Accelerated Partial Breast Irradiation Research Articles

Unlocking the adaptive advantage: correlation and machine learning classification to identify optimal online adaptive stereotactic partial breast candidates.

Online adaptive radiotherapy (OART) is a promising technique for delivering stereotactic accelerated partial breast irradiation (APBI), as lumpectomy cavities vary in location and size between simulation and treatment. However, OART is resource-intensive, increasing planning and treatment times and decreasing machine throughput compared to the standard of care (SOC). Thus, it is pertinent to identify high-yield OART candidates to best allocate resources. 
Approach. Reference plans (plans based on simulation anatomy), SOC plans (reference plans recalculated onto daily anatomy), and daily adaptive plans were analyzed for 31 sequential APBI targets, resulting in the analysis of 333 treatment plans. Spearman correlations between 22 reference plan metrics and 10 adaptive benefits, defined as the difference between mean SOC and delivered metrics, were analyzed to select a univariate predictor of OART benefit. A multivariate logistic regression model was then trained to stratify high- and low-benefit candidates.
Main Results. Adaptively delivered plans showed dosimetric benefit as compared to SOC plans for most plan metrics, although the degree of adaptive benefit varied per patient. The univariate model showed high likelihood for dosimetric adaptive benefit when the reference plan ipsilateral breast V15Gy exceeds 23.5%. Recursive feature elimination identified 5 metrics that predict high-dosimetric-benefit adaptive patients. Using leave-one-out cross validation, the univariate and multivariate models classified targets with 74.2% and 83.9% accuracy, resulting in improvement in per-fraction adaptive benefit between targets identified as high- and low-yield for 7/10 and 8/10 plan metrics, respectively. 
Significance. This retrospective, exploratory study demonstrated that dosimetric benefit can be predicted using only ipsilateral breast V15 Gy on the reference treatment plan, allowing for a simple, interpretable model. Using multivariate logistic regression for adaptive benefit prediction led to increased accuracy at the cost of a more complicated model. This work presents a methodology for clinics wishing to triage OART resource allocation.&#xD.

Multimodal radiotherapy dose prediction using a multi-task deep learning model.

In radiation therapy (RT), accelerated partial breast irradiation (APBI) has emerged as an increasingly preferred treatment modality over conventional whole breast irradiation due to its targeted dose delivery and shorter course of treatment. APBI can be delivered through various modalities including Cobalt-60-based systems and linear accelerators with C-arm, O-ring, or robotic arm design. Each modality possesses distinct features, such as beam energy or the degrees of freedom in treatment planning, which influence their respective dose distributions. These modality-specific considerations emphasize the need for a quantitative approach in determining the optimal dose delivery modality on a patient-specific basis. However, manually generating treatment plans for each modality across every patient is time-consuming and clinically impractical. We aim to develop an efficient and personalized approach for determining the optimal RT modality for APBI by training predictive models using two different deep learning-based convolutional neural networks. The baseline network performs a single-task (ST), predicting dose for a single modality. Our proposed multi-task (MT) network, which is capable of leveraging shared information among different tasks, can concurrently predict dose distributions for various RT modalities. Utilizing patient-specific input data, such as a patient's computed tomography (CT) scan and treatment protocol dosimetric goals, the MT model predicts patient-specific dose distributions across all trained modalities. These dose distributions provide patients and clinicians quantitative insights, facilitating informed and personalized modality comparison prior to treatment planning. The dataset, comprising 28 APBI patients and their 92 treatment plans, was partitioned into training, validation, and test subsets. Eight patients were dedicated to the test subset, leaving 68 treatment plans across 20 patients to divide between the training and validation subsets. ST models were trained for each modality, and one MT model was trained to predict doses for all modalities simultaneously. Model performance was evaluated across the test dataset in terms of Mean Absolute Percent Error (MAPE). We conducted statistical analysis of model performance using the two-tailed Wilcoxon signed-rank test. Training times for five ST models ranged from 255 to 430min per modality, totaling 1925min, while the MT model required 2384min. MT model prediction required an average of 1.82s per patient, compared to ST model predictions at 0.93s per modality. The MT model yielded MAPE of 1.1033±0.3627% as opposed to the collective MAPE of 1.2386±0.3872% from ST models, and the differences were statistically significant (p=0.0003, 95% confidence interval=[-0.0865, -0.0712]). Our study highlights the potential benefits of a MT learning framework in predicting RT dose distributions across various modalities without notable compromises. This MT architecture approach offers several advantages, such as flexibility, scalability, and streamlined model management, making it an appealing solution for clinical deployment. With such a MT model, patients can make more informed treatment decisions, physicians gain more quantitative insight for pre-treatment decision-making, and clinics can better optimize resource allocation. With our proposed goal array and MT framework, we aim to expand this work to a site-agnostic dose prediction model, enhancing its generalizability and applicability.

