搜索结果：Cancer informatics

Cancer remains a global health challenge, requiring diverse and multi-targeted therapeutic strategies. In recent years, natural compounds-particularly essential oils (EOs), which are widely available and chemically diverse-have gained growing attention in cancer prevention and treatment. In this study, we employed an in silico approach to identify essential oil-derived compounds with potential against cancer. A chemical library of 2,033 compounds was constructed based on GC-MS profiling of essential oils extracted from Vietnamese plants. Among these, 610 compounds were predicted to exhibit anticancer activity. Following IC50 and ADMET-based filtering, 477 compounds were identified as both cytotoxic and pharmacologically safe. These compounds were further evaluated through molecular docking against five key cancer-related targets: VEGF-A, PARP-1, mTOR, BRAF, and EGFR. 15 candidates showed strong binding affinities across multiple targets, including m-camphorene (- 9.9 kcal/mol with BRAF), β-amyrin (- 7.93 kcal/mol with PARP-1), β-sitostenone (- 9.33 kcal/mol with EGFR), trans-β-elemenone (- 7.67 kcal/mol with VEGF-A), and occidentalol (- 8.3 kcal/mol with mTOR). Molecular dynamics simulations further confirmed the structural stability of m-camphorene-BRAF complex. To evaluate its possible clinical relevance, the prognostic significance of m-camphorene-related gene signatures was analyzed using transcriptomic datasets from TCGA across ten common cancer types. Significant associations between these signatures and patient survival were observed in BRCA, KIRC, and SKCM, suggesting potential translational relevance. Overall, this study highlights the value of natural compound libraries and virtual screening strategies in accelerating drug discovery from traditional medicinal sources and provides a computational foundation for further experimental validation of EO-derived anticancer agents.

Sub-Saharan Africa faces twice the incidence and up to fifteen times the fatality rate of cervical cancer compared to developed countries. Screening coverage remains low at 7-25.3%, far below the WHO target of 70%. Increasing women's knowledge about cervical cancer screening is crucial for improving uptake and reducing this high burden. The study was conducted among 50,584 reproductive-age women across seven Sub-Saharan African countries. A combination of filter and wrapper methods was applied for feature selection. Data preprocessing and management were performed using Stata version 17 and Python (Colab, version 3.10.2). MinMaxScaler, StandardScaler, and RobustScaler were applied to normalize variable ranges. One-hot encoding was used for nominal categories, and ordinal encoding was applied for features with an inherent order. The dataset was split using an 80; 20 (40,467: 10,117) ratio for training and testing. Eight algorithms were selected for model training and development, including Decision Tree, Random Forest, K-Nearest Neighbors (KNN), Artificial Neural Network (ANN), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), Adaptive Boosting (AdaBoost), and Gradient Boosting (GB). Hyperparameter tuning was performed for XGBoost and LightGBM. Model performance was evaluated using Accuracy, AUC, F1 Score, Recall, and Precision. The XGBoost algorithm outperformed the other models, achieving an accuracy of 84%, an AUC of 82%, an F1 score of 83%, a recall of 82%, and a precision of 84%. Overall, 56% of reproductive-age women demonstrated good knowledge of cervical cancer screening. HIV status, educational status, media exposure, maternal age, health status, antenatal care attendance, wealth status, occupation, autonomy, place of delivery, distance to health facility, marital status, and fertility were identified as the top predictors of knowledge of cervical cancer screening. Knowledge of cervical cancer screening was low, at 56%, compared with the WHO target of 70%. Strengthen community-based educational programs through mass media, reinforce health education during antenatal care (ANC) follow-up and HIV programs, and implement strategies that promote women's autonomy, education, and economic empowerment are recommended.

