Screening for Financial Toxicity Among Patients with Cancer: A Systematic Review.

OBJECTIVE: Despite the pervasiveness and adverse impacts of financial toxicity (FT) in cancer care, there are no definitive measures for FT screening that have been widely integrated into clinical practice. The aim of this review is to evaluate current methods of assessing FT among patients with cancer and confirm factors associated with higher risk of FT. METHODS: A systematic review was performed according to PRISMA guidelines. We included peer-reviewed studies that cross-sectionally, longitudinally, or prospectively measured the self-reported financial impact of patients undergoing cancer care in the United States. RESULTS: Out of 1085 identified studies, 51 met final inclusion criteria. Outcomes evaluated included FT measures/tools, time and setting of screening, FT prevalence, and sociodemographic or clinical patient-level associated factors. Our findings demonstrate that there is wide variability in FT screening practices including in the timing (diagnosis vs treatment vs survivorship), setting (clinic-based, online, telephone/mail), utilized tools (21 unique tools, 7 previously validated), and interpretations of screening results (varying FT score cutoffs defining high vs. low FT). Younger age, lower income, lower education, non-white race, employment status change, advanced cancer stage, and systemic/radiation therapy, were among factors associated with worse FT across the studies. DISCUSSION: FT screening remains heterogenous within the United States. With the ever-escalating cost of cancer care, and the strong association between FT and poor patient outcomes, universal and routine FT screening is imperative in cancer care. Further research and multifaceted interventions identifying best practices for FT screening are needed.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

Out-of-Pocket Cost Modeling of Adjuvant Antiestrogen and Radiation Therapy After Lumpectomy for Early-Stage Breast Cancer Across Medicaid and Medicare Plans.

PURPOSE: The optimal adjuvant therapy (antiestrogen therapy [ET] + radiation therapy or ET alone, or in some reports radiation therapy alone) in older women with early-stage breast cancer has been highly debated. However, granular details on the role of insurance in the out-of-pocket cost for patients receiving ET with or without radiation therapy are lacking. This project disaggregates out-of-pocket costs by insurance plans to increase treatment cost transparency. METHODS AND MATERIALS: Several radiation therapy schedules are accepted standards as per the National Comprehensive Cancer Network guidelines. For our financial estimate model, we used the 5-fraction and 15-fraction radiation therapy and ET prescribed over a 5-year duration. The total aggregate out-of-pocket costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plans. The model assumes a Medicare- and/or Medicaid-eligible patient ≥70 years of age with node-negative, early-stage estrogen-receptor-positive breast cancer. Patient out-of-pocket costs were estimated from publicly available insurance data from plan-specific benefit coverage materials using a 5-year time horizon. RESULTS: Original Medicare beneficiaries face a total out-of-pocket treatment charge of $2738.52 for ET alone, $2221.26 for 5-fraction radiation therapy alone, $2573.92 for 15-fraction radiation therapy alone, $3361.26 for combined ET+ 5-fraction radiation therapy, and $3713.92 for combined ET + 15-fraction radiation therapy. Medigap Plan G beneficiaries have an out-of-pocket charge of $1130.00 with radiation therapy alone and face an out-of-pocket of $2270.00 for ET alone and combined ET+ radiation therapy. For Medicaid beneficiaries, all treatments approved by Medicaid are covered without limit, resulting in no out-of-pocket expense for either adjuvant treatment option. CONCLUSIONS: This model (based on actual cost estimates per insurance plan rather than claims data), by estimating expenses within Medicare and Medicaid plans, provides a level of transparency to patient cost. With knowledge of the costs borne by patients themselves, treatment decisions informed by patients' individual priorities and preferences may be further enhanced.

Financial Toxicity in Breast Reconstruction: The Role of the Surgeon-Patient Cost-of-Care Discussion.

