State of the Science of Scale-Up of Cancer Prevention and Early Detection Interventions in Low- and Middle-Income Countries: A Scoping Review.

PURPOSE: Cancer deaths in low- and middle-income countries (LMICs) will nearly double by 2040. Available evidence-based interventions (EBIs) for cancer prevention and early detection can reduce cancer-related mortality, yet there is a lack of evidence on effectively scaling these EBIs in LMIC settings. METHODS: We conducted a scoping review to identify published literature from six databases between 2012 and 2022 that described efforts for scaling cancer prevention and early detection EBIs in LMICs. Included studies met one of two definitions of scale-up: (1) deliberate efforts to increase the impact of effective intervention to benefit more people or (2) an intervention shown to be efficacious on a small scale expanded under real-world conditions to reach a greater proportion of eligible population. Study characteristics, including EBIs, implementation strategies, and outcomes used, were summarized using frameworks from the field of implementation science. RESULTS: This search yielded 3,076 abstracts, with 24 studies eligible for inclusion. Included studies focused on a number of cancer sites including cervical (67%), breast (13%), breast and cervical (13%), liver (4%), and colon (4%). Commonly reported scale-up strategies included developing stakeholder inter-relationships, training and education, and changing infrastructure. Barriers to scale-up were reported at individual, health facility, and community levels. Few studies reported applying conceptual frameworks to guide strategy selection and evaluation. CONCLUSION: Although there were relatively few published reports, this scoping review offers insight into the approaches used by LMICs to scale up cancer EBIs, including common strategies and barriers. More importantly, it illustrates the urgent need to fill gaps in research to guide best practices for bringing the implementation of cancer EBIs to scale in LMICs.

Role of sex in lung cancer risk prediction based on single low-dose chest computed tomography.

A validated open-source deep-learning algorithm called Sybil can accurately predict long-term lung cancer risk from a single low-dose chest computed tomography (LDCT). However, Sybil was trained on a majority-male cohort. Use of artificial intelligence algorithms trained on imbalanced cohorts may lead to inequitable outcomes in real-world settings. We aimed to study whether Sybil predicts lung cancer risk equally regardless of sex. We analyzed 10,573 LDCTs from 6127 consecutive lung cancer screening participants across a health system between 2015 and 2021. Sybil achieved AUCs of 0.89 (95% CI: 0.85-0.93) for females and 0.89 (95% CI: 0.85-0.94) for males at 1 year, p = 0.92. At 6 years, the AUC was 0.87 (95% CI: 0.83-0.93) for females and 0.79 (95% CI: 0.72-0.86) for males, p = 0.01. In conclusion, Sybil can accurately predict future lung cancer risk in females and males in a real-world setting and performs better in females than in males for predicting 6-year lung cancer risk.

Inequities in referrals to a breast cancer risk assessment and prevention clinic: a mixed methods study.

BACKGROUND: Inequitable access to personalized breast cancer screening and prevention may compound racial and ethnic disparities in outcomes. The Breast Cancer Personalized Risk Assessment, Education and Prevention (B-PREP) program, located within the Brigham and Women's Hospital (BWH) Comprehensive Breast Health Center (BHC), provides care to patients at high risk for developing breast cancer. We sought to characterize the differences between BWH primary care patients referred specifically to B-PREP for risk evaluation and those referred to the BHC for benign breast conditions. Through interviews with primary care clinicians, we sought to explore contributors to potentially inequitable B-PREP referral patterns. METHODS: We used electronic health record data and the B-PREP clinical database to identify patients referred by primary care clinicians to the BHC or B-PREP between 2017 and 2020. We examined associations with likelihood of referral to B-PREP for risk assessment. Semi-structured interviews were conducted with nine primary care clinicians from six clinics to explore referral patterns. RESULTS: Of 1789 patients, 78.0% were referred for benign breast conditions, and 21.5% for risk assessment. In multivariable analyses, Black individuals were less likely to be referred for risk than for benign conditions (OR 0.38, 95% CI:0.23-0.63) as were those with Medicaid/Medicare (OR 0.72, 95% CI:0.53-0.98; OR 0.52, 95% CI:0.27-0.99) and those whose preferred language was not English (OR 0.26, 95% CI:0.12-0.57). Interviewed clinicians described inconsistent approaches to risk assessment and variable B-PREP awareness. CONCLUSIONS: In this single-site evaluation, among individuals referred by primary care clinicians for specialized breast care, Black, publicly-insured patients, and those whose preferred language was not English were less likely to be referred for risk assessment. Larger studies are needed to confirm these findings. Interventions to standardize breast cancer risk assessment in primary care may improve equity.

