Adjuvant imatinib reduces recurrence risk after curative resection for intermediate- and high-risk gastrointestinal stromal tumors, but the optimal timing of postoperative initiation remains unclear. This multicenter real-world cohort study evaluated 596 patients with modified National Institutes of Health intermediate- or high-risk gastrointestinal stromal tumors who underwent R0 resection followed by adjuvant imatinib therapy at five centers in China. Postoperative imatinib initiation timing was modeled as a continuous variable using a multivariable restricted cubic spline Cox model, and the derived threshold was further evaluated using propensity score overlap weighting. The lowest recurrence risk occurred at 6.22 weeks after surgery, with a 95% confidence interval of 1.29-7.65 weeks; therefore, 8 weeks was selected as a clinically interpretable threshold. After overlap weighting, baseline covariates were well balanced between the planned initiation group (≤ 8 weeks, n = 476) and delayed initiation group (> 8 weeks, n = 120). Delayed initiation was associated with worse 5-year recurrence-free survival (70.8% vs. 82.4%) and remained independently associated with an increased risk of recurrence-free survival events in weighted analysis. Severe postoperative complications were independently associated with delayed initiation. These findings suggest that unnecessary delays in adjuvant imatinib initiation should be minimized once postoperative recovery permits and support timely transition to adjuvant targeted therapy as part of postoperative gastrointestinal stromal tumor management.

Venous thromboembolism (VTE) is a serious complication for breast cancer (BC) survivors. We identified records of female BC survivors from the Korean Health Insurance Service database between January 1, 2010, and December 31, 2016. After applying exclusion criteria (age < 18 years, prior cancers or VTE, absence of BC surgery, or missing data), 112,522 BC survivors were included; for the comparison group, BC survivors were matched (1:3) to women without cancer history. VTE risk was evaluated with a Fine and Gray model, accounting for death as a competing risk; multiple time periods were analyzed. Associations between VTE risk and treatment modalities also were estimated. Over a mean analysis period of 7.4 years, BC survivors had 3621 VTE events; their subdistribution hazard ratio (sHR) for VTE was greater than that of the comparison group (sHR 1.68, 95% CI 1.61-1.75). The risk was prominent within the first year post-diagnosis (sHR 7.78, 95% CI 6.88-8.80) and attenuated in analyses restricted to VTE events occurring beyond 1 year after diagnosis (sHR 1.34, 95% CI 1.28-1.40), but remained significantly elevated in landmark (delayed-entry) analyses starting at later time points. Anthracycline (sHR 1.11, 95% CI 1.00-1.23) and taxane (sHR 1.73, 95% CI 1.57-1.91) therapies were associated with an increased risk of VTE in 1-year landmark analysis. Female BC survivors are at increased risk of VTE, especially during the first year post-diagnosis, which underscores the importance of VTE risk assessment for BC survivors.

Human papillomavirus (HPV), the necessary cause of cervical cancer, is associated with an increased risk of other anogenital cancers. While HPV has frequently been detected in prostate specimens, its role in prostate carcinogenesis remains controversial. We synthesized and meta-analyzed the epidemiological literature on the association between HPV and prostate cancer. We completed a systematic search of Embase, MEDLINE, Scopus and Cochrane on January 31, 2025. Two reviewers independently screened articles and extracted data on study design and population, sample characteristics, HPV and prostate cancer ascertainment methods, and results. We pooled risk estimates using a random effects model and performed subgroup meta-analyses by HPV risk level, genotype, and control group. Our search identified 1874 unique records. Of 84 included articles (1990-2025), 57 were cross-sectional, 15 case-control, 6 nested case-control, and 6 were cohort studies. HPV detection methods reported were HPV DNA (n = 57); HPV serology (n = 17); subjects' self-report (n = 5); chart review, registry or claims data (n = 4); RNA (n = 3); and immunohistochemistry (n = 2). Most studies (58.3%) reported HPV prevalence below 20%. Our meta-analysis (39 studies) produced a pooled odds ratio (OR) of 2.35 (95% CI: 1.87-2.95). When restricted to high-risk HPV, the pooled OR was 2.75 (95% CI: 1.69-4.46). HPV16, HPV18, and HPV33 had positive associations with prostate cancer (pooled ORs: 2.28, 95% CI: 1.18-4.40; 2.37, 95% CI: 1.16-4.87; 3.73, 95% CI: 0.46-30.30, respectively) and the association was strongest when using normal tissue as controls (pooled OR:4.81, 95% CI: 1.83-12.69). Our findings support a positive association between the detection of oncogenic HPV DNA in prostate specimens and prostate cancer, although its etiologic significance remains unclear.

