Cancers最新文献

Background and Objective: Radiographic progression in prostate cancer (PCa) can occur even when prostate-specific antigen (PSA) levels are undetectable. We aimed to determine the frequency and characteristics of radiographic disease progression (rDP) on PSMA PET/CT in patients with undetectable PSA, referred to as PSA zero rDP. Methods: We analyzed the Mayo Clinic PSMA PET Prostate Cancer Registry to identify patients with rDP on PSMA PET/CT despite undetectable PSA levels. Disease progression was confirmed via biopsy or treatment response. The cohort included patients with non-metastatic and metastatic hormone-sensitive disease, as well as those with castration-resistant prostate cancer at the time of imaging. Overall survival (OS) was estimated using the Kaplan-Meier method. Group comparisons were performed with the log-rank test. Univariate Cox regression was used to identify factors associated with poor OS. Key findings and Limitations: Among 2141 patients imaged between 2021 and 2023, 257 (12%) had PSA zero rDP. Sixty-one percent had initially localized disease; 39% had de novo metastatic disease. Median (IQR) time from diagnosis to PSA zero rDP was 51.9 (18.4-115.5) months. A total of 184 patients (72%) progressed to castration-resistant PCa. Sites of rDP included bone (57%), visceral (15%), lymph node (18%), and local recurrence (10%). During median follow-up of 8.1 (3.5-11.9) months, 5% of patients died. Only visceral metastases were significantly associated with poorer OS (p < 0.0001). Conclusions and Clinical Implications: Prostate cancer patients frequently develop metastatic disease with undetectable PSA values. Our findings suggest the use of periodic advanced imaging techniques, irrespective of PSA value, for more prompt detection and early management of disease progress.

Background/Objectives: Head and neck adenoid cystic carcinoma (HNAdCC) is characterized by indolent growth but sustained long-term risk of late recurrence and disease-related mortality. Data describing very long-term outcomes using analytic approaches that explicitly account for competing mortality remain limited. We aimed to characterize late failures, competing causes of death, and clinically interpretable long-horizon risk estimates after primary surgery for HNAdCC. Methods: We performed a retrospective single-center cohort study of patients with HNAdCC treated with curative-intent surgery between 1984 and 2020. Overall survival (OS) and cancer-specific survival (CSS) were estimated using Kaplan-Meier method. Competing risks of disease-related and other-cause death, as well as first-failure patterns, were analyzed using cumulative incidence functions, including a 5-year landmark analysis. Conditional mortality and restricted mean survival time (RMST; τ = 25 years) were additionally assessed. Results: Fifty-seven patients were included (median age 54 years). Median follow-up was 133 months overall and 212 months among survivors. A first failure occurred in 19/57 (33.3%) of patients, with distant metastasis as the most common pattern; 7/19 (36.8%) of failures occurred beyond 5 years. OS at 5, 10, and 25 years was 68.4%, 64.9%, and 37.5%, respectively; corresponding CSS was 78.9%, 74.8%, and 51.7%. At 25 years, cumulative incidence of disease-related death was 41.7%, compared with 20.9% for other-cause death. Older age and advanced T category were independently associated with worse OS, while older age and perineural invasion predicted worse CSS. Among 5-year survivors, conditional risk of disease-related death by 25 years remained 32.7%. RMST analyses demonstrated substantial long-term life-years lost associated with perineural invasion and T3-4 disease. Conclusions: HNAdCC exhibits persistent long-term risk with clinically meaningful late failures and substantial competing mortality over decades. Conditional and RMST-based estimates provide patient-centered measures that support lifelong, risk-adapted surveillance, particularly focused on detection of distant metastases.

