Cancer Medicine

Background: Chemotherapy is a cornerstone of breast cancer treatment but is often accompanied by metabolic, hematological, and psychological changes that may negatively affect patients' health and quality of life. Dietary intake during chemotherapy may influence these treatment-related outcomes; however, prospective evidence based on repeated dietary assessments and comprehensive clinical outcomes remains limited. Objective: The primary objective of this study is to investigate the association between dietary intake during chemotherapy and changes in a predefined composite cardiometabolic risk profile in women with breast cancer. Secondary objectives are to evaluate associations of dietary intake with selected biochemical and psychological outcomes. Methods: In this prospective cohort study, 100 women with histologically confirmed breast cancer undergoing chemotherapy in Tehran, Iran, will be followed from the initiation of chemotherapy until completion of the planned chemotherapy course. Dietary intake will be assessed using nine repeated dietary records collected during the early, mid, and late phases of chemotherapy, and mean intake will represent overall dietary exposure during treatment. Cardiometabolic, biochemical, and psychological outcomes will be assessed at baseline and post-chemotherapy using clinical measurements, laboratory data, and validated questionnaires. Descriptive within-participant changes will be defined as post-chemotherapy minus baseline values and evaluated using paired tests. The primary analysis will examine the association between dietary intake during chemotherapy and the post-chemotherapy composite cardiometabolic risk score using multivariable linear regression adjusted for age, baseline BMI, mean energy intake during chemotherapy, physical activity level at the end of chemotherapy, tumor stage, treatment type, and the baseline composite score. Secondary analyses will use the same baseline-adjusted framework for selected biochemical and psychological outcomes. Exploratory analyses will also examine end-of-chemotherapy serum vitamin D concentration as a concurrent biomarker associated with end-of-treatment outcomes. Results will be reported as beta coefficients with 95% confidence intervals. Conclusion: This study will provide prospective evidence on the relationship of dietary intake and end-of-chemotherapy serum vitamin D status with treatment-related cardiometabolic, biochemical, and psychological changes in women with breast cancer. Keywords: Breast cancer; Chemotherapy; Dietary intake; Cardiometabolic risk factors; Quality of life; Prospective cohort study.

Background Hereditary cancers account for approximately 5% to 10% of all malignancies and are more frequently observed in individuals with early-onset disease or a significant family history of cancer. However, large pan-India datasets describing germline variant distributions across multiple cancer types remain limited. Methods We retrospectively analysed 23,070 individuals who underwent germline hereditary cancer testing at MedGenome Labs Ltd., Bangalore, India from 2016 to 2025. Clinical indication based major cancer sub-type groups were breast cancer (N=10486), ovarian cancer (N=3990), colorectal cancer (N=1275), prostate cancer (N=765), endometrial cancer (N=541) and asymptomatic individuals (N=2,775). Germline testing was conducted using clinically validated multigene next-generation sequencing (NGS) panels, with multiplex ligation-dependent probe amplification (MLPA) used for copy number variant detection in a subset of cases. Results The overall diagnostic yield of genetic testing was 23.85%, with the highest yields observed in colorectal (42%) and ovarian cancers (31.6%), followed by endometrial (22.6%), breast (20.2%) and prostate cancer (8.6%) formed the top 5 cancer types. In addition, there is an asymptomatic group where individuals with no symptoms reported but had a positive family history of cancer, where diagnostic rate was 18.9%. Among breast cancer patients diagnosed at [≤]50 years of age, one of the National Comprehensive Cancer Network (NCCN) criteria for hereditary cancer testing, the diagnostic yield was 24.2%. Individuals with a positive family history had a significantly higher diagnostic rate (2.5% to 16%) compared to those without a positive family history across all cancer types. BRCA1 and BRCA2 were the most frequent genes with pathogenic variants in breast and ovarian cancers, while mismatch repair genes (MLH1, MSH2, MSH6) predominated in colorectal and endometrial cancers, and BRCA2 was the most frequently altered gene in prostate cancer. The well-known BRCA1 gene founder frameshift variant (c.68_69delAG; p.Glu23ValfsTer17) was identified in 358 individuals, representing the most frequent pathogenic variant in the cohort. Additional BRCA1 gene recurrent variants observed in the sample set includes a canonical splice-site variant (c.5074+1G>A;N=123), followed by a non-sense mutation (c.3607C>T;p.Arg1203Ter;N=44). A strong concordance between clinical classification and functional annotations was observed when compared with BRCA1 saturation mutagenesis findings. Reanalysis of variants of uncertain significance and undiagnosed cases improved the diagnostic yield by approximately about 5% average across major cancer types. A multivariate regression analysis showed a positive family history significantly contribute to improved diagnosis. Notably, early genetic testing correlated well with significantly contribute to improved diagnosis, suggestive for universal genetic testing over guideline-based testing. In addition, the regression analysis showed a decline in diagnostic yield with increasing age for all five major cancer types analysed, suggesting that the universal criteria for genetic testing is preferable for early detection. Among breast cancer cases with hormone receptor data, the triple-negative and ER+PR-HER2+ cases had a higher diagnostic rate compared to other subtypes of breast cancer. The MLPA-based CNV analysis further validated additional clinically relevant variants in a subset of the cohort. Conclusions To the best of our understanding, this retrospective study showcases the largest comprehensive characterization of the hereditary cancer genetics in India and South Asian region till date, demonstrating a substantial burden of inherited cancer susceptibility and distinct gene-cancer associations across major tumor types. These findings support the implementation of comprehensive multigene testing, periodic variant reinterpretation, and population-adapted hereditary cancer testing strategies to improve hereditary cancer risk assessment and advance precision oncology in underrepresented populations.

