Pedro Leite-Silva

Introduction: Germline testing in breast cancer now guides treatment as well as risk assessment, and international guidelines have broadened eligibility toward the patient’s clinical features, raising the age-alone threshold to ≤50 years and adding therapy-determined indications with multigene-panel testing. We quantified the additional testing that full implementation of the current criteria would have required at a comprehensive cancer center.,Methods: Retrospective single-center cohort of 3791 patients with invasive breast cancer diagnosed at the Portuguese Oncology Institute of Porto in 2019–2022 and tested under contemporaneous criteria. We described testing uptake and gene-level diagnostic yield, operationalized the current personal-history criteria from registry data, and counted eligible patients not tested.,Results: Overall, 1266 patients (33.4%) underwent germline testing; 146 (11.5%) carried a pathogenic variant, 43.2% in genes other than BRCA1/2. Under current criteria, 1584 patients (41.8%) met at least one operationalizable indication, of whom 893 (56.4%) had been tested; covering the remainder would have required 691 additional tests (approximately 173 per year), a 55% increase. Additional demand was concentrated in groups with lower uptake but comparable yield: the 46–50-year band (uptake 43.5%; positivity 10.1%) and the treatment-driven PARP-inhibitor indications (uptake 56.7% and 55.5%; positivity 13.0% and 8.6%, versus 11.5% among all tested patients).,Conclusion: Full implementation of the current criteria would have increased germline testing by 55%, concentrated in groups less frequently tested under earlier practice but with comparable diagnostic yield; 43.2% of carriers were identifiable only through the multigene panel. This estimate provides a concrete basis for planning testing capacity.

Background: Early identification of bacteremia in immunosuppressed cancer patients remains difficult, especially in neutropenia. This study evaluated the diagnostic accuracy of NLR, PLR, and NLPR for identifying bacteremia and sepsis in patients undergoing blood culture episode. Methods: We conducted a retrospective diagnostic accuracy study at a tertiary oncology center between January 2023 and December 2024. All bacteremia identified were included as cases. Culture-negative episodes were subsequently sampled as controls using a frequency-matching strategy. Hematological parameters were obtained within ±24 h of first blood culture episode. Diagnostic performance was assessed using ROC curve analysis and multivariable logistic regression. Results: Of 369 screened episodes, 337 from 323 unique patients were included after excluding 31 records. NLPR showed the highest accuracy for bacteremia (AUC 0.730; 95% CI 0.671–0.788). The optimal cut-off was 0.038 (sensitivity 69.2%, specificity 72.3%) and remained consistent after excluding episodes with antibiotic therapy (AUC 0.768), corticosteroids (AUC 0.708), or growth factor use (AUC 0.718). In severe neutropenia, NLPR showed the highest accuracy (AUC 0.887; 95% CI 0.797–0.978). In multivariable analysis (n = 304), NLPR remained independently associated with bacteremia (p < 0.001), with good model discrimination (AUC 0.815; 95% CI 0.763–0.866). Diagnostic performance for sepsis was lower and not statistically significant. Conclusions: These findings suggest that NLPR may represent a simple, inexpensive, widely accessible adjunctive biomarker to support early bacteremia risk stratification in immunosuppressed cancer patients, particularly in patients with severe neutropenia. Although its overall discrimination was comparable to isolated lymphocyte count, NLPR may provide clinically relevant contextual information by integrating multiple dimensions of immune dysregulation. Further prospective multicenter validation is warranted.

