Navigating Breast Cancer Oligometastasis and Oligoprogression: Current Landscape and Future Directions.

PURPOSE: We examine the potential for curative approaches among metastatic breast cancer (MBC) patients by exploring the recent literature on local ablative therapies like surgery and stereotactic body radiation therapy (SBRT) in patients with oligometastatic (OM) breast cancer. We also cover therapies for MBC patients with oligoprogressive (OP) disease. KEY FINDINGS: Surgery and SBRT have been studied for OM and OP breast cancer, mainly in retrospective or non-randomized trials. While many studies demonstrated favorable results, a cooperative study and single-institution trial found no support for surgery/SBRT in OM and OP cases, respectively. CONCLUSION: While there is interest in applying local therapies to OM and OP breast cancer, the current randomized data does not back the routine use of surgery or SBRT, particularly when considering the potential for treatment-related toxicities. Future research should refine patient selection through advanced imaging and possibly explore these therapies specifically in patients with hormone receptor-positive or HER2-positive disease.

Racial Disparities in Breast Cancer: from Detection to Treatment.

PURPOSE OF REVIEW: Update on current racial disparities in the detection and treatment of breast cancer. RECENT FINDINGS: Breast cancer remains the leading cause of cancer death among Black and Hispanic women. Mammography rates among Black and Hispanic women have surpassed those among White women, with studies now advocating for earlier initiation of breast cancer screening in Black women. Black, Hispanic, Asian, and American Indian and Alaskan Native women continue to experience delays in diagnosis and time to treatment. Further, racial discrepancies in receipt of guideline-concordant care, access to genetic testing and surgical reconstruction persist. Disparities in the initiation, completion, toxicity, and efficacy of chemotherapy, endocrine therapy, and targeted drug therapy remain for racially marginalized women. Efforts to evaluate the impact of race and ethnicity across the breast cancer spectrum are increasing, but knowledge gaps remain and further research is necessary to reduce the disparity gap.

Implementation of a Breast Intraoperative Oncoplastic Form to Aid Management of Oncoplastic Surgery.

INTRODUCTION: Oncoplastic breast conservation surgery (BCS) uses concurrent reduction and/or mastopexy with lumpectomy to improve aesthetic outcomes. However, tissue rearrangement can shift the original tumor location site in relation to external breast landmarks, resulting in difficulties during re-excision for a positive margin and accurate radiation targeting. We developed the Breast Intraoperative Oncoplastic (BIO) form to help depict the location of the tumor and breast reduction specimen. This study seeks to assess physician perspectives of the implementation outcomes. METHODS: From February 2021 to April 2021, the BIO form was used in 11 oncoplastic BCS cases at a single institution. With institutional review board approval, surgical oncologists (SOs), plastic surgeons (PSs), and radiation oncologists (ROs) were administered a 12-question validated survey on Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM), using a 5-point Likert scale during initial implementation and at 6-month reassessment. RESULTS: Twelve physicians completed the survey initially (4 SOs, 4 PSs, and 4 ROs). The mean scores for Acceptability of Intervention Measure, Intervention Appropriateness Measure, and Feasibility of Intervention Measure were high (4.44, 4.56, and 4.56, respectively). Twelve completed the second survey (5 SOs, 3 PSs, and 4 ROs). The mean scores were marginally lower (4.06, 4.21, and 4.25). There were no significant differences when stratified by number of years in practice or specialty. Free text comments showed that 75% of physicians found the form helpful in oncoplastic BCS. CONCLUSIONS: The data indicate high feasibility, acceptability, and appropriateness of the BIO form. Results of this study suggest multidisciplinary benefits of implementing the BIO form in oncoplastic BCS.

Modified Radical Mastectomy in De Novo Stage IV Inflammatory Breast Cancer.