Patients' experiences undergoing breast evaluation in Rwanda's Women's Cancer Early Detection Program.

PURPOSE: There is urgent need for interventions to facilitate earlier diagnosis of breast cancer in low- and middle-income countries where mammography screening is not widely available. Understanding patients' experiences with early detection efforts, whether they are ultimately diagnosed with cancer or benign disease, is critical to optimize interventions and maximize community engagement. We sought to understand the experiences of patients undergoing breast evaluation in Rwanda's Women's Cancer Early Detection Program (WCEDP). METHODS: We conducted in-person semi-structured interviews with 30 patients in two districts of Rwanda participating in the WCEDP. Patients represented a range of ages and both benign and malignant diagnoses. Interviews were recorded, transcribed, translated, and thematically analyzed. RESULTS: Participants identified facilitators and barriers of timely care along the breast evaluation pathway. Community awareness initiatives were facilitators to care-seeking, while persistent myths and stigma about cancer were barriers. Participants valued clear clinician-patient communication and emotional support from clinicians and peers. Poverty was a major barrier for participants who described difficulty paying for transport, insurance premiums, and other direct and indirect costs of hospital referrals in particular. COVID-19 lockdowns caused delays for referred patients. Although false-positive clinical breast exams conferred financial and emotional burdens, participants nonetheless voiced appreciation for their experience and felt empowered to monitor their own breast health and share knowledge with others. CONCLUSION: Rwandan women experienced both benefits and burdens as they underwent breast evaluation. Enthusiasm for participation was not reduced by the experience of a false-positive result. Reducing financial, logistical and emotional burdens of the breast diagnostic pathway through patient navigation, peer support and decentralization of diagnostic services could improve patients' experience.

Implementation research: including breast examinations in a cervical cancer screening programme, Rwanda.

Objective: To evaluate whether integrating breast and cervical cancer screening in Rwanda's Women's Cancer Early Detection Program led to early breast cancer diagnoses in asymptomatic women. Methods: Launched in three districts in 2018-2019, the early detection programme offered clinical breast examination screening for all women receiving cervical cancer screening, and diagnostic breast examination for women with breast cancer symptoms. Women with abnormal breast examinations were referred to district hospitals and then to referral hospitals if needed. We examined how often clinics were held, patient volumes and number of referrals. We also examined intervals between referrals and visits to the next care level and, among women diagnosed with cancer, their initial reasons for seeking care. Findings: Health centres held clinics > 68% of the weeks. Overall, 9763 women received cervical cancer screening and clinical breast examination and 7616 received breast examination alone. Of 585 women referred from health centres, 436 (74.5%) visited the district hospital after a median of 9 days (interquartile range, IQR: 3-19). Of 200 women referred to referral hospitals, 179 (89.5%) attended after a median of 11 days (IQR: 4-18). Of 29 women diagnosed with breast cancer, 19 were ≥ 50 years and 23 had stage III or stage IV disease. All women with breast cancer whose reasons for seeking care were known (23 women) had experienced breast cancer symptoms. Conclusion: In the short-term, integrating clinical breast examination with cervical cancer screening was not associated with detection of early-stage breast cancer among asymptomatic women. Priority should be given to encouraging women to seek timely care for symptoms.

Cascade Analysis for Women Presenting With Breast Concerns to a Zonal Hospital in Mwanza, Tanzania.

PURPOSE: In Tanzania, high breast cancer mortality can be attributed to delays in diagnosis and treatment initiation. We adapted the cascade analysis method to depict sequential steps along the breast cancer care pathway in a tertiary hospital in Mwanza, to identify where correction of loss to attrition would have the biggest impact on improving outcomes. METHODS: This prospective cohort included adult women presenting with breast concerns between February 2020 and January 2022. Five cascade steps beginning with patients' initial clinical breast assessment (CBA) through cancer treatment were identified: (1) CBA, (2) ordering diagnostic test(s), (3) completion of diagnostic test(s), (4) receipt of final diagnosis, and (5) initiating cancer treatment. RESULTS: Overall, 721 eligible women with a median age of 42.8 years (IQR, 32.5-55.0) were included. Median time from presentation to treatment initiation was 35 days (IQR, 20-63). For step 1, 39.1% (n = 282) of patients were diagnosed with a benign concern and removed from the cascade. Completion rates for steps 2-4 were 95.0%, 90.2%, and 91.0, respectively. There were 156 (45.6%) patients diagnosed with breast cancer, and for step 5, 71.2% of patients initiated cancer treatment. In steps 2, 3, 4, and 5, there was a loss of 22, 41, 34, and 45 patients, respectively. If loss was eliminated at steps 2, 3, 4, or 5, an additional 6, 12, 11, or 45 patients, respectively, would have completed the pathway. CONCLUSION: Initiating cancer treatment was identified as the step with the biggest loss and, if remedied, would have the biggest impact on improving breast cancer outcomes at Bugando Medical Centre. These results will inform future programs focused on reducing overall loss in the system and supporting patients with breast cancer.

