lymph node biopsy (SLNB), breast cancer patients rarely experience regional recurrences (RRs). This study aimed to quantify the effects of nonsurgical treatments on RR incidence among SLNB-negative (SLNB N0) breast cancer patients.MethodsAll primary SLNB N0-staged breast cancer patients with a diagnosis between 2005 and 2008 and 5-year follow-up data on recurrences were selected from the Netherlands Cancer Registry. The cumulative incidence function (CIF) for RR was calculated as the first event at 5 years, taking into account any other first-event (local or distant recurrence, contralateral breast cancer, or death) as competing risk. Cox regression analysis was used to model the cause-specific hazard of RR developing as the first event to quantify the effect of adjuvant systemic therapy and whole-breast radiotherapy (RT) on RR incidence at 5 years.ResultsThe study included 13,512 patients. Of these patients, 162 experienced an RR. The CIF of RR at 5 years was 1.3% (95% confidence interval [CI], 1.1–1.5%), whereas the CIFs for death and other events were 4.4% and 9.5%, respectively. Cox regression analysis showed hazard ratios (HRs) of 0.46 (95% CI 0.33–0.64), 0.31 (95% CI 0.18–0.55), and 0.40 (95% CI 0.24–0.67) respectively for patients treated by RT as a routine part of breast-conserving therapy (BCT), chemotherapy, and hormonal therapy.ConclusionRT as routine part of BCT, chemotherapy, and hormonal therapy independently exerted a mitigating effect on the risk for the development of RR. The three methods at least halved the risk.