Lung cancer remains the leading cause of cancer mortality, yet blood-based biomarkers are not routinely used in diagnosis. This study evaluated four commercial blood protein assays, originally validated for other indications, in indeterminate pulmonary nodules (IPN). Using a prospective specimen collection, retrospective blinded evaluation design, samples were collected from patients with screening-detected, incidental, or symptomatic IPNs. Cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), and human epididymis protein 4 (HE-4) concentrations were quantified on commercial immunoassays. Logistic regression models were developed using internal training (Train), external testing (Test), and combined reestimation (Train + Test) cohorts and externally validated in an outcome-blinded multicenter cohort (Lung Team Project-2, LTP-2). This study included 816 patients: 371 in Train, 166 in Test, and 279 in LTP-2. Malignancy rates were 54%, 44%, and 64%, respectively. In Train + Test, the area under the receiver operating curve (AUC) for lung cancer was 0.60 (95% confidence interval, 0.56-0.65) for CYFRA 21-1, 0.62 (0.58-0.67) for CEA, 0.60 (0.55-0.65) for CA-125, and 0.65 (0.60-0.70) for HE-4. In LTP-2, AUCs were 0.63 (0.56-0.70), 0.64 (0.57-0.70), 0.48 (0.40-0.55), and 0.61 (0.54-0.68), respectively. Combining all four biomarkers yielded an AUC of 0.70 (0.65-0.74) in Train + Test and 0.61 (0.54-0.68) in LTP-2. In the first biomarker study reporting external validation in LTP-2, CYFRA 21-1, CEA, CA-125, and HE-4 demonstrated diagnostic value in IPNs. By leveraging commercial assays, this study highlights opportunities to enhance lung cancer risk stratification using widely available diagnostics that could be rapidly integrated into clinical workflows.

Prostate cancer remains one of the most prevalent malignancies in men worldwide, and early detection, accurate characterization, and staging are critical for optimal patient management. Diffusion magnetic resonance imaging (dMRI) has emerged as a powerful technique for non-invasive in vivo imaging of tissue microstructure, promising to enable unprecedented insights into the pathophysiology of prostate cancer. In this review, we examine the current state and future directions of dMRI techniques for microstructure MRI in prostate cancer applications. We describe the technical challenges of prostate imaging along with potential remedies, as well as techniques that go beyond measuring the conventional apparent diffusion coefficient. These include more sophisticated representations and models, such as intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), methods based on tensor-valued diffusion encoding such as q-space trajectory imaging (QTI), as well as time-dependent dMRI. Models, such as VERDICT (vascular, extracellular, and restricted diffusion for cytometry in tumors) and IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion), are highlighted for their ability to quantify the composition of prostatic tissues in the clinical setting. This review highlights the transformative potential of microstructure MRI in prostate cancer, while identifying key research priorities and technical developments needed to realize its clinical impact. Future directions include the adoption of high-performance MRI systems, improved image readout and processing techniques, integration of multiparametric and multidimensional approaches, development of parsimonious protocols, and standardization of robust biomarkers for personalized treatment stratification. Although there is yet to be a consensus of how microstructure MRI should be deployed, current evidence suggests that it can provide superior diagnostic performance compared to conventional measurements, with improved correlation to tumor aggressiveness and potential downstream advantages for prostate cancer diagnostics and treatment monitoring.

To explore the postoperative psychosocial adaptation challenges of young and middle-aged lung cancer survivors, with a focus on their lived experiences, perceptions, and underlying cultural influences, including social roles, etiquette, and family expectations, to guide the development of more precise and culturally sensitive psychosocial support. A qualitative descriptive design was conducted. A total of 21 young and middle-aged lung cancer survivors were purposively recruited and interviewed using a semi-structured guide. The data were organized by NVivo 11.0 and qualitatively analyzed using thematic analysis. We generated an overarching theme, "psychosocial adaptation challenges: striving for a new normal". Four themes were identified: (1) unbearable threat of death, including inability to endure death, and fear of cancer recurrence; (2) symptom distress, including clearly stated symptoms and subjectively ambiguous symptoms; (3) restrictions on daily life, including activity intolerance, imposed dietary restriction, withdrawal from social activities, and adjusted work engagement; and (4) being treated differently, including feeling isolated or discriminated against, a burden of goodwill, and longing for normal. Young and middle-aged survivors following lung cancer surgery experienced severe psychosocial adaptation challenges, including challenges specific to this life stage. This study emphasizes the need for postoperative care to attend to physical recovery, psychological adjustment, and social-role reconstruction among lung cancer survivors.

Bladder cancer accounts for 4 % of cancer diagnoses in the US. Current treatments primarily involve trans-urethral resection of bladder tumors (TURBT) and immunotherapy with Bacille Calmette-Guerin (BCG). Despite the efficacy of TURBT, issues with residual tumors persist. We chose to utilize Cell Painting to screen a set of 244 flavonoid compounds for bladder cancer cell toxicity. Using multiparametric high content analysis termed SPACe, we discover promising candidates underscoring the potential of flavonoids in targeting bladder cancer cells and elucidating their mechanisms of action. Notably, compounds such as xanthohumol show promise in reducing cancer cell viability by altering lipid metabolism. We further show the effectiveness of hit compounds in subsequent spheroid and chorioallantoic membrane systems. Overall, this research emphasizes the role of innovative screening methods in drug discovery and potential synergistic effects of combining flavonoids with existing therapies like BCG for improved bladder cancer treatment outcomes.