BACKGROUND: There are few studies on surgical management in patients with de novo metastatic inflammatory breast cancer (IBC). The objective of this study is to examine the association between modified radical mastectomy (MRM) and disease-specific survival (DSS) in patients with de novo stage IV IBC. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Result Program was queried for patients ≥18 years old with cT4d/pT4d pathology, histology type 8530 and 8533 with distant disease between 2010 and 2016. The sample was divided into two groups: (1) the MRM group, defined as MRM or mastectomy with at least ten lymph nodes removed, and (2) the no-surgery group. Sociodemographic and clinical variables were compared between the groups on bivariable analysis. After propensity score matching, Kaplan-Meier curves and a Cox proportional-hazards model examined DSS. RESULTS: 1293 patients were included in the study, of whom 240 underwent MRM. A higher percentage in the MRM group had only one metastatic site (69.8% versus 52.2%), received chemotherapy (88.3% versus 66.1%) and radiation (58.8% versus 26.0%) compared with the no-MRM group. MRM was associated with an increase in DSS compared with no MRM [HR 0.63 (95% CI 0.50-0.80), p < 0.001]. Patients with MRM had a 5-year DSS rate of 31.4% compared with 17.7% for patients not undergoing surgery (p = 0.001). Survival time was 38 months (range 27-45 months) for the MRM group versus 27 months (22-29 months) for the no-MRM group. CONCLUSION: MRM in patients with de novo metastatic IBC may improve DSS in a subset of patients.

Disparate Use of Chemoradiation in Elderly Patients With Localized Anal Cancer.

BACKGROUND: The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly among the elderly (age ≥65 years). We sought to compare patterns of care for the treatment of SCCA in elderly versus nonelderly patients. METHODS: Data for patients with stages I-III SCCA diagnosed from 2004 through 2015 were obtained from the National Cancer Database. Patients were categorized as having received standard-of-care (SOC) chemoradiation (CRT) with multiagent chemotherapy, non-SOC therapy, palliative therapy, or no treatment. Differences in treatment groups were tested using the chi-square test. We used logistic regression to identify predictors of SOC CRT and multiagent versus single-agent chemotherapy in patients receiving CRT. Propensity score matching was used to compare overall survival (OS) in elderly patients receiving multiagent versus single-agent chemotherapy for those receiving CRT. RESULTS: We identified 9,156 elderly and 17,640 nonelderly patients. A lower proportion of elderly versus nonelderly patients (54.5% vs 65.0%; P<.0001) received SOC CRT than other treatments or no treatment. In multivariate analysis, elderly patients were 38% less likely than nonelderly patients to receive SOC CRT (odds ratio, 0.62; 95% CI, 0.58-0.65; P<.0001). A higher proportion of the elderly were treated with single-agent versus multiagent chemotherapy (16.9% vs 11.8%; P<.0001), which resulted in a >1.5-fold increase in the likelihood of elderly patients receiving single-agent chemotherapy (odds ratio, 1.52; 95% CI, 1.39-1.66) in multivariate analysis. After propensity score matching, 3-year OS was higher in elderly patients who received CRT with multiagent versus single-agent chemotherapy (77.1% vs 67.5%; hazard ratio, 0.78; 95% CI, 0.68-0.89; P=.0002). CONCLUSIONS: In this comprehensive study of patients with stages I-III SCCA, elderly patients were less likely than nonelderly patients to receive SOC CRT. The low proportion of elderly patients receiving SOC CRT with multiagent chemotherapy for localized anal cancer suggests that the optimal treatment approach for this vulnerable population remains undefined.

Heterogeneity in Outcomes of Pathologic T1-2N1 Breast Cancer After Mastectomy: Looking Beyond Locoregional Failure Rates.

PURPOSE: A meta-analysis of 22 randomized trials accrued from 1964 to 1986 demonstrated significantly higher rates of locoregional failure (LRF) and breast-cancer mortality in women with 1-3 positive nodes without postmastectomy radiotherapy (PMRT) after mastectomy (mast.). Recent data demonstrate that PMRT reduces distant metastases (DM) in women with pN1 disease. The challenge today is whether all patients with pathologic T1-2pN1 disease have similar substantial LRF/DM risk that routinely warrants PMRT. METHODS: We reviewed patients with pT1-2N1 breast cancer treated with mast. ± adjuvant systemic therapy without PMRT from 2000 to 2013. The endpoints were LRF and DM rates, estimated by cumulative incidence method. RESULTS: We identified 468 patients with median follow-up of 6.3 years. Most (71%) were estrogen receptor/progesterone receptor + human epidermal growth factor receptor 2 (HER2). There were 269 patients with 1+ node, 140 patients with 2+ nodes, and 59 patients with 3+ nodes. The 6-year LRF/DM rates were 4.1%/8.4%. Patients with 1+, 2+, and 3+ nodes had 6-year LRF of 2.3, 5.1 and 8.9%, respectively (p = 0.13). The 6-year DM rate was higher in patients with 3+ nodes versus 1-2+ nodes: 15.7% versus 7.4% (p = 0.02). Several subgroups had low 6-year LRF and DM rates, including T1/1+ node (0.8%/4.1% LRF/DM) and micrometastases (0%/5.8% LRF/DM). CONCLUSIONS: Patients with pT1-2pN1 represent a heterogeneous group with a wide range of LRF/DM rates. In particular, patients with pT1 tumors and 1 + LN, and patients with micrometastases, had low event rates. These groups would derive small absolute reductions in LRF and DM with addition of PMRT, underscoring the importance of patient selection for PMRT in pT1-2pN1 breast cancer.