Introduction: This study aimed to provide population level survival trends during the era in which new systemic therapies transformed treatment guidelines for metastatic cancer, as well as insights on the real world use of these treatments and associated survival. Methods: Adults diagnosed with synchronous metastatic solid cancer in 2008 until 2022 (22 cancer types) were identified from the Netherlands Cancer Registry. Median overall survival (OS) was assessed by five year diagnostic period. For 2018 until 2022, systemic therapy use in any treatment line was analyzed and survival percentiles within treatment and cancer types were estimated with Kaplan Meier survival analyses. Results: Median OS in the overall cohort (n=280,419 patients) improved from 6 to 8 months between the period 2008 until 2012 and 2018 until 2022. Among patients diagnosed in 2018 until 2022, 15% received immunotherapy, 15% targeted therapy, 29% chemotherapy and/or traditional hormone therapy only, and 39% no systemic therapy. In some cancer types, a relatively large proportion of treated patients had longterm survival (e.g., immunotherapy in melanoma: p50 = 67 months). Other cancer types had a smaller subset of treated patients (p10 and p25) with substantially better outcomes than the median (e.g., targeted therapy in NSCLC: p50 = 22 months, p10 = 96 months). Conclusion: Population level survival for patients with synchronous metastatic solid cancer has modestly improved over time. The marked survival heterogeneity within cancer and treatment types highlights both the potential and uncertainty associated with (novel) treatments. Improved prediction of treatment effects and clear communication regarding survival expectation remain critical. Presenting multiple survival scenarios over median survival alone can support decision making.

Background: Sugar sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and fruit and vegetable juices are consumed worldwide, yet their associations with cancer remain unclear. Methods: Within World Cancer Research Fund International's Global Cancer Update Programme (CUP Global), we conducted a systematic review by searching PubMed and Embase until September 2024 for cohort studies of SSBs, ASBs, and juices and cancer risk. Meta-analyses were conducted to calculate the relative risks (RRs) and 95% CIs per 1 serving/day (355 mL for SSBs/ASBs; 177 mL for juices). Evidence was graded by the CUP Global Expert Panel. The CUP Global standard protocol was registered at: https://osf.io/7utbm/. Findings: We identified 158 publications from 51 cohorts. Evidence supported a judgment of a probable causal association of SSBs, including carbonated SSBs, with pancreatic cancer incidence (RR 1.09 [95% CI 1.01-1.16]; I2=8%, n=18 studies), and of SSBs with colorectal cancer incidence (RR 1.07 [95% CI 1.00-1.14]; I2=41%, n=13). Limited suggestive evidence supported positive associations of SSBs with ovarian (RR 1.61 [95%CI 1.03-2.53]; I2=0%, n=2), endometrial (RR 1.21 [95%CI 1.03-1.42]; I2=0%, n=3), and postmenopausal breast cancer (RR 1.05 [95%CI 1.00-1.10] ; I2=0%, n=6), and of carbonated ASBs with leukaemia (RR 1.29 [95%CI 1.01-1.64]; I2=0%, n=2). Evidence supported a judgment of a probable causal association of orange juice with melanoma (RR 1.21 [95%CI 1.08-1.34]; I2=0%, n=4), and skin basal (RR 1.12 [95%CI 1.06-1.17]; I2=46%, n=2) and squamous cell carcinoma (RR 1.13 [95%CI 1.04-1.24]; I2=0%, n=2). An interactive evidence platform is available at: Soft Drinks and Cancer Risk - CUP Global Evidence Platform. Interpretation: This review provides evidence supporting probable causal associations of SSBs with pancreatic and colorectal cancers, and of orange juice with skin cancers, with additional suggestive evidence for SSBs with other obesity-related cancers, extending concerns about sugary drink consumption beyond cardiometabolic health to cancer risk. Funding: World Cancer Research Fund network of charities (American Institute for Cancer Research; World Cancer Research Fund; Wereld Kanker Onderzoek Fonds).