The financial burden of breast cancer treatment and reconstruction is a significant concern for patients. Patient desire for preoperative cost-of-care counseling while navigating the reconstructive process remains unknown. A cross-sectional survey of women from the Love Research Army was conducted. An electronic survey was distributed to women over 18 years of age and at least 1 year after postmastectomy breast reconstruction. Descriptive statistics and multivariable modeling were used to determine desire for and occurrence of cost-of-care discussions, and factors associated with preference for such discussions. Secondary outcomes included the association of financial toxicity with desire for cost discussions. Among 839 women who responded, 620 women (74.1%) did not speak to their plastic surgeon and 480 (57.4%) did not speak to a staff member regarding costs of breast reconstruction. Of the 550 women who reported it would have been helpful to discuss costs, 315 (57.3%) were not engaged in a financial conversation initiated by a health care provider. A greater proportion of women who reported financial toxicity, compared to those who did not, would have preferred to discuss costs with their plastic surgeon (65.2% vs. 43.5%, p < 0.001) or a staff member (75.5% vs. 59.3%, p < 0.001). Among women with financial toxicity, those who had some form of insurance (private, Medicaid, Medicare, "other") were significantly more likely to prefer a cost-of-care discussion ( p < 0.001, p = 0.02, p = 0.05, p = 0.01). Financial discussions about the potential costs of breast reconstruction seldom occurred in this national cohort. Given the reported preference and unmet need for financial discussions by a majority of women, better cost transparency and communication is needed.

Are We Missing Acute Toxicities Associated With Hypofractionated Breast Irradiation? A Report From a Large Multicenter Cohort Study.

PURPOSE: The efficacy and long-term safety of hypofractionated whole breast irradiation (HF-WBI) have been established through multiple randomized trials, yet data about acute toxicities remain more limited. Since 2013, our group has prospectively collected acute toxicity data from weekly treatment evaluations and additional assessment after completion. In 2016, we intentionally shifted the posttreatment assessment follow-up visit from 1 month to 2 weeks to evaluate for missed acute toxicity occurring in that immediate posttreatment window. Here, we report whether 2-week follow-up has resulted in increased detection of acute toxicities compared with 4-week follow-up. METHODS AND MATERIALS: We prospectively compared acute toxicity for patients treated with HF-WBI between January 1, 2013, and August 31, 2015 (4 week follow-up cohort) to patients treated between January 1, 2016, and August 31, 2018 (2 week follow-up cohort). Analyses included a multivariable model that adjusted for other factors known to correlate with toxicity. We prospectively defined acute toxicity as maximum breast pain (moderate or severe rating) and/or occurrence of moist desquamation reported 7 days before the completion of radiation therapy (RT) until 42 days after completion. RESULTS: A total of 2689 patients who received postlumpectomy radiation and boost were analyzed; 1862 patients in the 2-week follow-up cohort and 827 in the 4-week follow-up cohort. All acute toxicity measures assessed were statistically similar between follow-up cohorts when compared in an unadjusted fashion. Overall acute composite toxicity was 26.4% and 27.7% for patients in the 4-week follow-up and 2-week follow-up cohorts, respectively. Overall acute composite toxicity remained similar between follow-up cohorts in a multivariable, adjusted model and was significantly related to patient's age, body mass index, smoking status, and treatment technique (intensity-modulated RT vs 3-dimensional conformal radiation therapy) but not follow-up cohort. CONCLUSIONS: An earlier posttreatment follow-up for HF-WBI patients did not reveal a significant increased incidence of acute toxicities at 2 weeks compared with 4 weeks. This study provides physicians and patients with additional data on the safety and tolerability of HF-WBI for early stage breast cancer.

Prehabilitation in radiation therapy: a scoping review.

PURPOSE/OBJECTIVES: Radiation therapy (RT) is a central component of cancer treatment with survival and long-term quality-of-life benefits across a spectrum of oncologic diagnoses. However, RT has been associated with varying levels of fatigue, pain, weight loss, and changes in mental health both during and post-treatment. Prehabilitation aims to optimize health prior to anti-neoplastic therapy in order to reduce side effects, increase adherence to treatment, expedite post-treatment recovery, and improve long-term outcomes. Though prehabilitation has been studied in those undergoing cancer-related surgery, literature on prehabilitation in individuals undergoing RT has not been comprehensively explored. Thus, this scoping review aims to summarize the existing literature focused on prehabilitation interventions for patients receiving RT. MATERIALS/METHODS: The PRISMA-ScR checklist for conducting scoping reviews was adopted to identify and evaluate studies investigating the efficacy of prehabilitation before and during RT for cancer over the past 21 years (10/2002-10/2022). A search of prehabilitation and RT was performed to identify studies investigating prehabilitation interventions in adult cancer patients undergoing RT. RESULTS: A total of 30 articles met inclusion criteria, yielding 3657 total participants. Eighteen (60%) studies were randomized controlled trials (RCTs) with sample sizes ranging from 21 to 221. The most commonly studied populations were patients with head and neck cancer, followed by rectal, breast, and lung cancer. A majority (80%) of studies evaluated one prehabilitation intervention (i.e., unimodal). Targeted physical exercises were the most common intervention, followed by general physical exercises and technology/apps. Adherence/feasibility was the most common primary outcome, representing 30% of studies. All studies reported data on sex, and 5 (17%) reported data on race and/or ethnicity. CONCLUSIONS: Prehabilitation interventions have been successfully implemented in patients with cancer undergoing surgical treatment. Based on limited current literature, prehabilitation appears to have a promising effect in reducing morbidity in adult cancer patients requiring RT. Though our review identified many RCTs, they were frequently small sample trials with primary outcomes focused on feasibility, rather than functional status or quality of life. Thus, there is a need for adequately powered, randomized controlled intervention trials to investigate the efficacy of prehabilitation and maximize the treatment outcomes for patients undergoing RT.

