Navigator-assisted hypofractionation (NAVAH) to address radiation therapy access disparities facing African-Americans with breast cancer.

Background: African-Americans have the highest overall cancer death rate and shortest survival time of any racial or ethnic group in the United States. The most common cancer studied in African-American radiation therapy (RT) access disparities research is breast cancer. The goal of this study is to evaluate the impact of patient navigation on RT access for African-American breast cancer patients. Material and methods: This study is a prospective survey-based evaluation of the impact of patient navigation on access to hypofractionated RT and financial toxicity in African-American breast cancer patients. The impact of patient navigation on RT access will be collated and analyzed from survey results pre-RT versus post-RT as well as for patients with versus without receipt of patient navigation. The validated COST-Functional Assessment of Chronic Illness Therapy score will be used to compare hypofractionation versus standard fractionated RT financial toxicity for patients with early-stage breast cancer who have received lumpectomy. Conclusion: This is the first study to investigate the impact of patient navigation on reducing RT access disparities facing African-American breast cancer patients. The natural progression of this work will be to expand this model to include additional breast cancer populations most vulnerable to suffering RT access disparities (Native American, Hispanic American, Appalachian) within the United States.

ACR Appropriateness Criteria® Ductal Carcinoma in Situ.

Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria local-regional recurrence (LRR) and salvage surgery-breast cancer.

Although both breast-conserving surgery and mastectomy generally provide excellent local-regional control of breast cancer, local-regional recurrence (LRR) does occur. Predictors for LRR include patient, tumor, and treatment-related factors. Salvage after LRR includes coordination of available modalities, including surgery, radiation, chemotherapy, and hormonal therapy, depending on the clinical scenario. Management recommendations for breast cancer LRR, including patient scenarios, are reviewed, and represent evidence-based data and expert opinion of the American College of Radiology Appropriateness Criteria Expert Panel on LRR.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel.The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

American Radium Society Appropriate Use Criteria Postmastectomy Radiation Therapy: Executive Summary of Clinical Topics.

PURPOSE: To conduct an appropriate use criteria expert panel update on clinical topics relevant to current clinical practice regarding postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An analysis of the medical literature from peer-reviewed journals was conducted from May 4, 2010 to May 4, 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to search the PubMed database to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures. RESULTS: Evidence for key questions in PMRT regarding benefit in special populations and technical considerations for delivery was examined and described. Risk factors for local-regional recurrence in patients with intermediate-risk disease that indicate benefit of PMRT include molecular subtype, age, clinical stage, and pathologic response to neoadjuvant chemotherapy. Use of hypofractionated radiation in PMRT has been examined in several recent randomized trials and is under investigation for patients with breast reconstruction. The use of bolus varies significantly by practice region and has limited evidence for routine use. Adverse effects occurred with both PMRT preimplant and postimplant exchange in 2-staged breast reconstruction. CONCLUSIONS: Most patients with even limited nodal involvement will likely benefit from PMRT with significant reduction in local-regional recurrence and potential survival. Patients with initial clinical stage III disease and/or any residual disease after neoadjuvant chemotherapy should be strongly considered for PMRT. Growing evidence supports the use of hypofractionated radiation for PMRT with equivalent efficacy and decreased acute side effects, but additional evidence is needed for special populations. There is limited evidence to support routine use of bolus in all patients. Timing of PMRT regarding completion of 2-staged breast reconstruction requires a discussion of increased risks with radiation postimplant exchange compared with increased risk of failure of reconstruction or surgical complications with radiation preimplant exchange.

Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA.

PURPOSE: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors. METHODS: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS. RESULTS: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively. CONCLUSION: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

Reduced Survival Outcome After Receiving a New Cancer Diagnosis in the Emergency Department: Findings from a Hospital Network in Rural Eastern North Carolina.

PURPOSE: Patients whose cancer was found during an Emergency Department (ED) visit often present at later stages when survival outcomes are worse. Limited research has characterized the survival experience of cancer patients who receive their diagnosis through the ED versus those who do not. METHODS: A retrospective cohort study identified all patients presenting to the ED between 2014 and 2015 in a rural, regional hospital system with a visit or resulting admission associated with an oncologic ICD-9 code. The chart was abstracted to determine a new cancer diagnosis versus an existing case. Cox proportional hazards (HR) estimated survival time. Patient and cancer characteristics were compared between those who were newly diagnosed through the ED and patients who were not. FINDINGS: Thirty-nine percent of patients in our sample received their new cancer diagnosis as a result of an ED visit. The median survival was lower in cancer cases diagnosed through the ED (13 vs. 39 months, P < .001), men (20 vs. 32 months, P < .001), and patients aged ≥ 65 (22 months vs. 32 months, P < .001). Factors associated with lower survival were having a type of cancer location other than breast (HR = 1.96; P < .001), followed by being newly diagnosed with cancer through the ED (HR = 1.71; P < .001), and stage IV at diagnosis (HR = 1.70; P < .001). CONCLUSIONS: Patients who received a new cancer diagnosis through the ED and required subsequent hospitalization had shorter overall survival and presented with advanced disease. Future research should address socioeconomic factors that may influence these patterns of cancer presentation.