Background Patients with advanced pancreatic ductal adenocarcinoma (aPDAC) often experience general health decline at diagnosis due to a high-symptom burden. The optimal management of symptoms and/or poor performance status (PS) in these patients remains an unmet medical need. Patients and Methods In this multicenter study, patients with PS[≥]2 and pathologically confirmed or imaging-suspected aPDAC were included at first oncology visit in a personalized 14-day emergency integrative supportive care program (14-EISCP) to manage pain, nutrition, diagnostics, and stenting procedures. The primary endpoint was the 14-EISCP success in feasibility of planned procedures and clinical benefit defined as post-EISCP PS[≤]1, [≥]5 points improvement in fatigue, pain, global health-related quality of life (HRQoL) scores (EORTC QLQ-C15-PAL), or chemotherapy initiation within 30 days. Results A total of 106 patients were included; 93 evaluable patients considered for primary endpoint analysis (median age: 76 years [68-80], PS3: 20.9%, metastases: 61.3%). The median overall survival was 4.1 months (IC95% 2.6-5.6). The 14-EISCP was successful in 59.1% (n=55) of patients, meeting the primary objective (clinically relevant). The 14-EISCP feasibility was achieved in 70.9% of cases. Post-EISCP clinical benefit was observed in 79.6% of patients, with PS improvement to 0/1 in 13.2%, HRQoL improvement in 23.9%, and chemotherapy initiation [≤]30 days in 73.1%. Among evaluable patients, 17.2% received mFOLFIRINOX or gemcitabine-nab-paclitaxel, 35.4% received FOLFOX, 25.3% had gemcitabine or 5-fluorouracil alone, and 22.2% received best supportive care. In patients with PS2 at baseline, the administration of doublet/triplet chemotherapy was associated with improved overall survival compared to single-agent. Discussion These results offer a promising framework for improving outcomes in aPDAC patients, bridging the gap between symptom management and systemic therapy administration. Conclusions In patients with PS[≥]2 and aPDAC, the personalized 14-EISCP was feasible and lead to meaningful clinical benefit, allowing doublet or triplet chemotherapy in half the patients.

Background: Patient-reported measures (PRMs), including patient-reported outcome and experience measures, capture patients perspectives on their health status and healthcare experiences. In cancer genetics, PRMs have been used to assess genetic knowledge, psychosocial outcomes, and decision-making. However, patients must understand these measures to provide useful information, an ability which is influenced by general and health literacy levels. Readability guidelines recommend that patient-facing materials be written at or below a Grade 6 level. This study evaluated the readability of PRMs used in a cancer genetic testing context. Objective: To assess whether PRMs used in heritable cancer genetic testing meet recommended readability levels using validated indices. Methods: PRMs were identified from a recent systematic review of PRMs used in heritable cancer genetic testing, which reported 83 instruments across eight categories. English-language PRMs containing structured question items and response scales were eligible for extraction and converted into plain text for analysis. Readability was assessed using four validated indices: Flesch Kincaid Grading Level (FKGL), FORd, CAylor, and STicht (FORCAST) formula, Flesch Reading Ease Score (FRES), and Simple Measure of Gobbledygook (SMOG) via an automated readability software. Descriptive analysis and numerical comparison evaluated readability levels across PRM categories and against the recommended Grade 6 reading level. Results: Sixty-five PRMs met the eligibility criteria, with most, including validated instruments, exceeding the recommended Grade 6 reading level. Across the eight categories, genetics-specific PRMs required the highest readability levels, indicating higher readability demands. Conclusions: Most PRMs, particularly those specific to genetics, do not meet readability guidelines. This may limit their accessibility to individuals with limited general and health literacy. Development of PRMs specific to genetics should consider strategies to improve readability, such as plain-language approaches and involvement of individuals with limited general or health literacy. Keywords: readability, patient-reported measures, cancer, genetic testing, health literacy

