Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society

Logistical barriers of time and travel created by the conventional six-week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.     

The American Brachytherapy Society consensus statement for accelerated partial breast irradiation

PurposeTo develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer.Methods and MaterialsMembers of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience.ResultsIncreasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selection for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age (≥50 years old), tumor size (≤3 cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment.ConclusionsThese guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection.     

Comparison of survival and regional failure between accelerated partial breast irradiation and whole breast irradiation

PurposeTo compare rates of regional recurrence (RR) and overall survival (OS) between a pooled set of 1400 patients treated on the American Society of Breast Surgeons MammoSite (Hologic, Inc., Bedford, MA) Registry Trial to a cohort of 3600 patients treated with whole breast irradiation (WBI).Methods and MaterialsA total of 1440 women underwent accelerated partial breast irradiation (APBI) between 2002 and 2004 as part of the American Society of Breast Surgeons Registry Trial and a total of 3593 patients who received WBI were evaluated from the Surveillance Epidemiology and End Results database with treatment received between 1980 and 2009. A matched-pair analysis was performed based on age, receipt of hormonal therapy, chemotherapy, nodal status, and tumor size (1051 patients per arm). Rates of RR and OS were then analyzed for each group.ResultsAfter the match, no differences in patient characteristics were noted when tumor size was evaluated as a continuous variable. Rates of RR and OS were similar between the WBI and APBI groups. A Cox regression model found no difference between WBI and APBI with regard to RR; however, OS was improved in the APBI cohort (hazard ratio 0.008, p < 0.0001).ConclusionsWith one of the largest patient populations to date comparing WBI and APBI, no difference in RR or OS was noted between WBI and APBI treatment. Until the publication of prospective Phase III trials, these data support the continued use of APBI on protocol and off protocol in appropriately selected patients.     

Accelerated partial breast irradiation using interstitial high dose rate iridium brachytherapy: Early Australian experience and review of the literature

Summary Accelerated partial breast irradiation (APBI) is an evolving new technique of adjuvant irradiation in selected women with early-stage breast cancer. We developed a pilot programme of APBI in 2000 and report end results in seven patients followed for a mean of 42.7 months (range 29-55 months). Good to excellent cosmesis and no loco-regional relapse or systemic metastases have occurred. The literature related to APBI is reviewed.     

The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation

PurposeAdjuvant radiation after breast-conserving surgery remains the standard-of-care treatment for patients with ductal carcinoma in situ and early-stage invasive breast cancer. Multiple alternatives to standard whole-breast irradiation exist including accelerated partial-breast irradiation (APBI). Therefore, the purpose of this APBI guideline is to provide updated data for clinicians as well as recommendations regarding appropriate patient selection and techniques to deliver APBI.MethodsMembers of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular created an updated guideline for appropriate patient selection based on an extensive literature search and clinical experience. In addition, data were evaluated with respect to APBI techniques and recommendations presented.ResultsAppropriate candidates for APBI include patients aged 45 years or older, all invasive histologies and ductal carcinoma in situ, tumors 3 cm or less, node negative, estrogen receptor positive/negative, no lymphovascular space invasion, and negative margins. With respect to techniques, the strongest evidence is for interstitial brachytherapy and intensity-modulated radiation therapy APBI with moderate evidence to support applicator brachytherapy or three-dimensional conformal radiotherapy APBI. Intraoperative radiation therapy and electronic brachytherapy should not be offered regardless of technique outside of clinical trial.ConclusionsThe updated guidelines presented offer clinicians with a summary of data supporting APBI and guidelines for the appropriate and safe utilization of the technique.     

