Cancers are a growing cause of morbidity and mortality in low-income countries. Geographic access plays a key role in both timely diagnosis and successful treatment. In areas lacking well-developed road networks, seasonal weather events can lengthen already long travel times to access care. Expanding facilities to offer cancer care is expensive and requires staffing by skilled medical professionals, which are often in short supply. In this article, we propose a mathematical model to improve geographic access to cancer care by jointly considering expansions to care facilities and improvements to the road network. We model this as a multi-period stochastic facility location network design problem. For each period, a decision maker must simultaneously choose a set of facilities at which to add tertiary cancer services and a set of roads to improve while facing demand and travel time uncertainty. Once demand for cancer care and weather events are realized, patients observe road conditions and use the transportation network to travel towards the closest facility with available cancer services. We create a new path-based formulation of this problem and develop a new branch-price-and-cut algorithm with acceleration techniques that take advantage of this formulation's structure. We demonstrate our approach using Rwanda as a case study and show that the reductions in travel time to cancer care directly attributable to the road network improvements can be as high as one hour.

Pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) predicts excellent prognosis, yet conventional morphological MRI achieves only 52-71% sensitivity. Radiomics models show promising discrimination, but performance variation across platforms limits clinical translation.

This prospective cohort study enrolled 615 LARC patients (cT3-T4 or cN+) across four centers. Centers 1-3 contributed the development cohort (n = 405); Center 4 was the sole external validation site, contributing mutually exclusive 1.5T (n = 98; 19 pCR, 19.4%) and 3T (n = 112; 24 pCR, 21.4%) cohorts. Baseline MRI yielded 107 radiomics features (42 retained). Clinical-only, radiomics-only and combined models predicting pCR (ypT0N0) were fitted by LASSO logistic regression in Python, with ComBat harmonization estimated on development data only, DeLong testing, calibration assessment and decision curve analysis.

Development pCR prevalence was 20.0% (81/405). The combined model achieved AUC 0.887 (95% CI 0.846-0.928; sensitivity 87.7% [71/81], specificity 84.6% [274/324]) versus radiomics-only 0.842 and clinical-only 0.723 (DeLong p < 0.001). External validation gave AUC 0.821 at 1.5T and 0.908 at 3T. ComBat improved 1.5T discrimination (ΔAUC + 0.060, p = 0.041) but did not abolish the field-strength gradient. Calibration slopes were 0.91-0.96. At a 15% threshold probability the combined model showed the highest net benefit (0.135). pCR predicted 3-year disease-free survival 98.8% versus 66.0% (p < 0.001).

Combined radiomics-clinical models discriminate pCR across MRI platforms. Because external validation was confined to one center and no management decision followed model output, these findings are hypothesis-generating and require prospective interventional verification.

Cancer-related cognitive impairment (CRCI) is a multifaceted symptom associated with various comorbid conditions, complicating management. This study aims to evaluate cumulative symptom burden and its impact on both subjective and objective CRCI in breast cancer survivors.

Enrollment data were analyzed from a randomized clinical trial involving women with stage 0-III breast cancer, free of oncology disease, reporting moderate or greater CRCI and insomnia. Subjective CRCI was measured using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), and objective CRCI with the Hopkins Verbal Learning Test-Revised (HVLT). Comorbid symptoms (insomnia, fatigue, pain, anxiety, depression) were assessed with validated self-report tools. A Cumulative Symptoms Score (CSS) was calculated to quantify symptom burden. Multivariable linear regression was used to examine associations with CRCI, adjusting for co-variables.

Among 260 participants (mean age 56.6 years), 21% were non-White and 10% Hispanic. Fatigue (90%) was the most common, followed by insomnia (70%), pain (45%), anxiety (35%), and depression (12%). Higher CSS was significantly associated with worse subjective CRCI after adjustment for age and chemotherapy (Coef. = -3.0, 95% CI: -3.6 to -2.4, p < 0.001). Each comorbid symptom was correlated with subjective CRCI (all p < 0.001). CSS was not associated with objective cognitive performance (p = 0.58), although insomnia correlated with HVLT scores (r = -0.20; p < 0.001).

Cumulative symptom burden was associated with subjective but not objective CRCI. Comprehensive symptom management has the potential to improve subjective appraisal of CRCI. Sleep disturbance may be a therapeutic target for improving objective outcomes.

HER2-low breast cancer is treatment-relevant, but whether it is clinically distinct from HER2-0 disease remains unclear. We evaluate metastasis-free interval (MFI), first metastatic site, and survival after metastasis among HER2 classes in metastatic breast cancer.

We retrospectively examined patients with metastatic breast cancer classified as HER2-0, HER2-low, or HER2-positive. Analyses included the chi-square test of independence, Welch one-way ANOVA, Kaplan-Meier estimation, and binary and ordinal logistic and Cox regression models.

