Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Consensus Quality Measures and Dose Constraints for Breast Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: Using evidence-based radiation therapy to direct care for patients with breast cancer is critical to standardize practice, improve safety, and optimize outcomes. To address this need, the Veterans Affairs (VA) National Radiation Oncology Program (NROP) established the VA Radiation Oncology Quality Surveillance Program to develop clinical quality measures (QMs). The VA NROP contracted with the American Society for Radiation Oncology to commission 5 Blue Ribbon Panels for breast, lung, prostate, rectal, and head and neck cancers. METHODS AND MATERIALS: The Breast Cancer Blue Ribbon Panel experts worked collaboratively with the NROP to develop consensus QMs for use throughout the VA system, establishing a set of QMs for patients in several areas, including consultation and work-up; simulation, treatment planning, and treatment; and follow-up care. As part of this initiative, consensus dose-volume histogram (DVH) constraints were outlined. RESULTS: In total, 36 QMs were established. Herein, we review the process used to develop QMs and final consensus QMs pertaining to all aspects of radiation patient care, as well as DVH constraints. CONCLUSIONS: The QMs and expert consensus DVH constraints are intended for ongoing quality surveillance within the VA system and centers providing community care for Veterans. They are also available for use by greater non-VA community measures of quality care for patients with breast cancer receiving radiation.

Mediators of Racial Disparities in Heart Dose Among Whole Breast Radiotherapy Patients.

BACKGROUND: Racial disparities in survival of patients with cancer motivate research to quantify treatment disparities and evaluate multilevel determinants. Previous research has not evaluated cardiac radiation dose in large cohorts of breast cancer patients by race nor examined potential causes or implications of dose disparities. METHODS: We used a statewide consortium database to consecutively sample 8750 women who received whole breast radiotherapy between 2012 and 2018. We generated laterality- and fractionation-specific models of mean heart dose. We generated patient- and facility-level models to estimate race-specific cardiac doses. We incorporated our data into models to estimate disparities in ischemic cardiac event development and death. All statistical tests were 2-sided. RESULTS: Black and Asian race independently predicted higher mean heart dose for most laterality-fractionation groups, with disparities of up to 0.42 Gy for Black women and 0.32 Gy for Asian women (left-sided disease and conventional fractionation: 2.13 Gy for Black women vs 1.71 Gy for White women, P < .001, 2-sided; left-sided disease and accelerated fractionation: 1.59 Gy for Asian women vs 1.27 Gy for White women, P = .002). Patient clustering within facilities explained 22%-30% of the variability in heart dose. The cardiac dose disparities translated to estimated excesses of up to 2.6 cardiac events and 1.3 deaths per 1000 Black women and 0.7 cardiac events and 0.3 deaths per 1000 Asian women vs White women. CONCLUSIONS: Depending on laterality and fractionation, Asian women and Black women experience higher cardiac doses than White women. This may translate into excess radiation-associated ischemic cardiac events and deaths. Solutions include addressing inequities in baseline cardiac risk factors and facility-level availability and use of radiation technologies.

Workplace Gender Inequity Is Driven by Broader Societal Inequity: A Qualitative Study of Senior Japanese and American Radiation Oncologists.

PURPOSE: Gender inequity in medicine harms society, and often originates in the context of broader societal discrimination. This study explores the experiences of older women in the radiation oncology specialty in Japan and the United States, with an emphasis on understanding how broader gender inequity affects career trajectory. Radiation oncology is an ideal setting to investigate cross-cultural physician gender equity issues, because few women enter the field despite fewer barriers (eg, frequent emergencies, evening/weekend hours, long procedures) that are commonly cited by women as deterrents in specialty selection. METHODS AND MATERIALS: Between 2012 and 2016, the authors interviewed 14 older women in radiation oncology (department chairs or full professors), with 6 from Japan and 8 from the United States. Multiple analysts identified themes to explore the impact of societal gender inequity on female radiation oncologists' careers. RESULTS: Five themes were identified: (1) childhood gender constructs affect career aspirations, (2) persistent sexism and gender-based workplace challenges affect women's careers, (3) gender inequity in the home affects women's careers, (4) non-gender-related factors intersect to affect women's career satisfaction, and (5) attaining gender equity appears to be even more challenging in Japan compared with the United States. CONCLUSIONS: Female radiation oncologists in 2 of the most technologically advanced countries report that gender discrimination across their lifespans substantially affects career success. Because gender inequality reflects societal injustice and negatively affects scientific progress and patient outcomes, future research should focus on global approaches to address professional and domestic gender constructs that impede women's career progress.