Breast brachytherapy: Building a bright future on the foundation of a rich history of advancement in technology,technique, and patient-centered care

For over 20 years, the concept of accelerated partial breast irradiation (APBI) has received considerable attention. Initially concentrating on the appropriateness of APBI as an alternative treatment to whole breast radiotherapy, investigation and innovation evolved towards dose delivery and technique appropriateness. The purpose of this article is to review the pertinent literature that supports the role brachytherapy serves in delivering APBI and the recognized brachytherapy techniques for dose delivery. Publications establishing techniques utilizing multicatheter brachytherapy, single-entry brachytherapy applicators, permanent breast seed implantation brachytherapy, noninvasive breast brachytherapy and electronic brachytherapy are described. The use of brachytherapy for repeat breast conservation therapy is additionally reviewed. A historical perspective and potential direction of future investigation and innovation are presented.     

Accelerated partial breast irradiation and posttreatment imaging evaluation

Accelerated partial breast irradiation (APBI) is a technique that allows irradiation of only that part of the breast that is at greatest risk for recurrence of breast cancer. Because only a portion of the breast is irradiated, APBI can be performed in a relatively short period of time, usually in 5 days rather than the traditional 6 weeks. When used in carefully selected patients, APBI also allows normal portions of the breast parenchyma and regional vital organs to be spared from unnecessary irradiation. Common post-APBI imaging findings include focal skin thickening, seroma, scar, and skin retraction. Studies are underway that will compare a cohort of patients who underwent whole-breast irradiation with a cohort who underwent APBI to help determine whether the two techniques lead to significantly different imaging findings. Additional multicenter studies will be needed to document and analyze any such differences. In the future, APBI may play a significant role in selected patients, with pretherapy dynamic contrast material-enhanced magnetic resonance imaging of the breast possibly aiding in the selection process.     

A Single-Institution Retrospective Study of Three-Fraction HDR Accelerated Partial Breast Irradiation

PURPOSEAccelerated partial breast irradiation (APBI) delivered with high-dose-rate brachytherapy is a standard of care treatment typically delivered over 10 fractions. The TRIUMPH-T multi-institutional study recently demonstrated promising results using a shorter three fraction regimen, however there are limited additional published series using this regimen. Here, we report our experience and outcomes for patients treated as per the TRIUMPH-T regimen.METHODS AND MATERIALSThis study was a retrospective single-institution analysis of patients who underwent lumpectomy followed by APBI (22.5 Gy in 3 fractions delivered over 2–3 days) using a Strut Adjusted Volume Implant (SAVI) applicator between November 2016 and January 2021. Dose-volume metrics were obtained from the clinically treated plan. Chart review was performed to determine locoregional recurrence and toxicities according to CTCAE v5.0.RESULTSBetween 2016 and 2021, 31 patients were treated per the TRIUMPH-T protocol. Median followup was 31 months from completion of brachytherapy. There were no acute/late Grade 3 or higher toxicities. Cumulative late Grade 1 and 2 toxicities were seen in 58.1% and 9.7% of patients, respectively. Of note, four patients experienced locoregional recurrence: three ipsilateral breast tumor recurrences and one nodal recurrence. All three ipsilateral breast tumor recurrences occurred in patients who would be classified as “cautionary” based on ASTRO consensus guidelines due to age ≤50, lobular histology, or high grade.CONCLUSIONSThree-fraction HDR brachytherapy APBI was well-tolerated with no grade 3 or higher toxicities and an acceptably small percentage of grade 2 toxicities. Given the small sample size, the number of recurrences suggests that attention to appropriate patient selection is necessary until more long-term followup data is available.     