Among 1,599 patients, 647 (40.5%) had HER2-0 tumors, 672 (42%) had HER2-low tumors, and 280 (17.5%) had HER2-positive tumors. HER2-positive tumors had the shortest MFI compared with HER2-low and HER2-0 tumors (median 2.7 vs. 3.3 vs. 3.7 years, respectively; p = 0.002) and lower odds of late recurrence (≥ 5 years) compared with HER2-0 tumors (OR 0.39, 95% CI 0.22-0.68). HER2-low and HER2-0 tumors had similar metastatic timing. First metastatic site differed across HER2 groups in unadjusted analyses, although HER2 status was not independently associated with bone-only or CNS-only presentation in adjusted binary models. In adjusted Cox regression, HER2-low disease (HR 0.85, 95% CI 0.74-0.97) and HER2-positive disease (HR 0.73, 95% CI 0.60-0.88) were associated with lower hazard of death compared with HER2-0 disease.

HER2-positive disease was associated with earlier metastatic recurrence but more favorable post-metastatic survival. HER2-low disease had modestly improved post-metastatic survival but otherwise resembled HER2-0 disease in metastatic timing and adjusted metastatic presentation. These findings support HER2-low status for outcome stratification but suggest it may not independently define a distinct metastatic pattern.

Not applicable.

Circulating miRNAs (c-miRNAs) are promising non-invasive biomarkers for breast cancer detection, but reproducible signatures remain limited. This study aimed to identify a circulating miRNA signature for invasive ductal breast carcinoma, evaluate its discriminatory performance in an independent serum cohort, and explore the biological context of the selected c-miRNAs.

Serum expression of 21 candidate c-miRNAs was analyzed by RT-qPCR in 46 treatment-naive invasive ductal breast carcinoma patients and 46 healthy controls. Whole-blood expression of immune checkpoint-related genes (PDCD1, CD274, CTLA4, and LAG3) was also assessed in 50 patients and 46 controls. Among the 21 candidates, 12 c-miRNAs were significantly dysregulated after FDR correction. miR-6838-5p and miR-195-5p showed the strongest discriminatory performance and were combined into a two-miRNA logistic regression model. This model achieved an AUC of 0.923 (95% CI: 0.873-0.974) in the discovery cohort and an optimism-corrected AUC of 0.917 after 1,000 bootstrap iterations. In the independent GSE73002 serum cohort, including 1,280 breast cancer patients and 2,684 non-cancer controls, the same two-miRNA combination retained strong ROC-derived discriminatory performance with an AUC of 0.939 (95% CI: 0.930-0.948). Exploratory downstream analyses provided additional biological context.

The miR-6838-5p/miR-195-5p combination represents a promising circulating miRNA signature for invasive ductal breast carcinoma. Its consistent discriminatory performance in the discovery cohort and an independent serum cohort supports further evaluation in larger prospective studies. Additional work in clinically diverse cohorts, including benign breast disease and early-stage populations, as well as paired serum-tissue and functional validation studies, is needed to define its clinical applicability and biological origin.

This study aimed to define a data-driven threshold in NSCLC using post-recurrence survival.

Patients who underwent lung resection for stage I-IIIA NSCLC and experienced recurrence at a single institution from 2010 to 2021 were identified. Exclusion criteria included indeterminate N stage, M1 status, neoadjuvant therapy, and positive surgical margins. Time to recurrence was measured from surgery to recurrence, and post-recurrence survival from recurrence to death or last follow-up. Grid search and Kaplan-Meier analysis identified the time cut-point with the greatest survival difference, which was validated using multivariable Cox regression adjusted for age, race, tumor size, smoking history (pack-years), comorbodities, pathological N stage, histology, surgical procedure, and receipt of adjuvant therapy.

A total of 227 patients met inclusion criteria, with 50% (114/227) female and 78% (177/227) white patients. The median age was 70 years (IQR 63-76), the tumor size was 2.6 cm (IQR 1.8-4.1), and time to recurrence was 17 months (IQR 9-30). Cut-point analysis identified 12 months as the threshold most strongly associated with survival after recurrence. Median post-recurrence survival was 14 months (IQR 4-32) versus 22 months (IQR 10-40) for patients that recurred within and after 12 months, respectively (log-rank p = 0.002). On multivariable analysis, the 12-month cut-point remained associated with survival after recurrence (HR 1.49, 95% CI 1.03-2.15, p = 0.03).

Recurrence within 12 months after resection of early-stage NSCLC is associated with worse post-recurrence survival, making this cutoff a useful indicator of early recurrence.

Eribulin is a non-taxane microtubule inhibitor that showed survival benefits for pretreated metastatic breast cancer (MBC) patients. Circulating tumor cells (CTCs) are a prognostic marker, but their role in predicting response to specific MBC treatments is less clear. In this trial, we assessed the clinical outcome and its association with CTC-dynamics in HER2-negative MBC treated with eribulin.

HER2-negative MBC-patients were screened for CTCs within the DETECT study program using the CellSearch® technology (Menarini Silicon Biosystems; Bologna, Italy). Patients with HER2-negative CTCs were eligible for the single-arm DETECT-IVb study treatment with eribulin. Primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), CTC-clearance rate and safety.