PURPOSE: Breast cancer (BC) is becoming a significant public health issue in Cape Verde. Understanding the profile of BC cases is crucial for improving patient outcomes and guiding public health initiatives. This study aimed to investigate the clinical and pathologic characteristics, treatment approaches, and outcomes of BC cases diagnosed and treated at Agostinho Neto University Hospital between January 2015 and July 2021 following implementation of an international treatment partnership. METHODS: A retrospective analysis was conducted on 158 female patients with BC diagnosed during the study period. Data were collected on patient demographics, tumor characteristics, treatment protocols, and survival outcomes. Immunohistochemistry was performed on a subset of 114 patients to identify molecular subtypes. Descriptive statistics were used to summarize all variables. Overall survival was analyzed, and log-rank tests were performed to formally compare the survival curves and assess the statistical significance of any observed differences. Cox proportional hazard models were used to determine the independent effect of sociodemographic factors and clinical characteristics. RESULTS: The median age at diagnosis was 52.5 years, with patients ranging from 28 to 91 years. Most patients resided on Santiago Island. Invasive ductal carcinoma was the most common type, found in 93% of cases. Over half of the tumors were poorly differentiated, and 57% were diagnosed at advanced stages (III and IV). Subtype distribution mirrored sub-Saharan patterns, with 24% triple negative and 11% human epidermal growth factor receptor 2 positive. Among patients with potentially curable BC, 61.4% received adequate therapy that followed the National Comprehensive Cancer Network (NCCN) Harmonized Guidelines for sub-Saharan Africa (SSA), including radiotherapy treatment, although this was performed abroad. The median follow-up calculated by reverse Kaplan-Meier was 33.7 months (IQR, 20.5-52.8 months). Patients treated according to stage-appropriate and phenotype-specific recommendations achieved better outcomes (79.9% 3-year survival). CONCLUSION: This study emphasizes the importance of early diagnosis and adoption of the NCCN Harmonized Guidelines for SSA. Access to radiotherapy abroad, necessitated by the absence of local radiotherapy facilities, was correlated with improved survival. These findings underscore the feasibility of improving outcomes in low-resource settings through standardized treatment frameworks.

INTRODUCTION: In 2018, a biennial fecal immunochemical test (FIT) screening program for colorectal cancer (CRC) was introduced in northern Portugal, targeting 1.1 million residents aged 50–74 years. The aim of this study was to evaluate trends in CRC incidence, early diagnosis, and survival before and after the program's implementation. METHODS: This was a population-based retrospective cohort study in northern Portugal. Data on CRC cases diagnosed between 2014 and 2020 were retrieved from the Portuguese National Cancer Registry. Early diagnosis was defined as stage I/II tumors. Net survival estimates for 2014–2016 vs 2018–2020 were compared. Data from Portuguese National Cancer Registry were linked to the FIT-based screening program of the Northern Portugal Regional Health Administration for the years 2018–2020 to assess screening outcomes. RESULTS: Between 2018 and 2020, the first 3 years of the program, 482,938 invitations for FIT screening were sent, resulting in an adherence rate of 34.4% (165,895). The negative predictive value of FIT was 99.95% (95% CI: 99.94–99.96). Overall, coverage by FIT and/or colonoscopy was 44.9%. The proportion of early cancers was significantly higher among individuals who accepted FIT screening (58.3%) or underwent colonoscopy (62.8%) compared with unscreened individuals (49.2%) ( P < 0.001). Net survival rates at 1 year and 3 years were significantly higher among individuals who accepted FIT screening or underwent colonoscopy compared with those who remained unscreened ( P < 0.001). DISCUSSION: Biennial FIT led to an increase in early diagnoses and improved survival, compared with no screening, in the short term after its introduction. A screening program that includes alternatives to FIT may increase population coverage and improve CRC outcomes.

