Cancer Medicine

BackgroundEnhanced Recovery After Surgery (ERAS) optimizes perioperative management for colorectal cancer (CRC), improving short-term outcomes, but its impact on long-term outcomes remains inconclusive, supporting the need for this meta-analysis. This study evaluates the effect of perioperative ERAS (therapy-focused) on 1-, 2-, 3-, and 5-year postoperative survival in patients with CRC. MethodsWe conducted a systematic review and meta-analysis following a pre-registered protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Embase, Medline Ovid, and Cochrane Library Wiley were searched up to December 31, 2025, for clinical studies reporting long-term postoperative survival outcomes of patients with CRC undergoing ERAS implementation. Of 1,063 retrieved reports, 10 studies (5,876 patients) were included in Kaplan-Meier-based meta-analyses and eight studies (5,556 patients) in aggregated data meta-analyses. Data extraction was performed independently by two reviewers, with study quality and risk of bias assessed using the Newcastle-Ottawa Scale (NOS) and RevMan software. Effect sizes were pooled using fixed- or random-effects models according to heterogeneity, with cross-validation and subgroup analyses examining the influence of tumor stage and ERAS adherence. The pre-specified primary outcome was postoperative overall survival (OS) [&ge;]12 months, and the secondary outcome was disease-free survival (DFS). ResultsERAS significantly improved OS at 1 year (93.2%, 95% CI: 92.3-94.2 vs. 90.2%, 95% CI: 89.1-91.2), 2 years (86.7% vs. 81.3%), 3 years (81.1% vs. 72.4%), 5 years (70.9% vs. 60.6%) (all P<0.01). The pooled HR for mortality was 0.72 (95% CI: 0.63-0.83, P<0.01), indicating a 28% reduction in long-term mortality. Stage I-II tumors and ERAS adherence [&ge;]70% conferred the greatest benefits. DFS did not show a statistically significant improvement (HR=0.90, 95% CI: 0.68-1.19, P=0.45). Included studies were of moderate to high quality (NOS score 6-9). ConclusionsPerioperative ERAS significantly improves 1- to 5-year OS and reduces long-term mortality in patients with CRC, with the greatest benefits in early-stage disease and high adherence. These findings support ERAS as a critical component of comprehensive CRC care.

PurposeTumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact and durability of a concise 3-4 minute video for patient education prior to TGT in community versus academic sites and across cancer types. Patients and MethodsPatients undergoing standard-of-care TGT were enrolled at a tertiary academic institution in three cohorts: Cohort 1-breast cancer; Cohort 2-lung cancer; Cohort 3-other cancers. Cohort 4 consisted of patients with any cancer type similarly undergoing SOC TGT at one of three community cancer centers. Participants completed survey measures prior to video viewing (T1), immediately post-viewing (T2), and after return of TGT results (T3). Outcome measures included: 1) 10-question objective genomic knowledge/understanding (GKU); 2) 10-question video message-specific knowledge (VMSK); 3) 11-question Trust in Physician/Provider (TIPP); 4) perceptions regarding TGT. ResultsA total of 203 participants completed all survey timepoints. Higher baseline GKU and VMSK scores were significantly associated with higher income and greater years of education. For the primary objective, there was a significant and sustained improvement in VMSK from T1:T2:T3 (Poverall p<0.0001), with no significant change in GKU (p=0.41) or TIPP (p=0.73). This trend was consistent within each cohort (all p[&le;]0.0001). Results for four VMSK questions significantly improved, including impact on treatment decisions, incidental germline findings, and insurance coverage of testing. ConclusionsA concise, 3-4 minute, broadly applicable educational video administered prior to TGT significantly and sustainably improved video message-specific knowledge in diverse cancer types and in academic and community settings. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.

