Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes.

A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers.

Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicating the tumor core.

Across organs and tumor types, tumor morphological phenotype on CT imaging is largely driven by a host tissue-related environmental "imprint" rather than the primary tumor site.

Context-aware modeling is essential for reliable radiomic biomarkers and could motivate a two-step AI pipeline that first identifies the organ habitat and refines lineage-specific predictions.

In a large, multicenter cohort, tumors exhibited distinct morphological clustering. These clusters did not align with primary tumor sites (ARI = 0.04). Stronger associations emerged between morphological clusters and the local anatomical environment (ARI = 0.37). Stratification by lesion type revealed even stronger associations between local anatomical context and solid organ metastases (ARI = 0.60).

Major head and neck surgeries are associated with significant perioperative morbidity. Despite extensive metabolic parameter investigations, consistent prognostic indicators remain undefined. This study aimed to elucidate metabolic predictors for perioperative prognosis.

A prospective observational study evaluated patients undergoing major head and neck surgeries (2019-2020). Nutritional status was assessed preoperatively and on postoperative days 2 and 10 using electric bioimpedance analysis. Phase angle, a bioelectrical marker of soft-tissue mass and hydration, served as a nutritional status indicator.

37 patients were included (mean age 61.3 ± 12.5 years; 45.9% males), predominantly with oral cavity origins (75.7%). Postoperative day 10 phase angle significantly correlated with one-year survival (p = 0.014). Neutrophil-to-lymphocyte ratio (NLR) on postoperative days 2 and 10 was associated with postoperative complications (p = 0.022 and 0.026). Preoperative nutritional support demonstrated improved phase angle, optimised NLR levels, and reduced risk of complications (p = 0.023).

Phase angle represents a significant prognostic indicator for survival of head and neck surgical patients. Preoperative nutritional intervention shows potential in reducing complications and enhancing post-surgical metabolic outcomes.

Neck management in oral cancer is crucial, as regional involvement strongly affects survival. Elective dissection leaves out 10% of recurrences, mainly at levels IV-V or contralateral. Sentinel node biopsy is a different strategy to detect unexpected lymphatic drainage. Our aim is to develop a tumour-specific lymphatic mapping approach for locally-advanced cN0 tongue cancers by combining scintigraphy biopsy with indocyanine green (ICG) guidance.

In this multicentre prospective pilot study lymphatic drainage was evaluated preoperatively using scintigraphy and intraoperatively with ICG fluorescence. Bilateral neck dissection was first performed removing ICG enhancing nodes, then those identified by gamma probe and lastly the remaining ones.

Nine patients were enrolled. Robbin's levels mostly enhanced were IB-IIA-III (83%), followed by level IV (66%), IIB (50%) and IA (33%). The ICG method showed a sensitivity of 100%, a positive predictive value of 47% compared to lymphoscintigraphy and of 6.3% compared to metastatic nodes. A negative predictive value of 100% was observed by both.

A tailored lymphography-guided neck dissection could provide an effective lymphatic mapping with any individual variation allowing to overcome the limitations of sentinel biopsy and pitfalls associated with traditional elective treatment.

The impact of socioeconomic factors on cancer outcomes is well documented; however, their role in access to and receipt of care within universal health systems for advanced lung cancer is less established. We investigated inequalities in specialized cancer consultation and treatment for stage IV non-small cell lung cancer (NSCLC).

We used a population-based cohort with administrative health data to study people aged 18+ diagnosed with stage IV NSCLC between 2010 and 2022 in Ontario. We measured consultations with medical oncologists, radiation oncologists, and thoracic surgeons as well as systemic therapy, radiation, surgery, and palliative care in the year following diagnosis, comparing consultation and treatment rates across quintiles of census measures of community material resources. Multivariable cause-specific Cox proportional hazards regression, accounting for death, was used.

We included 32,902 stage IV NSCLC patients. People living in the least materially resourced neighborhoods were less likely to have a cancer-directed consultation with a medical oncologist, radiation oncologist, or thoracic surgeon (hazard ratio [HR] = 0.91; 95% confidence interval [CI] 0.87-0.94) and less likely to receive any cancer-directed treatment (HR = 0.90; 95% CI 0.86-0.94) compared to those with the most material resources. We did not detect a difference in the rate of palliative care (HR = 1.04; 95% CI 1.00-1.08). Results were consistent in urban but not rural populations.