The incidence of early-onset colorectal cancer (CRC), commonly defined as diagnosis prior to age 50, is increasing. Studies of patients diagnosed prior to age 35 as a distinct subset of all early-onset patients have yielded inconsistent results. We extracted prospectively collected data from consecutive patients with metastatic colorectal cancer (mCRC) entered in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australasian registry. We focused on comparing demographic and clinicopathologic characteristics of those diagnosed < 35Y with remaining early-onset patients (35-49Y) whilst including a comparison to older patients (≥ 50Y) as a reference point. Molecular data were examined from 2015 when testing became reflexive. From July 2009 to December 2023, we identified 4399 patients with mCRC, including 133 (3.0%) < 35Y, and 537 (12%) 35-49Y. The proportion of < 35Y among newly diagnosed mCRC increased per calendar year (odds ratio 1.07, 95% CI 1.02-1.11). Gender, ECOG performance status and primary tumour location were similar for < 35Y and 35-49Y. Compared to 35-49Y, < 35Y had more de novo metastatic disease (79% vs. 70%; p = 0.04), BRAF V600E mutations (32% vs. 10%, p < 0.001) and deficient mismatch repair (dMMR) tumours (9.8% vs. 2.8%, p = 0.008). Rates of chemotherapy, rates of liver resection and overall survival (OS) were similar between < 35Y and 35-49Y. Multiple differences were observed between < fand 35-49Y, most notably a higher rate of BRAF V600E mutations and dMMR cancers. Collectively, these findings may inform the interpretation of clinical outcomes, refine screening approaches and advance understanding of CRC tumorigenesis in younger patients.

In a recent publication, Lapitz et al. reported differences in serum levels that predict the development of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis prior to clinical manifestation. We examined whether these biomarkers also predict the risk of gallbladder cancer (GBC) in European prospective plasma samples from 24 GBC cases and 90 control individuals. After logarithmic transformation and quantile normalisation of individual protein levels measured with a timsTOF PRO mass spectrometer, we fitted univariate logistic regression models and applied backward model selection to identify the optimal model for GBC risk prediction. CRP and MASP2, previously reported markers of CCA, were found to be predictive for GBC risk as well (p value < 0.05), and complemented by age at blood sampling, provided an area under the receiver operating characteristic curve of 0.80 (95% confidence interval 0.69-0.92) when combined in a prediction model for GBC risk. We further examined the mRNA expression of CRP and MASP2 in serum samples from 82 GBC cases and 79 control subjects from Chile. CRP mRNA levels were elevated in Chilean GBC cases, but MASP2 showed an opposite trend. While there are considerable differences in the design of the discovery study and ours, the finding that circulating levels of CRP and MASP2 are associated with the risk of both CCA and GBC in Europeans highlights the need for further research into potential shared mechanisms and strategies for the prevention of these two aggressive biliary tumours.

Allostatic load (AL) reflects the cumulative physiological burden of chronic stress throughout life, potentially influencing cancer onset and prognosis. However, its association with primary liver cancer (PLC) risk and potential interaction with genetic susceptibility remains unclear. To investigate this, we analyzed 374,632 UK Biobank participants. AL was evaluated using a composite score of 13 cardiovascular, metabolic, and immune biomarkers, while a weighted polygenic risk score (PRS) categorized genetic susceptibility. Multivariable Cox proportional hazards models and restricted cubic splines were utilized to estimate hazard ratios (HRs) and evaluate dose-response relationships. Over a median 12.4-year follow-up, a significant dose-response correlation between AL and PLC risk was observed. In the fully adjusted model, a 1-unit increase in AL was associated with a 17% increased risk (HR = 1.17, 95% CI: 1.12-1.23), and participants in the highest AL quartile exhibited a 2.60-times higher risk than those in the lowest (HR = 2.60, 95% CI: 1.72-3.95). Despite no multiplicative interaction, stratified analyses revealed AL's impact was most substantial in individuals with intermediate genetic risk (HR = 2.00, 95% CI: 1.38-2.90), who constitute the population majority. Additionally, the risk was heightened in overweight/obese individuals and more pronounced among non-smokers. Ultimately, cumulative physiological stress, indicated by AL, is strongly associated with PLC, supporting the "wear-and-tear" theory of its development. This research highlights a "malleable zone" in individuals with moderate genetic risk, suggesting that lowering AL may meaningfully aid in preventing PLC.