Gallbladder cancer (GBC) is a highly lethal malignancy with limited experimental models to study disease biology or evaluate therapeutic responses. Although canonical Wnt activation is commonly used for patient-derived organoid (PDO) development and expansion, gallbladder PDOs has also been generated under Wnt-inhibitory conditions. No comparative assessment has determined how Wnt pathway modulation influences gallbladder PDO development, phenotype or drug response. This study systematically compared the impact of canonical Wnt activation (WNTAct medium containing CHIR99021) versus inhibition (WNTInh medium containing DKK1) on the establishment, propagation, molecular features and therapeutic responses of PDOs generated from malignant or non-malignant gallbladder tissues derived from the same patient. Both media supported successful PDO generation with comparable efficiency, preserving biliary epithelial functions and marker expression. Transcriptomic profiling confirmed selective enrichment of canonical Wnt target genes in PDOs generated in WNTAct cultures. WNTAct conditions enabled markedly superior long-term propagation, whereas WNTInh cultures more consistently retained the dysplastic features in malignant samples. Gemcitabine response assays demonstrated significantly greater drug sensitivity in PDOs grown in WNTAct medium, a phenotype reversible upon media switching but requiring extended adaptation, indicating a dynamic and context-dependent influence of Wnt signaling on chemotherapeutic vulnerability. Collectively, the findings reveal a trade-off between long-term propagation and histological fidelity in gallbladder PDOs and show that Wnt signaling modulates gemcitabine sensitivity in a reversible manner. This comparative framework provides practical guidance for selecting culture conditions for gallbladder PDO based disease modelling and precision oncology applications.

BackgroundTamoxifen is a cornerstone of endocrine treatment for hormone receptor-positive breast cancer, reducing recurrence and breast cancer-specific mortality. However, its use is associated with a small, yet clinically relevant, increase in uterine cancer. As diagnosis of this cancer remains symptom-triggered, it is essential for patients to be aware of this risk and report symptoms promptly for optimal outcomes. We therefore assessed risk awareness among breast cancer survivors while exploring their attitudes towards potential future endometrial surveillance strategies. MethodsOver a 10-month period, a web-based survey was conducted among breast cancer survivors with/without tamoxifen treatment. The mixed-format questionnaire included closed-ended questions and optional free-text comments. Quantitative data were summarized descriptively and analyzed statistically; qualitative responses were reviewed thematically to contextualize survey findings. ResultsOf 163 respondents, 154 breast cancer survivors were included in the analysis, 128 of whom had received tamoxifen. Among tamoxifen-associated participants, 60% reported insufficient awareness of the associated uterine cancer risk, and half expressed uncertainty about the adequacy of the current symptom-triggered endometrial evaluation. Despite this, acceptance of tamoxifen therapy was high; only one patient declined treatment over concerns about side effects. Almost all participants (96%) were willing to adopt endometrial surveillance methods, if developed and validated. ConclusionAs evaluation of tamoxifen-associated uterine pathology is symptom-triggered, our data highlight the need for improved and standardized risk communication to promote timely symptom recognition, reporting, and diagnostic evaluation. Moreover, our findings support incorporating patient-reported preferences into the development of future endometrial detection strategies to improve survivorship care.

ObjectiveThis study aimed to investigate the anti-gastric cancer effect of Patchouli alcohol (PA), especially its influence on PD-L1-mediated immune evasion, and to elucidate the underlying molecular mechanisms. MethodsA CCK-8 assay was used to evaluate the effects of PA on the viability of the gastric cancer cell lines HGC-27 and MKN-45. RT-qPCR and western blotting were performed to analyze the mRNA and protein levels of NF-{kappa}B and PD-L1, respectively. In a coculture system of gastric cancer cells and peripheral blood mononuclear cells (PBMCs), the effect of PA pretreatment on the PBMC-induced apoptosis of cancer cells was analyzed by flow cytometry, and the cytotoxic activity of the PBMCs was assessed by a lactate dehydrogenase (LDH) release assay. Flow cytometry was also used to determine the proportions of CD3CD8 T cells and IFN-{gamma}CD8 T cells. ELISA was used to measure the levels of IFN-{gamma}, TNF-, and granzyme B in the coculture supernatants. Immunofluorescence staining was conducted to assess NF-{kappa}B nuclear translocation. In a mouse xenograft model, tumor volume and weight were measured after 14 days of PA treatment. Histopathological changes and apoptosis were analyzed by HE and TUNEL staining. A luciferase reporter assay was used to examine the transcriptional regulation of PD-L1 by NF-{kappa}B. ResultsPA inhibited the viability of HGC-27 and MKN-45 cells in a dose- and time-dependent manner and significantly downregulated the expression of NF-{kappa}B and PD-L1 at both the mRNA and protein levels. In a PBMC coculture model, PA pretreatment enhanced the ability of PBMCs to induce apoptosis and directly kill gastric cancer cells. Furthermore, PA pretreatment increased the proportions of CD3CD8 T cells and IFN-{gamma}CD8 T cells in a dose-dependent manner. Consistent with this immunostimulatory effect, PA increased the levels of IFN-{gamma}, TNF-, and granzyme B in the coculture supernatants. Mechanistically, western blotting analysis demonstrated that PA significantly reduced the protein levels of AKT, NF-{kappa}B, and PD-L1 in gastric cancer cells. Immunofluorescence staining further indicated that PA suppressed the nuclear translocation of NF-{kappa}B. In a mouse xenograft model, PA treatment significantly inhibited tumor growth, induced apoptosis, and downregulated NF-{kappa}B and PD-L1 protein expression in tumor tissues. Flow cytometry of tumor-infiltrating lymphocytes revealed increased proportions of CD3CD8 and IFN-{gamma}CD8 T cells following PA treatment. Finally, luciferase reporter assays demonstrated that NF-{kappa}B directly regulates PD-L1 transcription by binding to its promoter region. ConclusionPA exerts antitumor effects in gastric cancer by suppressing the NF-{kappa}B/PD-L1 axis, thereby enhancing CD8 T-cell-mediated cytotoxicity and inhibiting immune evasion.

