Cancers最新文献

The clinical management of Pancreatic Neuroendocrine Neoplasms (Pan-NENs) is complicated by the disease's intrinsic variability, which creates significant hurdles for accurate risk profiling and the standardization of treatment protocols. Recently, Artificial Intelligence (AI) has offered a promising avenue to address these challenges. By integrating and processing high-dimensional multimodal datasets (encompassing clinical history, radiomics, and pathology), these computational tools can refine survival forecasts and support the development of personalized medicine. However, the transition from experimental success to routine clinical use is currently obstructed by reliance on limited, retrospective cohorts that lack external validation, alongside unresolved concerns regarding algorithmic transparency and ethical governance. This review evaluates the current landscape of AI-driven prognostic modeling for Pan-NENs and critically examines the pathway towards their reliable integration into clinical practice.

Background/objectives: Peritoneal surface metastases (PSMs) from colorectal cancer have high rates of peritoneal recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior studies dichotomize peritoneal recurrence into "early" and "late," limiting insight into how clinicopathologic factors influence recurrence timing. This study aimed to identify predictors of peritoneal recurrence and quantify their continuous association with time to recurrence following CRS/HIPEC.

Methods: Patients undergoing CC-0 CRS/HIPEC for colorectal PSM from 2018 to 2024 were identified from a prospectively maintained database. The primary outcome was peritoneal surface recurrence. Variables included peritoneal cancer index (PCI), tumor location, histology, HIPEC regimen, and KRAS/BRAF/SMAD4 status. Factors with p < 0.10 on univariable analysis were entered into multivariable logistic regression (recurrence: yes/no) and linear regression (time to recurrence).

Results: Among 133 patients, 64 (48.1%) developed peritoneal recurrence. Median time to recurrence was 41.4 weeks (IQR 24.9-74.0), and PCI was higher among those who recurred (median 11.0 vs. 5.0, p < 0.01). Neither tumor stage, histology, intraperitoneal chemotherapy agent, nor molecular alterations were associated with increased risk of peritoneal recurrence. When controlling for PCI, right- and sigmoid-colon primaries independently predicted peritoneal recurrence compared to all other locations without influence on recurrence timing (right: OR 7.18; sigmoid: OR 6.54; p < 0.01). Among patients who recurred, each one-point increase in PCI corresponded to a 2.43-week earlier relapse (p < 0.01).

Conclusions: Nearly half of patients with colorectal PSM recurred despite complete CRS/HIPEC. Tumor location predicted peritoneal recurrence, while PCI independently shortened time to relapse. Modeling PCI as a continuous predictor refines postoperative risk stratification and may inform individualized surveillance strategies.

Meningiomas are the most common primary intracranial tumors, showing highly heterogeneous behavior and clinical outcomes. While the majority are benign, about one in five meningiomas are classified as higher grade (WHO Grade II-III), characterized by a more aggressive, treatment-resistant pathology. Although surgical resection remains the first-line therapy, peptide receptor radionuclide therapy is emerging as a novel and promising option for advanced, multifocal, or recurrent disease. The theranostic paradigm allows simultaneous detection and treatment of somatostatin receptor-expressing lesions using a single radiopharmaceutical. In this review, we explore the evolving role of PRRT in the management of meningiomas. We provide an integrated overview of preclinical findings-including radiosensitization mechanisms-and summarize the rapidly expanding clinical literature, which in recent years has grown both in patient numbers and in methodological sophistication. Particular emphasis is placed on advances in dosimetry, quantitative imaging, and radiomics, which are beginning to refine patient selection and improve response prediction. Together, current evidence highlights the therapeutic potential of radionuclide therapy in aggressive or refractory meningiomas and underscores the need for further prospective trials to define its optimal clinical application.