Accelerated partial breast irradiation: a review and description of an early North American surgical experience with the intrabeam delivery system.

BACKGROUND: Targeted intraoperative radiation therapy (IORT) as an alternative to whole breast irradiation (WBI) has been described for patients with early-stage breast cancer. The randomized phase III TARGiT trial demonstrated similar recurrence rates to WBI and a lower overall toxicity profile on short-term follow-up. We report on our early North American surgical experience using the Intrabeam radiotherapy delivery system and review the current literature. METHODS: Prospectively gathered estrogen receptor-positive, clinically node-negative patients with invasive breast cancer < 3 cm receiving IORT using the Intrabeam system were reviewed. IORT-related effects and early postoperative outcome were assessed. A literature review was also performed. RESULTS: Forty-two patients (median age 71 years) underwent lumpectomy, sentinel lymph node (SLN) biopsy, and concurrent IORT from January 2011 to July 2011. Ninety-one percent of patients had invasive ductal histology with a median tumor size of 1.0 cm. This review highlights the patient selection criteria, describes commercially available accelerated partial breast irradiation (APBI) treatment options, and discusses outcomes for the variety of APBI techniques currently utilized in clinical practice as well as an institutional review of our early surgical experience using the Intrabeam radiotherapy delivery system. CONCLUSIONS: While a variety of APBI techniques are currently available for clinical use, our early North American operative experience with IORT shows it is well tolerated with low morbidity. Delivery of IORT adds moderate operative time and may require creating subcutaneous tissue fl aps. The addition of WBI may be necessary in situations for positive residual margins or microscopic nodal disease in patients who do not undergo additional surgery.

Time-course of arm lymphedema and potential risk factors for progression of lymphedema after breast conservation treatment for early stage breast cancer.

The objective of this study was to describe the progression of arm lymphedema (ALE) after the initial presentation among patients receiving breast conservation therapy for early stage breast cancer and to identify potential risk factors contributing to ALE progression. The study sample was the 266 stage I or II breast cancer patients with documented ALE who underwent breast conservation therapy that included lumpectomy, axillary staging followed by radiation therapy. ALE were graded according to a difference of 0.5-2 cm (mild), 2.1-3 cm (moderate), and >3 cm (severe) in the circumference between the upper extremities for the treated and untreated sides. ALE at presentation was scored as mild, moderate, and severe in 109 (41%), 125 (47%), and 32 (12%) patients, respectively. One third of patients with ALE progressed to a more severe grade of lymphedema at 5 years of follow-up. Age older than 65 years at the time of breast cancer treatment was associated with higher risk of ALE progression when compared 65 year age or younger (p = 0.04). The patients who had regional lymph node irradiation including posterior axillary boost were at higher risk of lymphedema progression than the patients treated with whole breast irradiation only (p = 0.001). Progression of ALE is a common occurrence. The current study provides support for the utility of routine arm measurements after breast cancer treatment to facilitate timely diagnosis and treatment of ALE.

ACR appropriateness criteria(®) ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) describes a wide spectrum of non-invasive tumors which carry a significant risk of invasive relapse, thus prevention of local recurrence is vital. For appropriate patients with limited disease, management with breast conserving surgery (BCS) followed by whole-breast radiation (RT) is supported by multiple Phase III studies, but mastectomy may be appropriate in selected patients. Omission of RT may also be reasonable in some patients, though which criteria are to be utilized remain unclear, and the existing data are contradictory with limited follow-up. Various RT techniques such as boost to the tumor bed, partial breast radiation or hypofractionated, whole-breast RT are increasingly utilized but the data to support their use specifically in DCIS is limited. Tamoxifen also increases local control for ER + DCIS, adding to the complexity of the local treatment management. This article reviews the existing scientific evidence, the controversies surrounding local management, and clinical guidelines for DCIS based on the group consensus by the ACR Breast Expert Panel. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer.

PURPOSE: Accelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation. METHODS AND MATERIALS: This was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period. RESULTS: From 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience. CONCLUSIONS: APBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.

Cardiac morbidity and mortality in women with ductal carcinoma in situ of the breast treated with breast conservation therapy.