Abstract PO1-22-04: Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment

Abstract Introduction: Breast cosmesis results using Accelerated Partial Breast Irradiation (APBI) with IMRT external beam in 5 fractions (6Gy x 5 fractions) has been reported as good to excellent in the literature. This retrospective review compares breast cosmesis in patients treated with Daily versus Every Other Day APBI in the community practice setting. Methods: The patient electronic medical records (EMR) were used to identify APBI patients treated at the community cancer center with the 6Gy x 5 fraction regimen. Harvard breast cosmesis four point scale results (poor, fair, good, excellent results) were extracted for each treated APBI patient from clinical notes in the EMR to rate breast cosmesis. For many patients in this review, provider reporting of cosmesis in the EMR overlapped good and excellent categories and so a “good to excellent” score was assigned. Therefore, a three point scale was utilized in statistical analysis (poor-1, fair-2, good to excellent-3). Results: There were 62 patients treated with APBI at a single institution with greater than 6 months follow up (18 patients treated daily and 44 patients treated every other day). Median follow up was 12 months (range 6- 32 months). Of all patients treated there were 0 with poor cosmesis, 3 with fair (1 every other day treatment, 2 every day treatment), 59 with good to excellent cosmesis. Univariate logistical regression analysis revealed no significant difference between daily and every other day treatment (p=0.457) Conclusion: With careful patient selection, quality planning and treatment delivery, good to excellent cosmesis is achievable in the great majority of patients undergoing breast APBI (6Gy x 5 fractions) using IMRT in the community radiation oncology clinic with either daily or every other day treatment. More study is needed, but in this review cosmetic differences seem to be minimal between daily and every other day treatment schedules. Citation Format: Alex Goss, Ellaine Haroz, Anna Voltura, Jennifer McGrath, Olivia Sloan, Matthew Jackson, Savvas Morris, Bryan Goss. Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-04.

Abstract PO4-07-01: Deep learning guided radiation therapy machine selection via a multi-headed dose prediction model