Reliable prediction is critical for prognosis communication and informed decision-making, yet remains challenging for cancer patients-especially older adults with non-small cell lung cancer (NSCLC)-due to the uncertainty inherent in model-based predictions. This study presents a framework that integrates uncertainty quantification (UQ) into individual survival prediction using electronic health records from 4243 older NSCLC patients in Korea. We applied four Cox proportional hazard-based survival models and four artificial intelligence (AI)-based survival models, including DeepSurv, to predict 2-year survival probabilities. We introduce two novel UQ metrics: certainty score, capturing the relative model confidence in predicted mortality risk, and predictive multiplicity, quantifying model disagreement in risk stratification. Although the survival models achieved high mean areas under the receiver operating characteristics curve ranging from 0.840 to 0.851, 26% of patients in the test set were assigned to conflicting risk groups depending on the model used, indicating considerable variability in model-predicted prognosis. DeepSurv demonstrated the highest average certainty. All models showed substantial degrees of predictive ambiguity and discrepancy. We also developed a visual informatics tool that presents personalized best-, worst-, and most likely-case scenarios, risk group stratification, and interpretable feature importance to improve transparency and facilitate shared decision-making. This framework offers a practical approach for integrating uncertainty into AI-based prognosis, addressing the challenge of enhancing confidence in cancer prognosis communication by quantifying and visualizing model uncertainty. It can support clinicians in tailoring prognostic discussions based on the level of model consensus and confidence, helping guide when to communicate prognosis cautiously or emphasize shared decision-making. The proposed framework is model-agnostic and readily applicable to real-world clinical settings.

Breast cancer (BC) subtypes such as HR+, HER2+, and triple-negative (TNBC) show distinct molecular features, treatment responses, and outcomes. DNA methylation is a key, targetable epigenetic regulator in BC. This study examined whether the DNA methyltransferase inhibitor decitabine (DAC) produces subtype-specific epigenomic and transcriptional effects in breast cancer cell lines representing distinct molecular subtypes. Gene expression and DNA methylation data from DAC-treated and untreated T-47D (Luminal-A) and JIMT-1 (HER2-amplified, trastuzumab-resistant with a TNBC-like phenotype) breast cancer cell lines were obtained from a published dataset. Differential expressions were assessed using limma, and methylation changes were defined using β-value thresholds. Integrated epigenomic-transcriptional analysis, functional enrichment, Horvath clock CpG evaluation, and survival analysis were performed in the METABRIC and TCGA cohorts. In JIMT-1, DAC caused hypomethylation at 1195 CpG sites and upregulation of 187 genes, including TFAP2E, an age-associated locus selectively hypomethylated after DAC. In T-47D, DAC induced hypomethylation at 1937 CpGs and upregulated 248 genes. Amongst these, KRT20 was upregulated despite promoter hypermethylation, indicating a subtype-specific regulatory architecture. DAC-responsive genes in JIMT-1 were enriched for cytokine signaling and piRNA-mediated epigenetic silencing, whereas T-47D showed enrichment for extracellular matrix organization, collagen dynamics, and piRNA processing pathways. Horvath clock CpG analysis showed selective perturbation of age-associated sites. Survival analysis identified 114 DAC-responsive genes associated with overall survival in ER/PR-positive BC and 8 in the JIMT-1-derived gene set. DAC induces subtype-dependent epigenomic and transcriptional remodeling, selectively disrupts age-associated regulatory programs, and underscores the need for subtype-stratified evaluation of epigenetic therapies in breast cancer.

