Pancreatic cancer and pancreatitis cause substantial mortality and morbidity, yet their joint global burden, epidemiology and determinants are rarely assessed together. We quantified their joint incidence burden, identified co-occurrence patterns, and examined shared risk exposures across countries.

Incidence rates for both diseases among adults aged ≥ 25 years across 204 countries and territories were obtained from the Global Burden of Disease (GBD) 2021 study. Temporal trends were assessed through estimated annual percent changes (EAPC). Country-level co-occurrence clusters were identified using Gaussian mixture modeling. Random forest models with Shapley additive explanations were used to investigate associated risk exposures. Non-seasonal time-series models were used to forecast incidence to 2040.

High-income countries predominantly clustered as dual-high for both conditions and showed modest to rapidly increasing incidence, whereas most sub-Saharan African countries were dual-low and largely stable. Many middle-SDI (Sociodemographic index) settings remained low but increased moderately over time. Smoking, alcohol use, high body-mass index, and diets high in red and processed meat were shared risk factors, with higher exposure levels in high-SDI regions. Projections indicate that pancreatic cancer incidence will continue to rise globally through 2040, driven mainly by high- and high-middle SDI regions, while pancreatitis incidence will remain comparatively stable.

Co-occurrence of pancreatic cancer and pancreatitis follows a strong sociodemographic gradient that parallels the distribution of modifiable risk exposures. Integrated strategies combining targeted surveillance with lifestyle and metabolic risk reduction are needed to mitigate the growing joint burden of pancreatic diseases.

To develop interventions to reduce neighborhood-level disparities in pediatric cancer outcomes, it is necessary to understand their underlying mechanisms. It has been suggested that individual-level health insurance is a mediator of neighborhood deprivation and pediatric cancer survival.

This study was a population-based longitudinal study of children with cancer from 2000 to 2020 in the Iowa Cancer Registry and Louisiana Tumor Registry. Neighborhood deprivation was measured using the Area Deprivation Index. Log-binomial regression models were used to identify predictors of health insurance status at diagnosis. Cox regression models were used to assess the association between health insurance status at diagnosis and cancer-specific survival. Causal mediation analyses were conducted to investigate whether health insurance status serves as a mediator of the relationship between neighborhood deprivation and survival.

The study included 5782 children with cancer: 2069 in Iowa and 3723 in Louisiana. Children in more deprived neighborhoods, non-White children, and children in Louisiana were more likely to have non-private insurance. Compared with children with private insurance, those with non-private insurance had a 32% higher hazard of cancer death (aHR = 1.32, 95% CI: 1.13-1.55). Insurance status was observed to mediate the association between ADI and cancer-specific survival, mediating 7.33%-14.59% of the estimated association.

While individual-level health insurance status was a mediator of neighborhood-level disparities in pediatric cancer survival, it did not explain a large proportion of the observed disparities. This suggests that structural and systemic factors, beyond just individual insurance coverage, may play a significant role in shaping pediatric cancer outcomes.

PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Of the 312 cases evaluated, 192 harbored NSCLC-specific oncogenic alterations. Relative to EGFR-mutated tumors, TMB was significantly higher in KRAS (p_adj = 2.7 × 10^-4), ERBB2 (p_adj = .023), and BRAF (p_adj = .023) -mutated tumors but lower in ALK-rearranged tumors (p_adj = .005). Significantly higher PD-L1 expression was seen in tumors with KRAS (p_adj = .002) and MET exon 14 (p_adj = 1.06 × 10^-4) when compared to EGFR-mutated tumors. Strong positive correlations between TMB and PD-L1 were observed in ERBB2-, KRAS-, and BRAF-mutated tumors when evaluated as continuous variables. TP53 mutations further enhanced immunogenicity when co-occurring with KRAS, ERBB2, or BRAF mutations but this effect was not observed in EGFR-mutated tumors.

These findings demonstrate distinct TMB and PD-L1 profiles that may identify patients who will benefit from ICI therapy. Cytology specimens provide adequate material for biomarker testing, which underscores their value in guiding immunotherapy decisions.