Abstract Background: Accelerated Partial Breast Irradiation (APBI) is gaining popularity for the treatment of appropriately selected breast cancer patients in lieu of whole breast irradiation regimens due to its comparable clinical outcomes and improved patient convenience and quality-of-life. Currently, several machines for delivery of APBI are available such as CyberKnife, Elekta Unity, Varian Ethos and Varian TrueBeam. Each treatment machine yields a unique distribution of radiation dose, so a given modality may afford particular advantages or liabilities based on a patient’s anatomy. Existing methods for identification of an ideal modality that best suits a patient’s unique anatomical features are generally lacking, manual, and resource intensive. To overcome this limitation and personalize modality selection, we propose a deep learning (DL) based multi-modality dose prediction model. The model takes a patient’s computed tomography (CT) scan, segmented planning target volumes (PTVs) and segmented organs at risk (OARs) as input, and outputs predicted dose distributions for all trained modalities. Differences may then be evaluated between each radiation treatment modality’s corresponding dose distribution and dose volumetric histograms (DVH) to select the optimal modality for each patient. Methods: Our dataset contains 16 partial breast patients, each with 4 unique treatment plans generated for 4 distinct modalities – CyberKnife, Elekta Unity, Varian Ethos and Varian Truebeam. 10, 2, and 4 patients were dedicated to the train, validation and test datasets respectively. Our model’s architecture is a U-net with a shared encoder and 4 independent dose decoders, in which each decoder predicts dose for one modality. Each training patient’s CT scan, PTVs, OARs, and a PTV distance map are input to the model during training, and the shared encoder shares the input data’s latent representations with each of the 4 decoders. The 4 distinct dose distributions from each training patient are used as labels for the 4 corresponding decoders to supervise model training. The mean squared error, mean squared log error, and DVH losses are minimized during model training. The model trained until validation loss converged. The 4 dose distributions were predicted in ~ 1 minute per test patient, yielding 16 dose distributions in the test dataset. Model performance across the test dataset was evaluated by calculation of the mean absolute percent error (MAPE) of dose differences within the patient’s body between the model’s predicted doses and label doses, relative to patient prescription dose. Results: The performance of the multi-modal dose prediction model was evaluated in terms of dose differences throughout each patient’s body across the 16 test dose distributions as compared to the actual planned doses. The average MAPE of the multi-modal dose predictions was 1.27 ± 0.38% of a patient’s prescription dose as compared to the actual planned dose across the test dataset. For a prescription dose of 3000 cGy, that corresponds to an average MAPE of 38.1 ± 11.4 cGy. Conclusion: Our multi-modality dose prediction model’s novelty lies in its rapid provision and comparison of accurate and detailed dosimetric data for each treatment modality. This model can empower treating radiation oncologists to make informed decisions in radiation therapy machine selection on a patient-by-patient basis, potentially optimizing radiation treatment plans by reduction of delivered dose to organs at risk. Table. Citation Format: Austen Maniscalco, Ezek Mathew, David Parsons, Asal Rahimi, Mona Arbab, Prasanna Alluri, Xingzhe Li, Mu-Han Lin, Steve Jiang, Dan Nguyen. Deep learning guided radiation therapy machine selection via a multi-headed dose prediction model [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-01.

Partial-accelerated irradiation with stereotactic radiotherapy at a dose of 30Gy in 5fractions in early breast cancer.

To evaluate feasibility of accelerated partial breast irradiation (APBI) using stereotactic radiotherapy (SBRT) Thirty Gy delivered in 5 fractions for patients with early breast cancer. Between January 1st, 2018, and December 31s, 2022, we conducted 117 treatments for patients with early-stage breast cancer. All patients underwent conservative surgery followed by APBI using stereotactic external beam radiotherapy. We analyzed local, regional, distant control, overall survival, toxicity, and cosmetic outcomes. The average age was 62years. 21.3% ductal and 78.7% invasive carcinomas. Regarding the PTV volume, the median was 198.8 cc (38-794cc). Treatments were completed in all cases. The median follow-up period was of 21months (1-62 months). Regarding acute toxicity, no Grade 3-4 toxicities were recorded. One patient experienced Grade 2 neuropathic pain. One patient developed subacute fibrosis and two patients developed telangiectasia as subacute and chronic toxicity. Cosmetic results were "good" or "very good" in 96.3% of cases. None of the patients relapsed at any level (local, regional, or distant) and overall survival during follow.up was 100%. APBI with SBRT 30Gy in 5 fractions in early-stage breast cancer is a feasible technique, very-well tolerated and has excellent oncologic and cosmetic outcome during our follow-up period.

Long-term results of intraoperative multicatheter breast implant (IOMBI) for accelerated partial breast irradiation (APBI) on early breast cancer patients