IntroductionTelehealth use expanded rapidly in oncology during the COVID-19 pandemic, but determinants for ongoing use in metropolitan cancer care after the pandemic remain unclear.MethodsA multi-centre retrospective cohort study of 271,889 oncology outpatient consultations (face-to-face, telephone, video) from 1 January 2019 to 30 June 2024 across four cancer centres in Sydney, Australia was conducted. Consultations were divided into pre-COVID, during-COVID restrictions and post-COVID restriction time periods. Multivariable generalised estimating equations modelled the odds of telehealth use in the during and post-restriction periods, testing interactions between time periods and key covariates.ResultsAcross 271,889 consultations with 21,125 patients the proportion of telehealth consultations was negligible pre-pandemic (0.4%), peaked during restrictions (24.7%) then reduced but was sustained post-restrictions (11.4%). Post-restrictions, telehealth use was more likely for follow-up consultations (vs new, p&#x2009;<&#x2009;.001), medical oncology consultations (vs radiation, p&#x2009;<&#x2009;.001), patients enrolled on a clinical trial (p&#x2009;<&#x2009;.001) and primary tumours including brain and genitourinary (vs breast, p&#x2009;<&#x2009;.001). Patients from the most socioeconomically disadvantaged quintiles (vs highest, p&#x2009;<&#x2009;.001), those who required an interpreter (p&#x2009;<&#x2009;.001), those receiving active treatment in the cancer centre (vs not on treatment, p&#x2009;<&#x2009;.001) and with primary tumours including head and neck or skin (vs breast, p&#x2009;<&#x2009;.001) were less likely to undergo telehealth consultations.ConclusionsThere is modest but sustained use of telehealth in oncology post-pandemic restrictions particularly for follow-up consultations, with less utilisation in populations experiencing disadvantage. Strategic, equity-focused policies are needed to ensure that telehealth use enhances, rather than exacerbates, disparities in access to cancer care.

Gastric Cancer (GC) poses a significant global health challenge, necessitating effective biomarkers for early detection and prognosis. This study investigates the relationship between SDC2 expression and GC patient outcomes. We analyzed SDC2 expression in GC and its association with patient outcomes using Kaplan-Meier survival and Cox regression analyses. A pan-cancer analysis was performed to assess cross-tumor SDC2 expression patterns. Validation included immunohistochemistry and single-cell data analyses to confirm SDC2 expression in GC tissues and cell types, with findings supported by independent cohort studies. Elevated SDC2 expression correlates with poor prognosis in GC patients, marked by lower survival rates, enhanced tumor microenvironment heterogeneity, decreased tumor mutational burden, and reduced immunotherapy efficacy. Kaplan-Meier and Cox regression analyses confirm that higher SDC2 expression is associated with shorter overall survival, establishing it as an independent prognostic risk factor. Pan-cancer analysis reveals consistent SDC2 expression patterns across multiple cancers, indicating broad clinical relevance. Validation through immunohistochemistry and single-cell data analysis confirms SDC2 expression in GC tissues and cell types. Independent cohort studies further support these findings. In summary, this study underscores the potential of SDC2 as a promising target for early diagnosis and therapeutic intervention in GC, with implications for other malignancies.

Down syndrome is associated with the development of multiple morbidities throughout the life course, yet comprehensive data on its relative burden remains limited. This descriptive, matched, retrospective cohort study aimed to assess the 20-year period prevalence of morbidities and cancers in adults and children with Down syndrome. We analysed electronic health record data from January 1998 to December 2017, matching individuals with Down syndrome to up to five matched controls. Period prevalence and odds ratios (OR) were calculated for 30 morbidities and 24 cancers. This study included 4,648 individuals with Down syndrome (32,920 person-years) and 23,238 matched controls (236,883 person-years). Most morbidities had a significantly higher period prevalence in individuals with Down syndrome, including hypothyroidism (30.4%), congenital cardiac disease (27.8%), and epilepsy (21.9%). We found an increased comparative risk of autism (OR 7.5, 95% CI 6.4-8.0), chronic kidney disease (OR 2.4, 95% CI 2.1-2.8) and inflammatory bowel disease (OR 2.5, 95% CI 2.2-2.8). Individuals with Down syndrome also had a significantly higher period prevalence of leukaemia and testicular cancer. Conversely, most solid tumours were less prevalent in individuals with Down syndrome. This study presents findings from one of the largest described cohorts of individuals with Down syndrome, contributing to an understanding of the comparative prevalence of multiple comorbidities and cancers among both adults and children with Down syndrome. These findings support prioritising surveillance for a range of conditions such as hypothyroidism and childhood leukaemia and may justify de-emphasising routine screening for several solid tumours in Down syndrome.