BackgroundGastric cancer is one of the most common malignancies worldwide and is associated with poor prognosis, placing a considerable burden on public health. Overall treatment outcomes remain unsatisfactory, and accurate lymph node staging is essential for optimizing therapeutic strategies and improving survival. This study aimed to compare the prognostic value of different lymph node staging systems in patients with gastric adenocarcinoma and to provide a more refined prognostic assessment tool for clinical practice. MethodsWe included 4,054 patients with gastric adenocarcinoma from the SEER database (2015-2019) and 383 patients from the First Affiliated Hospital of Hainan Medical University. All patients underwent gastrectomy with D2 lymphadenectomy. Clinicopathological variables included sex, age, race, tumor size, T stage, AJCC N stage (AJCC-N), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDs). Between-group comparisons were performed using the chi-square test. Optimal cut-off values were determined with X-tile software. Survival differences were evaluated by Kaplan-Meier curves. Receiver operating characteristic (ROC) curves were used to compare predictive performance. Cox regression models were applied to identify independent prognostic factors, which were then incorporated into a nomogram. Model performance was assessed using calibration curves and decision curve analysis (DCA). ResultsAJCC-N, LNR and LODDs were strongly and positively correlated in all three datasets (P < 0.001). ROC analysis showed that LODDs had slightly larger areas under the curve than LNR and AJCC-N for predicting 1-, 3- and 5-year survival. Multivariable Cox regression confirmed that LODDs, together with sex, age, race, T stage and tumor size, were independent risk factors for overall survival (P < 0.05). The nomogram constructed from these factors showed good agreement between predicted and observed outcomes on calibration curves, and DCA indicated meaningful clinical net benefit across a broad range of threshold probabilities. ConclusionBy integrating the numbers of positive and negative lymph nodes, LODDs more sensitively reflects changes in metastatic tumor burden and showed the best prognostic performance among the evaluated systems for gastric adenocarcinoma. The proposed nomogram may serve as a useful tool for individualized prognostic assessment.

Purpose In resource-limited settings, locally advanced rectal cancer (LARC) often presents at advanced stages. Long-course chemoradiotherapy (LCCRT) remains a cornerstone of neoadjuvant therapy, yet outcome data from such settings remain limited. This study assessed tumor resectability, pathologic response, and factors associated with resectability following neoadjuvant LCCRT at Ethiopias largest tertiary oncology center. Methods A retrospective cohort study was conducted among patients with stage II-III rectal adenocarcinoma (cT3-4 and/or cN+) who completed neoadjuvant LCCRT at Tikur Anbessa Specialized Hospital between 2018 and 2023. Tumor resectability was determined by multidisciplinary team (MDT) assessment. Multivariable logistic regression was used to identify factors associated with post-LCCRT resectability, adjusting for initial T stage, circumferential resection margin (CRM) status, histologic subtype, radiotherapy technique, and neoadjuvant regimen. Results Among 58 eligible patients (median age 45 years; 62% male), 62% had cT4 tumors, 53% had cN2 disease, and 84.5% had involved CRM. The median diagnosis-to-LCCRT interval was 64 weeks (interquartile range [IQR], 37-82). After LCCRT, 27 patients (46.6%) were deemed resectable by MDT assessment; 19 patients (32.8%) ultimately underwent curative-intent surgery (median interval from LCCRT to surgery, 10 weeks; IQR, 7-15). Initial cT3 stage was associated with higher odds of resectability (adjusted odds ratio [AOR], 6.2; 95% CI, 1.06-36.37), whereas receipt of total neoadjuvant therapy was associated with lower odds (AOR, 0.10; 95% CI, 0.02-0.49). No pathologic complete responses were observed. Conclusion In this cohort characterized by advanced disease at presentation and treatment delays, neoadjuvant LCCRT resulted in low resectability and limited pathologic response. To enhance curative potential, concerted efforts are needed to expedite the timely initiation of radiotherapy, optimize multidisciplinary team assessment, and increase surgical capacity.