Impact of contraceptive coverage policies on contraceptive use and risky sexual behavior among adolescent girls in the USA.

OBJECTIVE: This study used representative data to examine the impact of changes in contraceptive coverage policies (contraceptive insurance mandates and pharmacy access to emergency contraception) on contraceptive use and risky sexual behavior among adolescent girls. STUDY DESIGN: Using 2003-17 Youth Risk Behavior Survey data on 116 180 adolescent girls from 34 states, we conducted difference-in-differences models to examine changes in contraceptive use and unprotected sexual intercourse with the implementation of contraceptive coverage policies. We also tested interactions between age and pharmacy access to emergency contraception. RESULTS: Findings indicate that contraceptive insurance mandates and pharmacy access to emergency contraception were not associated with changes in contraceptive use or unprotected sexual intercourse among adolescent girls, although some changes were observed in specific age groups. Despite this, our results show an overall increase in reported use of birth control pills and longer-acting methods from 2003 through 2017. CONCLUSIONS: Using representative data, this study lends support to existing evidence that increased access to emergency contraception does not impact contraceptive method used or unprotected sexual intercourse among adolescent girls. The results underscore the need for expanding access to a wide range of contraceptive options for adolescents, with a focus on safer and more effective longer-acting methods.

Screening MRI Does Not Increase Cancer Detection or Result in an Earlier Stage at Diagnosis for Patients with High-Risk Breast Lesions: A Propensity Score Analysis.

BACKGROUND: Guidelines recommend consideration of screening MRI for patients with high-risk breast lesions (HRLs), acknowledging limited data for this moderate-risk population. METHODS: This study identified patients with atypical ductal/lobular hyperplasia (ADH/ALH), lobular carcinoma in situ, (LCIS) or both evaluated at our high-risk clinic. Patients were categorized as having received screening mammography (MMG) alone vs. MMG and breast MRI (MMG+MRI). Inverse probability weighting based on propensity scores (PS) representing likelihood of MRI use was applied to Kaplan-Meier and Cox regression analyses to determine cancer detection and biopsy rates by screening group. RESULTS: Among 908 eligible patients, 699 (77%) patients with available follow-up data were analyzed (542 with ADH/ALH and 157 with LCIS). Of the 699 patients, 540 (77%) received MMG alone, and 159 (23%) received MMG + MRI. The median follow-up period was 25 months, during which a median of two MRIs were performed. After PS-weighting, the characteristics of each screening group were well-balanced with respect to age, race, body mass index (BMI), menopausal status, breast density, family history, HRL type, and chemoprevention use. The 4 year breast cancer detection rate was 3.6% with both MMG alone and MMG+MRI (p = 0.89). The breast biopsy rates were significantly higher with MMG+MRI (30.5% vs12.6%; hazard ratio [HR], 2.67; p < 0.001). All breast cancers were clinically node-negative and pathologic stage 0 or 1. Among five cancers in the MMG+MRI group, two were MRI-detected, two were MMG-detected, and one was detected on clinical exam. CONCLUSIONS: Screening MRI did not improve cancer detection, and cancer characteristics were favorable whether screened with MMG alone or MMG + MRI. These findings question the benefit of MRI for patients with HRL, although longer-term follow-up study is needed.

Massachusetts' innovative policy approach to expanding contraceptive options in primary care.

As health systems pivot toward value-based care and as the reversal of Roe vs Wade has significantly decreased access to abortion care in the United States, contraception is increasingly recognized as a high-value health service. However, the United States has a long and troubling history of using contraceptive policies and practices, including forced sterilization, to limit the reproductive rights of people of color and individuals with disabilities. We hope to highlight an innovative program developed by Massachusetts' Medicaid program, which seeks to expand access to long-acting reversible contraception (LARC) within primary care clinics in a way that promotes both value and reproductive justice. This program provides financial incentives for clinics that serve patients with Medicaid to offer LARC to all patients within the primary care space. Unlike LARC programs that exclusively target patients with Medicaid insurance and provide incentivizes based on number of LARC insertions, this policy has the potential to "lift all boats" and expand access to LARC for all patients regardless of payer. Careful evaluation of this program will be necessary to ensure that the intended outcomes-to increase access to LARC, promote reproductive justice, and deliver value to the health system-are achieved.