Background: Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood. Methods: This pilot study aimed to explore the metabolic crosstalk between MDA-MB-231 TNBC cells and MRC-5 lung fibroblasts within a co-culture system to replicate the lung metastatic TME. Co-cultures were also treated with Vitamin D or Vitamin E to evaluate the effects of these nutraceuticals on the metabolic crosstalk between TNBC cells and fibroblasts. Results: Our findings demonstrate that co-culture induced the activation of fibroblasts into cancer-associated fibroblasts (CAFs), evidenced by increased α-SMA and FAP expression. Metabolic profiling revealed that TNBC cells in co-culture displayed increased expression of enzymes associated with oxidative phosphorylation (OXPHOS) and glutamine metabolism, while fibroblasts exhibited a metabolic profile consistent with glycolysis and lactate metabolism. Vitamin D inhibited lactate metabolism and HIF-1α expression in fibroblasts while suppressing TCA cycle activity in cancer cells, suggesting a potential role in disrupting oncogenic metabolic crosstalk. Conversely, Vitamin E treatment was associated with increased expression of TCA cycle and oxidative metabolism-related markers in BrCa cells without significantly affecting fibroblast glycolysis. Such differential metabolic responses may contribute to metabolic heterogeneity within the tumour microenvironment. Conclusions: These results provide valuable insights into the metabolic dynamics of TNBC metastases in the lung TME and demonstrate that Vitamins D and E exert distinct effects on metabolic crosstalk between cancer cells and fibroblasts. These findings may have significant implications for the potential supplementation of Vitamins D and E in patients with metastatic TNBC and justify further in-depth analysis.

Background/Objectives: (P)rehabilitation, comprising structured exercise, nutritional optimisation, and/or psychological support delivered pre- or postoperatively, has demonstrated efficacy in improving outcomes across the cancer care continuum. However, access remains limited. Technology-enabled (p)rehabilitation offers a novel solution with the potential to enhance equity and continuity of care. This systematic review aimed to evaluate the efficacy of technology-enabled (p)rehabilitation on perioperative and patient-reported outcomes among individuals undergoing thoracic and/or abdominopelvic cancer surgery. Methods: Six databases were search from inception to October 2024. Eligible studies were randomised controlled trials (RCTs) comparing technology-enabled (p)rehabilitation with usual care, placebo, or non-technology-based interventions in adults undergoing thoracic and/or abdominopelvic cancer surgery. Outcomes included postoperative complications, hospital readmissions, hospital length of stay (LOS), quality of life (QoL), pain, anxiety, depression, fatigue, distress, and satisfaction. Higher scores indicated improved QoL or worse symptom severity. Risk of bias was assessed using the revised Cochrane tool, and evidence strength was determined using GRADE methodology. Relative risks (RR) and mean differences (MD) were calculated using random-effects meta-analysis. Results: Seventeen RCTs (18 publications, n = 1690) were included. Trials most commonly evaluated application-based platforms (n = 8) and the majority exhibited some risk of bias. Technology-enabled (p)rehabilitation was associated with a significant reduction in LOS (MD = 1.33 days; 95% CI: 0.59-2.07; seven trials), and improvements in pain (MD = 6.12; 95% CI: 3.40-8.84; four trials), depression (MD = 2.82; 95% CI: 0.65-4.99; five trials), fatigue (MD = 10.10; 95% CI: 6.97-13.23; three trials) and distress (MD = 1.23; 95% CI: 0.30-2.16; single trial) compared with controls. Conclusions: Technology-enabled (p)rehabilitation shows promise in reducing LOS and improving selected patient-reported outcomes following thoracic and abdominopelvic cancer surgery. Although evidence is limited due to the small number of studies, modest sample sizes, methodological heterogeneity, and intervention variability, the overall findings justify further investigation. Large-scale, adequately powered clinical trials are required to confirm efficacy and guide clinical effectiveness and implementation studies.

Background/objectives: Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). Unfortunately, data is rarely correlated with the incidence of GVHD and does not show whether smoking has a negative impact independent from underlying pulmonary comorbidities.

Methods: We retrospectively analyzed 407 patients who underwent Allo-HCT between January 2019 and May 2021 and evaluated the impact of smoking history and pre-transplant pulmonary comorbidities on the risk of outcomes including graft-versus-host disease (GVHD), overall survival (OS), and non-relapse mortality (NRM).