Results of accelerated partial breast irradiation in patients not suitable for external beam irradiation stratified by GEC-ESTRO,ASTRO, and ABS guidelines

PurposeThis study aims to review the outcome of an institution in multicatheter/interstitial accelerated partial breast irradiation (MC-APBI) for treatment of patients with breast cancer, either with strong criteria for APBI or unable to be treated with whole-breast irradiation. The outcomes were also stratified by the American Society for Radiation Oncology, American Brachytherapy Society, and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology patient selection criteria.MethodsThe study includes 118 patients and 120 MC-APBI treatments, treated in a single tertiary center, between November 2003 and August 2016. The analysis is focused on the clinical baseline characteristics, local control, relapse-free survival, disease-specific survival (DSS), and overall survival.ResultsIn accordance to the American Society for Radiation Oncology, American Brachytherapy Society, and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology, 17.1% were “unsuitable,” 19.2% were “unacceptable,” and 19.5% were “high risk,” respectively. The main reasons why high-risk patients were submitted to MC-APBI were as follows: cardiopathy (n = 7), social difficulties (n = 4), and mobility limitations (n = 4). At the median followup period of 86.5 months, ipsilateral breast tumor recurrence was observed in one (0.8%) patient. The 3-year and 5-year relapse-free survival were 100% and 99.1%, respectively. DSS was 100%.ConclusionsThis study demonstrated excellent control rates, DFS, and DSS of MC-APBI, rendering APBI as an excellent treatment for patients with breast cancer, even those who are not necessarily eligible for this treatment approach. The selection criteria for ABPI diverge according to different guidelines and are based on studies with discrepancies, making extremely possible that these recommendations could be changed.     

Magnetic resonance imaging of the breast: current indications.

Breast magnetic resonance imaging (MRI) plays an increasing role in the management of selected breast cancer patients. MRI is recognized as the most sensitive modality for the detection of invasive breast cancer. Several valuable clinical applications of MRI have emerged for breast cancer detection and diagnosis from clinical investigations. Breast MRI is helpful for women diagnosed with breast cancer who contemplate breast conserving surgery; it provides valuable information on the extent of the disease. MRI can also help assess for residual invasive cancer in patients who have undergone lumpectomy with positive margins at pathology. It is very reliable in differentiating scar tissue from recurrence at the lumpectomy site. MRI is also reliable in finding a breast cancer in women with axillary nodal metastases and unknown primary tumour. MRI can help to monitor the response to chemotherapy. Breast MRI could be a better screening tool than mammography in women with very high risks of developing breast cancer, such as breast cancer gene carriers and patients treated with chest radiation. Other potential uses of MRI include evaluation of the integrity of silicone breast implants and evaluation of the parenchyma in women with silicone gel implants or free injection of silicone gel. However, like any other technique, breast MRI has some drawbacks, including low-to-moderate specificity, high costs, and variability in technique and interpretation. Radiologists must have a clear understanding of valid indications and selection criteria to use this technique appropriately.     

Modern radiation techniques in early stage breast cancer for the breast radiologist

Partial breast irradiation (PBI) and ultra-hypofractionated whole breast irradiation (uWBI) are contemporary alternatives to conventional and standard hypofractionated whole breast irradiation (WBI), which shorten treatment from 3 to 6 weeks to 1–2 weeks for select patients. PBI and accelerated PBI (APBI) can be delivered with external beam radiation (3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT)), intraoperative radiation (IORT), or brachytherapy. These new radiation techniques offer the advantage of convenience and lower cost, which ultimately improves access to care. Globally, the COVID 19 pandemic has accelerated APBI/PBI and ultra-hypofractionated regimens into routine practice for carefully selected patients. Recent long-term data from randomized controlled trials (RCTs) have demonstrated these techniques are safe and effective in suitable patients demonstrating equivalent or improved local recurrence, acute/late toxicity, and cosmesis. PBI and APBI should be limited to low risk unifocal invasive ductal carcinoma and ductal carcinoma in situ with tumor size < 2 cm, clear margins (≥2 mm), ER+, and negative nodes. Based on the results from UK Fast-Forward and UK FAST ultra-hypofractionated breast radiation can be safely employed for early stage node negative patients, but is not yet considered an international standard of care. In this review, authors will appraise recent data for these shorter course radiation treatment regimens, as well as, considerations for breast radiologists including surveillance imaging and radiographic findings.     