IntroductionBiparametric magnetic resonance imaging (MRI) preserves enough information to enable the prediction of prostate cancer (PCa). This fast, cost-effective, and non-invasive modality includes acquisition of T2-weighted images, and accelerated diffusion-weighted imaging (DWI) sequences with corresponding apparent diffusion coefficient (ADC) maps. In this proof-of-concept study, we aimed to assess the prediction of PCa using a tumor location-(L) dependent risk score (LADCT₂) generated from an ADC and T2 images - based model.MethodsThe single-center institutional retrospective cohort study used 113 patients who underwent multiparametric MRI (mpMRI) for the diagnosis and management of PCa. A discovery cohort (n = 58) and an evaluation cohort (n = 55) were identified from a prospectively maintained institutional cancer registry. The discovery cohort consisted of patients who underwent MRI-guided TRUS biopsies, whereas the evaluation cohort consisted of patients who received only standard TRUS biopsy. Among the discovery cohort, we developed a predictive risk score (LADCT₂) using a multivariable logistic regression model that incorporated tumor location (L) with normalized mean signal differences of T2-and ADC- tumor region of interest. The primary outcome assessed the predictive accuracy of the LADCT₂ risk score in predicting PCa.ResultsOur results demonstrated that the LADCT₂ score exhibited excellent predictive accuracy for PCa among both the evaluation (AUC = 0.84, OR = 2.80 [95% CI, 1.04-7.52]; P = .04), and discovery (AUC = 0.77, OR = 2.71 [95% CI, 1.38-5.35]; P = .003) cohorts. Additionally, it also predicted for clinically significant PCa among both the discovery (AUC = 0.71, OR = 2.11 [95% CI, 1.16-3.84]; P = .01), and evaluation (AUC = 0.65, OR = 1.94 [95% CI, 1.02-3.69]; P = .04) cohorts.ConclusionThe novel LADCT₂ risk score may function as an effective risk stratification tool to support clinical decision-making in the management of PCa.

Cancer therapy-related cardiac dysfunction (CTRCD) is a well established and potentially life-threatening complication of contemporary oncologic treatment. Although comprehensive cardio-oncology guidelines have been developed, their integration into routine hematology and oncology practice remains inconsistent. This consensus statement, developed by a multidisciplinary panel of cardio-oncology experts, aims to provide practical, case-based guidance to help oncology providers recognize, assess, and manage CTRCD across a spectrum of malignancies and cardiovascular presentations.

We present representative clinical scenarios that illustrate real-world challenges in cardio-oncology and apply evidence-based recommendations from current guidelines, including those from the European Society of Cardiology (ESC) and the International Cardio-Oncology Society (ICOS)-to support informed decision-making. Key areas of focus include baseline cardiovascular risk stratification prior to initiating potentially cardiotoxic therapies, with an emphasis on biomarker and imaging surveillance strategies tailored to individual risk profiles. Also, this document outlines the application of guideline-directed medical therapy (GDMT) for cancer patients with heart failure.

By offering a structured, user-friendly framework, this document seeks to bridge the implementation gap between oncology and cardiology disciplines. Our goal is to equip oncology providers with accessible tools that facilitate early recognition, consistent surveillance, and timely referral, thereby preserving cancer treatment intensity while minimizing cardiovascular morbidity.

This study investigates the impact of radiotherapy (RT) on fatigue levels in prostate cancer (PC) patients, considering the significant physical and psychological impact of fatigue associated with cancer and its treatments.

PC patients undergoing a radical treatment from December 2002 to September 2022 were retrospectively evaluated. Fatigue was assessed using the Cancer Linear Analogue Scale (CLAS) across three dimensions: wellbeing (CLAS1), energy level (CLAS2), and daily activity performance (CLAS3), measured at baseline (T0), 1 month (T1), and 12 months (T2) post-RT. Changes in CLAS scores ≥ 2 points from T0 were deemed clinically significant for RT-induced fatigue.

