Cancers最新文献

Background/objectives: Fertility-sparing treatment (FST) is an accepted option for selected women with atypical endometrial hyperplasia (AEH) and early-stage endometrioid endometrial cancer (EC). While combined progestin therapy and hysteroscopic approaches yield the best outcomes, the surgical component has long lacked standardization. This study aimed to evaluate oncological and reproductive outcomes following a standardized hysteroscopic fertility-sparing approach.

Methods: This retrospective single-center study included women of reproductive age diagnosed with AEH or grade 1-2 endometrioid EC between 2021 and 2024 at the Digital Hysteroscopic Clinic CLASS Hysteroscopy, Fondazione Policlinico A. Gemelli IRCCS, Rome. All patients were treated using a standardized hysteroscopic approach based on lesion type and disease extension, combined with progestin therapy. Oncological outcomes included complete response (CR), time to CR and recurrence. Reproductive outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). Multivariate analysis was performed to identify factors associated with CR and relapse.

Results: A total of 138 patients were included (79 AEH, 59 EC). CR rates were high and comparable between AEH (94.9%) and EC (98.2%), with a median time to response of 6 months. Recurrence rates did not differ significantly between groups (16.7% AEH vs. 26.8% EC). CPR was similar (47.5% AEH vs. 54.8% EC), with LBR exceeding 50% among women who conceived. Multivariate analysis identified age ≥ 35 years as the only factor associated with reduced response and increased relapse risk.

Conclusions: A standardized hysteroscopic fertility-sparing approach combined with progestin therapy provides excellent oncologic control and favorable reproductive outcomes. Lesion severity did not affect outcomes when hysteroscopic removal was adequately performed, while patient age remains a key determinant of outcomes.

Background/Objectives: HPV status is a key prognostic determinant in head and neck squamous cell carcinoma (HNSCC), yet the immunological mechanisms underlying the survival advantage of HPV-positive (HPV⁺) over HPV-negative (HPV^-) disease remain poorly defined. This study aimed to characterize the tumor-infiltrating natural killer (NK) cell landscape in HPV-stratified HNSCC and identify novel therapeutic targets. Methods: We performed an NK-cell-centric re-analysis of published scRNA-seq data from 28 HNSCC patients (10 HPV⁺, 18 HPV^-; GEO: GSE139324, GSE164690), encompassing NK subset identification, pseudotime trajectory inference, and cell-cell interaction analysis. Key findings were validated by immunohistochemistry (IHC) in an independent cohort of 10 FFPE tissue sections, and prognostic associations were assessed using TCGA-HNSC data. Results: Four transcriptionally distinct NK cell subsets were identified: adaptive, cell-killing, CD56^bright, and virus-responsive. A cytotoxic CX3CR1⁺KLRB1^dim NK subset was specifically enriched in HPV⁺ tumors and independently associated with favorable survival. Conversely, HPV^- tumors upregulated CLEC2C and CLEC2D ligands on tumor cell surfaces, engaging the inhibitory receptor KLRB1 on NK cells; this CLEC2-KLRB1 axis correlated with suppressed NK activity and poorer prognosis, and was confirmed at the protein level by IHC. Conclusions: NK cell function in HNSCC is dichotomously regulated by HPV status. The CX3CR1⁺KLRB1^dim subset represents a candidate prognostic biomarker in HPV⁺ disease, and the CLEC2-KLRB1 axis is a targetable immune evasion mechanism in HPV^- HNSCC. These insights support the development of HPV-stratified immunotherapies; however, clinical translation requires validation in large, prospectively designed, subsite-matched cohorts to disentangle HPV-specific effects from anatomical site-dependent immune contextures.

