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PubMed2026

Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

Humans↗

PubMed2026

Whole-Genome Deep Learning Predicts Chemotherapy Response in Colorectal Cancer.

Chemotherapy response in colorectal cancer (CRC) exhibits significant heterogeneity, with current clinical predictors failing to capture complex genomic determinants of resistance. We developed a hybrid deep learning framework integrating convolutional neural networks (CNNs) and bidirectional long short-term memory (BiLSTM) networks to analyze whole-genome somatic mutations, evolutionary conservation, chromatin accessibility, and 3D genome architecture in 2,546 TCGA patients. An attention mechanism identified predictive genomic regions. The model achieved an AUC of 0.92 (95% CI: 0.89-0.94) in cross-validation and 0.88 (95% CI: 0.85-0.91) in independent validation, outperforming clinical models (ΔAUC = +0.18, p < 0.001). Key predictors included non-coding variants in TP53, KRAS, and PIK3CA regulatory regions. Triple-positive patients (mutations in all 3 regions) had significantly worse progression-free survival (HR = 4.7, p < 0.001). Our framework enables accurate chemotherapy response prediction and reveals novel non-coding resistance mechanisms, advancing precision oncology in CRC.

Humans↗

PubMed2026

Magrolimab Plus Azacitidine Versus Placebo Plus Azacitidine in Patients With Untreated Higher-Risk Myelodysplastic Syndromes: The Phase III ENHANCE Study.

PURPOSE: To evaluate the efficacy and safety of the cluster of differentiation 47-targeted antibody magrolimab plus azacitidine (Magro/Aza) versus azacitidine alone in treatment-naïve patients with higher-risk myelodysplastic syndromes (MDS) in the phase III ENHANCE study (ClinicalTrials.gov identifier: NCT04313881). METHODS: Based on the Revised International Prognostic Scoring System, patients with intermediate- to very-high-risk MDS were randomly assigned to receive Magro (1 mg/kg on days [D]1 and 4; 15 mg/kg on D8; 30 mg/kg on D11 and D15, and then once per week for five doses, followed by 30 mg/kg maintenance doses once every 2 weeks)/Aza (75 mg/m2 daily on D1-7 or on D1-5 and 8-9 in 28-day cycles) or matched placebo plus azacitidine (Placebo/Aza). Dual primary end points were complete remission (CR) rate (per 2006 International Working Group criteria) and overall survival (OS). RESULTS: At final analysis, 539 patients were randomly assigned to Magro/Aza (n = 268) or Placebo/Aza (n = 271) arms. Baseline characteristics were generally well balanced between treatment arms. In the Magro/Aza versus Placebo/Aza arms, the CR rate was 21.3% versus 23.6% (odds ratio, 0.876 [95% CI, 0.585 to 1.312]; P = .5218), and median OS was 15.9 versus 18.6 months (hazard ratio, 1.203 [95% CI, 0.947 to 1.528]; P = .1299). Magro/Aza had a higher incidence of grade ≥3 adverse events (AEs; 92.8% v 79.2%), AE-associated study drug discontinuations (24.0% v 12.1%), serious AEs (71.9% v 51.5%), and fatal AEs (15.2% v 9.8%) versus Placebo/Aza. CONCLUSION: ENHANCE did not meet the primary end points of CR rate and OS, and showed more frequent severe AEs in patients treated in the Magro/Aza arm.

Humans↗

PubMed2026

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans↗

PubMed2026

A reanalysis of the Hitachi cohort study evaluating the effectiveness of low-dose CT screening for lung cancer.

The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.

epidemiology/public health↗

PubMed2026

Targeting TP53 in triple-negative breast cancer: Molecular pathogenesis, therapeutic implications, and emerging pharmacological strategies.

Triple-negative breast cancer (TNBC) remains a highly aggressive and therapeutically challenging subtype, defined by the absence of oestrogen, progesterone, and HER2 expression. Tumour Protein 53 (TP53) mutations represent the most frequent genetic alteration, occurring in over 80% of cases and driving tumour initiation, progression, and therapeutic resistance. Mutant p53 proteins not only lose canonical tumour-suppressive functions but also often acquire gain-of-function (GOF) oncogenic properties that promote metastasis, genomic instability, and resistance to mechanisms like ferroptosis. This review examines the biological role of TP53 in TNBC pathogenesis and evaluates emerging pharmacological strategies aimed at targeting these vulnerabilities. Key approaches include the pharmacological reactivation of mutant p53 using small molecules such as APR-246, COTI-2, and the mutation-specific reactivator rezatapopt (PC14586), which has shown significant clinical tumour reduction in Y220C-mutant patients. Other strategies involve targeted protein degradation, the exploitation of synthetic lethal interactions (e.g., Chk1 or Aurora kinase B inhibition), and the use of natural products like cryptolepine or piperine derivatives. Recent clinical evidence further highlights the potential of combining epigenetic agents like decitabine with chemotherapy in TP53-mutant populations. Integrating TP53 mutation status into biomarker-driven treatment paradigms is a pivotal step toward achieving precision oncology and improving clinical outcomes for patients with TNBC.

Precision oncology↗

PubMed2026

Intersphincteric resection versus abdominoperineal resection for lower rectal cancer: A systematic review and meta-analysis.