Identifying Equitable Screening Mammography Strategies for Black Women in the United States Using Simulation Modeling.

BACKGROUND: Screening mammography guidelines do not explicitly consider racial differences in breast cancer epidemiology, treatment, and survival. OBJECTIVE: To compare tradeoffs of screening strategies in Black women versus White women under current guidelines. DESIGN: An established model from the Cancer Intervention and Surveillance Modeling Network simulated screening outcomes using race-specific inputs for subtype distribution; breast density; mammography performance; age-, stage-, and subtype-specific treatment effects; and non-breast cancer mortality. SETTING: United States. PARTICIPANTS: A 1980 U.S. birth cohort of Black and White women. INTERVENTION: Screening strategies until age 74 years with varying initiation ages and intervals. MEASUREMENTS: Outcomes included benefits (life-years gained [LYG], breast cancer deaths averted, and mortality reduction), harms (mammographies, false positives, and overdiagnoses), and benefit-harm ratios (tradeoffs) by race. Efficiency (benefits per unit resource), mortality disparity reduction, and equity in tradeoffs were evaluated. Equitable strategies for Black women were defined as those with tradeoffs closest to benchmark values for screening White women biennially from ages 50 to 74 years. RESULTS: Biennial screening from ages 45 to 74 years was most efficient for Black women, whereas biennial screening from ages 40 to 74 years was most equitable. Initiating screening 10 years earlier in Black versus White women reduced Black-White mortality disparities by 57% with similar LYG per mammogram for both populations. Selection of the most equitable strategy was sensitive to assumptions about disparities in real-world treatment effectiveness: The less effective treatment was for Black women, the more intensively Black women could be screened before tradeoffs fell short of those experienced by White women. LIMITATION: Single model. CONCLUSION: Initiating biennial screening in Black women at age 40 years reduces breast cancer mortality disparities and yields benefit-harm ratios that are similar to tradeoffs of White women screened biennially from ages 50 to 74 years. PRIMARY FUNDING SOURCE: National Cancer Institute at the National Institutes of Health.

Use and Outcomes of SBRT for Early Stage NSCLC Without Pathologic Confirmation in the Veterans Health Care Administration.

PURPOSE: Stereotactic body radiation therapy (SBRT) use has increased among patients without pathologic confirmation (PC) of lung cancer. Empirical SBRT without PC raises concerns about variation in workup and patient selection, but national trends have not been well described. In this study, we assessed patterns of empirical SBRT use, workup, and causes of death among a large national non-small cell lung cancer (NSCLC) cohort. METHODS AND MATERIALS: We identified 2221 patients treated with SBRT for cT1-T2aN0M0 NSCLC in the Veterans Affairs health care system from 2008 to 2015. We reviewed their pretreatment workup and assessed associations between absence of PC and clinical and demographic factors. We compared causes of death between PC and non-PC groups and used Cox proportional hazards modeling to compare overall survival and lung cancer specific survival (LCSS) between these groups. RESULTS: Treatment without PC varied from 0% to 61% among Veterans Affairs medical centers, with at least 5 cases of stage I NSCLC. Overall, 14.9% of patients were treated without PC and 8.8% did not have a biopsy attempt. Ten percent of facilities were responsible for almost two-thirds (62%) of cases of treatment without PC. Of non-PC patients, 95.5% had positron emission tomography scans, 40.6% had biopsy procedures attempted, and 12.7% underwent endobronchial ultrasound. Non-PC patients were more likely to have cT1 tumors and live outside the histoplasmosis belt. Age, sex, smoking status, and Charlson comorbidity index were similar between groups. Lung cancer was the most common cause of death in both groups. Overall survival was similar between groups, whereas non-PC patients had better LCSS (hazard ratio = 0.77, P = .031). CONCLUSIONS: Empirical SBRT use varied widely among institutions and appropriate radiographic workup was consistently used in this national cohort. Future studies should investigate determinants of variation and reasons for higher LCSS among non-PC patients.

