Jefferson Health Corp.

Men are often diagnosed with node-positive breast cancer and treated with mastectomy because of a lack of screening and an unfavorable tumor-to-breast ratio. The AMAROS trial showed no difference in outcomes between axillary lymph node dissection (ALND) and axillary radiation in women with cT1-2N0 breast cancer with positive sentinel lymph nodes (+SLNs). Axillary management in men remains unstandardized, so we assessed current trends and outcomes.

Males with cT1-2N0M0 breast cancer undergoing mastectomy with one to two +SLNs were identified from the National Cancer Database (2018–2021). Patients were stratified by axillary management. Postmastectomy radiotherapy (PMRT) included chest wall and axillary fields. Management strategies and overall survival were analyzed.

Among 445 patients, 25% had no further axillary treatment, 22% underwent ALND, 29% PMRT, and 24% ALND+PMRT. Patients with two +SLNs more often underwent ALND+PMRT (43% vs. 19%, p  < 0.001). The use of PMRT rose over time (23–36%), whereas ALND alone declined (27–12%). Additional positive nodes were found in 31% of ALND cases, with no difference between ALND and ALND+PMRT. Performance of ALND delayed PMRT (194 vs. 133 days from diagnosis, p  < 0.001). On multivariable analysis, two +SLNs predicted ALND+PMRT (odds ratio 2.5, p  = 0.006). Older age ( p  < 0.001) and two +SLNs ( p  = 0.03) were linked to worse overall survival, whereas axillary management was not ( p  = 0.23).

Although axillary strategies are proven safe and effective in women, their extrapolation to men is inconsistent. Half of men undergoing mastectomy are undertreated or overtreated, underscoring the need for multidisciplinary consensus and prospective male-specific data to guide care and reduce morbidity.

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia. CLL treatment has evolved dramatically from alkylator-based regimens to chemoimmunotherapy and targeted therapies. This study evaluated real-world survival outcomes across treatment eras using population-based data, focusing on patients who received active systemic therapy to assess treatment effectiveness rather than natural disease progression.

We conducted a retrospective cohort study using surveillance, epidemiology, and end results (SEER) data from 1995 to 2020, restricting analysis to CLL patients who received active systemic treatment. Patients were stratified into three treatment eras based on treatment initiation date: Pre-novel therapy era (1995-2004, alkylator-based regimens), Early novel therapy era (2005-2014, chemoimmunotherapy with anti-CD20 monoclonal antibodies), and modern novel therapy era (2015-2020, targeted therapies including BTK inhibitors and BCL-2 inhibitors). Era boundaries accounted for the lag between regulatory approval and community adoption. Overall survival was calculated from treatment initiation date, with era assignment based on first-line therapy to maintain temporal consistency.

Among 49,056 CLL patients across three treatment eras, median overall survival improved significantly from 3.5 years (95% CI, 3.2-3.8) in the pre-novel therapy era (1995-2004) to 5.2 years (95% CI, 4.9-5.6) in the early novel therapy era (2005-2014), and 7.8 years (95% CI, 6.9-8.7) in the modern novel therapy era (2015-2020). Multivariable Cox regression analysis demonstrated progressive reductions in mortality risk, with adjusted hazard ratios of 0.75 (95% CI, 0.68-0.82, P < .001) for the Early Novel era and 0.45 (95% CI, 0.38-0.53, P < .001) for the Modern era compared to the Pre-Novel era. Complete response rates increased from 15% to20% in the Pre-Novel era to over 60% in the Modern era with targeted therapies.

This analysis demonstrates significant improvements in survival outcomes for CLL patients across treatment eras, with the most pronounced benefits observed in the modern targeted therapy era. By focusing on treated patients and calculating survival from treatment initiation, we isolated the impact of therapeutic advances from disease biology and patient selection factors. However, the COVID-19 pandemic's disproportionate impact on immunocompromised CLL patients, particularly affecting the modern therapy era, represents an important limitation that may underestimate the true survival benefits of contemporary targeted therapies. These findings support the continued development and adoption of novel therapeutic strategies in CLL management.

Building equitable research collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs) requires effective coordination among international ethical review committees, which is often logistically challenging. This case report presents the insights gained when acquiring ethical approval for a cervical cancer research program conducted jointly by the University of Pennsylvania and the University of Botswana.

We conducted a descriptive case study of the Ipabalele project, a 6-year HIC-LMIC partnership involving three complex research protocols that required approvals by multiple distinct ethical bodies. We analyzed various challenges affecting review procedures, timelines, and staffing. We then documented strategies employed in Ipabalele and other global initiatives to strengthen ethical review processes and build research capacity in LMICs.

In Ipabalele, ethical approvals were initially delayed by 2 years because of fragmented review processes with variable timelines and conflicting recommendations. Innovations to the process included centralizing institutional review board oversight within Botswana, implementing joint virtual meetings among review bodies, enhancing digital infrastructure, and streamlining research staffing and communication.

By providing practical strategies, this study highlights how empowered local leadership, centralized review processes, joint review mechanisms, and intentional capacity building can overcome logistical barriers in multinational ethical review.