Cancers最新文献

Background: Cutaneous squamous cell carcinoma (cSCC) represents the second most common form of non-melanoma skin malignancy, and, when not amenable to curative surgery or radiotherapy, it is a life-threatening disease. The anti-PD-1 monoclonal antibody cemiplimab has transformed the outcome of advanced or metastatic cSCC, with response rates approaching 50% and sustained benefit beyond three years in clinical trials. Cemiplimab is now the first-line standard of care treatment for advanced disease.

Methods: This retrospective observational study included consecutive adult patients with locally advanced (lac) or metastatic (m) cSCC who received cemiplimab (350 mg every three weeks) at the Center for Immuno-Oncology, University Hospital of Siena, Italy, either through an Expanded Access Program or routine clinical practice. Clinical outcome and treatment related adverse events (TRAEs) are reported.

Results: Between December 2019 and December 2023, 27 patients (24 male; median age 82 years [range 41-90]) diagnosed with lacSCC (n = 20 [74.0%]) or mcSCC (n = 7 [25.9%]) were treated with cemiplimab as first line therapy and were followed until June 2024. Head and neck were the primary tumor location for 88.8% of patients, followed by trunk (7.4%) and lower extremities (3.7%). All patients had comorbidities, including six patients (22.2%) with hematologic malignancies. With a median follow-up of 31 months (data cut-off June 2024), the ORR was 66.6% (complete response 22.2%) and the disease control rate (DCR) 77.7%. Median progression-free survival (mPFS) and overall survival (mOS) were not reached, while 2-year PFS and OS rates were 65.2% and 71%, respectively. Treatment was well-tolerated, with three (11.1%) patients experiencing grade ≥3 TRAEs, and three patients discontinuing treatment due to TRAEs.

Conclusions: Our real-world experience confirms the high rate of durable objective responses, good tolerability and long treatment duration of cemiplimab in elderly and frail cSCC patients as well.

Background: Multidisciplinary tumor boards (MDTs) remain the foundation of gynecologic cancer management, yet increasing diagnostic complexity and rapidly evolving molecular classifications have intensified interest in artificial intelligence (AI) as a potential decision-support tool. This study aimed to evaluate the concordance between MDT-derived recommendations and those generated by ChatGPT 5.0 across a large, real-world cohort of gynecologic oncology cases. Methods: This single-center retrospective analysis included 599 consecutive patients with cervical, endometrial, ovarian, or vulvar cancer evaluated during MDT meetings over a 2-month period. Standardized anonymized case summaries were entered into ChatGPT 5.0, which was instructed to follow current ESGO guidelines. AI-generated staging and treatment recommendations were compared with MDT decisions. Discrepancies were independently assessed by two reviewers and stratified by malignancy type, disease stage, and treatment domain. Results: Overall concordance for FIGO staging was 77.0%, while treatment-related decisions demonstrated lower discordance, particularly in chemotherapy (8.2%) and targeted therapy (6.8%). The highest staging disagreement occurred in early-stage endometrial cancer (32.6%), reflecting the complexity of newly revised molecular classifications. In recurrent ovarian and cervical cancer, discrepancies were more pronounced in surgical and systemic therapy recommendations, suggesting limited AI capacity to integrate multimodal imaging, prior treatments, and individualized considerations. Vulvar cancer cases showed the highest overall agreement. Conclusions: ChatGPT 5.0 aligns with MDT decisions in many straightforward scenarios but falls short in complex or nuanced cases requiring contextual, multimodal, and patient-specific reasoning. These findings underscore the need for prospective, real-time evaluation, multimodal data integration, external validation, and explainable AI frameworks before LLMs can be safely incorporated into routine gynecologic oncology decision-making.