PurposeTreatment options of advanced oral squamous cell carcinomas (OSCC) are limited, and cisplatin toxicity and drug resistance are major clinical issues. Src is a central kinase that integrates multiple oncogenic pathways and a promising therapeutic target. However, Src inhibitors have shown suboptimal efficacy as monotherapies and their sensitivity in OSCC remains elusive. Experimental DesignWe examined the activation of major oncogenic signaling pathways and the antitumor effects of six Src inhibitors (dasatinib, ponatinib, vandetanib, saracatinib, PP2, bosutinib) in seven human OSCC cell lines (HSC-2, HSC-3, HSC-4, SAS, HO-1-u-1, CAL27, SCC-25). BALB/cAJcl nu/nu mice bearing CAL27 xenografts received dasatinib (30 mg/kg, intraperitoneally, daily), bosutinib (50 mg/kg, intraperitoneally, daily), cisplatin (2 mg/kg or 4 mg/kg, intraperitoneally, weekly), or combinations. Tumor volume, bioluminescence imaging, and body weight were monitored for 17 or 21 days, followed by histopathological assessment. ResultsThe activation of the key pathways, including Src and MAPK, considerably differed among the cell lines and was linked to heterogeneous sensitivity to Src inhibitors. Effective growth suppression required Src dephosphorylation and downstream MAPK pathway inhibition, which vary depending on the cell line. Additionally, combination treatment with a Src inhibitor and cisplatin showed additive antitumor effects, allowing the reduction of cisplatin doses by half without efficacy loss. Notably, dasatinib alone and in combination with cisplatin decreased tumor burden with characteristic internal tumor death in vivo. ConclusionsThese findings elucidate Src signaling dependency on OSCC and the potential of Src inhibition to decrease cisplatin toxicity, paving way for Src targeted therapeutic strategies.

The Receptor for Advanced Glycation End-products (RAGE) has been implicated in driving cancer growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarize and analyze current clinical and preclinical data to provide insight into the relationship between RAGE and cancer, cancer grade, metastasis, patient survival, and cellular processes. A multi-database search was performed to identify original clinical and preclinical research studies examining RAGE expression in cancer. After screening and review, 53 clinical and 233 preclinical studies were included. Associations of RAGE with clinical cancer outcomes were estimated using odds ratio (OR) and associated 95% confidence intervals (CI). The meta-analysis found that RAGE expression was highly correlated with cancerous tissue when compared to controls; high-grade tumors; regional lymph node invasion; and was somewhat negatively associated with patient survival. In addition, meta-analysis estimates of preclinical studies found positive associations between RAGE expression/activation and cancer growth, metastatic potential, evasion of apoptosis, and activated NF-{kappa}B expression. This systematic review and meta-analysis is the first comprehensive study through which both preclinical and clinical research in all available cancer types are assessed for correlations with RAGE expression and activation, demonstrating that RAGE does indeed play a significant role in cancer progression and that further research is warranted.