Although tumor budding has emerged as an indicator of tumor aggressiveness in several solid cancers, its prognostic significance in endometrial cancer is not well studied. This systematic review and meta-analysis aimed to quantify the association between tumor budding and clinicopathologic parameters in endometrial cancer. A comprehensive search of electronic databases was performed from inception to December 2025, and clinicopathologic data were extracted from studies that included patients with histologically confirmed endometrial cancer, assessed tumor budding on histopathology, reported clinicopathologic outcomes and/or survival outcomes, and provided effect estimates or sufficient data to calculate odds ratios or hazard ratios. In the pooled analysis of data from 12 eligible studies, tumor budding was found to be significantly associated with lymphovascular space invasion, lymph node metastasis, high tumor grade and deep myometrial invasion &#x2265;50% but not with advanced-stage disease at presentation and cervical stromal invasion. To conclude, though tumor budding is significantly associated with adverse clinicopathologic features in endometrial carcinoma, standardization of assessment methods and prospective validation are needed before routine clinical implementation as a predictive tool.

Cisplatin is a mainstay in cancer treatment, but toxicity and resistance limit its potential. Using RNA sequencing (RNA-seq), we show that ovarian cancer cells undergo broad changes in the microtubule cytoskeleton that correlate with resistance. Consistent with this, we find that cisplatin directly impacts microtubule dynamics in vitro and in cells. Paclitaxel counteracts cisplatin and increases resistance. By purifying tubulin from cisplatin-sensitive, -resistant, and -re-sensitized ovarian cancer cells, we demonstrate that resistance acquisition rewires the tubulin code, leading to microtubule stabilization. Furthermore, tubulin polymerization-promoting protein 3 (TPPP3) contributes to resistance. In vitro, TPPP3 synergizes with tubulin isotypes from resistant cells to yield maximal microtubule stabilization in response to cisplatin. Database analysis shows that patients with low TPPP3 levels have improved therapeutic outcome. Our findings implicate TPPP3 and microtubule dysregulation in cisplatin resistance, independent of effects through DNA damage, and have bearing on the etiology of cisplatin-associated neuropathies and ototoxicity.

Emerging evidence suggests that perturbation of TGF-&#x3b2; signaling in parenchymal cells drives malignant transformation and cancer progression in a subset of patients with primary liver cancer (PLC). TGF-&#x3b2; plays a crucial role in liver pathophysiology with diverse effects on various processes and cell types. In liver homeostasis, TGF-&#x3b2; signaling exerts tumor-suppressive functions that are often lost during carcinogenic transformation, when downstream signaling rebranches from tumor-suppressive to pro-tumorigenic, facilitating invasiveness and metastasis. In this study, primary patient-derived and established liver cancer cell lines were exposed to TGF-&#x3b2;1 and TGF-&#x3b2;2, and effects on tumor-initiating potential, invasion, and migration were assessed by in vitro analyses including colony/sphere formation and wound healing assays. RNA sequencing and reverse-phase protein array (RPPA) were employed to analyze differential gene and protein expression across treatments. Our findings demonstrate that TGF-&#x3b2;1 and TGF-&#x3b2;2 reduced proliferation, colony and spheroid formation in investigated cell lines. Notably, TGF-&#x3b2;1 increased migratory and invasive properties of both HCC and CCA cell lines, whereas TGF-&#x3b2;2 had no such effect. Transcriptome profiling revealed activation of gene sets associated with cell cycle regulation by both ligands. Pro-migratory effects of TGF-&#x3b2;1 were linked to epithelial-mesenchymal transition (EMT), including enrichment of matrix metalloproteinase (MMP) and actin cytoskeleton pathways. Specifically, TGF-&#x3b2;1 downregulated epithelial marker E-cadherin and upregulated mesenchymal markers Vimentin and SNAIL. RPPA indicated p21 induction by both ligands, causing cell cycle arrest, while TGF-&#x3b2;1 specifically upregulated MMP14, promoting EMT-related properties. In conclusion, targeting TGF-&#x3b2;1-MMP14-EMT pathway could complement TGF-&#x3b2;-based therapies in PLC management.