Background Colorectal cancer (CRC) screening strategies such as colonoscopy and fecal immuno-chemical testing (FIT) reduce CRC mortality through both early detection and prevention via precursor lesion removal. Multicancer early detection (MCED) blood tests offer the potential to detect multiple cancers with a single assay but provide little opportunity for cancer prevention. Whether the ability to detect multiple cancers can offset the loss of CRC prevention remains unclear. Methods We used microsimulation to compare MCED and guideline-recommended CRC screening strategies. CRC outcomes were simulated using CRC-SPIN v3.0 and non-CRC cancers using MCEDsim, calibrated to SEER incidence data. Assuming optimistic MCED preclinical sensitivity equal to published case-control estimates, we compared life-years gained and late-stage disease outcomes for annual FIT, decennial colonoscopy, and MCED-only strategies across a range of preclinical durations and survival benefit assumptions. Results: Relative to no screening, colonoscopy and FIT reduced late-stage diagnoses by 26% and 25%, respectively, versus 20%-32% for annual MCED screening. Across assumptions, MCED-only strategies generated 33%-51% as many life-years gained as colonoscopy. Conclusions Currently available MCED tests are unlikely to be effective replacements for guideline-recommended CRC screening, which derives substantial benefit from the detection and removal of precursor lesions. MCED screening may provide additional benefit as a supplement to recommended CRC screening.

Population-based mammography screening improves breast cancer outcomes, but its impact on real-world treatment pathways and quality indicators (QIs) remains incompletely described. We conducted a retrospective nationwide cohort study using linked data from the Czech National Cancer Registry and the National Registry of Reimbursed Health Services. Women aged [≥]18 years with a first breast cancer diagnosis between 2017 and 2024 were classified as screen-detected (SCR) or diagnostically-detected (DIG) according to the imaging modality preceding histological verification. Outcomes included stage distribution, untreated cases, first-line treatment, main treatment modality, time to treatment, multidisciplinary team discussion (MDT), centralization to Comprehensive Cancer Centres (COCs), and survival patterns. The verified cohort included 47,648 women: 26,817 SCR cases (56.3 %) and 20,831 DIG cases (43.7 %). In this nationwide analysis, SCR breast cancer was associated with earlier stage at diagnosis and better survival patterns, but also with longer time to treatment and longer time to MDT discussion than DIG-detected disease. Although treatment rates were high and centralization improved over time, substantial regional variation persisted in care pathways, MDT use, and access to COCs. These findings support continued strengthening of screening participation, monitoring of care intervals, and quality assurance of MDT reporting and regional oncology care delivery.

Background: Objective assessment of tumor burden in patients with solid tumors remains inexact. Furthermore, while mutation-based liquid biopsies are specific, they are limited by tumor heterogeneity and the requirement for detectable clonal mutations. Cell-free DNA (cfDNA) concentration, a cost-effective substrate for mutation-focused liquid biopsy, has shown promise as a "molecular tumor burden" biomarker. Methods: We analyzed cfDNA concentration from 1000 unique cancer patients using standardized protocols. Demographics, AJCC stage, clinical anatomic tumor burden and oncologic outcome variables were collected. Associations were assessed with non-parametric tests. Multivariable linear regression and Cox proportional hazards models were used to identify independent predictors and survival associations. Results: CfDNA concentration varied broadly (median 6.25 ng/mL; range 0.5-1132.9). Anatomic tumor burden, including tumor number (rho=0.25, p<0.0001) and largest tumor diameter (rho=0.25, p<0.0001), correlated significantly with cfDNA, especially in stage IV disease. Primary tumor site influenced cfDNA levels, with liver/bile duct cancers having higher cfDNA than other sites (median 13.5 vs 6.1 ng/mL, p<0.0001). Multivariable analysis confirmed overall tumor burden and hepatic tumor location (primary or metastatic) as principal drivers of cfDNA. Critically, cfDNA concentration was an independent predictor of shorter PFS (p=0.001) and DSS (p<0.0001), demonstrating increased value in advanced disease settings, irrespective of treatment intent. Conclusions: CfDNA concentration is a robust, biologically integrated biomarker that provides an objective measure of total systemic tumor burden and prognosis in a large, pan-cancer cohort. By capturing disease activity irrespective of mutational status, it offers a valuable adjunct to targeted profiling, particularly in heterogeneous or advanced malignancies. Although these findings require prospective clinical validation, cfDNA concentration may eventually augment patient selection for aggressive versus palliative interventions, especially in advanced disease.