Integrating Breast Cancer Early Detection Into a Resource-Constrained Primary Health Care System: Health Care Workers' Experiences in Rwanda.

PURPOSE: There is limited evidence to guide incorporation of breast cancer early detection into resource-constrained health systems where mammography screening is not yet available. To inform such strategies, we sought to understand health care workers' perspectives on a breast cancer early detection initiative integrated into community, primary, and secondary levels of care in Rwanda. METHODS: We conducted a qualitative study using semistructured interviews with 33 community health workers, clinicians, and administrators at health facilities participating in the Women's Cancer Early Detection Program (WCEDP), through which women received clinical breast examination if they were receiving cervical cancer screening, or had breast concerns. Through thematic analysis, we identified dynamics and patterns associated with successes and challenges of the program's breast health services. RESULTS: Successes and challenges identified by participants corresponded with the community- and primary care-based steps of cancer early diagnosis identified by the WHO. Regarding step 1 (community awareness/access), participants noted increases in awareness and care-seeking. Challenges included difficulty overcoming stigma and engaging older women. Regarding step 2 (clinical evaluation), all participants described increased breast health knowledge, skills, and confidence. Integrating the WCEDP with other services was challenging because of inadequate staffing; offering WCEDP services on a designated day/week had advantages and disadvantages. Although participants appreciated WCEDP referral mechanisms, they desired more communication from referral facilities. Patients' poverty was the most consistently identified impediment to referral completion. CONCLUSION: Rwandan health care workers identified real-world successes and challenges of implementing principles of early cancer diagnosis for breast cancer early detection. Future interventions should focus on engagement of older women, community awareness, patient socioeconomic support, and optimizing integration into primary care.

Immediate Postpartum Long-Acting Reversible Contraceptive Use Following State-Specific Changes in Hospital Medicaid Reimbursement.

Importance: Facilitating access to the full range of contraceptive options is a health policy goal; however, inpatient provision of postpartum long-acting reversible contraceptive (LARC) methods has been limited due to lack of hospital reimbursement. Between March 2014 and January 2015, the Medicaid programs in 5 states began to reimburse hospitals for immediate postpartum LARC separately from the global maternity payment. Objective: To examine the association between Medicaid policies and provision of immediate postpartum LARC, and to examine hospital characteristics associated with policy adoption. Design, Setting, and Participants: This cross-sectional study used interrupted time series analysis. The setting was population-based in Georgia, Iowa, Maryland, New York, and Rhode Island. Participants included individuals who gave birth in these states between 2011 and 2017 (n = 3 097 188). Statistical analysis was performed from June 2021 to August 2022. Exposures: Childbirth after the start of Medicaid's reimbursement policy. Main Outcomes and Measures: Immediate postpartum LARC (outcome), teaching hospital, Catholic-owned or operated, obstetrical care level, and urban or rural location (hospital characteristics). Results: The study included a total of 1 521 491 births paid for by Medicaid and 1 575 697 paid for by a commercial payer between 2011 and 2017. Prior to Medicaid reimbursement changes, 489 389 of 726 805 births (67%) were to individuals between 18 and 29 years of age, 219 363 of 715 905 births (31%) were to non-Hispanic Black individuals, 227 639 of 715 905 births (32%) were to non-Hispanic White individuals, 155 298 of 715 905 births (22%) were to Hispanic individuals, and 113 605 of 715 905 births (16%) were to individuals from other non-Hispanic racial groups. Among Medicaid-paid births, the policies were associated with an increase in the rate of immediate postpartum LARC provision in all states, although results for Maryland were not consistent across sensitivity analyses. The change in trend ranged from a quarterly increase of 0.05 percentage points in Maryland (95% CI, 0.01-0.08 percentage points) and 0.05 percentage points in Iowa (95% CI, 0.00-0.11 percentage points) to 0.82 percentage points (95% CI, 0.73-0.91 percentage points) in Rhode Island. The policy was also associated with an increase in immediate postpartum LARC provision among commercially paid births in 4 of 5 states. After the policy, only 38 of 366 hospitals (10%) provided more than 1% of birthing people with immediate postpartum LARC. These adopting hospitals were less likely to be Catholic (0% [0 of 31] vs 17% [41 of 245]), less likely to be rural (10% [3 of 31] vs 33% [81 of 247]), more likely to have the highest level of obstetric care (71% [22 of 31] vs 29% [65 of 223]) and be teaching hospitals (87% [27 of 31] vs 43% [106 of 246]) compared with nonadopting hospitals. Conclusions and Relevance: This cross-sectional study's findings suggest that Medicaid policies that reimburse immediate postpartum LARC may increase access to this service; however, policy implementation has been uneven, resulting in unequal access.