Precision oncology relies primarily on DNA-level alterations for therapeutic decisions, but the extent to which driver mutations propagate to protein abundance has not been systematically evaluated. Here, I developed a regression-based transmission score (TS_R[2]) to quantify driver alteration signal propagation across DNA, mRNA, and protein layers. Applying this framework to matched genomic, transcriptomic, proteomic, and phosphoproteomic data from 754 Clinical Proteomic Tumor Analysis Consortium (CPTAC) tumors across seven cancer types, I analyzed 86 driver gene-cancer type pairs, of which 83 were evaluable for the full two-layer transmission score. I employed covariate-adjusted regression for each molecular transition, assessing significance via permutation testing (n = 1000). Mixed-effects modeling then partitioned gene-intrinsic from cancer-type-dependent effects. Only 5 of 83 evaluable pairs (6%) demonstrated high transmission (TS_R[2] > 0.05), with receptor tyrosine kinases (EGFR, FGFR2) exemplifying this class. The primary bottleneck occurred at the mutation-mRNA transition, not mRNA-protein translation. Gene identity accounted for 49% of transmission efficiency variance, nearly double the contribution of cancer type (29%). Copy number alterations transmitted signals 13.8-fold more efficiently than point mutations, and truncating mutations showed higher transmission than missense variants (Wilcoxon p = 0.005). Microsatellite instability attenuated mRNA-protein transmission in UCEC and COAD. These findings demonstrate that many driver alterations show limited propagation to protein abundance. This challenges DNA-only interpretations in precision oncology and provides a framework for integrated functional driver prioritization.

While granulocyte colony-stimulating factor (G-CSF) is used to prevent and treat chemotherapy-induced neutropenia, it also regulates key immune cells and may therefore affect the efficacy of immunotherapy. Short-acting and long-acting G-CSF have similar efficacy in managing neutropenia, but they differ in effects on immune cells. However, the overall impact of G-CSF and its different formulations on survival in advanced lung cancer patients receiving chemoimmunotherapy remains unclear. This retrospective study enrolled patients with advanced primary lung cancer receiving first-line chemoimmunotherapy at Tianjin Medical University Cancer Institute and Hospital. The primary outcome was overall survival (OS). Inverse probability of treatment weighting (IPTW) was used to balance heterogeneity between groups. Kaplan Meier and Cox models were used to estimate OS and progression-free survival (PFS). Among 606 patients, 308 developed neutropenia and received G-CSF support (pegylated recombinant human G-CSF [PEG-rhG-CSF]: 183; recombinant human G-CSF [rhG-CSF]: 125); 298 without neutropenia received no G-CSF. After IPTW, no significant differences in PFS and OS were observed between G-CSF group and non-G-CSF group. Patients receiving rhG-CSF had significantly improved OS (42.6 vs. 28.2 months, p = 0.041) and PFS (15.4 vs. 9.4 months, p < 0.001) than those receiving PEG-rhG-CSF. Multivariable analysis confirmed rhG-CSF as a favorable independent prognostic factor for both PFS and OS. Among patients with advanced primary lung cancer receiving first-line chemoimmunotherapy, G-CSF support effectively abrogates the adverse survival impact of chemotherapy-induced neutropenia. Moreover, rhG-CSF was associated with improved clinical outcomes versus PEG-rhG-CSF. Prospective randomized trials are required to validate these findings and guide clinical practice.