BackgroundPancreatic ductal adenocarcinoma is one of the most aggressive and lethal malignancies of the gastrointestinal tract. The poor prognosis is largely attributed to late-stage diagnosis, pronounced tumor heterogeneity, and limited therapeutic efficacy. These challenges underscore the urgent need for the identification of robust molecular biomarkers and novel therapeutic targets. MethodsGene expression data from a total of 146 pancreatic tissue samples, comprising 72 normal and 74 tumor specimens obtained from the Pan-Cancer Atlas(TCGA) were analyzed. Differential gene expression analysis was conducted using the DESeq2 package, followed by functional enrichment analysis based on GO and KEGG. A classification model was developed using the XGBoost algorithm and evaluated through 500 bootstrapping iterations and 5-fold cross-validation to ensure robustness and generalizability. Model interpretability was assessed using SHAP (SHapley Additive exPlanations) values to identify genes with the highest predictive contribution. ResultsA comprehensive transcriptomic analysis revealed significant dysregulation of multiple genes between normal and tumor pancreatic tissues. Genes such as GJB3, S100A2, MSLN, and SLC2A1 were notably overexpressed, whereas DEFA6, APOB, and RBP2 exhibited marked downregulation, indicative of impaired exocrine function and aberrant epithelial reprogramming. The XGBoost classification model achieved an average area under the curve (AUC) of 0.9868 and an overall accuracy of 98.6%. SHAP (SHapley Additive exPlanations) analysis identified GJB3, LINC02086, and TSPAN1 as key predictive features. Six genes were concurrently identified as differentially expressed and highly influential within the model, supporting their potential utility as robust biomarkers for pancreatic tumor characterization. ConclusionsPancreatic ductal adenocarcinoma is marked by extensive transcriptomic reprogramming. The integration of differential gene expression analysis with interpretable machine learning enabled the identification of a molecular signature with potential diagnostic and therapeutic relevance.

BackgroundImmune checkpoint inhibitors (ICI) have improved outcomes in Merkel cell carcinoma (MCC). Population analyses suggest improved survival following the 2017 approval of ICI, but registry data lack treatment-level information including type of systemic therapy and initiation timepoint to directly estimate the benefit attributable to immunotherapy. This study compared Merkel Cell Carcinoma-specific survival between patients treated with first-line ICI versus cytotoxic chemotherapy. MethodsPatients were identified from the Seattle Merkel Cell Carcinoma Registry. Among 1,517 patients with MCC, 463 received first-line systemic therapy with either ICI or chemotherapy. Propensity scores were estimated using logistic regression including AJCC 8th stage, age, sex, MCPyV status, and immunosuppression. One-to-one nearest-neighbor matching produced balanced cohorts of 133 ICI-treated and 133 chemotherapy-treated patients. Merkel Cell Carcinoma-specific survival from therapy initiation was analyzed using Kaplan-Meier and Cox proportional hazards models with follow-up administratively censored at five years. ResultsBaseline clinical characteristics were comparable between matched cohorts. ICI therapy was associated with significantly improved Merkel Cell Carcinoma-specific survival compared with chemotherapy (log-rank p<0.0001). Five-year Merkel Cell Carcinoma-specific survival was 56.8% (95% CI 46.8-65.6) for ICI versus 23.9% (95% CI 16.9-31.6) for chemotherapy. In multivariable stage-stratified Cox analysis, ICI remained independently associated with improved Merkel Cell Carcinoma-specific survival (HR 0.32, 95% CI 0.21-0.50; p<0.0001), while immunosuppression was associated with worse Merkel Cell Carcinoma-specific survival (HR 2.03, 95% CI 1.10-3.74; p=0.0228). ConclusionsICI therapy was associated with substantially improved MCC-specific survival compared with chemotherapy.

Colonic adenocarcinoma (COAD) is a major cause of cancer-related mortality worldwide. Various tumors are linked to metastasis-associated in colon cancer 1 (MACC1). This study aimed to analyze public datasets to examine MACC1 expression, signaling pathways, copy number variations, and associations with immune cell subsets in COAD employing bioinformatics. MACC1 expression was elevated in COAD, especially in Wnt signaling and chromatin modifier pathways. Analysis of somatic copy number alterations in The Cancer Genome Atlas-COAD dataset revealed a link between MACC1 and DNA damage repair. MACC1 also showed a negative correlation with genes involved in immune cell infiltration in patients with COAD, including cluster of differentiation (CD)8+ T cells, activated dendritic cells, CD8 T cells, and cytotoxic cells. Collectively, these findings suggest MACC1 as a potential prognostic biomarker and therapeutic target for COAD.