Background: Fusion-negative rhabdomyosarcoma (FNRMS) represents the most prevalent subtype of rhabdomyosarcoma, the most common pediatric soft-tissue sarcoma. Although its invasion is a leading cause of recurrence and poor prognosis, its underlying mechanism remains unclear. We investigated how extracellular matrix density regulates FNRMS progression via mechano-transduction. Methods: We used three-dimensional spheroid invasion assays with FNRMS cells embedded in varying collagen concentrations. Mechanistic insights were gained through immunofluorescence, sequencing reanalysis, calcium live-cell imaging, and pharmacological inhibition of the YAP-PIEZO1 axis. Results: High extracellular matrix density significantly enhanced invasive spreading, correlating with increased YAP nuclear localization. YAP overexpression was sufficient to promote invasive spreading, while its inhibition attenuated the matrix-enhanced phenotype. We identified PIEZO1 as a direct transcriptional target of YAP. High extracellular matrix density stimulated PIEZO1-dependent calcium influx, which was required for invasion. Furthermore, elevated PIEZO1 expression was significantly associated with poorer overall survival in FNRMS patients. Targeting YAP effectively suppressed both calcium flux and invasion. Conclusions: Our findings establish a YAP-PIEZO1 axis linking extracellular matrix density to FNRMS invasion. This mechanosensitive pathway represents a potential therapeutic vulnerability in aggressive FNRMS.

Background/Objectives: There is little information on the definition and management of dyslipidemia in patients and survivors of childhood, adolescent and young adult (CAYA) cancer. However, it is known that this population is at higher risk of developing cardiovascular disease (CVD). Dyslipidemia, hypertension, and metabolic syndrome are common among CAYA cancer survivors due to the cancer itself or the treatment received. Therefore, managing dyslipidemia in this population is crucial to mitigate the risk of long-term CVD. The aim of this systematic review was to summarize currently used definitions and cutoffs for dyslipidemia, its prevalence, and management strategies in CAYA cancer survivors. This review further describes reported pharmacological and lifestyle interventions and their impact on lipid levels. Methods: We conducted a systematic literature search in PubMed, including studies published in English, German or French between January 2015 and February 2025. The population included individuals diagnosed with any type of CAYA cancer prior to 25 years of age and either receiving cancer treatment or in follow-up care. We considered all types of publications except for Phase I and II studies. We followed PRISMA guidelines, assessed the quality of the eligible studies according to the respective Joanna Briggs Institute's Critical Appraisal Tools, and reported the results descriptively. Results: Of 575 identified publications, 53 fulfilled the inclusion criteria. Forty-three studies reported on the definitions of abnormal lipid values, 40 stated the prevalence of abnormal lipid values, and 17 studies described management approaches, of which 12 were case reports and small case series. For all three outcomes, the results were very heterogeneous. Using the example of triglycerides (TGs), the cutoff values for high TGs ranged from 5.17 mmol/L to 6.2 mmol/L and the reported prevalence of high TGs ranged from 0% to 75%, with an average of 31%. The only reported intervention to prevent dyslipidemia in CAYA cancer survivors was lifestyle modification. Preventive strategies that started during treatment were lifestyle modifications and fish oil supplements. Conclusions: Our systematic review provides a comprehensive overview of existing definitions, prevalences, and management of abnormal lipid values in CAYA cancer patients and survivors. However, the identified heterogeneities indicate that reported prevalences and results of interventions must be interpreted cautiously. An internationally harmonized approach to defining and reporting lipid values in CAYA cancer survivors is urgently needed to enable tailored screening and treatment strategies.

Protein-based nanocarriers have gained considerable attention for targeted cancer theranostic applications due to their inherent biocompatibility, biodegradability, and facile functionalisation. In addition, some of their properties, such as self-assembling nature, low immunogenicity (if species matched), molecular recognition ability, and lack of persistence due to degradation into proteinogenic amino acids, make them highly suitable for oncology-related applications. Each protein-based nanocarrier exhibits unique physicochemical and biological properties. In this review, we summarise recent advances in targeted protein-based nanocarriers, including albumin, lipoproteins, ferritin, viral protein capsids, fibrin type proteins and silk proteins, emphasising receptor-specific targeting mechanisms, the integration of various imaging modalities along with their advantages and limitations, and the importance of employing advanced preclinical models for translational theranostic applications. This review also discusses the most recent and significant studies in the field, providing useful insights into future directions of protein-based nanocarriers for cancer theranostics.