Clinical and sonographic examination of breasts and axillae is standard in breast cancer (BC) care. The aim of this study is to highlight the value of axillary ultrasound in identifying axillary recurrences in male BC, which is still little considered in the literature. This was a registry-based observational multicenter cohort study in Germany. Five hundred and seventy-seven male patients with invasive non-metastatic BC were included. Five hundred and sixty three patients underwent a clinical examination of the axilla, and 500 had an axillary ultrasound. The examination results were used to determine sensitivity and specificity for predicting lymph node metastases depending on the nodal status. The axillary recurrences were determined during follow-up. The sensitivity and specificity were 30.4% and 93.2% for axillary palpation, 42.2% and 88.9% for ultrasound, and 49.5% and 85.3% for both methods combined. Both methods, considered either separately or combined, showed an increase in sensitivity with increasing lymph node involvement. In the combined analysis, the sensitivity varied from 38.5% (pN1) to 80.0% (pN3). Sensitivity was higher in Grade 3 compared to Grades 1 or 2 carcinomas, in patients aged > 68 years compared to younger patients, and in non-obese compared to obese patients (BMI > 30 kg/m[2]). The axillary recurrence rate was 1.21%. The axillary examination is an important part of pre-therapeutic diagnostics in male patients; however, ultrasound and palpation appear less sensitive than in female disease. The probability of axillary recurrence is very low after adequate therapy in male BC patients without distant metastases and in those with a low risk of metastases based on tumor biology.

Primary screening for human papillomavirus (HPV) followed by treatment with thermal ablation (TA) is an important component of the global strategy to eliminate cervical cancer. However, evidence on post-TA outcomes in women living with HIV (WLWH) remains limited. The aim of this study is to evaluate the risk and determinants of post-TA CIN2+. As part of the AIMA-CC study, WLWH from Côte d'Ivoire, Burkina Faso and Cambodia were screened using HPV testing (GeneXpert). All HPV-positive women were biopsied and those with positive triage (positive visual inspection and/or HPV-161845) were treated with TA using a flat probe and followed for 12 months with HPV testing and biopsies. Among the 456 WLWH (age: 30-59 years) treated with TA and with valid histology, 396 (86%) attended the 12-month follow-up visit. HPV persistence (HPV of same GeneXpert channel at baseline and 12-month post-treatment) was 40% and was associated with baseline HPV16 positivity (p = 0.007), age ≥ 40 years (p = 0.03) and CD4 ≤ 500 cells/mm[3] (p = 0.02). CIN2+ was detected at 12 months in 12 (4%) of the 318 WLWH with valid histology and was associated with 12-month HPV positivity (OR: 5.29 [1.46-28.46]). The risk of CIN2+ was particularly high among women with HPV-16 at 12 months (OR: 15.53 [3.49-91.17]). HPV positivity at 12 months had a sensitivity for detecting CIN2+ of 83% but a specificity of 54%. HPV-16 positivity had lower sensitivity (42%) but high specificity (> 90%). In conclusion, there is an urgent need to improve TA management in WLWH who are at high risk of CIN2+ re-occurrence post-treatment.

Although Helicobacter pylori (H. pylori) infection, a well-established risk factor for gastric cancer, has been implicated as causative in biliary tract cancer (BTC) and pancreatic cancer (PC), the evidence remains inconclusive. Moreover, while germline pathogenic variants may modify the association between H. pylori infection and gastric cancer risk, their roles in BTC and PC are unclear. We examined these associations while accounting for genetic susceptibility and lifestyle factors. Two case-control studies were conducted, including 116 BTC cases, 417 PC cases, and 3086 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, sex, study version, carrier status of pathogenic variants, smoking, and alcohol consumption. H. pylori infection was defined by antibody seropositivity, pepsinogen-based atrophic gastritis (AG), and their combination. Subsite-specific analyses were also performed. No significant association was observed between H. pylori infection and BTC risk. However, higher H. pylori antibody titers (per 10 U/mL increase) were positively associated with overall PC risk (OR 1.04, 95% CI: 1.01-1.07). In subsite analyses, AG without detectable antibodies was positively associated with pancreatic head cancer risk (OR 3.04, 95% CI: 1.23-7.54), whereas H. pylori seropositivity was positively associated with pancreatic body cancer risk (OR 1.75, 95% CI: 1.10-2.77). No interaction between H. pylori infection and pathogenic variants, smoking, or alcohol consumption was observed for either cancer. These findings suggest that H. pylori infection may be associated with pancreatic cancer risk in specific anatomical regions, with limited evidence for modification by genetic or lifestyle factors.