Left-sided breast irradiation has been associated with increased risk of cardiac morbidity and mortality in some studies. This study examines the cardiac toxicity of irradiation in left- versus right-sided patients with ductal carcinoma in situ (DCIS). The medical records of 129 patients with DCIS treated with breast conservation therapy (BCT) at the Moffitt Cancer Center from 1986 to 2002 were reviewed and data regarding subsequent breast cancer and cardiac events were recorded. There were 59 left-sided and 70 right-sided patients treated. Mean age was 55 years. At 8 years, there was no significant difference observed between right- and left-sided breast cancer patients in the development of coronary artery disease, myocardial infarction, congestive heart failure, arrhythmia, valvular disease, cardiomyopathy, or cardiac-related death. Among those patients with left-sided breast cancer, 13.5% of patients developed a cardiovascular event compared to 7% of right-sided patients (p = 0.25). The overall survival at 8 years was 96% and the relapse-free survival was 85%. There were no significant differences in cardiac mortality or morbidity between right- and left-sided DCIS patients treated with BCT. Longer follow-up will be required to ascertain whether late events are more prevalent in left-sided patients.

ACR Appropriateness Criteria® conservative surgery and radiation--stage I and II breast carcinoma: expert panel on radiation oncology: breast.

Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long-term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments.

ACR appropriateness criteria® locally advanced breast cancer.

Locally advanced breast cancer (LABC) is a disease that is heterogeneous in its presentation, potentially curable, and generally necessitating multidisciplinary management. Radiation therapy (RT) plays an important role in the management of LABC. The integration of radiation with surgery, chemotherapy, and sometimes breast reconstruction can be complex. The American College of Radiology Appropriateness Criteria Breast Committee aims to provide guidance for the management of a variety of LABC cases. The American College of Radiology Appropriateness Criteria is evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Breast Radiation and the Heart: Cardiac Toxicity and Cardiac Avoidance.

The purpose of this invited review is to discuss the most recent and relevant outcome studies assessing the risk of late cardiac toxicity in women treated with radiotherapy for breast cancer and to describe the evidence-based technical factors associated with late cardiac toxicity. This review will also discuss the common radiation techniques for reducing radiation dose to the heart, which will lead to better outcomes and lower rates of late toxicity that can cause morbidity and mortality in women who have been cured of their breast cancer.

Genomically Guided Breast Radiation Therapy: A Review of the Current Data and Future Directions.

PURPOSE: To highlight the current evidence and the limitations in data to support a personalized approach in breast oncology radiation therapy management and define steps needed for clinical implementation. METHODS AND MATERIALS: A critical review of the current literature on the use of genomics in breast radiation therapy was undertaken by a group of breast radiation oncologists to discuss current data, future directions, and challenges. RESULTS: A summary of the existing data, ongoing clinical trials, and future directions is provided. The authors note many groups have developed radiation-specific genomic assays, which demonstrate promise in prediction of local control and benefit from radiation therapy; however, prospective validation of their utility is needed. Limitations continue to exist in our understanding of tumor biology and how it can be integrated into clinical practice. CONCLUSIONS: Given the relative ubiquity of breast radiation therapy, the variety of dose and fractionation approaches, and the current data to support a personalized approach, it is our belief that the delivery of breast radiation therapy is uniquely poised for a genomically personalized radiation therapy approach. Prospective clinical trials implementing genomic signatures are needed at this time to advance the field.

Accelerated partial breast irradiation: potential roles following breast-conserving surgery.

BACKGROUND: Multiple randomized trials comparing mastectomy to lumpectomy and whole breast irradiation (WBI) have shown equivalent survival outcomes in early-stage breast cancer. WBI requires a treatment course of several weeks, which has resulted in limited access to breast-conserving therapy in certain populations. A shorter accelerated course of partial breast irradiation (APBI) has been investigated recently. METHODS: This article reviews the current medical literature, including randomized trials and prospective institutional studies of APBI and the current recommendations regarding the use of this emerging technique. RESULTS: Several APBI techniques have been developed, including brachytherapy and external beam methods. The longest follow-up data are available for multicatheter interstitial brachytherapy, a technique that is not commonly used. Other methods, including balloon brachytherapy and external beam three-dimensional conformal techniques, have limited follow-up that shows similar local control rates to whole breast irradiation in highly selected patients. Guidelines for the appropriate use of APBI have been published. CONCLUSIONS: While APBI may increase access to breast conservation therapy for some women with early-stage breast cancer, follow-up data demonstrating the efficacy of this relatively new treatment approach are limited. Therefore, strict evidence-based selection criteria should be applied when evaluating patients who may be appropriate for APBI.