Background and purposeMulticatheter breast brachytherapy is a standard technique for accelerated partial breast irradiation (APBI) in early breast cancer patients. Intraoperative multicatheter breast implant (IOMBI) followed by perioperative high-dose-rate brachytherapy (PHDRBT) offers a novel and advantageous approach. We present long-term oncological, toxicity, and cosmesis outcomes for a well-experienced single institution. Materials and methodsEligible women aged ≥ 40 years with clinically and radiologically confirmed unifocal invasive or in situ ≤ 3 cm breast tumors underwent IOMBI during breast-conserving surgery. Patients meeting APBI criteria by definitive pathologic results received 3.4 Gy × 10fx with PHDRBT. Patients not suitable for APBI received PHDRBT-boost followed by WBRT. ResultsA total of 171 patients underwent IOMBI during BCS, 120 patients (70.1 %) were suitable for APBI and 51 (29.8 %) for anticipated PHDRBT-boost. The median age was 61 years (range: 40–78), the median tumor size was 1.1 cm (range: 0.2–3.5), with a histological diagnosis of invasive ductal carcinoma in 78.9 % and ductal in situ in 21.1 %. A median of 9 catheters (range: 4–14) were used. For APBI, the median CTV and V100 were 40.8 cc (range: 8.6–99) and 35.4 cc (range: 7.2–94). The median of healthy breast tissue irradiated represents 7.2 % (range: 2.3–28 %) and the median local treatment duration was 10 days (range: 7–16). With a median follow-up of 8.8 years (range: 0.3–16.25), the 8-year local, locoregional, and distant control rates were 99 %, 98.1 %, and 100 %. G1-G2 late-toxicity rate was 53.4 %. Long-term cosmetic evaluation was excellent-good in 90.8 %. ConclusionIOMBI&PHDRBT program reports excellent long-term oncological outcomes, with a reduction from unnecessary irradiation exposure which translates into low long-term toxicity and good cosmesis outcomes, especially on well-selected APBI patients.

6 Mini Oral - Adjuvant Hypofractionated Whole Breast Irradiation (WBI) Versus Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5-Years Update of the HYPAB Trial

6 Mini Oral - Adjuvant Hypofractionated Whole Breast Irradiation (WBI) Versus Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5-Years Update of the HYPAB Trial

Brachytherapy in Breast Cancer Treatment: Physical and Biological Aspects

This scientific paper focuses on the treatment of breast cancer, one of the most common cancers among women. Despite increased awareness and the popularity of screening tests, statistics indicate a significant rise in incidence. The paper presents breast-conserving treatment methods, including brachytherapy, as a modern technique with promising outcomes. It describes the physical properties of ionizing radiation used in brachytherapy, discussing the photoelectric effect, Compton effect, and the phenomenon of pair production.
 The paper then delves into the biological effects of ionizing radiation, emphasizing the dependence on the cell cycle phase. It highlights lethal, sublethal, and potentially lethal cellular damage, categorizing the effects of radiation interaction into early and late responses.
 The discussion transitions to the application of brachytherapy in breast cancer treatment, focusing on various techniques such as LDR, PDR, and HDR. The paper provides a detailed description of brachytherapy's use in breast-conserving treatment, considering contraindications, treatment planning, and Accelerated Partial Breast Irradiation (APBI) techniques.
 The radioisotopes used in brachytherapy are also presented, with special attention to Iridium-192. The physical and practical aspects related to this isotope are discussed, along with other commonly used radioisotopes such as Cesium-137, Cobalt-60, and Strontium-90.
 The paper concludes with a summary, emphasizing the significance of brachytherapy in breast cancer treatment and outlining its prospects for development. The authors highlight precision and shortened therapy duration.

Accelerated partial breast irradiation: Current evidence and future developments

AbstractWhole breast irradiation after breast‐conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high‐dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI.

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.

Post- versus intra-operative implant for breast cancer interstitial brachytherapy: How to choose?

Breast brachytherapy (BB) represents an important radiation therapy modality in modern breast cancer treatments. Currently, BB is mainly used for accelerated partial breast irradiation (APBI), local boost after whole breast radiation therapy (WBRT), and as salvage re-irradiation after second lumpectomy (APBrl). Two multi-catheter interstitial brachytherapy (MIB) techniques can be offered: intra-operative (IOB) and post-operative (POB) brachytherapy. The aim of this article was to summarize current available data on these two different brachytherapy approaches for breast cancer. A literature search was performed, and different experiences published by BB expert teams were analyzed and compared. These two different brachytherapy approaches for breast cancer have also been presented and discussed during meetings of the GEC-ESTRO BCWG. In addition, expert recommendations were defined. A comprehensive description and practical comparison of both the techniques, i.e., IOB and POB, considering the latest available published data were presented. Different technical, logistic, and clinical aspects of both the methods were thoroughly examined and analyzed. This detailed comparison of the two breast brachytherapy techniques was supported by scientific data from extensive experience of experts, facilitating an objective analysis that, to our knowledge, has not been previously published. Based on the comprehensive analysis of both the brachytherapy techniques available, this article serves as a valuable resource to guide breast teams in selecting the optimal BB technique (POB or IOB), considering hospital environment, multi-disciplinary collaboration, and patient logistics.