Background: The tumor microenvironment (TME) plays a critical role in cancer progression and treatment response. Stromal components, including cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), and angiogenesis, contribute to tumor aggressiveness. However, a comprehensive stromal activity score integrating multiple stromal dimensions for pan-cancer prognosis prediction is lacking. Methods: We developed a Stromal Activity Score (SAS) integrating five stromal dimensions: CAF signature (12 genes), ECM remodeling (15 genes), TGF-{beta} signaling (13 genes), angiogenesis (12 genes), and complement activation (11 genes). SAS was calculated using single-sample Gene Set Enrichment Analysis (ssGSEA) on TCGA pan-cancer data comprising 1,303 samples across 12 cancer types. Prognostic value was evaluated using Kaplan-Meier analysis and Cox regression. Immunotherapy response prediction was validated in two independent cohorts (IMvigor210, n=88; Liu2019, n=105). Results: Pan-cancer Cox regression demonstrated a significant association between SAS and overall survival (HR = 1.165, 95% CI: 1.065-1.275, P = 0.001). Per-cancer analysis identified BRCA (HR = 1.942, P = 0.022), STAD (HR = 1.684, P = 0.024), and LUSC (HR = 1.552, P = 0.038) as significant, though none survived FDR correction. SAS correlated strongly with ESTIMATE Stromal Score (Spearman {rho} = 0.835) and moderately with Immune Score ({rho} = 0.396). Immunotherapy validation showed consistent trends (IMvigor210: AUC = 0.602; Liu2019: AUC = 0.617). Time-dependent ROC analysis showed 1-year AUC = 0.596, 3-year = 0.579, 5-year = 0.559. Leave-one-out analysis identified angiogenesis removal as enhancing prognostic signal (HR = 3.737, P = 0.0002). Three distinct TME subtypes were identified with differential SAS profiles. Conclusions: SAS is a novel pan-cancer stromal activity score that captures TME biology with strong construct validity. Its clinical utility as a standalone biomarker remains modest, but it may complement existing immunotherapy biomarkers.

Background with objective: Detecting EGFR mutations is critical for treating lung adenocarcinoma with highly effective targeted therapies. However, standard genetic testing is expensive, complex, and often unavailable in resource-limited settings like Bangladesh. Because elevated serum CEA has been linked to these genetic alterations, it could serve as an accessible screening tool. This study aims to evaluate the association between serum CEA levels and EGFR mutation status to determine if routine CEA testing can reliably predict these mutations and guide treatment. Methodology: In this cross-sectional analytical study, we recruited 58 patients with histologically confirmed treatment naive lung adenocarcinoma. The presence of EGFR mutations in the ctDNA was determined via ARMS (Amplification Refractory Mutation System) PCR. Patient data was statistically analyzed to assess the diagnostic correlation between serum CEA levels and the presence of EGFR mutations. Result: The overall EGFR mutation rate was 43.1% with exon 19 deletion (48%) and exon 21 mutations (44%) were the predominant types. Median serum CEA levels were significantly higher in patients with EGFR mutations compared to wild-type cases (14.6 ng/ml vs 2.8 ng/ml, p<0.001). A multivariate analysis revealed a 14% increased likelihood of an EGFR mutation for 1 ng/ml rise in serum CEA. Furthermore, serum CEA showed strong diagnostic accuracy for ctDNA samples at a 6.39 ng/ml cut-off (AUC 0.82, sensitivity 68.0%, specificity 84.8%). Conclusion: Serum CEA is a valuable, cost-effective, and non-invasive biomarker demonstrating significantly higher levels and strong diagnostic accuracy in EGFR-mutated lung adenocarcinoma compared to wild-type cases.

Background: Financial toxicity is an increasingly recognized survivorship issue, but whether diabetes identifies a distinct high-risk financial-toxicity phenotype among U.S. cancer survivors is not well characterized. Methods: We conducted a cross-sectional study using pooled 2021-2024 National Health Interview Survey Sample Adult data. Adults were classified into four mutually exclusive groups: neither cancer nor diabetes, diabetes only, cancer only, and cancer plus diabetes. The primary outcome was any financial toxicity, defined as cost-related care disruption or medication underuse in the prior 12 months. Survey-weighted prevalence estimates and multivariable Poisson regression were used to calculate adjusted prevalence ratios (aPRs). Results: The weighted analytic population included 210.4 million adults with neither condition, 20.6 million with diabetes only, 20.9 million with cancer only, and 4.3 million with both cancer and diabetes. Any financial toxicity was present in 18.8%, 18.8%, 11.6%, and 17.2% of these groups, respectively. Among cancer survivors, diabetes was associated with higher prevalence of any financial toxicity (aPR 1.51, 95% CI 1.33-1.73), inability to afford prescriptions (aPR 1.71, 95% CI 1.40-2.08), skipped medication doses (aPR 1.91, 95% CI 1.48-2.46), any emergency department visit (aPR 1.35, 95% CI 1.24-1.47), and [&ge;]2 emergency department visits (aPR 1.55, 95% CI 1.32-1.83). In treatment-stratified analyses, the burden was greatest among insulin-treated survivors. Conclusions: Cancer survivors with diabetes represent a high-risk financial-toxicity phenotype despite frequent healthcare contact.