Out-of-Pocket Cost Modeling of Adjuvant Radiation Therapy Duration in Standard-of-Care Early Stage Breast Cancer Treatment Across Medicaid and Medicare Plans.

PURPOSE: For early stage breast cancer (BC), the choice of radiation therapy duration (1 vs 3 weeks) is highly debated. Cost and financial toxicity are major concerns that patients with BC face. Nonetheless, there remain limited discussions providing granular details of the role of insurance in the aggregate cost of 1 week versus 3 weeks of radiation therapy for patients. This project aims to disaggregate costs by plan to increase transparency of out-of-pocket (OOP) cost estimates in radiation therapy. METHODS AND MATERIALS: Treatment procedures were determined through the National Comprehensive Cancer Network guidelines. OOP treatment costs, deductibles, and copays/coinsurance were calculated by using Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D prescription plans. The medicare.gov, medicaid.oh.gov, aarpmedicareplans.com, and the physician fee schedule from cms.gov were used to determine costs by treatment. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting. One-week radiation therapy was defined as 5 fractions without boost, and 3-week radiation therapy was defined as 15 fractions without boost. RESULTS: Medicare beneficiaries with Original Medicare coverage face an OOP treatment charge of $649.24 for 1 week of radiation therapy and $1006.20 for 3 weeks of radiation therapy. Assuming the deductible is met postlumpectomy, Medigap Plan G beneficiaries are faced with no additional charges for both lengths of radiation therapy. Similarly for Medicaid beneficiaries (assuming treatment is approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense. CONCLUSIONS: Considerations of 1 and 3 weeks of radiation therapy for postlumpectomy early-stage BC are often dependent on cancer characteristics and patient preferences. This model (based on actual cost estimates per insurance plan rather than claims data) compares OOP costs across Medicaid and Medicare plans, which more holistically informs providers and patients in radiation therapy duration decision making.

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.

Racial and Ethnic Differences in Long-Term Adverse Radiation Therapy Effects Among Breast Cancer Survivors.

PURPOSE: Breast and skin changes are underrecognized side effects of radiation therapy for breast cancer, which may have long-term implications for quality of life (QOL). Racial and ethnic disparities in breast cancer outcomes, including long-term QOL differences after breast radiation therapy, are poorly understood. METHODS AND MATERIALS: We conducted a cross-sectional survey study of patients from the Texas Cancer Registry who received diagnoses of stage 0-II breast cancer from 2009 to 2014 and treated with lumpectomy and radiation therapy; 2770 patients were sampled and 631 responded (23%). The BREAST-Q Adverse Effects of Radiation overall score and subindices measured the effect of radiation therapy on breast tissue. Multivariable logistic regression evaluated associations of demographic and treatment characteristics with outcomes. RESULTS: The median age was 57 years (IQR, 48-65), median time from diagnosis to survey response 9 years (IQR, 7-10), and the cohort included 62 Asian American or Pacific Islander (9.8%), 11 American Indian or Alaskan Native (AIAN) (1.7%), 161 Black (25.5%), 144 Hispanic (22.8%), and 253 White (40.1%) patients. Mean BREAST-Q Adverse Effects of Radiation score was worse for AIAN patients (-22.2; 95% CI, -39.9 to -4.6; P = .01), Black patients (-10.8; 95% CI, -16.1 to -5.5; P < .001), and Hispanic patients (-7.8; 95% CI, -13.0 to -2.5; P = .004) compared with White patients, age <50 compared with ≥65 (effect size -8.6; 95% CI, -14.0 to -3.2; P = .002), less than a college education (-5.8; 95% CI, -10.0 to -1.6; P = .01), bra cup size of D/E versus A/B (-5.3; 95% CI, -9.9 to -0.65; P = .03), and current smokers (-11.3; 95% CI, -18.3 to -4.2; P = .002). AIAN, Black, and Hispanic patients reported worse changes in skin pigmentation, telangiectasias, dryness, soreness, and/or irritation compared with White patients. CONCLUSIONS: AIAN, Black, and Hispanic patients reported substantially worse long-term breast and skin QOL outcomes after radiation therapy. Additional work is needed to understand these differences and how to alleviate them.