Recent Changes in the Patterns of Breast Cancer as a Proportion of All Deaths According to Race and Ethnicity.

BACKGROUND: Recent reports suggest that racial differences in breast cancer incidence rates have decreased. We examined whether these findings apply to breast cancer mortality while considering age, period, and cohort influences on both absolute and relative measures of breast cancer mortality. METHODS: Using publicly available datasets (CDC WONDER, Human Mortality Database), we developed an age-period-cohort model of breast cancer mortality and breast cancer deaths as a proportion of all deaths during 1968-2019 among all women and by 5 race/ethnicity groups with sufficient numbers for estimation: Hispanic (all races), American Indian/Alaska Native and Asian/Pacific Islanders (regardless of ethnicity), non-Hispanic Black, and non-Hispanic White. RESULTS: Initially increasing after 1968, age-adjusted breast cancer mortality rates have decreased among all racial/ethnic groups since 1988. The age-adjusted percent of all deaths due to breast cancer also has been declining for non-Hispanic White women since about 1990 while increasing or holding steady for other race/ethnic groups. In 2019, the age-adjusted percent of deaths due to breast cancer for women was highest for Asian/Pacific Islanders (5.6%) followed by non-Hispanic Black (4.5%), Hispanic (4.4%), non-Hispanic White (4.1%), and American Indian/Alaska Native women (2.6%). CONCLUSIONS: Breast cancer mortality disparities are now greater on both relative and absolute scales for non-Hispanic Black women, and using the relative scale for Asian/Pacific Islander and Hispanic women, compared with non-Hispanic White women for the first time in 50 years.

Why Racial Justice Matters in Radiation Oncology.

Recent events have reaffirmed that racism is a pervasive disease plaguing the United States and infiltrating the fabric of this nation. As health care professionals dedicated to understanding and alleviating disease, many radiation oncologists have failed to acknowledge how structural racism affects the health and well-being of the patients we aim to serve. The literature is full of descriptive statistics showing the higher incidence and mortality experienced by the Black population for health conditions ranging from infant mortality to infectious disease, including coronavirus disease 2019 (COVID-19). Acknowledgment that the root of health disparities experienced by Black people in this country are based in racism is essential to moving the nation and the field of radiation oncology forward. With this lens, a brief overview of structural and institutional racism shapes a discussion of what radiation oncologists and the organizations that represent them can do to address this scourge. As members of a technological field, we often harness the power of data to advance human health and approach challenging diseases with optimism that multidisciplinary effort can produce cure. A few principles to mitigate the longstanding issues of Black marginalization within the field have been recommended via the ATIP (Acknowledgment, Transparency, Intentionality, and rePresentation) and LEADS (Learn, Engage, Advocate, Defend, Support) approaches. However, additional introspection is encouraged. Just as individuals, practices, and organizations rallied to determine how best to address the issues related to the COVID-19 pandemic, the same investigational fervor must be applied to the issue of racism to combat this sinister and often deadly disease.

Association between PSA values and surveillance quality after prostate cancer surgery.