Background: Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17-20% of the human genome. These retroelements are normally silenced early in embryonic development through epigenetic mechanisms and reawakened during oncogenesis, leading to transcriptional dysregulation, genomic instability, and immune evasion. Methods: In the present study, we categorized LINE-1 transcripts across 121 non-small cell lung cancer (NSCLC) cell lines from the Cancer Cell Line Encyclopedia (CCLE) by subfamily, length, orientation, chromosomal origin, and distribution. In addition, high-prevalence insertions were mapped to nearby genes to assess potential functional interactions. Results: LINE-1 transcript abundance and length in NSCLC were dominated by evolutionarily young subfamilies, particularly L1HS and L1PA2 through L1PA5. Chromosomal patterns were conserved across NSCLC subtypes, with modest enrichment of L1HS activity on Chromosome 4 and the X Chromosome. The lung squamous cell carcinoma (LSQCC) subtype exhibited the highest total levels of L1HS expression relative to other NSCLC subtypes. Race modestly influenced LINE-1 transcript abundance, with cell lines derived from self-identified African American individuals showing elevated overall LINE-1 and L1HS expression. Age showed a weak positive correlation with total LINE-1 abundance. Integrative analysis revealed recurrent hotspots at 22q12.1 and 20p11.21 that were transcriptionally active across subtypes and coincided with previously reported intact LINE-1 elements active in epithelial cancers. Recurrent insertions were located near cancer-associated genes, including RB1, NEDD4, FTO, LAMA2, NOD1, and KCNB2, implicating LINE-1 activity in cis-regulatory remodeling of oncogenic pathways. Conclusions: Together, these findings indicate that LINE-1 transcript heterogeneity in NSCLC is shaped by host genomic architecture and conserved functional hotspots, providing new insights into the mechanisms of genetic and epigenetic dysregulation associated with LINE-1 retroelements.

Background/Objectives: Chronic inflammation and oxidative stress are key contributors to colorectal cancer (CRC) development. However, prospective evidence in Asian populations remains limited. This study aimed to investigate the associations between circulating inflammatory cytokines, oxidative markers, and CRC risk in a Korean population. Methods: We conducted a case-cohort study nested within the Korean National Cancer Community (KNCCC) Cohort to investigate associations between inflammatory cytokines, oxidative stress markers, and CRC risk. A total of 128 incident CRC cases and 822 subcohort participants were included. Serum levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, interferon-γ (IFN-γ), IL-10, reactive oxygen species (ROS), and nitric oxide (NO) were measured. Hazard ratios (HRs) were estimated using the Cox proportional hazards models with Barlow's weighting. Results: Higher serum IL-6 levels were strongly associated with increased CRC risk, with HRs of 6.20 (95% CI: 2.38-16.19), 8.31 (3.24-21.33), and 10.22 (3.95-26.46) for the second through fourth quartiles, compared to the lowest. Detectable levels of IL-1β and IFN-γ were also significantly associated with CRC risk (HRs: 2.16 and 1.53, respectively). Stratified analysis showed that IL-6 and IL-1β were associated with CRC risk in both obese and non-obese participants, while TNF-α, IL-10, and NO were associated with increased risk only among obese individuals. No significant associations were observed for ROS. Conclusions: Elevated levels of inflammatory cytokines (IL-6, IL-1β, IFN-γ) and NO were associated with higher CRC risk, suggesting their potential as early biomarkers. Obesity may modify the associations between certain markers and CRC risk. These findings highlight the role of systemic inflammation and oxidative stress in colorectal carcinogenesis.

Epithelial-mesenchymal transition (EMT) is a key driver of invasion, metastasis, and treatment resistance in gastric cancer, yet its post-transcriptional regulation by microRNAs (miRNAs) is not fully delineated. We performed a structured literature search in PubMed, Web of Science, and Scopus for studies evaluating miRNAs in relation to EMT in gastric cancer and synthesised tumor-intrinsic, microenvironmental, and circulating EMT-related miRNA networks. Downregulated, predominantly tumor-suppressive miRNAs, including miR-34a, miR-200 family, miR-148a, miR-204, miR-30a, miR-101, miR-218, miR-26a, miR-375, miR-506, and others, converge on EMT transcription factors and pathways such as ZEB1/2, Snail, TGF-β/SMAD, Wnt/β-catenin, c-Met, and PI3K/AKT, and their restoration reverses EMT phenotypes in preclinical models. Upregulated oncomiRs, such as miR-21, miR-17-5p, miR-106b-5p, miR-23a, miR-130a-3p, miR-196a-5p, miR-181a, miR-616-3p, miR-301a-3p, miR-150, miR-27a-3p and miR-192/215, target tumor suppressors and reinforce these pathways. Cancer-associated fibroblast, macrophage, neutrophil, and natural killer cell-derived miRNAs, together with systemic indices such as the neutrophil-to-lymphocyte ratio and mediators like FAM3C, add microenvironmental layers of EMT regulation. Several EMT-related miRNAs show consistent associations with invasion, metastasis, peritoneal dissemination, prognosis, and chemoresistance, and many are detectable in circulation. Overall, EMT-related miRNAs orchestrate gastric cancer cell plasticity and tumor-microenvironment crosstalk and represent promising biomarker and therapeutic candidates that warrant validation in prospective, subtype-stratified, and translational studies.