Assessment of Eligibility and Utilization of Accelerated Partial Breast Irradiation in Korean Breast Cancer Patients (KROG 22-15).

We investigated the proportions of patients eligible for accelerated partial breast irradiation (APBI) among those with pT1-2N0 breast cancer, based on the criteria set by the American Society for Radiation Oncology (ASTRO), the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO), the American Brachytherapy Society (ABS), and the American Society of Breast Surgeons (ASBS). Additionally, we analyzed the rate of APBI utilization among eligible patients. Patients diagnosed with pT1-2N0 breast cancer in 2019 were accrued in four tertiary medical centers in Korea. All patients had undergone breast conserving surgery followed by radiotherapy, either whole breast irradiation or APBI. To determine which guideline best predicts the use of APBI in Korea, the F1 score and Matthews Correlation Coefficient (MCC) were determined for each guideline. A total of 1,251 patients were analyzed, of whom 196 (15.7%) underwent APBI. The percentages of eligible patients identified by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria were 13.7%, 21.0%, 50.5%, and 63.5%, respectively. APBI was used to treat 54.4%, 37.2%, 27.1%, and 23.7% of patients eligible by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria, respectively. The ASTRO guideline exhibited the highest F1 score (0.76) and MCC (0.67), thus showing the best prediction of APBI utilization in Korea. The proportion of Korean breast cancer patients who are candidates for APBI is substantial. The actual rate of APBI utilization among eligible patients may suggest there is a room for risk-stratified optimization in offering radiation therapy.

Phase II Trial of Five-Fraction Accelerated Partial Breast Irradiation (APBI) Using Noninvasive Image-Guided Breast Brachytherapy (NIBB)

NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in the fraction number is desirable. Final results of a prospective phase II trial are reported. NIBB APBI was delivered using 28.5Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2mm. The primary endpoint was grade ≥ 2 subcutaneous fibrosis/induration <30%. Secondary endpoints included any late toxicity, cosmetic outcome, and local control. 40 patients were treated with a median follow-up of 59.7 months. The mean age was 67 years (50-89 years) and tumor size was 1.0cm (0.3-2.0cm). 80% had invasive carcinoma. The mean breast separation with compression was 6.7cm (3.5-8.9cm). The 5-year actuarial local control was 96.6% and overall survival was 96.9%. Grade 2 and 3 late toxicities were 15% and 0%, respectively. The rate of grade 2 subcutaneous fibrosis/induration was 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia; 22.5% grade 1 and 15% grade 2. Only breast separation was associated with telangiectasia risk, p=0.002. Overall cosmetic outcome was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0cm. The local failure rate was appropriately low. Further investigation of this technique is warranted.

Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.

A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40years, tumor unifocal and unicentric, ≤ 3cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34Gy in 10 fractions administered twice daily. Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.

Early Results of the French Multicenter, Randomized SHARE Trial Comparing Whole Breast Irradiation vs. Accelerated Partial Breast Irradiation in Postmenopausal Women with Early-Stage Breast Cancer