Socioeconomic position (SEP) influences cancer care and outcomes, even in countries with government-funded healthcare. This population-based study examined associations between SEP, rectal cancer care and survival of patients in the Netherlands. Data from 25,995 patients with Stage I-III rectal cancer diagnosed between 2015 and 2023 were obtained from the Netherlands Cancer Registry. SEP was categorised as lower, intermediate or higher using income-based postal code data. Associations between SEP and detection method, treatments, and outcomes were analysed using multivariable logistic regression. Relative survival and relative excess risk (RER) of death were calculated using a generalised linear model. Compared to lower SEP, higher SEP patients were younger (median age 66 vs. 71 years), more often male (65% vs. 59%), had better performance status (71% vs. 52% PS0), fewer comorbidities (63% vs. 50% CCI 0) and lower obesity rates (15% vs. 23%). Higher rates of Stage I tumours (34% vs. 30%), screen-detection (45% vs. 38%), laparoscopic surgery use (93% vs. 90%), and lower rates of colostomies (64% vs. 71%) and adverse in-hospital outcomes (44% vs. 55%) were observed among higher SEP patients (all p < 0.001). Five-year relative survival improved with increasing SEP (79.5% lower, 82.4% intermediate, 84.9% higher SEP; p < 0.001), with lower excess mortality for higher SEP patients (RER 0.90, 95% CI 0.81-0.99). SEP-related differences were observed in screening, stage at diagnosis, surgical treatment and survival. Although several disparities were partly explained by comorbidity and BMI, others persisted, highlighting the need for targeted strategies to reduce differences between SEP groups in rectal cancer management and outcomes.

Neutrophils are the most abundant immune cells in bone marrow (BM); their differentiation, maturation, and clearance are tightly regulated by the BM microenvironment. Multiple myeloma (MM) is a malignant plasma cell disorder that leads to multi-organ damage, including BM disruption, which may subsequently affect resident neutrophils. The present study was designed to systematically characterize BM neutrophils in MM, to advance the understanding of their potential biological roles in disease initiation and progression, and to identify potential neutrophil-based biomarkers of clinical relevance. Firstly, developmental profiling of BM neutrophils via cytomorphology and flow cytometry revealed a pronounced enrichment of mature neutrophils in MM patients. Furthermore, single-cell RNA sequencing (scRNA-seq) was utilized to characterize the transcriptional heterogeneity of BM neutrophils, with particular focus on the mature subsets. This analysis revealed a disease-specific subpopulation of CD83[+] neutrophils exhibiting anti-apoptotic and senescence-like features. The prolonged lifespan of these cells likely facilitates a phenotypic shift toward an immunosuppressive state, as evidenced by the upregulation of multiple inhibitory molecules. Clinical data, integrated with flow cytometric and bioinformatic analyses, were further applied to investigate the pro-tumor features of CD83[+] neutrophils and to uncover their potential tumor-promoting pathways. Notably, the abundance of CD83[+] neutrophils correlates with adverse clinical features in MM patients. In conclusion, this study demonstrates that the MM BM microenvironment shapes the maturation trajectory of neutrophils, driving the emergence of a CD83[+] senescence-like and pro-tumor neutrophil subset. This provides new insights into neutrophil-based biomarkers for risk stratification and disease monitoring in MM.

Early detection of pancreatic cancer remains challenging, and reliable circulating biomarkers are needed to enable earlier diagnosis and improve clinical outcomes. We conducted a plasma proteomics study using the Olink Explore HT platform to identify novel biomarker candidates for early-stage pancreatic cancer. The study included 42 patients with stage I-II pancreatic cancer and 43 matched controls. Plasma protein levels were quantified using the Olink Proximity Extension Assay, and differential abundance was assessed using Welch's t-test with correction for multiple testing. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among 5419 proteins analyzed, 982 showed significant differences between cases and controls. Carboxylesterase 3 (CES3) was the most significantly decreased protein, whereas leukocyte immunoglobulin-like receptor B4 (LILRB4) was the most significantly increased protein; both demonstrated excellent diagnostic performance (AUC = 0.91). In addition, pancreatic polypeptide (PPY) showed markedly reduced levels in patients with tumors arising in the head of the pancreas, suggesting anatomical specificity. This comprehensive Olink-based proteomic analysis identifies CES3 and LILRB4 as promising plasma biomarkers for early-stage pancreatic cancer and highlights PPY as informative for tumor localization. These findings provide a valuable resource for biomarker discovery and support further validation of these candidates for noninvasive early detection and risk stratification.