ObjectiveThe purpose of the present study is to describe the survival outcomes of patients with low-grade serous ovarian cancer (LGSOC) in the post-operative setting from a tertiary gynecologic oncology referral centre in Quebec, including evaluation of patient characteristics, clinical outcomes and prognostic factors. MethodsThe study included 25 patients: 1) with a post-surgical histopathologic diagnosis of a low-grade serous tumour of the ovary, 2) underwent primary cytoreductive surgery prior to adjuvant therapy, and 3) for whom clinical data was available. Clinical and demographic features were characterized by descriptive statistics. Clinical endpoints of progression-free survival (PFS) and overall survival (OS) were assessed, utilizing the Kaplan-Meier method for estimating survival probabilities. ResultsThe median age of this cohort was 61 years (range, 26-81). Median OS was 140.6 months in patients with no residual disease (R0), 71 months in patients with microscopic residual disease (R1), and 27.7 months in patients with macroscopic residual disease (R2) (p=.001). Residual disease was also found to significantly impact PFS (p=.008). Administration of adjuvant chemotherapy failed to improve survival outcomes altogether (PFS, p = .270; OS, p = .300). ConclusionsThis study supports the shifting consensus that optimal cytoreductive surgery, where feasible, is paramount for successful treatment of LGSOC. Furthermore, treatment with adjuvant chemotherapy may lead to worse survival outcomes.

PurposeLarge language models (LLMs) offer significant potential for automating the classification of clinical trials by eligibility criteria. However, a critical question remains regarding the optimal input data: while abstracts provide a condensed, high-density signal, full-text articles contain a much higher volume of information. It remains unclear whether the additional signal found in full texts improves classification performance or if the accompanying noise (in the form of thousands of words irrelevant to the question at hand in a complete manuscript) negatively affects the models reasoning capabilities. MethodsGPT-5 was applied to classify 200 randomized controlled oncology trials from high-impact medical journals, labeling them whether patients with localized and/or metastatic disease were eligible for inclusion. Each trial was classified twice - once using only the abstract and once using the full text - and GPT-5s outputs were compared with the ground-truth labels established by manual annotation. Performance was assessed by calculating and comparing accuracy, precision, recall, and F1 score, and the McNemar test was used to assess the statistical significance of the differences between the two input formats. ResultsFor identifying trials including patients with localized disease, GPT-5 achieved an accuracy of 86% (95% CI: 81% - 91%; F1 = 0.90) when using abstracts and 92% (95% CI: 88% - 95%; F1 = 0.92) when using full texts (p = 0.027). Performance for detecting trials, which include patients with metastatic disease, was comparably high, with accuracies of 99% (95% CI: 99% - 100%; F1 = 1.00) based on abstracts and 98% (95% CI: 97% - 100%; F1 = 0.99) based on full texts. Overall accuracy for assigning combined labels per trial increased from 86% (95% CI: 81% - 91%) using abstracts to 92% (95% CI: 88% - 95%) using full texts (p = 0.027). ConclusionProviding full-text articles to GPT-5 significantly improved the classification of trial eligibility criteria. These findings suggest that, for this task, the benefit of the additional signal contained within the full text outweighed the potential for performance degradation caused by increased noise. Utilizing full-text analysis appears particularly valuable for extracting specific eligibility criteria in oncology that are frequently omitted or not explicitly described within the abstract.

Background: Rectal cancer (RC) is traditionally grouped within colorectal cancer (CRC), despite growing evidence of distinct epidemiologic features. However, global comparative assessments of lifetime risks of RC relative to CRC remain limited. We aimed to estimate lifetime risks of developing and dying from RC and CRC worldwide and to examine geographic, socioeconomic, and temporal variations in the proportional contribution of RC within CRC. Methods: Age-specific incidence and mortality estimates for RC and CRC across 185 countries were obtained from GLOBOCAN 2022, together with population and all-cause mortality data from the United Nations. Lifetime risks of incidence (LRI) and mortality (LRM) were calculated using the adjusted-for-multiple-primaries (AMP) method by sex, country, region, and Human Development Index (HDI). The RC-to-CRC lifetime risk ratio quantified the proportional contribution of RC. Temporal trends were assessed in 42 countries using Cancer Incidence in Five Continents Plus (CI5plus) data and average annual percent change (AAPC). Results: In 2022, the global lifetime risk of developing RC was 1.61% and dying from RC was 0.95%, accounting for approximately 35% of the corresponding CRC lifetime burden (4.61% and 2.68%). Absolute lifetime risks of both RC and CRC increased with HDI. In contrast, the proportional contribution of RC varied markedly, peaking at 41%-43% in Central and South-Eastern Asia but falling below 20% in the Caribbean and Central America, and showed a negative association with HDI. The LRI/LRM ratio increased with socioeconomic development. Temporal analyses showed increasing LRI trends in 17 of 42 countries for CRC versus 9 for RC, while declines occurred in 14 countries for RC and 11 for CRC. Conclusions: RC constitutes a substantial yet epidemiologically distinct component of the global CRC burden. Its proportional contribution varies across regions and does not parallel absolute risk patterns, supporting the need for subsite-specific surveillance and prevention strategies.