Pectoralis Muscle Dosimetry and Posttreatment Rehabilitation Utilization for Patients With Early-Stage Breast Cancer.

PURPOSE: Up to 50% of women treated for localized breast cancer will experience some degree of arm or shoulder morbidity. Although radiation is thought to contribute to this morbidity, the mechanism remains unclear. Prior studies have shown biologic and radiographic changes in the pectoralis muscles after radiation. This study thus aimed to investigate the relationship between radiation to the pectoralis muscles and referrals for rehabilitation services posttreatment for arm and shoulder morbidity. METHODS AND MATERIALS: A retrospective 1:1 matched case-control study was conducted for patients with breast cancer who were and were not referred for breast or shoulder rehabilitation services between 2014 and 2019 at a single academic institution. Patients were included if they had a lumpectomy and adjuvant radiation. Patients who underwent an axillary lymph node dissection were excluded. Cohorts were matched based on age, axillary surgery, and use of radiation boost. Muscle doses were converted to equivalent dose in 2 Gy fractions assuming an α:ß ratio of 2.5 and were compared between the 2 groups. RESULTS: In our cohort of 50 patients of a median age 60 years (interquartile range, 53-68 years), 36 patients (72%) underwent a sentinel lymph node biopsy in addition to a lumpectomy. Although pectoralis muscle doses were generally higher in those receiving rehabilitation services, this was not statistically significant. Pectoralis major V20-40 Gy reached borderline significance, as did pectoralis major mean dose (17.69 vs 20.89 Gy; P = .06). CONCLUSIONS: In this limited cohort of patients, we could not definitively conclude a relationship between pectoralis muscle doses and use of rehabilitation services. Given the borderline significant findings, this should be further investigated in a larger cohort.

Can I Leave? Perspectives on Parental Leave and Parenthood in Medical Training Among Program Directors and Trainees in Oncologic Specialties.

Purpose: Peak fertility commonly occurs during medical training, and delaying parenthood can complicate pregnancies. Trainee parental leave policies are varied and lack transparency. Research on the impacts of parenthood on trainee education is limited. Methods: A Qualtrics-based survey was distributed via e-mail/social media to program directors (PDs) within oncologic specialties with a request to forward a parallel survey to trainees. Questions assessed awareness of parental leave policies, supportiveness of parenthood, and impacts on trainee education. Statistical analyses included descriptive frequencies and bivariable comparisons by key groups. Results: A total of 195 PDs and 286 trainees responded. Twelve percent and 29% of PDs were unsure of maternity/paternity leave options, respectively. PDs felt they were more supportive of trainee parenthood than trainees perceived they were. Thirty-nine percent of nonparent trainees (NPTs) would have children already if not in medicine, and >80% of women trainees were concerned about declining fertility. Perceived impacts of parenthood on trainee overall education and academic productivity were more negative for women trainees when rated by PDs and NPTs; however, men/women parents self-reported equal impacts. Leave burden was perceived as higher for women trainees. Conclusions: A significant portion of PDs lack awareness of parental leave policies, highlighting needs for increased transparency. Trainees' perception of PD support for parenthood is less than PD self-reported support. Alongside significant rates of delayed parenthood and fertility concerns, this poses a problem for trainees seeking to start a family, particularly women who are perceived more negatively. Further work is needed to create a supportive culture for trainee parenthood.

The Effect of Wire Versus Magnetic Seed Localization on Lumpectomy Cavity Size.