We identified inequities in access to cancer-directed consultation and treatment among adults with stage IV NSCLC by material resources, limited to urban and suburban populations. Future research should explore root causes and identify interventions to address these inequities.

Colorectal cancer is the third most commonly diagnosed cancer and the third leading cause of cancer-associated deaths in the US. Hispanic and non-Hispanic Black patients experience higher colorectal cancer mortality rates compared with non-Hispanic White patients. More data are needed to understand the role of cancer biology in colorectal cancer survival disparities among racial and ethnic minority groups.

To evaluate racial and ethnic differences in KRAS variant frequency and the association of presence of a KRAS variant with colorectal cancer-specific survival.

This population-based cross-sectional study used data from the Surveillance, Epidemiology, and End Results Program and included patients diagnosed with colorectal cancer from 2010 through 2015, with follow-up through December 31, 2018. Data were analyzed between December 2023 and August 2024.

Racial and ethnic differences in KRAS variant frequency.

Outcomes of interest were cumulative incidence of colorectal cancer-specific death, assessed using cumulative incidence functions, and subdistribution hazard ratio (sHR) for colorectal cancer-specific death, assessed using Fine-Gray regression models.

A total of 21 354 patients (mean [SD] age at diagnosis, 62.54 [13.78] years; 9653 females [45.2%]; median [IQR] follow-up, 2.67 [1.25-4.17] years) were included in the analysis, including 1680 Asian or Pacific Islander patients (7.8%), 2459 Hispanic patients (11.5%), 2761 non-Hispanic Black patients (12.9%), and 14 454 non-Hispanic White patients (67.7%). Hispanic patients and non-Hispanic Black patients had higher KRAS variant frequencies than non-Hispanic Asian or Pacific Islander patients and non-Hispanic White patients (44.2% and 48.3% vs 37.5% and 39.3%, respectively). Among patients with KRAS wild-type tumors, the unadjusted cumulative incidence of colorectal cancer-specific death was highest for Hispanic patients (59.5%; 95% CI, 55.4%-63.3%; P < .001); among patients with KRAS variant tumors, colorectal cancer-specific death was highest for non-Hispanic Black patients (67.3%; 95% CI, 63.3%-70.9%; P < .001). Among patients with KRAS wild-type tumors, Hispanic patients showed a significantly increased risk of colorectal cancer-specific death (sHR, 1.11; 95% CI, 1.01-1.22; P = .03). Among patients with KRAS variant tumors, non-Hispanic Black patients had a significantly increased risk of colorectal cancer-specific death (sHR, 1.18; 95% CI, 1.07-1.29; P < .001).

In this cross-sectional study of patients with colorectal cancer, Hispanic patients and non-Hispanic Black patients had higher KRAS variant prevalence than non-Hispanic White patients. Among patients with a KRAS variant, non-Hispanic Black patients had worse cause-specific survival than non-Hispanic White patients. Among patients with wild-type KRAS, Hispanic patients had worse survival compared with non-Hispanic White patients. These findings highlight the need for further research on racial and ethnic differences in KRAS-related outcomes.