The aim is to report toxicity and cosmetic outcomes at 3 and up to 9 years of follow-up of post-menopausal patients randomized to receive either standard whole breast irradiation (WBI), including hypofractionated options, versus accelerated partial breast irradiation (APBI). From December 2010 to July 2015, 1006 patients were enrolled in 34 French centers. Among the whole population, 28 patients who did not meet the final selection criteria or withdrew consent were excluded leading to a modified intention to treat analysis dataset of 978 patients (WBI: n = 488; APBI: n = 490). Median age (65y) and tumor stage pT1 (99%) rates were similar in both arms. Patients had conservative surgery with clip placement in the tumor bed. Clear margins (> 2mm) were observed in 99% of the patients. In both arms, 96-97% of the patients had negative sentinel lymph node biopsy. The median time interval between surgery and radiotherapy was 57d in WBI vs 62d in APBI. WBI schedules consisted of 50 Gy in 25 fr+16 Gy (n = 212) or 40 Gy in 15 fr (n = 156) or 42.5 Gy in 16 fr (n = 120). APBI arm consisted of 38.5 Gy or 40 Gy in 10 fr, 2 fr/day. Overall, 94 patients from the APBI arm finally received standard WBI. For statistical considerations, SHARE trial, sponsored by UNICANCER (NCT01247233) is a non-inferiority randomized controlled trial comparing APBI versus WBI in terms of local control as primary objective. Secondary endpoints were severe toxicity (NCI-CTCAE v4 grade ≥ 2), and cosmetic results. For both outcomes, we estimated the cumulative incidences (CI) using Kalbfleish and Prentice method, considering disease relapse, secondary cancer or death as competing events. Treatment effect (APBI vs WBI) was estimated by cause-specific Hazard Ratios (cs-HR) from Cox models. Median follow-up was 5.8y (range, 0.13-9.5). The number of deaths was 27, and the number of local relapses was 8. Among the 978 patients, 582 and 396 had finally WBI and APBI, respectively. The rates of post-operative hematoma, edema and infection were low: 8-9%, 2%, 3-2%, respectively. When considering any type of severe toxicity, we observed a significant reduction rate in APBI compared to WBI: cs-HR = 0.73 (95% confidence interval: 0.61-0.88); p = 0.001, and 3-year CI of severe toxicity at 45% in WBI vs 36% in APBI arm. The difference was also in favor of APBI when considering breast skin toxicity alone: cs-HR = 0.55 (0.44-0.70), p<0.001 and 3-year CI at 36% in WBI vs 21% in APBI arm. Conversely, for breast other toxicities, WBI was found less toxic than APBI with a 3-year CI of 8% vs 15%, respectively. When considering cosmetic results, we observed no significant difference between the two arms in both evaluations by physicians and patients. Historically SHARE is the first APBI trial that included hypofractionated schedules in the standard arm. We report increased risk of severe toxicity and skin breast toxicity in standard arm as compared with APBI arm without any difference in terms of cosmetic results. Longer follow-up is needed.

Five Fraction Accelerated Partial Breast Irradiation vs. Intraoperative Radiation Therapy for Early-Stage Breast Cancer

Accelerated partial breast irradiation (APBI) represents an alternative to whole breast irradiation (WBI), reducing the target volume and potentially treatment duration. APBI delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable outcomes to WBI with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were initially promising, concerns regarding long-term rates of local recurrence exist. We present a comparison of 5 fraction APBI versus IORT. We performed a retrospective review of 473 patients with early-stage breast cancer (Stage 0-IIA) treated at a single institution with 258 receiving APBI and 215 IORT from October 2011 to May 2021. APBI patients received 30 Gy in 5 fractions delivered with IMRT daily or every other day. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface delivered at the time of surgery. Kaplan-Meier analysis was used to estimate locoregional control rates and overall survival among the 2 groups. Mean age was 70.7 years old (IQR:67-74) for the IORT patients and 66.6 years old (IQR:62-72) for the APBI patients (p<0.001). Median follow up was 5.7 years for IORT patients and 2.4 years for APBI patients (p<0.001). For IORT patients, 11%/83.5%/5.5% of patients and for APBI 17.8%/77.5%/4.7% of patients had Tis/T1/T2 disease (p = 0.005). With regards to adjuvant therapies, 79%/76% of IORT/APBI patients were offered endocrine therapy (p = 0.50) and 1.4%/6.2% chemotherapy (p = 0.008). Recurrence at any time was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving APBI. APBI was however no differences in recurrence free survival (92.6% vs. 98.5%, p = .079) or overall survival were noted (92.8% vs. 95.1%, p = 0.99). In a series of almost 500 patients with stage 0-IIA breast cancer, IORT was associated with higher rates of locoregional recurrence compared to APBI with no survival difference at 5 years. These outcomes, consistent with other series and current guidelines, suggest a limited role for IORT as monotherapy following breast conserving surgery.