Colorectal cancer (CRC) is a leading cause of tumor-related mortality. Recent studies have shown that the transcriptome plays an important role in the development and occurrence of CRC. However, a comprehensive repository of CRC transcriptome sequencing data is unavailable. In the present study, we constructed a colorectal database (iCRCexp; http://icrcexp.omicsbio.info/). We collected CRC-related transcriptome datasets from The Cancer Genome Atlas (TCGA) and National Center for Biotechnology Information (NCBI) Gene Ontology Omnibus (GEO) databases up to 2022. The sequencing data were preprocessed through a unified pipeline and subsequently analyzed. CRC-related genes and drugs were identified via text mining of the PubMed abstracts. A total of 18&#x2009;466 tissue samples from 231 studies, 2429 CRC-related genes, and 1852 CRC-related drugs were collected and integrated into iCRCexp. Among these studies, 251 CRC-related datasets were identified with abundant characteristic information, including tissue source, baseline characteristics, therapeutic responses, recurrence and metastasis, and survival. We conducted differential correlation and survival analyses. We predicted potential target drugs for CRC-related genes by calculating connectivity scores. Consequently, we integrated these analysis results through network construction and presented them in a CRC database. A comprehensive resource, including CRC-related gene and medication information and an expression analysis platform, was constructed for the CRC community.

Currently, mendelian randomization (MR) has played an important role in studying causality. However, due to the unique role of third-party variables, false positive conclusions may arise in the process of causal inference. We aimed to assess the body mass index (BMI)-mediated effect of modifiable lifestyle factors on colorectal cancer (CRC) risk. The MR phenome-wide association study (MR-pheWAS) was initially performed to identify BMI-relevant lifestyle factors. Heritability estimation, genetic correlation, inverse-variance weighted MR analysis, and mediation analysis were conducted to evaluate the causal relationships among lifestyle, BMI, and CRC in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The FinnGen database was used to replicate the above results on genetic results and the UK Biobank cohort provided population-level validation for the causality. We initially analyzed the causal relationship between 32,760 phenotypes and BMI through MR-pheWAS. Five lifestyles (i.e., alcohol intake, time spent watching television, walking, walking pace, and smoking status) were found to causally affect BMI. Our results supported a causal association between genetically proxied BMI and CRC [odds ratio (OR)GECCO = 1.192 (95% confidence interval (CI): 1.038-1.369); ORFinnGen = 1.567 (95%CI: 1.398-1.756)]. Notably, alcohol intake [&#x3b2;GECCO = 0.252 (95%CI: 0.002-0.502), &#x3b2;FinnGen = 0.285 (95%CI: 0.085-0.484)] and time spent watching TV [&#x3b2;GECCO = 0.470 (95%CI: 0.015-0.924), &#x3b2;FinnGen = 0.421 (95%CI: 0.084-0.758)] had a direct causal effect on increasing CRC risk. The following effect decomposition indicated that the effect of alcohol intake on CRC was marked by BMI [proportionGECCO = 5.556% (95% CI: 0.397-9.518%) and proportionFinnGen = 8.421% (95% CI: 4.912-12.982)]. The proportion of the effect of time spent watching television on CRC mediated by BMI was 9.722% (95% CI: 0.198-19.246%) in GECCO and 16.936% (95% CI: 11.650-22.977%) in FinnGen. In contrast, the full effects of walking, walking pace, and smoking status on CRC were entirely mediated by BMI. A similar mediation pathway was observed in the UK Biobank cohort. This study, combining genetics-driven causal inference, provides evidence for the relationship between lifestyle factors and the risk of CRC ,helping to prioritize strategies for CRC prevention in populations. The online version contains supplementary material available at 10.1007/s43657-025-00270-5.

Communicating genetic test results within families can facilitate cascade testing that informs cancer prevention and surveillance. Researchers at the University of Washington, USA, developed a public website called ConnectMyVariant to support family communication of genetic test results. Australian families share similar challenges communicating genetic information. To explore the acceptability of ConnectMyVariant resources, identify content requiring adaptation, and need for further resources. Semi-structured interviews were conducted across three stages to review the ConnectMyVariant resources, assess relevance and acceptability for Australians, and identify need for adaptation. Stages 1 and 2 involved individuals with an identified hereditary cancer variant and their relatives. Stage 3 involved genetic counsellors. Resource content was revised between stages based on interview findings. Content analysis was used to analyse the interviews. Stage 1 interviews (n&#xa0;=&#xa0;31) highlighted the value of the resources but identified changes needed to make them suitable for an Australian context. Adaptations included adding ethics and consent around risk communication, reducing communicator burden, simplifying and softening language, incorporating local support services and genetic testing processes, including implications on life insurance. Stage 2 interviews (n&#xa0;=&#xa0;6) confirmed the adaptations were acceptable. In stage 3 interviews (n&#xa0;=&#xa0;7), genetic counsellors recognised the need for a communication resource and recommended minor changes to reflect local genetic testing processes, clinical language, and service preferences. This study demonstrates there is value in a communication resource for Australian families, and highlights the importance of undertaking cultural adaptation of resources. The authors are actively disseminating resources across community and clinical settings.