Pancreatic cancer frequently presents with obstructive jaundice resulting from distal malignant biliary obstruction. Neoadjuvant chemotherapy (NAC) is increasingly applied in resectable and borderline resectable disease. In this context, uncontrolled cholestasis or cholangitis may hinder timely chemotherapy initiation and cause unplanned hospitalizations and treatment delays; therefore, preoperative biliary drainage is essential to ensure safe and uninterrupted NAC. This review summarizes current biliary drainage strategies during NAC, focusing on key clinical goals, maintaining durable patency throughout the planned NAC course, minimizing infectious and procedure-related morbidity, reducing the need for reintervention, and avoiding adverse effects on subsequent pancreatoduodenectomy, as well as on practical decision-making in clinical practice. We compare transpapillary drainage via endoscopic retrograde cholangiopancreatography (ERCP) using plastic stents and self-expandable metal stents (SEMSs) and discuss the emerging "slim" fully covered SEMSs designed to reduce the risks of pancreatitis and cholecystitis while maintaining sufficient patency. Endoscopic ultrasound-guided biliary drainage is also reviewed as an important salvage option after failed ERCP and as a potential primary approach in selected patients, and we also discuss conventional percutaneous approaches. Overall, current evidence supports an individualized, algorithm-based strategy that prioritizes durable internal drainage to maintain NAC schedules, reserves percutaneous transhepatic biliary drainage for specific indications, and underscores the need for further prospective studies evaluating long-term surgical and oncologic outcomes in resectable disease.

Background: Peritumoral brain edema (PTBE) is the most frequent complication for intracranial meningiomas following radiotherapy, yet no clinically validated biologically effective dose (BED) threshold capable of reliably predicting PTBE has currently been established. Although conventional radiobiological models typically assume an α/β ratio of 2-4 for benign meningiomas, whether these values accurately reflect the dose-response characteristics underlying radiation-induced PTBE remains unclear. Methods: We analyzed 67 intact meningiomas in the convexity, parasagittal, or falcine regions treated with primary linear accelerator (LINAC)-based radiotherapy. The BED values were recalculated using α/β ratios ranging from 2 to 20, and receiver operating characteristic (ROC) analyses were performed to identify the optimal BED thresholds for predicting PTBE. The most informative α/β ratio was defined as the value yielding the highest Youden's J statistic. Results: The ROC analyses showed that an assumed α/β ratio of 14 provided the highest discriminative accuracy for predicting PTBE in the overall cohort and markedly superior performance in patients younger than 70 years (area under the curve (AUC) 0.945; Youden's J = 0.871). The optimal BED threshold for predicting PTBE was approximately 41 Gy (α/β = 14), corresponding to ~18 Gy in a single fraction and ~5.8 Gy per fraction in a five-fraction regimen. Conclusions: The BED values calculated using α/β ratios near 14 provide the most reliable estimate of PTBE risk following primary LINAC-based radiotherapy for convexity, parasagittal, and falcine meningiomas. Maintaining prescription doses below this threshold may help reduce the likelihood of PTBE in this patient population.

Background: The tumor microenvironment (TME) plays a central role in pancreatic ductal adenocarcinoma (PDAC) progression, yet how mechanical cues shape stromal cell behavior remains poorly defined. Here, we investigate how dimensional priming of adipose-derived stromal cells (ADSCs) alters their immunomodulatory functions and subsequent impact on PDAC growth.