BackgroundPrecision oncology is predominantly focused on nuclear genomic alterations, while mitochondrial DNA (mtDNA) variation remains largely excluded from routine pharmacogenomic testing. However, mitochondria regulate oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS) production, apoptosis, and metabolic reprogramming pathways central to chemotherapy response. Methods468 Complete mitochondrial genomes from Kenyan individuals representing diverse ethnolinguistic groups were analyzed. Seven variants associated with effect on cancer treatment were identified. These include; m.310T>C(D-loop), m.10398A>G (MT-ND3), m.13708G>A (MT-ND5), m.16189T>C, m.13928G>C, m9055G>A and m.16519T>C (D-loop). Allele frequencies and distribution were assessed. ResultsThe coding-region variants (m.10398A>G and m.13708G>A) occur in Complex I subunits and are associated with altered oxidative phosphorylation efficiency and ROS production. The control-region variants (m.16189T>C and m.16519T>C) influence mtDNA replication and copy number. These variants have been implicated in differential response to chemotherapeutic agents including platinum-based therapies and anthracyclines. m.13928G>C sits in the MT-CYB gene and could possibly affect mitochondrial respiratory function; this variant could influence how tumors respond to therapies that rely on apoptosis or ROS generation.m.9055G>A is a MT-ATP6 variant classified as benign in mitochondrial disease but may represent a marker of haplogroup background rather than a direct cancer driver. While m.310T>C itself does not encode a protein, its location in the regulatory D-loop influences mitochondrial function, which can affect how tumor cells respond to chemotherapies that rely on mitochondrial-mediated apoptosis or oxidative stress. ConclusionPharmacogenomics relevant mitochondrial variants are present in the Kenyan population. With the rise of cancer burden in Kenya there is a need carry out more studies to understand the impact of these variations on cancer treatment. This can inform the integration of mtDNA analysis into precision oncology strategies in African populations.

BackgroundLeptomeningeal disease (LMD) is a serious complication of metastatic breast cancer (MBC) with poor survival. This single-institution retrospective study compares overall survival (OS) among MBC patients with LMD based on CSF parameters (glucose, protein, and WBC count) MethodologyMBC patients who were diagnosed with LMD between 2010-2023 at Wilmot Cancer Institute were screened for eligibility. Only those with available data on CSF glucose, protein, and WBC count were included. OS was assessed via the Kaplan-Meier method and compared using the log-rank test. Cox models were used for multivariate analysis. ResultsOut of 69 patients with MBC LMD, 28 had CSF data and were included in the final analysis. The CSF cytology-positive cohort had significantly lower glucose levels vs the CSF cytology-negative cohort [median (IQR) 40 (18-58) vs 64 (53-92) mg/dl, p=0.006]. Median CSF WBC count was significantly higher in the CSF cytology positive cohort vs the CSF cytology negative cohort [median (IQR) 13 (6-44) vs. 2(2-4)cells/mm3, p=0.001]. When stratified by CSF cytology results and CSF glucose levels, the CSF cytology negative, glucose-low group was associated with the worst OS, while the CSF cytology negative, normal/high glucose group was associated with the best OS(p=0.03) in an unadjusted analysis. Multivariate analysis confirmed that low CSF glucose was independently associated with poorer survival [HR 4.64 (1.71, 13.2)]. Neither CSF protein levels nor CSF WBC counts were significantly associated with OS in unadjusted and multivariate analyses. ConclusionLow CSF glucose was associated with worse OS than normal/high CSF glucose. There was insufficient evidence to suggest that CSF protein or CSF WBC counts were associated with OS.