Results: Patients were divided into the following groups: Group A: smokers with pre-transplant pulmonary comorbidity, 40 pts (9.8%); Group B: non-smokers with pre-transplant pulmonary comorbidity, 71 pts (17.4%); Group C: smokers without pre-transplant pulmonary comorbidity, 105 pts (25.8%); and Group D: non-smokers without pre-transplant pulmonary comorbidity, 191 pts (46.9%). Smokers were also grouped by their smoking history (<10 pack-years (59 pts), 11 to 25 pack-years (50 pts), and >25 pack-years (35 pts)) and by smoking recency: Recent (until Allo-HCT), Former (quit > 1 year ago), and Remote smokers (quit > 10 years ago). Our results showed that Group A demonstrated increased chronic lung GVHD compared to the other groups (p = 0.01). The 3-year OS was lowest in Group A at 45.0%, compared to 70.4%, 62.4%, and 69.4% (p = 0.006), and the NRM was highest at 37.5%, compared to 15.5%, 18.2%, and 14.7% in Groups B, C, and D, respectively (p = 0.001). Smoking recency and higher pack-year dose were associated with worse outcomes.

Conclusions: Our study demonstrated the negative synergistic effect of smoking history and pre-transplant pulmonary comorbidities on the incidence of lung GVHD, OS, and NRM.

Background/Purpose: Primary urethral cancer is a rare malignancy, accounting for less than 1% of all urogenital cancers. Current epidemiological data from Europe are scarce and outdated. Therefore, the analyzes and comparison of the incidence and mortality of PUC in selected European countries, with particular focus on Poland, based on the most recent available registry data, were performed. Methods: Our study is based on country-level data and is descriptive in nature. Incidence data for PUC were obtained from the national cancer registries of Poland, Latvia, Slovenia, and Hungary. Mortality data were sourced from the WHO Mortality Database. Age-standardized incidence rates were calculated for two time intervals (2000-2009 and 2010-2019). Age-standardized mortality rates for individuals aged ≥45 years were calculated using the European Standard Population (ESP2013). Trends in incidence and mortality in Poland were analyzed using a five-year moving average. Results: The highest incidence of PUC was observed in Hungary, while Poland showed the lowest incidence. Latvia had the highest ASMRs for both sexes, whereas Poland and Greece reported the lowest mortality rates. Despite slight annual fluctuations, the overall PUC mortality rate in Poland has remained stable. Our study is limited by the relatively short analyzed period (2000-2021), restricted availability of C68.0 incidence data from national cancer registries, and incomplete mortality data in the WHO mortality database. Conclusions: This first contemporary comparative analysis of PUC epidemiology in Europe highlights the rarity of this malignancy and the limited data availability. Based on the knowledge drawn from the literature presented in the article on the impact of centralization on the increase in overall survival and the decrease in mortality in rare cancers, the authors believe that centralization of care can improve PUC patient outcomes.

Background: Colorectal cancer (CRC) demonstrates substantial clinical and biological diversity across age groups, ancestral backgrounds, and treatment settings, alongside a rising incidence of early-onset disease (EOCRC). The mitogen-activated protein kinase (MAPK) pathway is a major driver of CRC development and therapy response; however, the distribution and prognostic value of MAPK alterations across distinct patient subgroups remain unclear.

Methods: We analyzed 2515 CRC tumors with harmonized demographic, clinical, genomic, and treatment metadata. Patients were stratified by ancestry (Hispanic/Latino [H/L] vs. non-Hispanic White [NHW]), age at diagnosis (early-onset [EO] vs. late-onset [LO]), and FOLFOX chemotherapy exposure. MAPK pathway alterations were identified using a curated gene set encompassing canonical EGFR-RAS-RAF-MEK-ERK signaling components and regulatory nodes. Conversational artificial intelligence (AI-HOPE and AI-HOPE-MAPK) enabled natural language-driven cohort construction and exploratory analytics; findings were validated using Fisher's exact testing, chi-square analyses, and Kaplan-Meier survival estimates.