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

PURPOSE: To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT). METHODS: This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS. RESULTS: Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS (p = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered (p = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61-69 Gy or ≥70 Gy (p = 0.001). CONCLUSIONS: Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.

Imaging of the axilla before preoperative chemotherapy: implications for postmastectomy radiation.

Postmastectomy radiation therapy (PMRT) improves breast cancer survival in many women with lymph node-positive disease who undergo surgery followed by adjuvant chemotherapy. The role of PMRT after women receive neoadjuvant chemotherapy (NAC) is less clear. The available data suggest that clinical extent of disease at presentation before NAC, pathologic residual disease (especially pathologically involved lymph nodes) after NAC, and response to NAC are key prognostic factors for locoregional recurrence. Therefore, accurate axillary staging before the initiation of NAC and assessment of response to chemotherapy are critically important. Here, the authors review the literature addressing the radiotherapy management of patients with breast cancer who received NAC and underwent mastectomy with a special focus on the imaging modalities used to assess axillary lymph node status.

Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists.

OBJECTIVES: For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. METHODS: From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. RESULTS: A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. CONCLUSIONS: HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns. CONCLUSIONS: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI.

Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy.

PURPOSE: Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. METHODS AND MATERIALS: Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. RESULTS: Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P = .001); and those with AF saw worse disease progression (hazard ratio, 1.54; P = .03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. CONCLUSIONS: Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.

Advances in Radiotherapy for Breast Cancer.

Breast cancer is the most prevalent cancer in women, and the second leading cause of cancer death in women in the United States. Radiation therapy is an important component in the multimodal management of breast cancer, including early stage and locally advanced breast cancers, as well as metastatic cases. Breast cancer radiation therapy has seen significant advancements over the past 20 years. This article discusses the latest advances in the radiotherapeutic management of breast cancer, especially focusing on the technological advances in radiation treatment planning and techniques that have exploited the understanding of radiation biology.

Not Too Little, Not Too Much: Optimizing More Versus Less Locoregional Treatment for Older Patients With Breast Cancer.

Although undertreatment of older women with aggressive breast cancers has been a concern for years, there is increasing recognition that some older women are overtreated, receiving therapies unlikely to improve survival or reduce morbidity. De-escalation of surgery may include breast-conserving surgery over mastectomy for appropriate candidates and omitting or reducing extent of axillary surgery. Appropriate patients to de-escalate surgery are those with early-stage breast cancer, favorable tumor characteristics, are clinically node-negative, and who may have other major health issues. De-escalation of radiation includes reducing treatment course length through hypofractionation and ultrahypofractionation regimens, reducing treatment volumes through partial breast irradiation, omission of radiation for select patients, and reducing radiation dose to normal tissues. Shared decision making, which aims to facilitate patients making decisions concordant with their values, can guide health care providers and patients through complicated decisions optimizing breast cancer care.

The Axillary Lateral Vessel Thoracic Junction Is Not an Organ at Risk for Breast Cancer-Related Lymphedema.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a treatment complication that significantly reduces patient quality of life. Regional nodal irradiation (RNI) may increase the risk of BCRL. Recently, a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) was identified as a potential organ at risk (OAR). Here, we set out to validate whether radiation dose to the ALTJ is associated with BCRL. METHODS AND MATERIALS: We identified patients with stage II-III breast cancer treated with adjuvant RNI from 2013 to 2018, excluding those with BCRL preradiation. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb >2.5 cm at any 1 encounter or ≥2 cm on ≥2 visits. All patients suspected of having BCRL at routine follow-up visits were referred to physical therapy for confirmation. The ALTJ was retrospectively contoured and dose metrics were collected. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. RESULTS: The study population included 378 patients with a median age of 53 years, median body mass index of 28.4 kg/m2, and median of 18 axillary nodes removed; 71% underwent mastectomy. Median follow-up was 70 months (interquartile range, 55-89.7 months). BCRL developed in 101 patients at a median of 18.9 months (interquartile range, 9.9-32.4 months), with a corresponding 5-year cumulative incidence BCRL of 25.8%. On multivariate analysis, none of the ALTJ metrics were associated with BCRL risk. Only increasing age, increasing body mass index, and increasing number of nodes were associated with a higher risk of developing BCRL. The 6-year locoregional recurrence rate was 3.2%, the axillary recurrence rate was 1.7%, and the isolated axillary recurrence rate was 0%. CONCLUSIONS: The ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL.