ObjectivePopulation-based information regarding adherence to first-line chemotherapy in epithelial ovarian cancer is scarce. This study aimed to evaluate chemotherapy adherence, reasons for chemotherapy modifications, and associations with overall survival. MethodsAdvanced-stage epithelial ovarian cancer patients diagnosed between January 2015 and December 2021 were identified from the Netherlands Cancer Registry. Patients who underwent cytoreductive surgery combined with platinum- and taxane-based chemotherapy were included. Patients were categorized into two groups: adherent (patients without modifications) and non-adherent (patients with modifications: dose reduction, chemotherapy interruption, and/or reduction in chemotherapy cycles). Reasons for modifications were assessed. Kaplan-Meier survival curves and Cox proportional hazards models were used to analyze overall survival. ResultsAmong the cohort (N = 3,687), 54% of patients underwent chemotherapy modifications. Dose reduction (38%) was the most common, followed by interruption (24%) and reduction in chemotherapy cycles (9%). Non-adherence was associated with poorer performance scores, higher comorbidity indices, and undergoing primary cytoreductive surgery. Neurotoxicity and hematologic toxicity were the primary reasons for modifications in platinum (33% and 37%) and taxane (47% and 35%) agents. No association with survival was found for dose reduction and interruption. However, reduction in chemotherapy cycles was associated with lower 5-year overall survival (32% (95% CI 26%-38%) vs. 36% (95% CI 34%-38%)), remaining significant after multivariable adjustment (hazard ratio 1.36; 95% CI 1.17-1.59). ConclusionA significant proportion of Dutch advanced-stage epithelial ovarian cancer patients undergo chemotherapy modifications. No impact on overall survival was found for dose reduction or chemotherapy interruption, warranting prospective studies. Reduction in chemotherapy cycles was negatively associated with overall survival, possibly reflecting underlying treatment ineffectiveness. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSGuideline-recommended chemotherapy for advanced epithelial ovarian cancer is often difficult to deliver in routine practice, and real-world data on adherence and its impact on survival are limited. What this study addsIn this nationwide retrospective cohort, over half of patients experienced chemotherapy modifications; dose reductions and interruptions were not associated with poorer overall survival, whereas a reduction in the number of cycles showed an association with worse outcomes, although this may partly reflect underlying disease severity or treatment response. How this study might affect research, practice or policyOur findings suggest that standard dosing and treatment duration of six cycles may not always be necessary, emphasizing the need to tailor treatment plans to optimize both efficacy and tolerability in advanced-stage epithelial ovarian cancer patients

Immune checkpoint inhibitors such as anti-PD1 antibodies are essential in cancer therapy. Emerging data suggest that lower doses may be effective and more economical, though further evidence is needed. We conducted a retrospective study at Centre Leon Berard to assess the efficacy and safety of low-dose nivolumab (20 mg every three weeks) in patients with advanced cancer, mainly squamous cell carcinomas (SCC). Between 2023 and 2024, 53 patients were treated, with a median age of 74 years; 39.6% were over 80. Most were male (64%) and had ECOG >1 (69.9%). Primary tumor sites included cutaneous SCC (34%), head and neck SCC (32%), and soft tissue sarcoma (15%). After a median follow-up of 8.3 months, median overall survival was 7.5 months. The objective response rate (ORR) was 20.8% overall, rising to 35.3% in cutaneous SCC and 23.5% in head and neck SCC-comparable to standard-dose nivolumab. Toxicity was manageable: 18.7% experienced immune-related adverse events, with only 3.7% grade 3. Low-dose nivolumab demonstrates encouraging efficacy and tolerability in a frail population, supporting its potential role in resource-limited settings. Prospective trials are warranted to confirm these findings in broader populations.

BackgroundFamily history of cancer is a well-established risk factor for several malignancies, including colorectal, breast, and ovarian cancers. Estimating the prevalence of familial cancer history is essential for identifying high-risk populations and guiding targeted prevention strategies. ObjectiveThis study aimed to estimate the prevalence of family history of colorectal, breast, and ovarian cancer among residents of Derna City, Libya. MethodsA cross-sectional survey was conducted among 300 participants aged 17-45 years, selected using stratified random sampling. Data were collected through structured questionnaires covering sociodemographic characteristics and family history of cancer. Descriptive statistical analyses were performed to estimate prevalence rates. ResultsThe mean age of participants was 24.65 {+/-} 4.70 years, with the majority under 25 years of age (67.3%). Females constituted 79.9% of the sample, and most participants had a university-level education (93.5%). A family history of breast cancer was reported by 30.0% of participants, followed by colorectal cancer (23.3%) and ovarian cancer (13.3%). These findings indicate a substantial proportion of individuals with potential genetic susceptibility to these cancers within the study population. ConclusionA notable prevalence of family history of colorectal, breast, and ovarian cancers was observed in Derna City. These results underscore the importance of incorporating family history assessment into routine healthcare practice and strengthening genetic counseling, screening, and public awareness programs. Targeted prevention strategies may help reduce the burden of hereditary cancers in this region.