Clinical Diagnoses and Outcomes After Diagnostic Breast Ultrasound by Nurses and General Practitioner Physicians in Rural Rwanda.

PURPOSE: To scale up early detection of breast cancer in low- and middle-income countries, research is needed to inform the role of diagnostic breast ultrasound performed by nonradiologists in resource-constrained settings. The authors examined 2-year clinical follow-up and outcomes among women who underwent diagnostic breast ultrasound performed by nonradiologist clinicians participating in a breast ultrasound training and mentorship program at a rural Rwandan hospital. METHODS: Imaging findings, management plans, and pathologic results were prospectively collected during the training using a standardized form. Data on follow-up and outcomes for patients receiving breast ultrasound between January 2016 and March 2017 were retrospectively collected through medical record review. RESULTS: Two hundred twenty-nine breast palpable findings (199 patients) met the study's eligibility criteria. Of 104 lesions initially biopsied, 38 were malignant on initial biopsy; 3 lesions were identified as malignant on repeat biopsy. All 34 patients ultimately diagnosed with cancer received initial recommendations for either biopsy or aspiration by trainees. The positive predictive value of trainee biopsy recommendation was 34.8% (95% confidence interval, 24.8%-45.0%). The sensitivity of trainees' biopsy recommendation for identifying malignant lesions was 92.7% (95% confidence interval, 84.2%-100%). Of 46 patients who did not receive biopsy and were told to return for clinical or imaging follow-up, 37.0% did not return. CONCLUSIONS: Trained nonradiologist clinicians in Rwanda successfully identified suspicious breast lesions on diagnostic breast ultrasound. Loss to follow-up was common among patients instructed to return for surveillance, so lower biopsy thresholds, decentralized surveillance, or patient navigation should be considered for patients with low- or intermediate-suspicion lesions.

Health system costs of a breast cancer early diagnosis programme in a rural district of Rwanda: a retrospective, cross-sectional economic analysis.

OBJECTIVES: This study aimed to quantify the health system cost of the first 2 years of a Breast Cancer Early Detection (BCED) programme in a rural district in Rwanda. We also aimed to estimate the cost of implementing the programme in other districts with different referral pathways and identify opportunities for enhanced cost efficiency. DESIGN: Retrospective, cross-sectional analysis using time-driven activity-based costing, based on timed patient clinical encounters, retrospective patient data and unit costs of resources abstracted from administrative and finance records. SETTING: The BCED programme focused on timely evaluation of individuals with breast symptoms. The study evaluated the health system cost of the BCED programme at seven health centres (HCs) in Burera district and Butaro Cancer Centre of Excellence (BCCOE) at Butaro District Hospital. OUTCOME MEASURES: Health system costs per patient visit and cost per cancer diagnosed were quantified. Total start-up and recurring operational costs were also estimated, as well as health system costs of different scale-up adaptations in other districts. RESULTS: One-time start-up costswere US$36 917, recurring operational costswere US$67 711 and clinical costswere US$14 824 over 2 years. Clinical breast examinations (CBE) at HCs cost US$3.27/visit. At BCCOE, CBE-only visits cost US$13.47/visit, CBE/ultrasound US$14.79/visit and CBE/ultrasound/biopsy/pathology US$147.81/visit. Overall, clinical cost per breast cancer diagnosed was US$1482. Clinicalcost drivers were personnel at HCs (55%) and biopsy/pathology supplies at BCCOE (46%). In other districts, patients experience a longer breast evaluation pathway, adding about US$14.00/patient; this could be decreased if ultrasound services were decentralised. CONCLUSION: Clinical costs associated with BCED services at HCs were modest, similar to other general outpatient services. The BCED programme's start-up and operational costs were high but could be reduced by using local trainers and virtual mentorship. In other districts, decentralising ultrasound and/or biopsies to district hospitals could reduce costs.