Utilizing the genomically adjusted radiation dose (GARD) to personalize adjuvant radiotherapy in triple negative breast cancer management.

BACKGROUND: Utilizing the linear quadratic model and the radiosensitivity index (RSI), we have derived an expression for the genomically adjusted radiation dose (GARD) to model radiation dose effect. We hypothesize GARD is associated with local recurrence and can be used to optimize individual triple negative breast cancer (TNBC) radiation dose. METHODS: TN patients from two independent datasets were assessed. The first cohort consisted of 58 patients treated at 5 European centers with breast conservation surgery followed by adjuvant radiotherapy (RT). The second dataset consisted of 55 patients treated with adjuvant radiation therapy. FINDINGS: In cohort 1, multivariable analysis revealed that as a dichotomous variable (HR: 2.5 95% CI 1-7.1; p = .05), GARD was associated with local control. This was confirmed in the second independent dataset where GARD was the only significant factor associated with local control (HR: 4.4 95% CI 1.1-29.5; p = .04). We utilized GARD to calculate an individualized radiation dose for each TN patient in cohort 2 by determining the physical dose required to achieve the GARD target value (GARD ≥ 21). While 7% of patients were optimized with a dose of 30 Gy, 91% of patients would be optimized with 70 Gy. INTERPRETATION: GARD is associated with local control following whole breast or post-mastectomy radiotherapy (RT) in TN patients. By modeling RT dose effect with GARD, we demonstrate that no single dose is optimal for all patients and propose the first dose range to optimize RT at an individual patient level in TNBC.

The impact of comorbidities on outcomes for elderly women treated with breast-conservation treatment for early-stage breast cancer.

PURPOSE: Breast cancer incidence increases with age and is a major cause of morbidity and mortality in elderly women, but is not well studied in this population. Comorbidities often impact on the management of breast cancer in elderly women. METHODS AND MATERIALS: From 1979 to 2002, a total of 238 women aged 70 years and older with Stage I or II invasive carcinoma of the breast underwent breast-conservation therapy. Outcomes were compared by age groups and comorbidities. Median age at presentation was 74 years (range, 70-89 years). Age distribution was 122 women (51%) aged 70-74 years, 71 women (30%) aged 75-79 years, and 45 women (19%) aged 80 years or older. Median follow-up was 6.2 years. RESULTS: On outcomes analysis by age groups, 10-year cause-specific survival rates for women aged 70-74, 75-79, and 80 years or older were 74%, 81%, and 82%, respectively (p = 0.87). Intercurrent deaths at 10 years were significantly higher in older patients: 20% in those aged 70-74 years, 36% in those aged 75-79 years, and 53% in those 80 years and older (p = 0.0005). Comorbidities were not significantly more common in the older age groups and did not correlate with cause-specific survival adjusted for age. Higher comorbidity scores were associated with intercurrent death. CONCLUSIONS: Older age itself is not a contraindication to standard breast-conservation therapy, including irradiation. Women of any age with low to moderate comorbidity indices should be offered standard breast-conservation treatment if otherwise clinically eligible.

Association between tangential beam treatment parameters and cardiac abnormalities after definitive radiation treatment for left-sided breast cancer.

PURPOSE: To examine the association between radiation treatment (RT) parameters, cardiac diagnostic test abnormalities, and clinical cardiovascular diagnoses among patients with left-sided breast cancer after breast conservation treatment with tangential beam RT. METHODS AND MATERIALS: The medical records of 416 patients treated between 1977 and 1995 with RT for primary left-sided breast cancer were reviewed for myocardial perfusion imaging and echocardiograms. Sixty-two patients (62/416, 15%) underwent these cardiac diagnostic tests for cardiovascular symptoms and were selected for further study. Central lung distance and maximum heart width and length in the treatment field were determined for each patient. Medical records were reviewed for cardiovascular diagnoses and evaluation of cardiac risk factors. RESULTS: At a median of 12 years post-RT the incidence of cardiac diagnostic test abnormalities among symptomatic left-sided irradiated women was significantly higher than the predicted incidence of cardiovascular disease in the patient population, 6/62 (9%) predicted vs. 24/62 (39%) observed, p = 0.001. As compared with patients with normal tests, patients with cardiac diagnostic test abnormalities had a larger median central lung distance (2.6 cm vs. 2.2 cm, p = 0.01). Similarly, patients with vs. without congestive heart failure had a larger median central lung distance (2.8 cm vs. 2.3 cm, p = 0.008). CONCLUSIONS: Contemporary RT for early breast cancer may be associated with a small, but potentially avoidable, risk of cardiovascular morbidity that is associated with treatment technique.