Background: Oral mucositis is a clinically significant, potentially severe side effect of systemic chemotherapy in children with cancer. Understanding genetic predisposition to this side effect may assist in development of stratified prophylactic and treatment strategies. However, existing literature primarily focuses on children with haematological malignancies. Methods: We performed a candidate gene study of 101 children with solid tumours enrolled in the MARVEL-PIC study at the Royal Children's Hospital, Melbourne. Clinical data were extracted from the electronic medical record, with NCI-CTCAE v6.0 grade >2 oral mucositis defined as the primary outcome. Genetic variants previously associated with oral mucositis were analysed under an additive genetic model to identify significant associations. Exploratory gene-drug interactions were identified based on chemotherapy exposure. Results: 29 patients (28.7%) developed grade >2 oral mucositis. MTHFR A1298C (rs1801131) was associated with lower odds of grade >2 oral mucositis, lower peak mucositis grade, and lower odds of opioid use for oral mucositis. 25 exploratory gene-drug interaction signals were identified, including miR-1206 rs2114358 with methotrexate exposure and ABCB1 rs1045642 with anthracycline exposure. Conclusions: MTHFR A1298C (rs1801131) demonstrated a protective effect against chemotherapy-induced oral mucositis in our cohort of children with solid tumours. Larger, ancestry-informed studies are required to validate our findings.

Preclinical cancer sojourn time, defined here as the duration a cancer is undetected but detectable, is important for understanding disease progression and evaluating screening policies. This study aims to robustly characterise empirical evidence and existing knowledge over mean sojourn times across 21 stageable tumour sites, including stage-specific preclinical cancer sojourn times and the sojourn time of circulating tumour DNA (ctDNA)-positive cancers. We updated an existing systematic review through to February 2025 to extract population-level empirical sojourn time estimates derived from mathematical models of primary screening data. To synthesise this heterogeneous literature, quantify uncertainty, and obtain estimates for cancer-sites lacking empirical evidence, we conducted a formal Structured Expert Elicitation involving 15 clinical experts. The elicitation was grounded on the systematic review results, supplemented by an evidence dossier that included survival data and outcomes from relevant ctDNA cancer studies. The systematic review revealed heterogeneity in existing literature, which focused on a small subset of screened cancers (e.g., breast, cervical, colorectal). The elicitation successfully generated comprehensive probability distributions of overall mean sojourn times for all 21 cancer-sites (representing the site of tumour origin), as well as stage-specific sojourn times and overall sojourn times for ctDNA-positive cancers across 14 cancer-sites. This study used robust methodology to quantitatively describe existing evidence and experts' beliefs on the sojourn time of multiple cancer-sites, also describing uncertainty. Such estimates are important for future evaluations of the clinical impact, potential for overdiagnosis and subsequent cost-effectiveness of emerging screening technologies, including multi-cancer detection tests.

Aim: To assess temporal trends in incidence and mortality and project the future burden of five major gastrointestinal cancers in Jiangsu Province, China. Methods: Population-based cancer registry data from Jiangsu Province between 2010 and 2021 were used to analyze the burden of esophageal, gastric, colon, rectal, and liver cancers. Age-standardized incidence and mortality rates were calculated and compared by cancer type, sex, and urban-rural residence. Joinpoint regression was used to estimate annual percentage changes (APC) and average annual percentage changes (AAPC). The APC from the most recent Joinpoint segment was used to project incidence and mortality rates to 2030. Results: In 2021, gastric cancer had the highest age-standardized incidence and mortality among the five cancers. Incidence and mortality were consistently higher in males than in females and increased markedly after 50 years of age. From 2010 to 2021, age-standardized incidence and mortality declined for esophageal, gastric, and liver cancer, but increased for colon and rectal cancer. Colon cancer showed the steepest increase in both incidence and mortality. Rural areas experienced faster increases in colon and rectal cancer burden than urban areas. Projections to 2030 suggest continued declines in esophageal, gastric, and liver cancer, while colon cancer incidence and mortality are expected to rise further. Conclusion: Jiangsu Province is experiencing a transition in gastrointestinal cancer burden, with continued declines in esophageal, gastric, and liver cancers but an emerging and growing burden of colorectal cancer, especially colon cancer. Prevention strategies should focus on expanding colorectal cancer screening and early diagnosis, particularly in rural areas, while sustaining control of esophageal, gastric, and liver cancers.