Results: MAPK pathway disruption demonstrated marked heterogeneity across ancestry and treatment contexts. Among EO H/L patients, FGFR3, NF1, and RPS6KA6 mutations were significantly enriched in tumors not receiving FOLFOX, whereas PDGFRB alterations were more frequent in FOLFOX-treated EO H/L tumors relative to EO NHW counterparts. In late-onset H/L disease, NTRK2 and PDGFRB mutations were more common in non-FOLFOX tumors. Distinct MAPK-associated alterations were also observed among NHW patients, particularly in non-FOLFOX settings, including AKT3, FGF4, RRAS2, CRKL, DUSP4, JUN, MAPK1, RRAS, and SOS1. Survival analyses provided borderline evidence that MAPK alterations may be linked to improved overall survival in treated EO NHW patients. Conversational AI markedly accelerated analytic throughput and multi-parameter discovery.

Conclusions: Although MAPK alterations are pervasive in CRC, their distribution varies meaningfully by ancestry, age, and treatment exposure. These findings highlight NF1, MAPK3, RPS6KA4, and PDGFRB as potential biomarkers in EOCRC and H/L patients, supporting the need for ancestry-aware precision oncology approaches.

Background: The prognostic value of treatment-induced necrosis in soft STS remains uncertain. This study evaluated whether MRI-based changes in necrosis (Δ necrosis) between pre- and post-neoadjuvant chemotherapy scans correlate with pathologic necrosis and clinical outcomes. Methods: In this retrospective cohort, 27 patients with STS who received neoadjuvant chemotherapy and underwent pre- and post-treatment MRI were analyzed. Necrosis was graded categorically (<5%, 5-25%, 25-50%, 50-75%, 75-95%, and >95%), and Δ necrosis was calculated as the change in estimated necrosis between scans. Correlations between MRI-derived and pathologic necrosis were assessed using Spearman's rank coefficient. Survival analyses (progression-free, local recurrence-free, and disease-specific overall survival) were performed using Kaplan-Meier and log-rank tests. Results: Post-treatment MRI necrosis moderately correlated with pathologic necrosis (ρ = 0.44, p = 0.028), whereas Δ necrosis showed a weaker, nonsignificant correlation (ρ = 0.24, p = 0.24). Neither MRI-based nor pathologic necrosis thresholds were associated with survival outcomes. Conclusions: MRI-based Δ necrosis did not predict pathologic necrosis or oncologic outcomes in STS, suggesting that radiologic changes in necrosis may not serve as reliable markers of therapeutic response. Future studies integrating quantitative imaging and standardized pathology protocols together with future exploration of molecular tools such as ctDNA are needed to refine treatment assessment in STS.

Background/Objectives: There is conflicting data on which factors predict progression events in active surveillance for early prostate cancer. Here, we explored the value of different clinicopathological variables and whether progression endpoint definitions impact predictive utility. Methods: Clinicopathological variables were extracted from the STRATified CANcer Surveillance (STRATCANs) prospective AS database and included biopsy features (core positivity, cancer core length, and percentage core involvement) and MRI features (Likert score, lesion size, and location), as well as baseline PSA density [PSAd] and Cambridge Prognostic Group (CPG). These were tested against AS endpoint definitions of (1) progression to ≥CPG3, (2) any pathological progression and two definitions from the literature, (3) ≥GG3 or change to treatment, and (4) ≥GG4, metastasis or cancer-related mortality. Predictors were assessed using regression analysis. Results: Data from 296 men were included (median age, 66; follow-up, 5 years). Progression per definition (1-4) occurred in 46 (15.5%), 54 (18.2%), 84 (28.4%), and 10 (3.4%) men. In univariate analysis using Definition 1, no biopsy parameter was independently predictive of progression, while the MRI Likert score (p = 0.02) was the only significant imaging parameter. For Definition 2, core positivity (p = 0.003) and MRI Likert score (p = 0.01) were significant predictors in univariate analyses, while for Definition 3, tumour core length (p = 0.005), core positivity (p = 0.002), and MRI Likert score (p = 0.003) were all predictive in univariate analyses. In multivariate analysis, however, the only consistent independent predictor was PSAd, regardless of endpoint definition. No variables predicted Definition 4 progression. Conclusions: AS endpoint selection appears to define which variables predict progression. Using progression to ≥CPG 3 as an unambiguous AS endpoint, neither biopsy nor MRI variables added incremental value in predicting progression. PSAd, however, appears to be a robust and independent generalisable progression predictor.