IntroductionCancer clinical trials do not always represent the real-world cancer population, as older adults and marginalized racial groups are often underrepresented. This study assessed patterns of enrollment of underrepresented patients and how trial and site factors may influence enrollment.MethodsThis retrospective, pooled cross-sectional study used de-identified data from ECOG-ACRIN (EA)-sponsored breast cancer therapeutic clinical trials from 2002-2020. Patient- and trial-level data were extracted from EA trials and ClinicalTrials.gov. Site-level data were from de-identified Landscape Assessment surveys voluntarily completed by National Cancer Institute Community Oncology Research Program sites. Outcomes included the proportions of underrepresented patients enrolled on a trial. Fractional regression models evaluated associations between trial-level factors and enrollment proportions of underrepresented patients using adjusted means and 95% confidence intervals (CI). Weighted Kappa (Kw) statistics and corresponding 95% CI estimated the level of agreement between patient populations served by sites versus enrolled on a trial.ResultsOf 9,015 patients enrolled across 12 trials, 18% were aged ≥65 years old, 12% were Black, 15% were Medicare beneficiaries, and 15% were rural residents (unadjusted enrollment). Adjusted mean proportion enrollment of underrepresented patients was similar to unadjusted results. Over half of trials were randomized and 92% of studies had two or more drugs in the protocol, yet these did not appear to influence mean enrollment of underrepresented groups. Moderate levels of agreement were found between Black patients served versus enrolled (Kw 0.64; 95% CI 0.50-0.78), and low or no agreement for Medicare beneficiaries and patients aged ≥65 (Kw 0.18, 0.05-0.31; Kw 0.02, -0.06-0.11; respectively).ConclusionsEA-sponsored breast trials continue to enroll few individuals from underrepresented backgrounds. Trial design had a minimal impact on enrollment and patient populations sites served did not typically match the patients enrolled on trials. More research is needed to engage sites and test strategies for enrolling underrepresented patients.

IntroductionS100 calcium-binding protein A2 (S100A2) is associated with various tumors. However, its expression profile, clinical relevance, and prognostic value in hepatocellular carcinoma (HCC) remain unclear; therefore, this study assessed S100A2 expression levels in HCC and adjacent normal tissues.MethodsTo investigate the role of S100A2 in HCC, RNA sequencing and DNA methylation data were obtained from The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC) cohort comprising 374 tumor and 50 normal liver tissues. A retrospective cohort of 216 HCC patients was also evaluated for correlations between S100A2 expression and clinicopathological characteristics. In a subset of 62 paired tumor and adjacent normal tissues, S100A2 protein and mRNA levels were assessed by immunohistochemistry (IHC) and quantitative RT-PCR. Finally, the relationship between S100A2 overexpression and clinicopathological variables was examined using the Cox proportional hazards regression model.ResultsAnalysis of the TCGA-LIHC dataset revealed a marked elevation in S100A2 expression in tumor tissues compared to normal liver tissues. Consistently, DNA methylation analysis showed hypomethylation of several S100A2-associated CpG sites in liver hepatocellular carcinoma, suggesting a potential epigenetic mechanism for its upregulation. Correlation analysis demonstrated that increased S100A2 expression was associated with advanced histological grade, lymph node metastasis, serum alpha-fetoprotein level, microvascular invasion, tyrosine kinase inhibitor level, concurrent treatment, and higher Tumor, Node, Metastasis stage. Univariate analysis showed that elevated S100A2 levels were associated with significantly poorer recurrence-free survival (RFS) and overall survival (OS). Moreover, multivariate analysis identified S100A2 as an independent prognostic indicator for both RFS and OS. Kaplan-Meier survival curves also confirmed that patients with high S100A2 protein levels had significantly worse 5-year OS and RFS rates.ConclusionThese findings indicate that S100A2 overexpression is associated with poor prognosis in patients with HCC, highlighting its potential utility as a diagnostic biomarker.

Actinic keratosis is a common, chronic, and potentially pre-cancerous skin disease that can negatively impact patients' health-related quality of life. This systematic review aimed to identify and describe the questionnaires used to assess health-related quality of life in patients with actinic keratosis and summarize reported impacts. Four databases (EMBASE, PsycINFO, PubMed, and Cochrane Library) were searched up to February 2025. Two reviewers independently screened articles, and risk of bias was assessed using tools appropriate to study design. Of 639 records, 37 studies including 9,326 patients met inclusion criteria. Most studies were interventional (59%) and of moderate to high quality (64%). Health-related quality of life was assessed using 3 disease-specific, 3 dermatology-specific, and 2 generic questionnaires. The most frequently used instruments were the Actinic Keratosis Quality of Life (n = 13) and the Dermatology Life Quality Index (n = 16). All questionnaires detected health-related quality of life impairment, especially during treatment. Actinic Keratosis Quality of Life identified patient subgroups with greater health-related quality of life reduction, including females, younger individuals, patients with comorbidities, and those with a history of skin cancer. All health-related quality of life questionnaires captured impairment in patients with actinic keratosis. The Actinic Keratosis Quality of Life and Dermatology Life Quality Index questionnaires were widely used. Actinic Keratosis Quality of Life identified subpopulations with health-related quality of life impairment. Among studies reporting mean health-related quality of life scores, the Dermatology Life Quality Index ranged from 1.55 to 24 and the Actinic Keratosis Quality of Life from 4.22 to 17, reflecting very broad variability and underlying differences in actinic keratosis severity across study populations.

