Cancers最新文献

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies.

The increased complexity of CLL management, driven by the advent of targeted therapies, makes it necessary to redefine the concept of fitness, which until a few years ago was limited to the patient's ability to undergo chemoimmunotherapy. In the current therapeutic landscape, fitness assessment must also consider biological age, comorbidities, and frailty, which have become increasingly relevant due to evolving treatment options and a more nuanced understanding of the elderly CLL population. In this context, the general condition of the patient should be preserved with greater attention to physical activity and nutrition. This narrative review analyzed in depth all these aspects with the aim of providing insights into fitness assessments and their actualization.

The creation of a specific culture medium for colorectal organoids in 2011 heralded a new era in human primary cultures by enabling the indefinite expansion of normal and pathological epithelial organoids. The original formula has been used ever since, with only minor, lab-specific modifications. The goal of culturing organoids from different tissues has relied on saving and propagating the pluripotent stem cell. The "magic bullet" and all its subsequent derivatives have pursued this goal. Consequently, agonist and antagonist signals are chronically activated in the organoid medium, forcing organoid cells (as well as any other co-cultured cellular model) into constrained signaling pathways. This extremely artificial condition is often overlooked in experimental approaches and may bias the results. Furthermore, some molecules in the organoid medium have unpredictable off-target effects that significantly impact the behavior and maturation of certain cell populations. Nicotinamide, gastrin and PGE2 inhibit immune responses. SB202190, A83-01 and vanadate (from advanced DMEM-F12) modify intracellular signaling. N-AcetylCysteine and Primocin modify the redox response and mitochondrial metabolism, respectively. Thus, the unintentional addition of these molecules to the organoid medium introduces biases under specific experimental settings. While the original organoid medium formula is the gold standard for propagating organoids in vitro, more focused, reliable conditions are necessary for specific organoid-based tests.

Intrahepatic cholangiocarcinomas (iCCAs) are histologically subdivided into small duct-type (SD-iCCA) and large duct-type (LD-iCCA). LD-iCCA versus SD-iCCA may differ in the molecular/genetic profiles and oncogenesis, including precursor lesions. While several precursors, such as high-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), have been proposed for LD-iCCA, the potential SD-iCCA precursors remain to be identified. Amid growing interests in the precursors of SD-iCCA, benign "biliary lesions/neoplasms developing in the hepatic parenchyma (BLNP)" such as von Meyenburg complexes (VMCs), bile duct adenomas (BDAs), and biliary adenofibroma (BAF), have been noted to determine whether they have the potential for precursor of SD-iCCA. Herein, these BLNPs were reviewed. BLNP can be classified into three categories. First, traditional VMC and BDA in normal livers which lack atypical features are categorized as "traditional BLNP". Second, a constellation of several lesions such as VMC and BDA detectable in the background livers of SD-iCCA and in chronic liver disease (unusual VMC and BDA), VMC with dysplastic features, BDA located in the deep hepatic parenchyma, multiple BDA, BDA presenting the BRAF V600E mutation, and BAF harboring variable dysplasia or in situ carcinomas, which may include neoplastic lesions but do not show invasive growth, are categorized as "unusual/dysplastic BLNP". Third, tubulocystic carcinoma with BAF-like features (AI-TCC) and SD-iCCA with ductal plate malformation (DPMP) which share overlapping features and show relatively good post-operative outcomes and retained features of VMC or DPM, and BDA and BAF, are categorized as "low-grade malignant BLNP". While the first category is benign and may not be related to SD-iCCA, some of the second category may be related to SD-iCCA, and the third category is malignant and shows invasive growth. The latter two categories may form a common biliary tumorigenic spectrum involving BLNP. Precursors of SD-iCCA, if they exist, may be included in the second category, and the third category may represent unique carcinomas possibly associated with or followed by conventional SD-iCCA. In conclusion, this novel approach to categorize BLNPs into three categories guarantees further studies of precursors of and their progression to conventional SD-iCCA.

Objective: To evaluate the role of serum albumin in predicting surgical outcomes after radical cystectomy.

Methods: Retrospective cohort analysis of adults who underwent radical cystectomy from 2019 to 2022 within the ACS NSQIP dataset. Patients were stratified into three groups based on preoperative serum albumin: <3.0 g/dL, 3.0-3.5 g/dL, and >3.5 g/dL. Primary outcomes were surgical site infections, wound disruption, reoperation rates, prolonged hospitalization, and 30-day mortality. Regression analyses assessed the impact of hypoalbuminemia (<3.5 g/dL) on outcomes.