BACKGROUND: Although prostate-specific antigen (PSA) testing is used for prostate cancer detection and posttreatment surveillance, thresholds in these settings differ. The screening cutoff of 4.0 ng/mL may be inappropriately used during postsurgery surveillance, where 0.2 ng/mL is typically used, creating missed opportunities for effective salvage radiation treatment. We performed a study to determine whether guideline concordance with annual postoperative PSA surveillance increases when PSA values exceed 4 ng/mL, which represents a screening threshold that is not relevant after surgery. METHODS: We used US Veterans Health Administration data to perform a retrospective longitudinal cohort study of men diagnosed with nonmetastatic prostate cancer from 2005 to 2008 who underwent radical prostatectomy. We used logistic regression to examine the association between postoperative PSA levels and receipt of an annual PSA test. RESULTS: Among 10 400 men and 38 901 person-years of follow-up, annual guideline concordance decreased from 95% in year 1 to 79% in year 7. After adjustment, guideline concordance was lower for the youngest and oldest men, Black, and unmarried men. Guideline concordance significantly increased as PSA exceeded 4 ng/mL (adjusted odds ratio 2.20 PSA > 4-6 ng/mL vs PSA > 1-4 ng/mL, 95% confidence interval 1.20-4.03; P = .01). CONCLUSIONS: Guideline concordance with prostate cancer surveillance increased when PSA values exceeded 4 ng/mL, suggesting a screening threshold not relevant after prostate cancer surgery, where 0.2 ng/mL is considered treatment failure, is impacting cancer surveillance quality. Clarification of PSA thresholds for early detection vs cancer surveillance, as well as emphasizing adherence for younger and Black men, appears warranted.

Prostate Cancer Surveillance After Radiation Therapy in a National Delivery System.

Guideline concordance with PSA surveillance among veterans treated with definitive radiation therapy was generally high, but opportunities may exist to improve surveillance among select groups.

Gynecologic radiation oncology patients report unmet needs regarding sexual health communication with providers.

PURPOSE: Following radiation therapy (RT), women with gynecologic malignancies report high rates of sexual dysfunction, but little is known regarding sexual health communication between these patients and health-care providers. This study assessed these patients' beliefs/attitudes toward providers' sexual history taking. METHODS: Surveys were administered to women who presented for follow-up care for gynecologic cancers in an academic radiation oncology department. The surveys assessed patient sexual health beliefs and inquiry preferences. Sexual functioning was assessed using the Female Sexual Function Index (FSFI). Ordered logistic regressions were performed to assess for correlations between survey responses, FSFI, and demographic characteristics. RESULTS: Seventy-five subjects participated. Most (89.8%) had FSFI scores indicating sexual dysfunction. Most patients agreed that sexual function is an important component of overall health (78.7%) and that providers should inquire regularly (62.8%). Few (12.0%) reported embarrassment around provider discussions. Most (62.7%) preferred discussion with female providers, especially married patients (p = 0.03). Half (53.4%) agreed that sexual problems are an unavoidable part of aging, a view that was more common as education level decreased (p = 0.01). Most (62.7%) patients agreed that providers should regularly ask about their sexual history, with patients having significant differences in education level. Patients with low FSFI scores were less likely to report inquiry from their OB/Gyn (p = 0.03). CONCLUSIONS: Gynecologic cancer radiotherapy patients want to discuss sexual health, but report suboptimal provider inquiry. Patient views and experiences varied based on marital status, education level, and FSFI score. This work highlights the need for improved sexual health communication between cancer patients and providers.

Deformable image registration-based contour propagation yields clinically acceptable plans for MRI-based cervical cancer brachytherapy planning.

PURPOSE: To study the dosimetric impact of deformable image registration-based contour propagation on MRI-based cervical cancer brachytherapy planning. METHODS AND MATERIALS: High-risk clinical target volume (HRCTV) and organ-at-risk (OAR) contours were delineated on MR images of 10 patients who underwent ring and tandem brachytherapy. A second set of contours were propagated using a commercially available deformable registration algorithm. "Manual-contour" and "propagated-contour" plans were optimized to achieve a maximum dose to the most minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25 Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] + brachytherapy, respectively). Plans were compared using geometric and dosimetric (total dose [EQD2] EBRT + brachytherapy) parameters. RESULTS: The differences between the manual- and propagated-contour plans with respect to the HRCTV D90 and bladder, rectum, and sigmoid D2cc were not statistically significant (per-fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the manually contoured OARs by the propagated-contour plans ranging 98-107%, 95-105%, and 92-108% of the dose delivered by the manual-contour plans (max 90.4, 70.3, and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose in the propagated-contour plans was 97-103% of the dose in the manual-contour plans (maximum difference 2.92 Gy). Increased bladder filling resulted in increased bladder dose in manual- and propagated-contour plans. CONCLUSIONS: When deformable image registration-propagated contours are used for cervical brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual-contour plans and the doses delivered to the OARs are clinically acceptable, suggesting that our algorithm can replace manual contouring for appropriately selected cases that lack major interfractional anatomical changes.