Adjuvant chemotherapy provides limited benefit in unselected stage II colon cancer. Postoperative ctDNA has higher prognostic value than classical clinical markers, with ctDNA positivity indicating an unfavourable outcome. Patients with UICC II, pMMR/MSS colon cancer were tested for ctDNA using an academic, tumour-informed, NGS-based test. ctDNA-positive patients were randomised 2:1 to CHEMO (capecitabine &#xb1; oxaliplatin) versus observation (OBS). ctDNA-negative patients were randomised 1:4 to OBS versus OFF-STUDY. ctDNA results were not disclosed in the OBS group. The primary endpoint was DFS in ctDNA-positive patients. All differences were tested using one-sided log-rank tests. The trial ended early due to funding expiry. From 06/2020 to 07/2025, 2,126 patients were screened in Germany and Austria. Overall, 1,396 patients (2.9% ctDNA-positive) were randomised: 1,083 to OFF-STUDY, 287 to OBS, and 26 to CHEMO, of whom 81% started therapy. DFS and OS were significantly lower in ctDNA-positive versus ctDNA-negative patients (3-year DFS 52% versus 87%, HR 4.28 [95% CI: 2.32-7.93], P < 0.001; 3-year OS 88% versus 98%, HR 5.48 [1.64-18.28], P = 0.001). In the intention-to-treat cohort, the between-arm differences were not significant (3-year recurrence 36% versus 62%, HR 0.48 [95% CI: 0.17-1.33], P = 0.075; 3-year DFS 61% versus 38%, HR 0.55 [95% CI: 0.21-1.48], P = 0.12). In the per-protocol analysis (excluding untreated CHEMO patients), time-to-recurrence (TTR) and DFS were improved with CHEMO compared to OBS (3-year recurrence 19% versus 62%, HR 0.23 [0.06-0.87], P = 0.009; 3-year DFS 77% versus 38%, HR 0.31 [95% CI: 0.09-1.03], P = 0.021). The primary ITT endpoint was not met, potentially related to the lower power due to premature trial closure. The per-protocol analysis suggests a benefit from adjuvant therapy in ctDNA-positive patients, supporting ctDNA testing for adjuvant decision making in the future.

To develop a predictive model for pathological complete response (pCR) after total neoadjuvant therapy (TNT) to inform selection for watch-and-wait (W/W). Patient selection for W/W after TNT for locally advanced rectal cancer remains challenging. An ensemble of tabular foundation models was fine-tuned in adults with clinical stage II or III microsatellite stable primary rectal adenocarcinoma undergoing TNT and total mesorectal excision (TNT+TME) from 2018-2023 to predict pCR, using pre-TNT, post-TNT and pre-TME variables. This model was externally validated on patients having TNT and W/W (TNT+W/W) to predict persistent clinical complete response (pcCR; the absence of local regrowth, distant metastases, or persistent near-cCR). Area under the receiver operator curve (AUROC), area under the precision-recall curve (AUPRC), and Brier score were calculated with 95% confidence intervals (CI). Among 308 patients that underwent TNT+TME (median age 56; 40% female), the model predicted pCR with an AUROC 0.71 (95% CI 0.65-0.77), AUPRC 0.44 (95% CI 0.35-0.57), and was well calibrated with a Brier score of 0.17 (95% CI 0.15-0.20). At external validation in a cohort of 83 patients that are being managed with TNT+W/W (median age 57; 37% female), the model predicted pcCR with an AUROC 0.69 (95% CI 0.57-0.82), AUPRC 0.90 (95% CI 0.82-0.96), and Brier score of 0.30 (95% CI 0.26-0.33), improving to 0.17 with recalibration. This novel predictive model demonstrated good discrimination and calibration for pCR after TNT+TME with utility in TNT+W/W for pcCR after appropriate recalibration, supporting its application for W/W patient selection.