Over 90% of all thyroid cancers are differentiated thyroid cancer (DTC) with an excellent overall survival rate after thyroidectomy with or without radioactive iodine (RAI) therapy. There is a large variation in the use of RAI therapy in DTC. This population-based study was performed to study the survival advantage offered by RAI therapy in DTC.

In this population-based retrospective cohort study, we reviewed the medical records of 3330 patients with DTC operated on between 1970 and 2020 and recorded patient and disease characteristics and the oncological status to January 1, 2025. Disease-specific survival (DSS) and disease-free survival (DFS) were estimated by the Kaplan-Meier product limit method, and the association of the individual prognostic factors on DSS and DFS was assessed by the log-rank test. Multivariable analyses were performed with Cox proportional hazards models. Inverse probability of treatment weighting was used to adjust for the difference between the prognostic factors in RAI and non-RAI groups using propensity scores. Secondary analyses were performed using competing risk models to account for the competing influence of non-DTC-related causes of death.

Our cohort included 783 males and 2547 females with a mean age of 48 years. RAI therapy was administered to 34.9% of all cases (24.2% of low, 31.1% of intermediate, and 68.4% of high-risk cases, respectively). 10-year DSS was 97.2% after a median follow-up of 14.1 years. DSS was adversely influenced by the presence of distant metastasis, incomplete resection, advanced age, male sex, non-papillary histology, and advanced T stage. RAI therapy was not significantly associated with DSS overall, but it was associated with over 80% risk reduction in metastatic DTC in the Cox proportional hazards model (hazard ratio 0.192; [CI: 0.088-0.417]; p < 0.001) and competing risk analysis (sub-hazard ratio 0.162; [CI: 0.072-0.368]; p < 0.001).

Excellent DSS can be achieved in DTC with selective use of adjuvant RAI, with the greatest benefit of RAI seen in those with metastatic DTC.

A randomized phase II screening trial of gemcitabine, nab-paclitaxel, and cisplatin with a medically supervised ketogenic diet (MSKD) versus usual diet (non-MSKD) was conducted in patients with treatment-naive metastatic pancreatic ductal adenocarcinoma (PDAC).

Patients with untreated metastatic PDAC were randomized 1:1 to MSKD or non-MSKD while receiving gemcitabine, nab-paclitaxel, and cisplatin on days 1 and 8 of a 21-day cycle. The MSKD was guided by a remote health care team and daily ketone (beta-hydroxybutyrate) levels, with goal beta-hydroxybutyrate of 0.5 to 3.0 mM. The primary endpoint was progression-free survival (PFS) using a one-sided alpha level of 0.20. Secondary endpoints included overall survival (OS), safety, and quality of life (QOL). Changes in microbiome were an exploratory endpoint.

Overall, there were 32 evaluable patients. In the MSKD arm, 15 of 16 patients achieved nutritional ketosis; the median proportion of days in ketosis was 39.4%. The median PFS was 8.5 months in MSKD patients and 6.2 months in non-MSKD patients: hazard ratio, 0.53 (95% CI, 0.21-1.37); one-sided p = .096. The median OS was 13.7 months with MSKD and 10.2 months in the non-MSKD arm: hazard ratio, 0.58 (95% CI, 0.25-1.37); one-sided p = .107). All MSKD-related adverse events were grade 1-2. There were no significant differences in grade ≥3 chemotherapy-related adverse events between the arms. MSKD patients had no decline in QOL and had significant enrichment of beneficial taxa in the microbiome (p < .05, log-fold change ≥2).

The MSKD is feasible in patients with PDAC and, although not powered for definitive outcomes, shows trends in improved PFS and OS when combined with gemcitabine, nab-paclitaxel, and cisplatin, without added toxicity or detriment to QOL. Larger studies are required to confirm these findings and establish the value of the MSKD in pancreatic cancer treatment.