Background/Objectives: Active surveillance (AS) has emerged as a safe alternative to primary therapy for low- and select intermediate-risk prostate cancer (PCa), but optimal patient selection and surveillance strategies remain challenging due to limited risk stratification tools enabling early detection of lesions with high potential for histopathological progression. This study presents an integrated method for predicting prostate cancer progression within 12 months, aiming to improve AS patient selection by categorizing patients into two risk groups: rapid progressors who would benefit from immediate treatment and slow progressors suitable for AS. Methods: The risk assessment platform combines convolutional neural networks for automatic segmentation of prostate and suspicious-for-cancer lesions on multiparametric MRI (mpMRI) with logistic regression to estimate progression risk. The networks were trained on annotated lesions from radical prostatectomy specimen mapped to mpMRI. The prediction model incorporated pre-biopsy clinical variables (age, PSA, PI-RADS) and MRI-derived intratumoral radiomic features from 163 participants of a prospective clinical trial, using histopathological progression within 12 months as endpoint. Results: The clinical-radiomics model achieved an AUC of 0.84 in distinguishing rapid from slow progressors, using non-invasive monitoring techniques. In an independent test set, the model significantly improved AS patient selection, increasing negative predictive value by 18.5% compared to current standard-of-care (p < 0.001). Conclusions: The risk assessment platform shows promise for use during annual follow-up visits to reliably differentiate suitable AS candidates with stable disease from PCa patients who are likely to experience early progression.

Central nervous system (CNS) evaluation for leukemic involvement is essential both at initial diagnosis and throughout relapse surveillance in childhood acute lymphoblastic leukemia (ALL). Accurate CNS risk classification is a cornerstone of individualized chemotherapy and has significantly advanced treatment strategies. However, detecting leukemic cells in the cerebrospinal fluid (CSF) is challenging, particularly when only a small number of cells are present. While cytomorphology remains a standard diagnostic method, it is limited by low sensitivity and interobserver variability, especially in low-cellularity or equivocal samples. Flow cytometry offers superior sensitivity and specificity and is increasingly recommended to confirm or clarify ambiguous findings. Current guidelines support the use of both cytomorphologic review and flow cytometry to maximize diagnostic accuracy. Evidence consistently demonstrates that any detectable CSF blasts-even in the setting of low WBC counts-are associated with increased risk of CNS relapse and poorer outcomes, underscoring the importance of risk-adapted CNS-directed therapy. Although the prognostic significance of isolated flow-only positivity remains under study, emerging data suggest that timely therapeutic intensification may mitigate adverse outcomes. Additional modalities, including advanced flow cytometry and molecular assays, may further refine CSF assessment in the future. This review summarizes current diagnostic approaches and highlights the need for standardized protocols for CSF evaluation in pediatric ALL.

Background: Carinal resections remain a challenging and demanding surgical technique for both the patient and medical professionals. The most common indications are adenoid cystic carcinoma and bronchogenic carcinoma. There have been no randomized controlled trials because of the low incidence of pathologic processes suited to carinal resections and the difficulties associated with designing such studies. Methods: The known data are limited to a few single-institutional, retrospective studies over the last several decades. In this review article, we focus on the available data regarding surgical techniques and the types of ventilation that can help in the construction of the anastomosis-the most crucial part of the operation. Important issues regarding carinal resections are discussed in detail. Results: The available literature is reviewed in detail regarding indications, surgical techniques and approaches, types of ventilation, the rates of morbidity and mortality, and 5-year survival. The authors present their experience with two patients, where they utilized ECMO and crossfield ventilation. The role of minimally invasive surgery in carinal resections is also discussed. Conclusions: Carinal resections are complex surgical procedures, but acceptable mortality and morbidity rates can be achieved in carefully selected patients. Excellent cooperation between the surgeon and anesthesiologist is essential in the construction of the anastomosis. Various types of airway management, especially ECMO, help to reduce complication rates and facilitate secure airway reconstruction.