Background: The da Vinci single-port reduced-port robotic distal gastrectomy (spRRDG) approach shows promise in enhancing surgical recovery while maintaining oncologic safety, but robust multicenter comparative data across diverse robotic platforms are lacking. We aimed to compare clinical outcomes between spRRDG and conventional RRDG (cRRDG) using Korean Laparoendoscopic Gastrointestinal Surgery Study-13 data.

Methods: Clinicopathologic variables and perioperative outcomes concerning 820 patients who underwent curative RRDG with D1+ or D2 lymph node dissection (LND) (da Vinci spRRDG, n = 86; cRRDG, n = 734) were analyzed. We compared continuous variables using Student's t- or Wilcoxon rank-sum tests, as appropriate, and categorical variables using χ² or Fisher's exact tests. Subgroup analyses were performed according to the extent of LND (D1+ vs. D2). Statistical significance was defined as p < 0.05.

Results: spRRDG involved a longer operative time than cRRDG (227.06 ± 6.19 vs. 183.58 ± 2.18 min, p < 0.0001) and fewer retrieved LNs (rLNs) (36.38 ± 1.53 vs. 46.52 ± 0.66, p < 0.0001), but showed superior enhanced recovery after surgery (ERAS)-related outcomes, including shorter hospital stay (4.06 ± 0.23 vs. 5.95 ± 0.13 days), and earlier gas passage (postoperative day [POD] 2.24 ± 0.10 vs. 3.08 ± 0.04) and soft diet initiation (POD 1.59 ± 0.14 vs. 2.89 ± 0.07; all p < 0.0001). In subgroup analyses, the number of rLNs was lower in D1+ spRRDG (34.09 ± 1.58 vs. 44.36 ± 0.72, p < 0.0001), but remained above the oncologic threshold (≥16 LNs). In D2 dissections, no significant difference was observed (45.71 ± 3.69 vs. 53.30 ± 1.39, p = 0.1030). Faster postoperative recovery in spRRDG persisted after adjustment.

Conclusion: spRRDG exhibited lower rLNs than cRRDG but remained within an oncologically acceptable range. Comparable complication rates and significantly improved ERAS outcomes suggest spRRDG is safe and feasible; however, its clinical application should remain limited to early gastric cancer until robust evidence from prospective studies emerges.

Thyrotroph pituitary neuroendocrine tumors (PitNETs) are rare functional pituitary tumors characterized by autonomous secretion of thyroid-stimulating hormone (TSH), leading to central hyperthyroidism. Under the 2022 World Health Organization classification, these tumors are defined as PIT1-lineage PitNETs, reflecting lineage-specific differentiation and improving pathological accuracy. Clinically, thyrotroph PitNETs often present as macroadenomas with invasive growth, making complete surgical resection challenging and necessitating multimodal treatment strategies. From a molecular oncology perspective, thyrotroph PitNETs lack recurrent driver mutations and instead exhibit heterogeneous alterations involving dysregulated cell-cycle control, impaired thyroid hormone-mediated negative feedback, and aberrant growth factor signaling. Immunohistochemically, tumor cells express PIT1 and TSH and show strong membranous expression of somatostatin receptor subtype 2, providing a biological rationale for somatostatin receptor ligand -based therapy. Somatostatin receptor ligands play a central role in the management of thyrotroph PitNETs as preoperative, adjuvant, or primary treatment and achieve effective hormonal control and tumor stabilization or shrinkage in many patients. Accurate differentiation between thyrotroph PitNETs and resistance to thyroid hormone β is essential, as these entities share biochemical features but require fundamentally different management. Advances in lineage-based tumor classification, receptor profiling, and molecular pathology have refined diagnostic strategies and enabled a more personalized, tumor-oriented therapeutic approach. This review highlights current insights into the tumor biology and treatment of thyrotroph PitNETs and discusses future perspectives for receptor-targeted and molecularly informed therapies.