The cohort consisted of 1253 patients, with a median age of 72 years (range 45-90). Approximately 30% of patients experienced moderate or high levels of fatigue at baseline. At T1, RT-related fatigue onset (decrease of CLAS1, 2, and 3 values) was observed in 10.8%, 14.3%, and 14.8% of patients, respectively. These figures slightly increased at T2 (12.7%, 18.8%, and 19.4%, respectively). Logistic regression identified hypofractionated RT, ADT, surgery, alcohol consumption, and higher-grade toxicities as predictors of worsened fatigue across various dimensions.

In this extensive cohort of PC patients, approximately 30% experienced moderate to severe fatigue before initiating RT, with less than 20% reporting new or exacerbated fatigue post-treatment. Factors including treatment-related toxicities, hypofractionation, alcohol use, and ADT were significant contributors to fatigue. These findings underscore the complexity of managing fatigue in PC, highlighting the influence of both treatment modalities and lifestyle factors.

To evaluate the efficacy and safety of sequential immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (CCRT) in older (≥70 years) patients with locally advanced esophageal squamous cell carcinoma (ESCC).

A total of 193 older patients (≥70 years) with locally advanced ESCC treated between January 2022 and December 2023 were retrospectively analyzed and divided into two groups: the CCRT group (radiotherapy with concurrent S-1, n=108) and the CCRT+ICIs group (sequential ICIs after CCRT, n=85). Baseline imbalances were adjusted via inverse probability of treatment weighting (IPTW). The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints included safety and prognostic factors.

After IPTW adjustment, OS in the CCRT+ICIs group tended to improve compared with that in the CCRT alone group (HR = 0.70, 95% CI: 0.48-1.04, p=0.071), although the difference was not statistically significant. In contrast, PFS was significantly improved in the CCRT+ICIs group (HR = 0.59, 95% CI: 0.42-0.84, p=0.003). Multivariate analysis identified age ≥75 years (OS: HR = 1.893; PFS: HR = 2.097), ECOG score =2 (OS: HR = 3.310; PFS: HR = 2.188), T4 stage (OS: HR = 2.221; PFS: HR = 2.080), and N3 stage (OS: HR = 3.841; PFS: HR = 2.920) as independent adverse prognostic factors. Immunotherapy-specific toxicities, including hypothyroidism and pneumonitis, occurred more frequently in the CCRT+ICIs group, which is consistent with the toxicity profile of ICIs, whereas neutropenia and vomiting were less common. A lower incidence of vomiting was also observed in the CCRT+ICIs group, although the difference did not reach statistical significance (p=0.053).

Sequential ICI therapy after CCRT significantly improved PFS and reduced mortality risk in older ESCC patients, though close monitoring is warranted for pneumonitis and skin-related toxicities. The reduced incidence of neutropenia suggests a hematologic safety advantage of the sequential strategy. Patients aged ≥75 years, with an Eastern Cooperative Oncology Group (ECOG) score of 2, or with N3 disease constitute high-risk subgroups and warrant individualized treatment approaches.

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the western world. Its pathophysiology is intertwined with immune dysfunction. Emerging evidence suggests an inverse association between serum immunoglobulin E (IgE) and hematologic malignancies, but previous studies linking low IgE to CLL risk were limited by small cohorts and a lack of adjustment for confounding factors, particularly hypogammaglobulinemia.

This study aimed to evaluate the association between low serum IgE levels and the future development of CLL in a large, real-world cohort, while accounting for other immunoglobulins and confounding factors.

We conducted a retrospective quantitative observational study of 118,740 adults from a large health maintenance organization. The primary exposure was a baseline IgE level of less than 25 IU/mL. We used Kaplan-Meier curves and a multivariable Cox proportional hazards model to assess the association between low IgE and CLL diagnosis over a seven-year follow-up period, adjusting for age, sex, and other potential confounders, including hypogammaglobulinemia and atopy-related conditions.

A serum IgE level of less than 25 IU/mL was significantly associated with an increased hazard of developing CLL (HR = 1.94, 97.5% CI: 1.47-2.56). This association persisted after adjusting for all confounding variables. Established risk factors, such as older age (HR = 1.07) and male sex (HR = 1.82), were also significant. Kaplan-Meier curves showed a sustained and a statistically significant increased risk in the low IgE group throughout the follow-up period.