PURPOSE: Our purpose was to assess whether an association exists between surgical localization technique and lumpectomy cavity size on radiation therapy planning computed tomography (CT) scan. METHODS AND MATERIALS: A single-institution retrospective review was conducted of women undergoing breast conserving surgery with wire or magnetic seed guided lumpectomy followed by adjuvant radiation therapy from 2018 to 2021. Patients of a surgeon only performing 1 localization technique or undergoing bracketed localization were excluded. The primary outcome was lumpectomy cavity size on simulation CT. Confounding due to imbalance in patient and tumor factors was addressed with overlap weights derived from a propensity score analysis and used in a weighted multivariable analysis. Secondary outcomes included positive margins, total pathologic volume, boost delivery, and boost modality. RESULTS: Of 617 women who received lumpectomy during the study period, 387 were included in final analysis. Tumors of patients undergoing seed localization were more likely unifocal, assessable by ultrasound, and smaller. Seed use rates ranged from 27.7% to 70.7% per surgeon. There was no difference in positive margins (6.4 vs 5.4%, P = .79) or second surgeries (9.4 vs 8.1%, P = .79) between groups. Close margin rates were similar for ductal carcinoma in situ (P = .35) and invasive carcinoma (P = .97). In unadjusted bivariable analyses, wire localization was associated with larger total pathology volume (P = .004), but localization technique showed no association with CT cavity volume (P = .15). After adjusting for potentially confounding variables, multivariable analysis failed to show an association between localization technique and either CT cavity (P = .35) or total path volume (P = .08). There was no difference in indicated-boost delivery (P = .15) or electron boost (P = .14) by localization technique. CONCLUSIONS: There was no significant difference in CT cavity size by localization technique, suggesting choice between surgical techniques does not impede radiation therapy boost delivery.

Attributions and perpetrators of incivility in academic surgery.

Purpose: Although incivility has been described in other specialties, little is known about the attributes and perpetrators of it in academic surgery. The goal of this study was to identify attributes and commonly associated perpetrators of incivility experienced by trainees and faculty at academic surgery programs in the U.S. Methods: A web-based survey including the Workplace Incivility Scale (WIS) and questions regarding attributions and perpetrators of incivility was sent to trainees and faculty at academic institutions across the U.S. In addition to descriptive statistics, multivariable regression models were built to determine the impact of perpetrator type and number on overall incivility scores. Results: We received 367 of 2,661 (13.8%) responses. Top three reasons for incivility were surgery hierarchy (50.1%), respondent's gender (33.8%) and intergenerational differences (28.1%). Faculty (58.6%), patients (36.8%), and nursing staff (31.9%) were the most reported parties responsible for incivility. Female surgeons reported experiencing incivility more frequently from all three top responsible parties (i.e., faculty, patients, and nurses) when compared to other gender identities. Additionally, those who reported faculty (ß = 0.61, 95%CI 0.39-0.82) or nurses (ß = 0.23, 95%CI 0.009-0.45) as perpetrators of incivility reported an increase in overall incivility scores. Conclusions: Incivility in surgery is frequently attributed to surgery hierarchy, gender, and intergenerational differences. Surgical trainees and faculty reported that faculty, patients, and nurses were the most commonly identified as responsible for uncivil events in the surgical workforce. Exposure to a greater variety of perpetrators of incivility increases overall levels of incivility, emphasizing the importance of eliminating incivility from all sources. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-023-00129-1.

When Headlines Harm Patients With Cancer.

This Viewpoint discusses journalists' responsibility to report study results objectively, without dramatic headlines, to avoid hindering patients' decision-making about treatments.

Optimizing Informed Consent in Cancer Clinical Trials.

The concept of informed consent has evolved considerably over the course of the 20th century, leading to its establishment as a foundational ethical principle for the conduct of biomedical research in the United States. Even though it is now a highly regulated part of cancer research, the process of obtaining informed consent is often impeded by systemic, clinician, and patient factors that require both small- and large-scale intervention. New challenges and considerations continue to emerge due to innovations in clinical trial design, increases in utilization of genomic sequencing, and advances in genomic editing and artificial intelligence. We present a review of the history, policy, pragmatic challenges, and evolving role of the central ethical tenet of informed consent in clinical trials.

Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial.

Importance: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments. Objective: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival. Design, Setting, and Participants: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023. Exposure: Receipt of RNI (targeting at least the supraclavicular region). Main Outcome(s) and Measure(s): Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk. Results: Of 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P = .87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P = .16). Conclusions and Relevance: In this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.