ABSTRACT Background: Despite its high prevalence and established impact on women's health, the long-term biological effects of Intimate Partner Violence (IPV) remain poorly understood. In particular, its potential role in increasing cancer risk has received limited attention. This review examines whether IPV may be associated with elevated cancer risk in women. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA and MOOSE guidelines to evaluate whether IPV may be associated with cancer risk. Eligible studies included adult women ([&ge;]18 years) with documented IPV exposure and cancer or precancerous outcomes. We searched PubMed, Web of Science, Scopus, and Google Scholar for articles published from 2000 to 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was performed on longitudinal studies reporting adjusted risk estimates. Results: Thirteen studies were included in the qualitative synthesis, but only two met criteria for meta-analysis, both reporting on cervical cancer. The pooled odds ratio was 3.00 (95% CI: 2.05 - 4.38; I2 = 0%). A separate pooled prevalence analysis of six retrospective studies showed that 32.2% of women with cancer reported a lifetime history of IPV. Study quality ranged from low to high. Conclusions: This review underscores the limited and heterogeneous nature of the existing evidence on IPV as a potential cancer risk factor. While preliminary findings suggest a possible association, particularly with cervical cancer, the scarcity of high-quality longitudinal studies and the methodological variability in the studies reviewed prevent definitive conclusions regarding causal linkage. Further research, particularly prospective and mechanistic studies, is needed to clarify the relationship between IPV and oncogenesis across different cancer types and to identify underlying biological pathways.

Purpose: Metastatic pancreatic ductal adenocarcinoma (PDAC) portends a poor prognosis. Prior studies have assessed the association of socioeconomic deprivation (SED) in PDAC often with large geographic areas. This study employed a causal framework to characterize neighborhood SED on treatment receipt and survival in metastatic PDAC. Methods: Using the incidence-based Florida Cancer Data System, metastatic PDAC patients diagnosed from 2007-2015 were identified. The Area Deprivation Index, a composite measure of SED that ranks neighborhoods from 1-100 (higher scores = higher deprivation), was used to assess receipt of systemic therapy and overall survival (OS). Exposures and covariates were assessed using descriptive statistics and a causal inference framework. Results: Overall, 9,574 patients met inclusion criteria. 46.6% of patients received systemic therapy, ranging 39.4% to 54% in the highest and lowest SED quartiles, respectively. After adjustment, the lowest quartile had increased odds of systemic therapy relative to the highest (OR 1.93; 95% CI 1.70-2.18). Median OS was 3.8 months for the lowest quartile and 2.4 months for the highest (p = 0.01). Patients in the highest quartile had an estimated 32% higher hazard of death than the lowest (HR 1.32, 95% bootstrap CI 1.20-1.40). Conclusion: In an incidence-based statewide cohort, most patients did not receive treatment for metastatic PDAC and median OS was poor-2.9 months. Using a causal inference framework, higher SED led to lower rates of systemic therapy receipt and worse overall survival in metastatic PDAC. Future research should focus on the mechanisms that shape these findings.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurotoxicity of cancer treatment with limited diagnostic, monitoring, and treatment options. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released during neuroaxonal injury and a promising biomarker of CIPN, but prospective evidence for NfL as a marker of CIPN from vincristine-containing lymphoma chemotherapy treatment remains limited. To fill this gap, we conducted a pragmatic single-center prospective observational cohort study of adults with non-Hodgkin lymphoma (NHL) receiving first-line vincristine-containing chemotherapy to evaluate NfL dynamics across multiple pre-cycle visits and assess 68 relationships with patient-reported and clinician-graded neuropathy measures. We followed 25 participants during 4-6 months of chemotherapy, and a small subset of those participants (n=6) for 24-42 months post-chemotherapy. Serial plasma NfL was measured and CIPN symptoms were assessed using patient- and clinician-reported measures. Longitudinal changes were analyzed using mixed-effects models. Plasma NfL increased relative to pre-cycle1 at all timepoints (all p<0.001), increasing more than threefold by pre-cycle4. Patient-reported CIPN scores and clinician-graded neuropathy also increased during treatment. Exploratory pooled visit-level analyses showed a modest NfL-CIPN association (Spearman {rho}=0.393, p=0.004), while timepoint-specific, lagged, and post hoc sensitivity analyses suggested potential to predict persistent CIPN symptoms from early NfL concentrations. To our knowledge, these findings provide the first prospective evidence that NfL is sensitive to vincristine exposure in adults with NHL and may complement patient-reported symptom assessment, clinician grading, and dose-modification context in future CIPN monitoring studies.