Most patients with non-small-cell lung cancer (NSCLC) present with advanced/metastatic disease at diagnosis, and molecular profiling is critical in guiding treatment decisions. This retrospective cohort study aimed to characterize EGFR mutations (EGFRm) in advanced/metastatic NSCLC patients, treatment patterns, and real-world outcomes. Adults diagnosed between 2018 and 2021 and treated at a Comprehensive Care Center were included. Time-to-event outcomes were analyzed using the Kaplan–Meier method. A total of 110 patients were included, with a median age of 69.0 years (range, 37–93), 76.4% female, and 83.2% non-smokers. About 97.3% had adenocarcinomas, with 93.6% at stage IV, 40.9% with ≥ three metastatic sites (brain metastases in 24.5%), 33.6% ECOG 2–4, and 58.2% with an EGFR exon-19 deletion. A minority started supportive care or curative-intent treatment, and 81.8% underwent first-line palliative systemic therapy (TKIs, 91.1%; chemotherapy, 8.9%). Median real-world overall survival (rwOS) was 18.9 months (95% CI, 13.8–28.1). Worse rwOS was observed in patients with ECOG 2–4 versus ECOG 0–1 (10.3 vs. 22.8 months; HR 1.82, 95% CI 1.17–2.85; p = 0.008) and in patients with exon-21 L858R versus exon 19 deletions (15.8 vs. 24.2 months; HR 1.59, 95% CI 1.00–2.54; p = 0.048). In patients treated with palliative systemic treatment, median progression-free survival was 10.9 months (95% CI, 8.8–13.6). This study provides important insights regarding real-world characteristics, treatment patterns, and outcomes from a cohort of EGFRm advanced/metastatic NSCLC patients.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is an effective treatment option for appropriately selected patients with peritoneal carcinomatosis. Our aim was to analyze a multidisciplinary approach and to study the perioperative risk factors associated with morbidity and mortality. We reviewed all patients who underwent CRS + HIPEC from January 2019 till December 2020 at our oncologic center. Patient demographics, risk scores, intraoperative variables, postoperative care, analgesia protocol, and adverse events (AE) within 30 days after treatment were collected and statistically analyzed. Of the 98 patients evaluated preoperatively by a multidisciplinary team, 39 patients required active optimization. The median age was 61 years, and 67 were women. Most tumors were appendiceal in origin. The median peritoneal cancer index (PCI) score was 12, and the median operative time length (OTL) was 400 minutes. Body mass index, Physiological and Operative Severity Score for the enUmeration of morbidity, PCI score, crystalloid volume, cell concentrates, and OTL were associated with postoperative intensive care unit admission (p <0.05). Epidural analgesia was given to 74 patients. AEs occurred in 39 patients, and 25 of the AEs were classified as mild or moderate. The intraoperative variables associated with development of AEs were anesthesia technique, estimated blood loss, crystalloid volume, cell concentrates, OTL, and analgesia protocol (p 6 L, intravenous sufentanil analgesic protocol, and OTL were associated with 67%, 38%, and 15% increased risk of AE, respectively. Our study highlighted the importance of a perioperative protocol with a standardized multidisciplinary approach in order to decrease the incidence of postoperative AE.

Purpose Non-muscle invasive bladder cancer (NMIBC) is a highly recurrent disease that progresses to muscle-invasive bladder cancer (MIBC) in 5–25% of the cases. Epithelial-mesenchymal transition (EMT) has been associated with features of disease progression. Thus, we aimed to characterize the cadherin switch (CS), an EMT hallmark, and its regulatory mechanisms in bladder cancer (BlCa) progression, as well as the biological role of RCAD, a lesser-known cadherin, in bladder carcinogenesis. Methods Cadherin mRNA and promoter methylation levels were retrieved from The Cancer Genome Atlas (TCGA). Validation was performed in an independent set of 121 primary BlCa (NMIBC and MIBC) and 40 normal bladder samples from IPO Porto, using RT-qPCR and qMSP. Immunohistochemistry was performed in these samples and in 14 additional sarcomatoid BlCa. CRISPR-Cas9 was performed to explore the potential in vitro impact of RCAD on BlCa cell migration and invasion. Results In both the TCGA and IPO Porto BlCa cohorts, cadherin gene deregulation was observed compared to normal tissue samples, independent of promoter methylation. At the protein level, decreased E-cadherin and increased P- and R-cadherin expression was noted in BlCa tissues. In sarcomatoid BlCa the same trend was observed, with a more intense staining compared to that in conventional MIBCs. RCAD knockout considerably reduced the malignant properties of BlCa cells. Conclusions Our data indicate that E-, P- and R-cadherin switches occur in BlCa, being associated with tumor progression. Promoter methylation is not the likely mechanism underlying cadherin expression deregulation. Our findings suggest an oncogenic role of RCAD in BlCa progression.