Background/Objectives: Early death (ED) remains the primary barrier to long-term survival in acute promyelocytic leukemia (APL). Since current risk stratification models rely solely on static baseline parameters, they fail to capture the high biological volatility during the induction phase. We aimed to evaluate the prognostic value of the dynamic evolution of the endothelial activation and stress index (EASIX). Materials and Methods: This multicenter, retrospective study analyzed 131 newly diagnosed adult APL patients treated with the AIDA protocol. EASIX scores were calculated at admission (D0) and day 7 (D7). ROC, landmark, multivariable logistic and Cox regression analyses were performed to assess the impact of dynamic endothelial changes (ΔEASIX) on mortality and survival. Results: The ED rate was 25.2%. While baseline EASIX successfully predicted very early death (<7 days), dynamic assessment provided superior risk stratification. Worsening endothelial status (ΔEASIX > 0.35) was an independent predictor of early mortality (OR: 12.41, p = 0.007), inferior EFS (HR: 5.70, p = 0.004), and poor OS (HR: 3.69, p = 0.023). Landmark analysis stratified by the kinetic trajectory of ∆EASIX confirmed that patients above the optimal cut-off had significantly inferior 3-year EFS (56.3% vs. 77.8%, p = 0.041) and OS (59.5% vs. 78.0%, p = 0.026). Conclusions: To our knowledge, this is the first study to establish EASIX as a dynamic prognostic marker in APL. Our findings indicate that the "kinetic trajectory" of endothelial stress is a more accurate predictor of survival than static baseline assessment alone. While dynamic EASIX monitoring offers a valuable tool for real-time risk reclassification, these results require validation through prospective studies.

Introduction: Front-line therapy with Azacitidine (AZA) + Venetoclax (Ven) improved overall survival (OS) and remissions in acute myeloid leukemia (AML) patients ineligible for standard induction. Less is known about the outcome of AML treated with AZA + Ven in the "real world". Methods: We assessed the comparative pattern of administration, tolerability, efficacy and safety of AZA vs. AZA + Ven administered at our cancer centre. We retrospectively reviewed all patients treated with AZA alone or AZA + Ven. Patients who received less than one cycle or proceeded with consolidative stem cell transplant were excluded. Results: A total of 53 patients, median age 77 years, received AZA, and 23 patients, median age 73 years, received AZA + Ven. Among those, 69% and 47.8% were ≥75 years old, respectively. Only 52% received Ven doses above 200 mg. Mean time on therapy was 13.1 months in AZA vs. 5.9 months in AZA + Ven. Treatment delays occurred in 22.6% of AZA and 34.8% of AZA + Ven patients, primarily due to infections and cytopenias. Neutropenia grade 3/4 occurred in 28.3% of AZA vs. 56.5% of AZA + Ven patients. Thrombocytopenia grade 3/4 occurred in 15.1% of AZA and 51.2% of AZA + Ven patients. Anemia grade 3/4 occurred in 5.7% of AZA vs. 30.4% of AZA + Ven patients. Moreover, 69.8% of AZA and 69.5% AZA + Ven patients reached stable disease/partial and complete remission. Median overall survival (OS) was similar: 18 months in AZA vs. 14 months in the AZA + Ven group, p = 0.905. Conclusions: In a community setting, the addition of Venetoclax to AZA did not improve overall survival or disease control, mainly due to low tolerability and higher toxicity. However, these results should be interpreted cautiously due to a significant imbalance in the cytogenetic risk profiles and lower tolerability in the combined group. This suggests the need for a larger study with adjusted analyses.

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains incurable in approximately 30-40% of patients despite advances in immunochemotherapy. Although gene expression profiling has improved risk stratification, there is an ongoing need for non-invasive, cost-effective, and clinically practical biomarkers to identify patients at high risk of treatment resistance or relapse (R/R). Systemic inflammation plays a pivotal role in DLBCL pathogenesis, impacting both tumor progression and treatment response. The C-reactive protein-albumin-lymphocyte (CALLY) index, integrating markers of inflammation, nutritional status, and immune competence, has demonstrated prognostic relevance in solid tumors; however, its relevance in hematologic malignancies remains unexplored. Methods: We retrospectively analyzed 180 adults with newly diagnosed DLBCL, NOS (not otherwise specified) who received frontline rituximab-based immunochemotherapy (R-CHOP or CHOP-like regimens) between January 2014 and December 2019 at three tertiary centers in Serbia. The median age was 67 years (IQR 59-73), and 56.1% were female. Receiver operating characteristic (ROC) analysis determined 6.5 as the optimal CALLY index cut-off (AUC 0.744, 95% CI 0.670-0.817; p < 0.001). Results: A low CALLY index (<6.5) was significantly associated with adverse clinical features, including anemia, elevated lactate dehydrogenase and β2-microglobulin, poor ECOG performance status, bulky disease, advanced stage, and unfavorable IPI, R-IPI, and NCCN-IPI scores (all p < 0.001). In contrast, no associations were observed with tumor subtype, immunophenotype, or comorbidities. Furthermore, patients with CALLY <6.5 showed lower overall response rates to treatment (59.6% vs. 85.5%, p < 0.001) and higher relapse rates (21.0% vs. 6.2%, p = 0.014). They also experienced reduced 3- and 5-year overall survival (OS) and event-free survival (EFS) (all p < 0.001). In multivariate analysis, a low CALLY index independently predicted poorer OS (HR 2.04, 95% CI 1.13-3.67; p = 0.017) and EFS (HR 1.89, 95% CI 1.13-3.14; p = 0.015). In addition, it independently identified patients at risk of relapsed/refractory (R/R) disease (OR 2.50, 95% CI 1.02-10.10; p = 0.04), outperforming standard prognostic indices. Conclusions: The CALLY index is a simple, low-cost, and widely accessible biomarker that independently predicts prognosis in DLBCL, NOS. It outperforms standard indices in identifying R/R cases. The CALLY index may enhance risk stratification and guide individualized treatment strategies.