Background: Recreational physical activity has been shown to improve survival among colorectal cancer (CRC) patients. With a growing survivor population, it is necessary to understand whether there are survival benefits across physical activity levels and across sociodemographic and clinical features. Methods: Disparities and Cancer Epidemiology (DANCE) is a population-based cohort of CRC survivors from metro-Detroit and Louisiana. Self-reported moderate and vigorous recreational physical activity was modeled continuously and categorically as none, low (<7.5 MET-hrs/wk), and high (7.5+ MET-hrs/wk). Survival models estimated hazard ratios (HRs) for physical activity with all-cause and CRC-specific survival. Models were stratified by sociodemographic and clinical features; cross-product terms estimated interaction with physical activity. Results: Of 1,107 participants, 26.5% were inactive, 49.1% had low physical activity, and 24.5% had high physical activity. Compared to inactivity, low activity was associated with 44% higher overall survival (HR= 0.56, 95% CI: 0.42, 0.75), and high activity with 66% higher survival (HR=0.34, 95% CI: 0.22, 0.53; P-trend=0.01). Adjustment for comorbidities, quality of life, BMI, and BMI-change did not alter results. Results remained significant for CRC-specific survival (low: HR=0.65, 95% CI: 0.44, 0.96; high: HR=0.45, 95% CI: 0.25, 0.80). Associations were consistent across sociodemographic and clinical features other than BMI and race; survival benefits were larger among White survivors. Conclusion: Any recreational physical activity is associated with longer overall and CRC-specific survival, regardless of sociodemographic or clinical characteristics for the most part. Any physical activity may have survival benefits for CRC survivors, but meeting physical activity guidelines may have the greatest benefit.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. It is associated with limited targeted treatment options, early relapse, and a high propensity for visceral metastasis. Data describing metastatic patterns and treatment characteristics of TNBC in Nigeria remain limited. Methods: This retrospective descriptive cohort study included 869 patients with TNBC managed at the Medserve-LUTH Cancer Center, Lagos University Teaching Hospital, Nigeria between June 2019 and June 2024. Demographic, clinicopathologic, metastatic, and treatment-related data were extracted from electronic medical records. Descriptive statistics were used to summarize patient characteristics, metastatic patterns, and treatment profiles. Associations between metastatic disease and selected clinicopathologic and treatment variables were explored using Pearsons chi-square test. Complete-case analysis was applied throughout. Results: The mean age at presentation was 52.09 {+/-} 12.26 years. Most patients were married (79.1%), postmenopausal (64.3%), and of Yoruba ethnicity (56.8%). Advanced disease predominated, with Stage III and Stage IV disease accounting for 42.9% and 35.6% of cases, respectively. Invasive ductal carcinoma was the most common histologic subtype (77.0%), while Grade II tumours constituted 51.3% of graded cases. Surgery was performed in 73.1% of patients, predominantly mastectomy (70.9% of surgical procedures). Chemotherapy was administered to 83.2% of patients, most commonly anthracycline-based regimens (41.8%), while radiotherapy was delivered to 63.5% of patients, with hypofractionated schedules of 42-43 Gy in 15-16 fractions accounting for 47.2% of radiotherapy courses. Metastatic disease was documented in 32.9% of evaluable patients. Lung metastasis was the most frequent site (62.5%), followed by bone (46.3%), regional lymph node invasion (38.5%), liver (23.0%), and brain (22.6%). Tumour grade and histologic subtype were not significantly associated with metastatic disease, whereas radiotherapy exposure demonstrated a significant association with metastatic status ({chi}{superscript 2} = 10.35, p = 0.001). Conclusion: TNBC in this Nigerian cohort was characterized by advanced-stage presentation, invasive ductal predominance, extensive use of multimodality treatment, and substantial visceral metastatic burden. Lung metastasis was the most common metastatic site. These findings provide contemporary real-world data on TNBC in Nigeria and highlight the continuing need for earlier diagnosis, timely referral, and sustained investment in comprehensive cancer care services.