Median PFS and OS were 4.6 months and 13.4 months, respectively. Multivariable adjusted analyses showed that patients with CTC-clearance at first follow-up (34.7%) had significantly improved PFS (p = 0.043) but not OS (p = 0.192) compared to patients with at least 1 CTC. Likewise, patients with CTC-clearance at the end of the treatment (23.1%) achieved a significantly better PFS (p = 0.015) but not OS (p = 0.218). Neutropenia, leukopenia, anemia and fatigue were the most common adverse events and no new or unexpected safety signals were obtained.

In this trial, we could confirm eribulin as an effective treatment option in high-risk HER2-negative MBC. CTCs proved their role as a prognostic marker and our results support the potential role of CTC dynamics as an early biomarker of treatment response to eribulin.

EudraCTNo2013-001269-18 http://ClinicalTrials.gov , TRN NCT02035813, Registration date 2014-01-12.

Angiogenesis plays a central role in bladder cancer progression. VEGFA regulates angiogenesis, whereas YKL-40 is a pro-angiogenic biomarker. The relationship between VEGFA polymorphism and circulating YKL-40 remains unclear.

A hospital-based case-control study involving 120 bladder cancer patients and 120 age- and sex-matched healthy controls was conducted. VEGFA rs833061 genotyping was performed using ARMS-PCR and confirmed by Sanger sequencing. Serum YKL-40 concentrations were measured by ELISA. Multivariable binary logistic regression analysis adjusted for age, sex, and smoking status demonstrated that the CT and TT genotypes remained independently associated with an increased risk of bladder cancer. Serum YKL-40 concentrations were significantly elevated in patients and increased progressively with tumor stage. TT genotype carriers exhibited the highest serum YKL-40 levels.

After adjustment for age, sex, and smoking status, the VEGFA rs833061 polymorphism remained independently associated with bladder cancer susceptibility and circulating YKL-40 concentrations. These findings provide preliminary evidence of a genotype-phenotype relationship; however, validation in larger multicentre cohorts is required.

In 2016 and 2019 respectively, the American Society of Breast Surgeons published consensus statements discouraging contralateral prophylactic mastectomy (CPM) in average-risk women with unilateral breast cancer and recommending genetic testing be made available for all patients with breast cancer. We sought to evaluate trends in CPM and genetic testing across two academic healthcare systems before and after the publication of the 2016 statement.

Retrospective chart review was performed from 2011 to 2020 for women with newly diagnosed unilateral stage 0 to III breast cancer who underwent surgery. Patients treated at the University of Kentucky or within the academic health system at the University of Minnesota were included and divided into two cohorts: before the 2016 CPM publication and after. Rates of CPM and genetic testing and factors associated with CPM were evaluated.

6,203 patients were identified. 2,619 patients were diagnosed between 2011 and 2015, and 3,584 were diagnosed between 2016 and 2020. Genetic testing was higher in the later cohort, with 2% prior to 2016 and 22% in 2016 or later. Rates of CPM were similar in the earlier and later cohorts (19% and 15%, respectively; p < 0.001). Factors associated with receipt of CPM were younger age, white race, lobular histology, increasing tumor size, HER2 positivity and genetic testing.

CPM trends at two academic institutions remained relatively stable over a time period when societal guidelines discouraged the use of CPM in average-risk women with unilateral breast cancer. Further work to understand these trends and identify interventions to reduce the rates of CPM is needed.

Multi-agent neoadjuvant therapy (NAT) with immune checkpoint blockade is standard treatment for Stage II-III triple-negative breast cancer (TNBC), though its role in smaller node-negative tumors remains unclear.

We performed a retrospective multi-institutional cohort study evaluating demographics, treatment patterns, and outcomes in a contemporary "small TNBC" population (n = 215) comprising Stage I (n = 154) and Stage II, T < 3 cm TNBC (n = 61).

Within the small TNBC cohort, Stage II, < 3 cm tumors demonstrated higher rates of grade 3 histology (93.4% vs 74.7%, p = 0.0013), NAT (85.2% vs 61.0%, p = 0.0006), adjuvant pembrolizumab (56.8% vs 24.7%, adjusted p = 0.0024), and neoadjuvant KEYNOTE-522 (75.0% vs 45.7%, adjusted p = 0.0052) compared with Stage I disease. Despite these treatment differences, recurrence and mortality rates were similar between groups. Among NAT-treated patients with small TNBC (n = 146), the pathologic complete response (pCR) rate was 51.3% (75/146), without significant difference between Stage I and Stage II, < 3 cm tumors (51.1% vs 51.9%, p = 0.92). There were no significant differences in regimen-specific pCR rates or event-free survival (EFS) when comparing NAT between Stage I and Stage II, < 3 cm tumors, or comparing NAT vs. no NAT for the small TNBC cohort.

Stage I and Stage II, < 3 cm TNBC demonstrated overlapping clinicopathologic features, pCR rates, and short-term survival outcomes despite substantially different treatment approaches. These findings suggest that current stage-based treatment distinctions may not fully capture the clinical behavior of small TNBC and support further prospective evaluation of risk-adapted and size-based treatment frameworks to better individualize NAT selection in this understudied population.