Background/Objectives: This study assesses the cost-effectiveness of integrating artificial intelligence (AI) into breast cancer screening programs in Singapore. It evaluates AI as a standalone reader and as a companion reader alongside a consultant radiologist and compares these with double reading by two radiologists to determine economic viability and impact on healthcare resource use. Methods: A Markov model compared costs and outcomes of three strategies: double reading, a hybrid AI-assisted model (radiologist plus AI), and AI-only. These were applied to biennial mammography for 10,000 women aged 50-69 years in Singapore, with a 50-year horizon. Epidemiological and cost data were sourced from Asian and local studies and standardized to 2023 values, with a 3% annual discount. Outcomes were incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses assessed uncertainty. Results: Double reading cost USD 19.18 million with 218,460.4 QALYs. The AI-companion model cost USD 18.86 million with 218,476.3 QALYs, saving USD 316,090 and gaining 15.9 QALYs. The AI-only model cost USD 20.53 million with 218,532.4 QALYs, yielding 72.0 QALYs gained and an ICER of USD 18,743 per QALY. Specificity was the most influential parameter. At a willingness-to-pay threshold of USD 50,000 per QALY, AI-only screening had >75% probability of being most cost-effective. Conclusions: AI-assisted screening was cost-saving, while AI-only was cost-effective with greater health gains but higher costs and false positives. A phased, human-in-the-loop approach offers the most economically favourable strategy for AI integration.

Background/Objectives: Many breast cancer patients treated with taxanes experience chemotherapy-induced peripheral neuropathy (CIPN). The early detection of CIPN may be facilitated by scoring systems. The existing Utah Early Neuropathy Scale (UENS) requires the presence of medical staff members. A self-assessment tool usable by patients is desired. Such an instrument was recently developed but had not yet been evaluated for the detection of CIPN. This prospective study aimed to identify the optimal cut-off score for the identification of moderate-to-severe CIPN in breast cancer survivors. Methods: Twenty-six breast cancer survivors (patients) who previously received taxane-based chemotherapy were included. Eighteen patients presenting with moderate-to-severe CIPN and eight patients without CIPN used the new scoring system (0-44 points). For each cut-off score, sensitivity, specificity, Youden index, and positive (PPV) and negative (NPV) predictive values were calculated. Patients rated their satisfaction with the tool. Dissatisfaction rates of >20% and >40%, respectively, would mean that it needed optimization or could not be used. Afterwards, the UENS (0-42 points) was applied by medical staff members. Results: For the new tool, a cut-off score of 9 points was found to be optimal for identifying moderate-to-severe CIPN. The sensitivity, specificity, Youden index, and PPV and NPV were 100% in each case. The dissatisfaction rate was 7.7%. When applying the UENS, the sensitivity, specificity, Youden index, and PPV and NPV were each 100% for a cut-off score of 6 points. Conclusions: The new self-assessment scoring system was highly accurate regarding the identification of moderate-to-severe CIPN. Patient satisfaction was high. When considering the limitations of this trial, the new instrument may be used in future studies.