Results: In total, 6748 patients were included in the analysis. Distribution of preoperative albumin levels included 4.8% with albumin less than 3.0 gm/dL (Cohort A), 10.7% with albumin between 3.0 and 3.5 gm/dL (Cohort B), and 84.4% with albumin > 3.5 gm/dL (Cohort C). The incidence of superficial SSI (7.7%), deep SSI (2.2%), wound disruption (4.0%), unplanned reoperation (8.6%), and still in hospital at 30 days (5.5%) was significantly higher in Cohort A (p for all < 0.05). Moreover, 30-day mortality was significantly higher in Cohorts A and B, as compared to Cohort C (2.2% vs. 2.3% vs. 1.3%, p = 0.03). On multivariate logistic regression, albumin < 3.5 gm/dL was significantly associated with reoperation (OR = 1.39, p = 0.031), prolonged hospitalization (OR = 1.28, p = 0.038), and 30-day mortality (OR = 1.74, p = 0.025).

Conclusions: Preoperative hypoalbuminemia is independently associated with increased morbidity and mortality following radical cystectomy. Given its modifiable nature, serum albumin should be considered a key target for preoperative optimization.

Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) have transformed cancer therapy for patients harbouring homologous recombination repair (HRR) deficiencies, notably BRCA1/2 mutations. However, resistance to PARPi remains a clinical challenge, with restoration of BRCA1 function via hypomorphic variants representing an understudied scenario.

Methods: Here, we engineered a doxycycline-inducible BRCA1 expression system in the BRCA1-mutant, triple-negative breast cancer cell line MDAMB436, permitting controlled analysis of functionally distinct BRCA1 hypomorphs in vitro and in vivo.

Results: Among multiple BRCA1 variants generated-including RING, coiled-coil, and BRCT domain mutants-only overexpression of the ∆exon11 hypomorph robustly conferred resistance to olaparib and carboplatin, with drug sensitivity correlating to ∆exon11 expression levels. While ∆exon11 BRCA1 mediated HRR restoration, its efficiency was consistently lower than full-length BRCA1, as measured by RAD51 foci formation and interaction with repair partners such as PALB2. In vivo, tumours expressing Δexon11 BRCA1 exhibited only partial resistance to olaparib compared to those expressing full-length BRCA1. Importantly, the combination of olaparib and the ATR inhibitor, ceralasertib, overcame ∆exon11-mediated resistance, impairing RAD51 foci formation in ∆exon11-expressing cells.

Conclusions: Our findings identify a dose-dependent, hypomorphic HRR restoration by ∆exon11 BRCA1, help explain the variable resistance observed in BRCA1-mutant pre-clinical models expressing this hypomorph, and propose ATR inhibition in combination with PARPi as a clinical strategy to counteract therapeutic resistance mediated by ∆exon11 BRCA1 hypomorphs.

Background: The persistently low 5-year survival rate for pancreatic cancer (PC) underscores the critical need for early detection. However, population-wide screening remains impractical. Artificial Intelligence (AI) models using electronic health record (EHR) data offer a promising avenue for pre-symptomatic risk stratification.

Objective: To systematically review and meta-analyze the performance of AI models for PC prediction based exclusively on structured EHR data.

Methods: We systematically searched PubMed, MedRxiv, BioRxiv, and Google Scholar (2010-2025). Inclusion criteria encompassed studies using EHR-derived data (excluding imaging/genomics), applying AI for PC prediction, reporting AUC, and including a non-cancer cohort. Two reviewers independently extracted data. Random-effects meta-analysis was performed for AUC, sensitivity (Se), and specificity (Sp) using R software version 4.5.1. Heterogeneity was assessed using I² statistics and publication bias was evaluated.

Results: Of 946 screened records, 19 studies met the inclusion criteria. The pooled AUC across all models was 0.785 (95% CI: 0.759-0.810), indicating good overall discriminatory ability. Neural Network (NN) models demonstrated a statistically significantly higher pooled AUC (0.826) compared to Logistic Regression (LogReg, 0.799), Random Forests (RF, 0.762), and XGBoost (XGB, 0.779) (all p < 0.001). In analyses with sufficient data, models like Light Gradient Boosting (LGB) showed superior Se and Sp (99% and 98.7%, respectively) compared to NNs and LogReg, though based on limited studies. Meta-analysis of Se and Sp revealed extreme heterogeneity (I² ≥ 99.9%), and the positive predictive values (PPVs) reported across studies were consistently low (often < 1%), reflecting the challenge of screening a low-prevalence disease.

Conclusions: AI models using EHR data show significant promise for early PC detection, with NNs achieving the highest pooled AUC. However, high heterogeneity and typically low PPV highlight the need for standardized methodologies and a targeted risk-stratification approach rather than general population screening. Future prospective validation and integration into clinical decision-support systems are essential.