Lower serum IgE levels are independently associated with an increased risk of developing CLL.

Immunosenescence is characterized by immune decline and chronic inflammation. With advancing age, the incidence of tumors increases significantly. Understanding how immunosenescence influences the initiation and progression of tumors, as well as its implications for tumor immunotherapy, has become a matter of urgent importance. This review begins with an analysis of the phenotypic changes and underlying mechanisms associated with immune system and immune cell aging, and further explores the interplay between immunosenescence and tumorigenesis. Evidence indicates that cytokines, cell interactions and other mediators serve as critical links connecting aging and cancer, exerting complex anti-tumor and pro-tumor effects. However, in the context of immunosenescence, these factors collectively contribute to the formation of an immunosuppressive tumor microenvironment (TME) that facilitates tumor immune evasion and proliferation. Clinical data reveal that immunotherapy in older adults is often challenged by variable treatment efficacy and reduced tolerance. This review systematically summarizes the data related to elderly patients in immunotherapy for different types of cancers, and discusses potential immunotherapy sensitization strategies tailored for elderly patients and the mechanisms and immunomodulatory effects of senescence-modulating drugs, with the aim of enhancing therapeutic response rates and improving safety profiles.

First-line immunotherapy combined with chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC) has been consistently recommended by clinical guidelines, but the improvement in overall survival remains limited. There is an urgent need to identify reliable predictive biomarkers for immunotherapy to select patients who would benefit most. Serum ferritin (SF) is a key regulator in ferroptosis and plays a significant role in immunotherapy of lung cancer. Therefore, we hypothesized that the change rate of serum ferritin (ΔSF) during immunotherapy, combined with inflammation-related indicators, could serve as a useful predictive marker for treatment response in ES-SCLC patients.

We comprehensively reviewed the medical records of 550 ES-SCLC patients, divided into an experimental group (425 patients receiving immune checkpoint inhibitors (ICIs) plus chemotherapy) and a control group (125 patients receiving chemotherapy alone). The study analyzed the correlation between pre-immunotherapy SF levels and molecular subtypes, clinical stage, tumor location, and programmed death-ligand 1 (PD-L1) expression in ES-SCLC patients; the correlation of SF levels and ΔSF with objective response rate (ORR); the correlation of ΔSF combined with a multidimensional inflammation model-including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP)-with ORR; and survival analysis for these parameters.

Patients with lower SF levels before immunotherapy had a higher ORR (χ² = 4.837, P = 0.035) and longer progression-free survival (PFS) (median 6.9 vs. 4.1 months). Patients with a high ΔSF during immunotherapy showed a higher ORR (χ² = 6.475, P = 0.019). Patients with high ΔSF combined with low NLR and LDH levels before immunotherapy were more likely to achieve a higher ORR (P < 0.001). After integration, patients with low SF levels and high ΔSF before immunotherapy had the best PFS, whereas those with high SF levels and low ΔSF before immunotherapy had the worst PFS (median 8.9 vs. 4.5 months). Within the high ΔSF group, patients with lower NLR had longer PFS than those with higher NLR (median 9.8 vs. 5.2 months); similarly, patients with lower LDH levels had longer PFS than those with higher LDH levels (median 9.2 vs. 5.6 months). Multivariate analysis identified SF levels before immunotherapy (HR = 1.58, P = 0.026) and ΔSF during immunotherapy (HR = 0.52, P = 0.002) as independent prognostic factors. SCLC clinical stage (HR = 0.56, P = 0.037) and molecular subtype (SCLC-A: HR = 1.67, P = 0.003; SCLC-N: HR = 1.51, P = 0.012; SCLC-P: HR = 0.73, P = 0.004; SCLC-Y: HR = 0.64, P = 0.003) were also independent prognostic factors. However, NLR and LDH levels alone were not independent prognostic factors and required combined assessment with ΔSF.

Our study suggests that the serum ferritin change rate combined with the NLR and LDH inflammation model can serve as a biomarker for predicting the efficacy and survival outcomes of immunotherapy in ES-SCLC.