Background: Patients with coexisting lung cancer and COPD are highly susceptible to unplanned readmissions. This study aimed to develop and internally validate a robust predictive nomogram based on the "inflammation-nutrition-tumor" framework to quantify this risk. Methods: A retrospective cohort of 207 clinical episodes from male patients with lung cancer and COPD was analyzed. Participants were categorized into Planned Readmission (PR, n = 165) and Unplanned Readmission (UR, n = 42) groups. Independent risk factors were identified via univariate and multivariable analyses using Generalized Estimating Equations (GEE). A nomogram was subsequently constructed, and its performance was rigorously evaluated using the Area Under the Curve (AUC), calibration plots, and Decision Curve Analysis (DCA). Results: Multivariable GEE analysis demonstrated that the Systemic Immune-Inflammation Index (SII) was a highly significant independent risk factor (OR for a 500-unit increase = 1.490, 95% CI: 1.234-1.798, p < 0.001). Advanced cancer stage (III-IV) was also a significant predictor (OR = 3.590, 95% CI: 1.301-9.909, p = 0.014), while prealbumin (OR = 0.950, 95% CI: 0.896-1.007, p = 0.087) was identified as a key nutritional predictor. The integrated four-variable nomogram (age, cancer stage, SII, prealbumin) demonstrated good discriminative ability with an AUC of 0.809 (95% CI: 0.733-0.885). The calibration plot indicated excellent agreement, and DCA confirmed a substantial clinical net benefit. Conclusions: This SII-based nomogram provides a reliable and practical tool for individualized risk stratification, facilitating targeted clinical interventions to mitigate unplanned readmission rates in this vulnerable population.

Cancer continues to be a major cause of death, with an anticipated 2,114,850 new cases and almost 626,140 deaths from the disease in 2026 [...].

Background/Objectives: Co-testing may improve cervical cancer prevention by stratifying women into groups with different absolute risks of CIN2+, CIN3+, and cervical cancer. We evaluated real-world co-testing with cervical cytology and a genotype-specific HPV E6/E7 mRNA assay targeting HPV16, HPV18, and HPV45 (PreTect SEE) in routine clinical practice. Methods: We conducted a retrospective, registry-based cohort study at the Department of Clinical Pathology, University Hospital of North Norway. Eligible co-test samples (liquid-based cytology with concurrent HPV mRNA testing, both with valid results) from routine screening, follow-up, and clinically indicated testing were identified from the laboratory information system and passively followed for worst histological outcome through December 2025. Outcomes were no biopsy/Results: Among 116,217 eligible co-test samples (mean age 43.9 years), cumulative risks were 4.4% for CIN2+, 1.5% for CIN3+, and 0.1% for cervical cancer. Baseline HPV mRNA positivity was 3.9%, and cytology was ASC-US+ in 12.2% of samples. Co-testing produced a clear stepwise risk gradient. Double-negative results (NILM/mRNA-; 86.7%) had very low risks (CIN3+ 0.2%; cervical cancer 0.02%). ASC-US+/mRNA- results (9.3%) showed intermediate risks (CIN3+ 4.1%; cervical cancer 0.2%). NILM/mRNA+ results (1.1%) showed substantially higher risks despite normal cytology (CIN3+ 13.0%; cervical cancer 0.5%). Double-positive results (ASC-US+/mRNA+; 2.8%) had the highest risks (CIN3+ 28.5%; cervical cancer 2.3%). Within NILM, mRNA positivity captured 42.7% of CIN3+ cases and 25.0% of cancers. Genotype-specific analyses showed highest risks for HPV16, followed by HPV18 and HPV45. Conclusions: Co-testing with cervical cytology and a 3-type HPV mRNA assay provided strong, clinically interpretable risk stratification and identified a small but high-risk subgroup among women with normal cytology. These findings support genotype-specific HPV mRNA testing as an adjunct to cytology in routine care.