Background: Kaposi sarcoma (KS) is a multifocal, angioproliferative neoplasm strongly associated with human herpesvirus-8 infection. Radiotherapy(RT) is a well established treatment due to the intrinsic radiosensitivity of KS lesions. High-dose-rate contact brachytherapy allows precise dose delivery with optimal sparing of surrounding tissues; however, its application in KS remains poorly documented. Methods: We conducted a retrospective analysis of 10 patients with histologically confirmed KS treated with c-HDR-BRT between June 2010 and June 2023. A total of 40 cutaneous lesions were treated using Leipzig applicators with hypofractionated regimens: 10 Gy in 1 fraction, 20 Gy in 2 fractions, or 30 Gy in 3 fractions. Treatment parameters were individualized based on lesion size and location. Local control (LC), overall survival (OS), disease-specific survival (DSS), and toxicity (graded by the RTOG criteria) were evaluated. Follow-up assessments were performed every four months during the first year and annually thereafter. Results: At a median follow-up of 10.3 years, the 2-year LC, OS, and DSS rates were 100%. Complete response was achieved in 62.5% of lesions, with a partial response observed in 37.5%. Grade 1-2 acute skin toxicities were recorded in 55% of treated lesions, while grade 3 toxicity occurred in a single case (2.5%) and was managed conservatively. The hypofractionated schedule significantly improved patient compliance, particularly in those with multiple lesions requiring sequential irradiation. Conclusions: Our long-term institutional experience supports c-HDR-BRT as a feasible and well tolerated local treatment option for the management of KS, providing favorable long-term local outcomes. These results support the inclusion of c-HDR-BRT in the multidisciplinary treatment of KS, warranting further prospective evaluation.

Background: The combination of hepatic arterial infusion chemotherapy (HAIC) with immune checkpoint inhibitors (ICIs) and anti-angiogenic agents represents a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). This study aimed to compare the efficacy and safety of triple therapies combining HAIC with ICIs and either bevacizumab or tyrosine kinase inhibitors (TKIs) in these patients.

Methods: This retrospective single-center study enrolled 65 consecutive patients with advanced HCC who received HAIC combined with ICIs plus either bevacizumab (bevacizumab group, n = 31) or TKIs (TKIs group, n = 34) between June 2021 and June 2023. Primary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety profiles.

Results: The bevacizumab group demonstrated significantly prolonged median PFS (10.9 vs. 7.4 months, p = 0.001) and higher ORR (83.9% vs. 61.8%, p = 0.047) compared with the TKIs group. DOR was longer in the bevacizumab group (7.9 vs. 5.3 months, p = 0.008). Median overall survival (OS) was not reached in the bevacizumab group versus 22.6 months in the TKIs group. Grade 3-4 adverse events occurred in 67.7% of the bevacizumab group and 73.5% of the TKIs group, with distinct toxicity profiles. Gastrointestinal hemorrhage (45.2%) and gastric ulcer (22.6%) predominated in the bevacizumab group, whereas the TKIs group exhibited more hepatic enzyme elevations (aspartate aminotransferase, 67.6%; alanine aminotransferase, 61.8%), proteinuria (29.4%), diarrhea (26.5%), hand-foot syndrome (20.6%), and reactive cutaneous capillary endothelial proliferation (11.8%).

Conclusions: Bevacizumab-containing triplet therapy was associated with improved tumor control and delayed progression compared to TKIs-based regimens in advanced HCC. The higher bleeding risk in the bevacizumab group highlights the necessity of standardized baseline evaluation and adequate preventive measures.

Background/Objectives: Adolescents and young adults (AYAs) with cancer often begin their careers later in life and are at risk of negative work-related outcomes. Research into and tailored support programs for AYAs diagnosed during higher education remain limited. An improved understanding of AYAs' experiences is essential in guiding the development of age-appropriate support programs. This study explored the impact of cancer and the challenges AYAs face in educational participation and the transition to work. Methods: A qualitative study was conducted with thirteen AYAs diagnosed with cancer during higher education. Participants were interviewed using a semi-structured guide. In collaboration with patient experts as co-researchers, data were analyzed via thematic analysis. Results: Eight analytically derived themes reflected AYA students' experiences: (1) Meaning and importance of education, (2) Reduced performance, (3) Recovery and expectations, (4) Interruption and delay, (5) Transition to work, (6) Disclosure, (7) Challenges related to the context of students, and (8) Experienced lack of support. The themes were clustered into four overarching thematic categories: Meaningful participation, Impact on performance, Academic progress and career transition, and Challenges in navigation. Conclusions: Our findings provide greater insight into the significance of educational participation for AYAs. AYA students encounter challenges stemming from both diagnosis-related changes in functioning and from contextual factors tied to their roles as students and new starters in the labor market. Navigating the healthcare, education, and social systems is complex and AYAs often lack adequate support when resuming their education or transitioning to work. Tailored support programs in healthcare and educational settings should be developed to help AYAs harness their strong motivation to resume studies, enter the labor market, and achieve their full potential.