Absence of adverse early quality of life outcomes of radiation therapy in breast conservation therapy for early breast cancer

The New South Wales Breast Radiation Oncology Group has completed a prospective multicentre study of the impact of radiation therapy (RT) on acute toxicity and quality of life (QoL) in women with early breast cancer treated with breast conservation therapy. The patient group received adjuvant breast tangential RT after wide local excision of breast cancer. Acute toxicity and cosmesis was assessed quantitatively and qualitatively. European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) and Perceived Adjustment to Chronic Illness Scale (PACIS) were the QoL instruments used. Of 175 women, 34.3% described lethargy leading to a significant disruption to normal activity during RT. At week 6, this had reduced to 7.5% reporting significant lethargy. No negative effects on QoL were noted over the time period of RT; EORTC demonstrated no difference (P = 0.79). PACIS recorded a significant improvement in functioning (P < 0.001) from baseline to week 6. Univariate analysis on potential predictive patient, tumour and treatment factors demonstrated an association of baseline pre-RT breast discomfort with worse lethargy (P = 0.03), EORTC (P < 0.01) and PACIS (P < 0.01) measures. This study confirms the minimal impact of RT on patient functioning at 6 weeks post-treatment.     

Retrospective review of three-fractioned accelerated partial breast irradiation

MethodsThis retrospective study evaluated patients who received three-fraction accelerated partial breast irradiation (APBI) via brachytherapy for breast cancer between January 2016 and April 2020. Inclusion criteria included age ≥18 years and early-stage unilateral breast cancer with negative lymph nodes. We evaluated acute toxicity (<6 weeks), late toxicity (≥6 weeks), and cosmetic outcomes. Frequencies of each variable were calculated. Cancer-specific outcomes were determined via the Kaplan-Meier method.ResultsThirty consecutive patients received three-fraction APBI of 2,250 cGy over 2 d. All cancers were stage T2 or less. Median time to last follow-up was 22 months. Local recurrence-free survival was 95.8% at 22 months. Seventeen (56.7%) patients reported an acute toxicity event. All were grade 1 except one patient with grade 2 (fatigue). No patient experienced ≥ grade 3 acute toxicity. One (3.3%) patient reported grade 3 late toxicity (tissue fibrosis). No patients had breast edema, fat necrosis, or non-healing wounds. There were no ≥ grade 3 cosmetic events.DiscussionThree-fraction APBI via brachytherapy was successful in preventing disease recurrence and death in this study, with still limited follow-up. Although acute and late toxicities or adverse cosmetic outcomes were seen, very few were grade 2 or higher and compare favorably to those reported in prior 10-fraction APBI studies.ConclusionsThis study provides early single institutional evidence that three-fraction APBI may become a feasible treatment alternative.     

Attitudes and treatment outcome of breast conservation therapy for stage I & II breast cancer using peroperative iridium-192 implant boost to the tumour bed

Breast conservation therapy for early breast cancer is an established but grossly under-utilized treatment option in India for various reasons. Breast conservation therapy was offered to 200 suitable breast cancer patients between June 1993 and June 1998. Fifty-one patients (25%) opted for breast conservation and the remaining preferred mastectomy. In patients agreeing to conservation therapy, surgery was performed first along with peroperative implantation of iridium-192 to deliver a boost. Whole breast irradiation of 45 Gy was delivered 3-4 weeks after the boost. Cosmesis was assessed at the end of 6 months from completion of therapy. The main reason for refusal of breast conservation therapy was fear of recurrence in the remaining breast (60%). There were no locoregional failures in our study at a median follow up of 42 months; one patient experienced a systemic relapse. Cosmesis was good to excellent in 80% of patients. Breast conservation therapy using peroperative iridium-192 implant provides excellent locoregional disease control and cosmesis. The results of our study indicate that patient preference for mastectomy is an important reason for the under-utilization of breast conservation therapy in India.     