Methods: ADSCs were cultured under two-dimensional (2D) or three-dimensional (3D) conditions and evaluated using in vitro co-culture systems with PDAC organoids and in vivo xenograft models. Stromal phenotype, cytokine secretion, tumor growth, invasion, and immune cell infiltration were assessed.

Results: ADSCs cultured in three-dimensional (3D) hydrogels exhibited reduced Caveolin-1 (CAV-1) expression and reprogramming toward a stress-adapted, CAF-like phenotype compared with two-dimensional (2D) cultures. In vitro, 2D-primed ADSCs constrained PDAC organoid growth, increased MMP-2 activity, and required direct cell-cell contact to suppress tumor viability. By contrast, 3D-primed ADSCs preserved organoid structure but markedly enhanced tumor cell migration through soluble factors, accompanied by increased IL-6 and TNF-α and reduced IL-10 secretion during co-culture. In vivo, 3D-primed ADSCs promoted the largest tumors with aggressive invasion and loss of Col-Tgel containment associated with tumor expansion, whereas 2D-primed ADSCs suppressed tumor growth and maintained gel boundaries. Immunohistochemistry confirmed elevated Ki-67 in tumors containing 3D-primed ADSCs, while macrophage infiltration (F4/80⁺) was highest in 2D-primed tumors and lowest in 3D-primed tumors.

Conclusions: Dimensional priming fundamentally reprograms ADSC phenotype and alters their stromal-immune interactions, generating a tumor-permissive state that accelerates PDAC progression. These findings identify mechanical cues as critical regulators of stromal plasticity and highlight dimensional priming as a potentially targetable axis within the PDAC microenvironment.

Historically, systemic therapy has been the primary treatment for metastatic prostate cancer (MPC), with radiotherapy and surgery reserved for palliation. The recent literature suggests that adding local therapy (i.e., radiotherapy or surgery) to systemic therapy may improve survival for MPC patients with low metastatic burden (LMB). While some evidence supports the use of early intervention with local therapy targeting both the primary tumor and limited metastatic sites, the definition of LMB disease requires further clarification. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans play a vital role in staging MPC because they offer superior sensitivity and specificity compared to conventional imaging. PSMA PET thus improves patient selection and helps direct treatment planning. Local therapy in MPC can be separated into the treatment of primary and metastatic tumors. Furthermore, treatment of both the primary tumor and metastases can be managed using either radiotherapy or surgical intervention. Studies exploring the use of local therapy for both the primary tumor and oligometastatic sites have demonstrated promising clinical outcomes in patients with LMB or oligometastatic disease. This review provides a detailed description of the current optimal management of patients with metastatic prostate cancer with limited disease.

Background: Malignant neoplasms are a leading cause of death among older adults, and population ageing is expected to further increase the cancer burden. Analysing long-term mortality trends is essential for evaluating the effectiveness of cancer prevention and oncological care. The aim of the study was to analyse long-term trends in mortality from malignant neoplasms among adults aged 65 years and older in Poland between 2000 and 2022. Methods: This nationwide population-based study analysed all deaths due to malignant neoplasms among Polish residents aged ≥65 years between 2000 and 2022 using national mortality data from Statistics Poland. Mortality trends were assessed separately for women and men in early (65-74 years) and late (≥75 years) old age. Standardised death rates (SDRs) were calculated using the European Standard Population. Joinpoint regression was applied to estimate annual (APC) and average annual percentage changes (AAPC). Results: Overall cancer mortality declined steadily among men in both age groups, while trends among women were heterogeneous. In men aged 65-74 years, SDRs decreased from 1140.1 to 1006.0 per 100,000 (AAPC = -1.7%), largely driven by declining lung cancer mortality (AAPC = -2.6%); similar patterns were observed in men aged ≥75 years. Among women aged 65-74 years, overall cancer mortality declined modestly (AAPC = -0.4%), but lung cancer mortality increased markedly, with SDRs nearly doubling between 2000 and 2022 (AAPC = 3.5%). Conclusions: Sustained declines among men contrast with less favourable trends among women, particularly for smoking-related cancers, highlighting the need for targeted prevention, screening, and age-adapted oncological care.