MRI-Based Evaluation of the Vaginal Cuff in Brachytherapy Planning: Are We Missing the Target?

PURPOSE: Although recurrences and toxicity occur after vaginal cuff (VC) brachytherapy, little is known about dosimetry due to the inability to clearly visualize the VC on computed tomography (CT). T2-weighted (T2W) magnetic resonance imaging (MRI) is superior to CT in this setting, and we hypothesized that it could provide previously unascertainable dosimetric information. METHODS AND MATERIALS: In a cohort of 32 patients who underwent cylinder-based brachytherapy for endometrial cancer with available MR simulation images, the VC was retrospectively contoured on T2W images, and cases were replanned to treat the upper VC to a dose of 7 Gy/fraction prescribed to 5 mm. Relevant dose-volume parameters for the VC were calculated. RESULTS: T2W MRI identified significant underdosing not observed on CT or T1-weighted imaging. Over two-thirds (69%) of patients had at least 1 cm(3) of VC that received less than 75% of the prescription dose and half (50%) of patients had a least 1 cm(3) of VC that received less than 50% of the prescription dose. The mean minimum point dose to the VC was 2.4 Gy, or 34% of the intended prescription dose (range: 0.53-6.4 Gy). CONCLUSIONS: We identified previously unreported VC underdosing in over two-thirds of our patients, with most of these patients having volumes of undistended VC that received less than half of the prescription dose. The maximum dimension was along the craniocaudal axis in some patients or left-right/anterior-posterior axis in others, suggesting that suture material may be restricting access to the vaginal apex and that alternative applicators may be needed when the diameter of the apex is larger than the introitus. Additional follow-up will be needed to determine whether underdosing is associated with isolated VC failure or whether low failure rates across the cohort suggest that some patients are being exposed to excessive dose and unnecessary risk of toxicity.

Postmastectomy Radiotherapy After Neoadjuvant Chemotherapy: A Review of the Evidence.

Multiple randomized trials and their meta-analysis have demonstrated an overall survival benefit from postmastectomy radiotherapy (PMRT) in women with node-positive breast cancer. However, none of the patients treated in these trials received neoadjuvant chemotherapy, which is now an increasingly common approach. It is unclear how best to apply data from trials conducted in patients treated with adjuvant chemotherapy to this population. To illuminate these issues, this article first reviews the history of PMRT and the current indications for its use based on contemporary data. It focuses on the ways in which staging and outcomes differ for patients who undergo neoadjuvant chemotherapy before mastectomy (as compared with those who receive postoperative adjuvant therapy) and how pathologic features such as response to therapy are correlated with recurrence and survival outcomes. It highlights key information obtained from analysis of the pooled data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) prospective neoadjuvant chemotherapy trials B-18 and B-27 and separate retrospective single-institution studies; this includes the low risk of locoregional recurrence in early-stage patients in whom a pathologic complete response (pCR) was achieved after neoadjuvant chemotherapy without PMRT and the high risk of recurrence in patients with stage III disease, even in the setting of a pCR. It also discusses the ongoing NSABP B-51/Radiation Therapy Oncology Group 1304 and Alliance A011202 trials, which will provide information on whether PMRT can be omitted in patients who have a pathologic complete response (pCR) in the lymph nodes, and whether axillary lymph node dissection will improve recurrence rates compared with sentinel lymph node biopsy and radiotherapy in patients who do not achieve a pCR in the lymph nodes. Finally, it identifies directions for future research.