Radiation recall secondary to adjuvant docetaxel after balloon-catheter based accelerated partial breast irradiation

For early stage breast cancer, wide local excision and post-operative whole breast irradiation is a standard treatment. If adjuvant chemotherapy is recommended, radiation is usually given after completion of chemotherapy. In recent years, accelerated partial breast irradiation (APBI) with balloon-cathetered based brachytherapy has become an option for selected patients. For these patients, adjuvant chemotherapy would have to be administered after radiation. The sequence of treatment with radiation followed by chemotherapy results in increased risk of radiation recall reaction (RRD) in these patients. Docetaxel is becoming a more commonly used drug as adjuvant treatment for breast cancer. Here we report a case of docetaxel induced RRD after APBI with balloon-cathetered based brachytherapy. Such reaction would have an adverse impact on the cosmetic outcome and quality of life of the patient. For patients who develop an intense skin reaction after the administration of docetaxel following APBI, RRD should be considered in the differential diagnosis.     

Management of ductal carcinoma in situ with accelerated partial breast irradiation brachytherapy: Implications for guideline expansion

PurposeAccelerated partial breast irradiation (APBI) for patients with ductal carcinoma in situ (DCIS) is controversial, and the suitability criteria from the American Brachytherapy Society (ABS), American Society of Therapeutic Radiology and Oncology (ASTRO), and the European Society for Radiotherapy and Oncology (GEC-ESTRO) have important differences.Methods and MaterialsThis is a single-institution retrospective review of 169 consecutive patients with DCIS who underwent lumpectomy followed by APBI intracavitary brachytherapy from 2003 to 2018. Outcomes, including overall survival, recurrence-free survival (RFS), ipsilateral breast tumor recurrence, and distant metastasis, were estimated with the Kaplan–Meier method.ResultsThe median followup time was 62.5 months. Median age was 66 years (47–89 years). The majority of patients had estrogen receptor–positive disease (89%). Fifty patients (30%) had Grade 3 disease. Of the 142 patients with adequate pathology interpretation, 91 and 108 cases had margins ≥ 3 mm and ≥2 mm, respectively. Most patients (72%) were prescribed and started endocrine therapy. Of the patients evaluable for ABS criteria (N = 130), 97 met the suitability criteria. Of the patients evaluable for ASTRO criteria (N = 129), 42 were deemed cautionary and 33 were deemed unsuitable. Of the patients evaluable for GEC-ESTRO criteria (N = 143), 141 cases were at intermediate risk and two were at high risk. Five-year ipsilateral breast tumor recurrence, RFS, and overall survival were 0.6%, 97.7%, and 97.2%, respectively. The ABS, ASTRO, and GEC-ESTRO criteria failed to significantly predict for RFS.ConclusionsThese results, although limited by short-term followup, indicate that expansion of the eligibility criteria of APBI for patients with DCIS should be considered.     

Brachytherapy-based partial breast irradiation is associated with low rates of complications and excellent cosmesis

BackgroundRecent retrospective, claims-based analyses have suggested a potential increased rate of toxicities associated with brachytherapy-based accelerated partial breast irradiation (APBI). The purpose of this analysis was to examine cosmesis and toxicity data from the prospective American Society of Breast Surgeons (ASBS) breast brachytherapy registry trial to compare to the findings from the claims analyses.MethodsThe ASBS breast brachytherapy registry is a prospective nonblinded multi-institutional registry trial. Patients with Stage 0–II breast cancer undergoing breast conserving therapy were eligible. A total of 1665 patients were enrolled and 1449 treated between 2002 and 2004 with a median followup of 63 months. All patients were treated with the MammoSite (Hologic, Inc.) single-lumen device to deliver adjuvant APBI (34 Gy in 3.4 Gy fractions).ResultsThe rate of excellent/good cosmesis was 90.6% at 84 months. The rate of a complication (symptomatic seroma, infection, fat necrosis, telangiectasias) at 1 year/any time point was 24.2%/38.5%, whereas the rate of noninfectious complications at 1 year/any time point was 14.8%/28.9%. The rate of symptomatic seroma, fat necrosis, infection, and telangiectasia at any time was 13.4%, 2.5%, 9.6%, and 13.0%, respectively.ConclusionsThe final toxicity analysis from ASBS breast brachytherapy registry trial confirms the previously noted excellent cosmesis and toxicity profiles and fails to confirm retrospective claims analyses that have suggested higher rates of toxicity for brachytherapy-based APBI.     