Accelerated Partial Breast Irradiation (APBI) For HER2+ Early-Stage Breast Cancer

Historically, HER2+ breast cancer exhibited poor outcomes and, hence, has not been well-studied among trials of accelerated partial breast irradiation (APBI). We hypothesized that in contemporary practice with effective HER2-targeted agents, patients with HER2+ breast cancer now have excellent disease control and survival outcomes when treated with adjuvant APBI. Using a prospectively-maintained institutional database, we identified all HER2+ breast cancer patients treated with breast conserving surgery (BCS) and adjuvant APBI from 2000 - 2022. Salient clinicopathologic parameters were collected, as were receipt of systemic and endocrine therapies. All patients received external beam APBI to a total dose of 40Gy in 10 daily fractions over 2 weeks. We analyzed outcomes including local recurrence (LR), regional recurrence, distant recurrence, and death. Cumulative incidence functions were calculated to estimate the incidence of LR with the competing risk of death. All statistical analyses were performed in R version 4.2.2. The study cohort comprised 52 patients with HER2+ breast cancer (median age 64 years; range 44-87). Nearly all had T1 tumors (98%; median size 15 mm; range 1 - 21 mm). Approximately 10% had multifocal disease, with one exhibiting suspicion for lymphovascular invasion. Most patients had ER+ disease (88%). All patients had negative final surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. 42 (81%) received chemotherapy, 40 (77%) endocrine therapy, and 42 (81%) HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range 7 - 226 months for each patient), we observed two LR events, at 14 and 26 months, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any contralateral invasive breast cancer events or breast-specific mortality events. Two deaths were noted in the cohort, both without evidence of disease. Among a cohort of HER2+ early-stage breast cancer patients managed with BCS and APBI, we observed a 2-year LR rate of 3.8% with no regional or distant recurrences, and excellent overall survival. These findings merit longer term follow-up among larger cohorts, although are thus far consistent with the results of contemporary randomized trials of APBI unselected for HER2-status.

The Impact of Tumor Location on Cardiac Toxicity in Patients Receiving Partial Breast Irradiation

Accelerated partial breast irradiation (APBI) is an appropriate modality for select women with low-risk breast cancer. While APBI delivers radiation dose to a smaller volume of breast tissue compared to whole breast irradiation, dose to the heart and coronary vessels may be relatively high, depending on the proximity of the tumor bed to these structures. The purpose of this study is to determine if there is a correlation between tumor location and risk of adverse cardiac events in women receiving APBI. This retrospective study included 341 women who received ABPI from 1993 to February 2017 at a single institution. APBI was delivered by catheter-based high-dose-rate (HDR) brachytherapy via single lumen or multi-channel devices (n = 340), or external beam brachytherapy (n = 1). Neither the heart nor cardiac substructures were contoured for patients receiving APBI with HDR brachytherapy. Univariate analysis (UVA) and multivariable analysis (MVA) were conducted to correlate patient age, smoking status, Charlson Comorbidity Index score (CCI), receipt of systemic therapy, and tumor location (right outer, right inner/central, left outer, left inner/central) with subsequent cardiac events. Univariate analyses for patient age, smoking status, CCI, receipt of systemic therapy, and tumor location in correlation to subsequent cardiac events were performed. On UVA, age at diagnosis and CCI score ≥2 were both significant with HR of 1.07 [1.05-1.10] (p<0.001) and HR of 7.02 [3.22-15.3] (p<0.001), respectively. On MVA, age at diagnosis and CCI score ≥2 remained significant with HR of 1.06 [1.03-1.09] (p = <0.001) and HR of 4.56 [2.02-10.40] (p = <0.001), respectively. There was a trend of statistically significant correlation between cardiac events and left inner/central tumor location when compared to right outer tumor location with a HR of 2.06 [1.00,4.24] (p = 0.05). Treatment of tumor beds located in the inner/central portion of the left breast may increase the risk of developing cardiac toxicity in patients receiving APBI. These data support careful contouring and avoidance of cardiac structures during APBI treatment planning, including HDR brachytherapy.