Quality and Safety Considerations in Intensity Modulated Radiation Therapy: An ASTRO Safety White Paper Update.

PURPOSE: This updated report on intensity modulated radiation therapy (IMRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology (ASTRO) addressing patient safety. Since the first white papers were published, IMRT went from widespread use to now being the main delivery technique for many treatment sites. IMRT enables higher radiation doses to be delivered to more precise targets while minimizing the dose to uninvolved normal tissue. Due to the associated complexity, IMRT requires additional planning and safety checks before treatment begins and, therefore, quality and safety considerations for this technique remain important areas of focus. METHODS AND MATERIALS: ASTRO convened an interdisciplinary task force to assess the original IMRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology, and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who select "strongly agree" or "agree" indicated consensus. CONCLUSIONS: This IMRT white paper primarily focuses on quality and safety processes in planning and delivery. Building on the prior version, this consensus paper incorporates revised and new guidance documents and technology updates. IMRT requires an interdisciplinary team-based approach, staffed by appropriately trained individuals as well as significant personnel resources, specialized technology, and implementation time. A comprehensive quality assurance program must be developed, using established guidance, to ensure IMRT is performed in a safe and effective manner. Patient safety in the delivery of IMRT is everyone's responsibility, and professional organizations, regulators, vendors, and end-users must work together to ensure the highest levels of safety.

Treatment Patterns and Outcomes for Patients with Ampullary Carcinoma Who Do Not Undergo Surgery.

Surgical resection is the standard of care for ampullary adenocarcinoma (AC). Many patients are ineligible due to comorbidities/advanced disease. Evidence for the optimal non-operative management of localized AC is lacking. We hypothesize that patients treated with chemotherapy (CT) and definitive radiation (DRT) will have superior survival (OS) compared to those treated with CT alone. We performed a retrospective review of the National Cancer Database from 2004 to 2017 to identify patients with non-metastatic AC and no surgical intervention. Patients were categorized as having received no treatment, palliative radiotherapy (PRT) alone, CT alone, CT + PRT, DRT alone, or CT + DRT. We utilized Kaplan-Meier analysis to determine OS and the log-rank test to compare survival curves. Among 2176 patients, treatment groups were: No treatment (71.2%), PRT alone (1.9%), CT alone (13.1%), CT + PRT (1.6%), DRT alone (2.4%), and CT + DRT (9.7%). One-year OS varied by treatment group, ranging from 35.1% (PRT alone) to 59.4% (CT + DRT). The one-year OS in a matched cohort was not significantly different between CT alone and CT + DRT (HR 0.87, 95% CI 0.69-1.10, p = 0.87). Most patients with non-metastatic AC not treated with surgery do not receive any treatment. There is no difference in one-year OS between those undergoing CT alone and CT + DRT.

Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment.

Radiation treatment (RT) is a mainstay treatment for many types of cancer. Recommendations for RT and the radiation plan are individualized to each patient, taking into consideration the patient's tumor pathology, staging, anatomy, and other clinical characteristics. Information on germline mutations and somatic tumor mutations is at present rarely used to guide specific clinical decisions in RT. Many genes, such as ATM, and BRCA1/2, have been identified in the laboratory to confer radiation sensitivity. However, our understanding of the clinical significance of mutations in these genes remains limited and, as individual mutations in such genes can be rare, their impact on tumor response and toxicity remains unclear. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN), provide limited guidance on how genetic results should be integrated into RT recommendations. With an increasing understanding of the molecular underpinning of radiation response, genomically-guided RT can inform decisions surrounding RT dose, volume, concurrent therapies, and even omission to further improve oncologic outcomes and reduce risks of toxicities. Here, we review existing evidence from laboratory, pre-clinical, and clinical studies with regard to how genetic alterations may affect radiosensitivity. We also summarize recent data from clinical trials and explore potential future directions to utilize genetic data to support clinical decision-making in developing a pathway toward personalized RT.