Secondary breast angiosarcoma following accelerated partial breast irradiation with intracavitary multicatheter applicator brachytherapy

PURPOSESecondary angiosarcoma of the breast is a rare complication of breast radiotherapy and is associated with a poor prognosis. There are many reported cases of secondary angiosarcoma following whole breast irradiation (WBI), however development of secondary angiosarcoma following brachytherapy-based accelerated partial breast irradiation (APBI) is not as well characterized.METHODS AND MATERIALSWe reviewed and reported a case of a patient who developed secondary angiosarcoma of the breast following intracavitary multicatheter applicator brachytherapy APBI.RESULTSA 69-year-old female was originally diagnosed with T1N0M0 invasive ductal carcinoma of the left breast and treated with lumpectomy followed by adjuvant intracavitary multicatheter applicator brachytherapy APBI. Seven years following her treatment, she developed secondary angiosarcoma. However, the diagnosis of secondary angiosarcoma was delayed due to nonspecific imaging findings and a negative biopsy.CONCLUSIONSOur case highlights the need for secondary angiosarcoma to be considered in the differential diagnosis when patients present with symptoms such as breast ecchymosis and skin thickening following WBI or APBI. Prompt diagnosis and referral to a high-volume sarcoma treatment center for multidisciplinary evaluation is vital.     

Radiation recall reaction with docetaxel administration after accelerated partial breast irradiation with electronic brachytherapy

PurposeAccelerated partial breast irradiation (APBI) offers several advantages over whole breast irradiation. Electronic brachytherapy may further reduce barriers to breast conserving therapy by making APBI more available. However, its toxicity profile is not well characterized.Methods and MaterialsA 60-year-old woman was treated with APBI using Axxent (Xoft, Sunnyvale, CA) electronic brachytherapy. One month after APBI, a cycle of docetaxel and cyclophosphamide was given. Within 3 weeks, the patient developed an ulcerative radiation recall reaction in the skin overlying the lumpectomy cavity. To investigate this toxicity, the skin dose from electronic brachytherapy was compared with the dose that would have been delivered by an iridium-192 (¹⁹²Ir) source. Additionally, a dose equivalent was estimated by adjusting for the increased relative biologic effectiveness (RBE) of low energy photons generated by the electronic source.ResultsUsing electronic brachytherapy, the skin dose was 537 cGy per fraction compared with 470 cGy for an ¹⁹²Ir source. Given an RBE for a 40 kV source of 1.28 compared with ¹⁹²Ir, the equivalent dose at the skin for an electronic source was 687 cGy-equivalents, a 46% increase.ConclusionsWe present a case of an ulcerative radiation recall reaction in a patient receiving APBI with electronic brachytherapy followed by chemotherapy. Our analysis shows that the use of electronic brachytherapy resulted in the deposition of significantly higher equivalent dose at the skin compared with ¹⁹²Ir. These findings suggest that standard guidelines (e.g., surface-to-skin distance) that apply to ¹⁹²Ir-based balloon brachytherapy may not be applicable to electronic brachytherapy.     

Breast imaging and the conservative treatment of breast cancer

Breast conservation, where appropriate, offers effective treatment for breast cancer while preserving the breast. The increased use of mammographic screening has led to increased detection of small, curable breast cancers that are amenable to breast-conserving surgery. Mammography and other imaging modalities, such as sonography and MRI, assist in the determination of the appropriateness of breast conservation and in the differentiation of recurrence from benign sequelae of treatment.