KV-CBCT-Guided Daily Adaptation Improves Target Coverage and Spares Normal Tissue for Accelerated Partial Breast Irradiation

Linear accelerator based accelerated partial breast irradiation (APBI) in early-stage breast cancer necessitates a reduction in non-target breast tissue to decrease long term toxicity and adverse cosmetic outcome. In particular, lumpectomy cavity seromas may decrease in size and deform in shape during the course of short course APBI. Online adaptive RT (oART) offers considerable prospect for treating mobile targets through pendulous breast anatomy. However, there are limited studies outlining the methods and outcomes of CBCT-based oART for APBI. Here we present a retrospective, single institutional study analyzing the treatment process for patients receiving stereotactic kV-CBCT guided oART APBI. Fourteen patients were treated to 30 Gy in 5 fractions for a total of 70 fractions. Time between simulation and treatment, change in gross tumor volume (GTV), and differences in DVH metrics with adaption were analyzed. The Wilcoxon paired, non-parametric test was utilized to test for DVH metric differences between the scheduled plans (initial plans recalculated on daily CBCT anatomy) and treated plans, which were either the scheduled or adapted plan (initial plans re-optimized using daily anatomy), depending on the preference of the treating physician or physicist. Median (inter-quartile range) time from simulation to first treatment was 28 days (21-33 days). During this same time, GTV volume reduced to 72.5% (57.8-87.3%) of the simulation lumpectomy cavity volume. Adaptive treatments required 31.1 min (27.2-37.1 min) from start of CBCT to treatment session end. Table 1 summarizes differences between scheduled and treated plan metrics for 70 fractions, 62 (89%) of which were treated adaptively and 8 (11%) of which were treated using the scheduled plan. Significant improvement in prescription planning target volume coverage (p = 0.003), significant reduction in 5/6 organ-at-risk metrics evaluated (p ≤ 0.003), and significant improvement in conformity index and high dose spillage (p ≤ 0.001) were realized with adaption. Table 1: Scheduled versus treated plan metrics. APBI using oART decreased most organs at risk DVH metrics, improved plan quality metrics, and increased target coverage, justifying the use of kV-CBCT-guided oART for APBI.

Effectiveness and Toxicity of Five Fraction Prone Accelerated Partial Breast Irradiation

Accelerated partial breast irradiation (APBI) after breast conserving therapy (BCT) is increasingly used to treat women with early stage breast cancer. Our institution was an early adopter of 5-fraction ABPI and delivers APBI primarily to patients in the prone position. This study reports long term oncologic and cosmetic outcome in a large cohort of women treated with 5-fraction external beam APBI. We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Late toxicities and clinician and patient rated cosmesis were evaluated for patients with > 6 month follow up. Univariate and multivariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities, clinician and patient rated cosmesis. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS). Four hundred and forty-two patients received APBI either daily (56%) or every other day (44%). Most of the patients (92%) were treated in the prone position. Average mean heart dose was 23 cGy for left-sided and 11 cGy for right-sided breast cancers. Ipsilateral lung V30% ≤ 30%. At a median follow up of 48 months (range: 5.96 - 155 months), 12 (2.7%) patients developed a local recurrence, 14 (3.2%) patients developed a contralateral breast primary, 10 patients (2.3%) developed a distant metastasis and one patient (0.2%) developed a local recurrence followed by a distant metastasis 1 month later. Out of 258 patients with > 6 month follow up, rates of late grade 1-2 telangiectasia, fibrosis, edema, atrophy and hyperpigmentation were 4%, 18%, 1%, 19% and 7% respectively. There was only one late grade 3 event in a patient who developed significant breast atrophy. The rate of good-excellent physician and patient rated cosmesis was 95% and 89% respectively (N = 256 at median follow up of 80 months). On multivariate logistic regression, patients who did not receive any adjuvant endocrine or chemotherapy were at increased risk of developing a local recurrence. Patients with PR negative disease were at increased risk of distant metastasis. Patient who experienced any grade of acute dermatitis during treatment were at increased risk of any high grade (grade ≥ 2) late adverse event and worse physician rated cosmesis. Daily or every other day treatment did not correlate with worse toxicity or clinical outcomes. Plastic surgery involvement, LVI, EIC, lobular histology, and ER negativity did not correlate with an increased risk of recurrence. Five-year LR-RFS, DFS and OS were 98%, 92.5% and 98.6% respectively. Five- fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity and excellent cosmetic scores at long term follow up.