BACKGROUND: The optimal surgical approach for lower rectal cancer (LRC) remains debated, particularly between intersphincteric resection (ISR) and abdominoperineal resection (APR). While ISR offers potential sphincter preservation, its oncological efficacy compared to APR is unclear. METHODS: A systematic review was conducted to compare clinical and oncological outcomes of ISR versus APR in LRC patients. On December 8, 2024, a comprehensive search of Medline, Embase, Cochrane Library, Scopus, and Web of Science identified 24 retrospective studies involving 4502 patients. Key outcomes analyzed included positive circumferential resection margin (CRM), number of harvested lymph nodes (LNs), local recurrence (LR), length of hospital stay (LOS), early postoperative complications, and survival. RESULTS: Twenty-four retrospective studies involving 4502 patients (ISR: 2266 (50.3%) and APR: 1558 (34.6%)) met the eligibility criteria. ISR was associated with significantly lower rates of positive CRM (risk ratio (RR): 0.41, p < 0.001), decreased early postoperative complications (RR: 0.76, p < 0.001), lower LR (RR: 0.63, p = 0.0038), and improvement in five-year overall survival (5YOS) (hazard ratio (HR) = 0.42, p < 0.001) and five-year disease-free survival (5YDFS) (HR = 0.59, p < 0.001). CONCLUSIONS: ISR demonstrates several advantages over APR in selected LRC patients, including lower rates of positive CRM, fewer early postoperative complications, reduced LR, greater LN harvest, shorter LOS, and improved long-term survival outcomes (5YOS and 5YDFS). Therefore, ISR can be considered a safe and effective alternative to APR in appropriately chosen patients, with careful patient selection and surgical expertise remaining essential.

Humans↗

PubMed2026

Hilar lymph node involvement in pediatric liver cancer and its impact on outcomes: A systematic review.

UNLABELLED: Management of liver tumors in children is well-defined, with clear treatment protocols established by organizations such as the International Society of Pediatric Oncology-Liver group (SIOPEL), the Children's Oncology Group (COG), and the Japanese Study Group for Pediatric Liver Tumors (JPLT). However, no structured approach exists for hilar lymph node (LN) resection. Surgical practices vary among centers, reflecting the adult setting. This systematic review aims to examine the current evidence on hilar lymphadenectomy in pediatric patients with primary liver tumors and to assess LN positivity rates and their associations with recurrence and survival. METHODS: A structured literature search was conducted on MEDLINE, Embase, and Web of Science (2004-January 2025) using keywords: lymph node, hepatoblastoma, hepatocellular carcinoma, and liver tumor. Patients under 21 years were included. The study protocol was registered on PROSPERO (CRD42024501895), and Rayyan software supported screening and review. RESULTS: Eight studies (880 patients) were included. Diagnoses were hepatoblastoma (HB, n = 277), hepatocellular carcinoma (HCC, n = 507), and other tumors (n = 96). LN dissection details were available for 431 patients: 349 (80.9%) had no metastases. In the HB group, 43% underwent hilar LN dissection with 0% positivity. In HCC, 33.6% had positive nodes. In other tumors, 7.8% showed LN involvement. Data on survival impact were limited. CONCLUSIONS: In HB, routine LN dissection may be unnecessary due to universally negative nodes. For HCC, the one-in-three positivity rate supports further evaluation of lymphadenectomy. Evidence remains limited for other tumors. Prospective multicenter studies using standardized protocols are needed to define the role of LN evaluation beyond HB.

Humans↗

PubMed2026

Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis.

INTRODUCTION: Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS: The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS: RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.

Humans↗

PubMed2026

Minimally invasive versus open surgery for gallbladder cancer: A systematic review and meta-analysis.

INTRODUCTION: Minimally invasive surgery (MIS) is increasingly being used in gallbladder cancer (GBC) for radical tumour extirpation. However, there are conflicting results on the morbidity outcomes following MIS. The aim of this meta-analysis was to compare the post-operative morbidity and mortality in patients undergoing radical surgery for GBC between MIS and open surgery. MATERIAL AND METHODS: Studies comparing MIS (laparoscopic, robotic or both techniques) to open surgery were included. The databases of MEDLINE, Cochrane and EMBASE were searched from 2001 till March 2025. The primary end point was post-operative morbidity and mortality. The secondary end points were hospital stay, blood loss, operative time and R1 resection rates. Random effect models were used for analysis. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Thirty-two studies (laparoscopic [n = 19], robotic [n = 6] or both [n = 7]) involving 8568 (MIS = 3287 and open = 5281) patients were included. For overall and major morbidity (Clavian-Dindo >/ = III), the odds ratio (OR) of 0.60 (95% CI: 0.46-0.78) and 0.72 (95% CI: 0.52-1.0) respectively was obtained, favouring the MIS approach. Similarly, MIS showed lower odds for mortality [OR:0.62 (95% CI: 0.40-0.95)] compared to open surgery. MIS was associated with shorter hospital stay (less by mean of 3 days) and lesser blood loss (less by mean of 115 ml) but longer operative time (higher by mean of 5.8 min) and higher R1 resection rates (OR: 1.34; 95% CI: 1.05-1.71). Oncological outcomes, however, were comparable. The certainty of evidence was very low to low across the studies. CONCLUSION: MIS for GBC was associated with relatively lower post operative morbidity and mortality with similar oncological outcomes but with a small but heightened risk of margin positive (R1) resection, especially in primary GBC. The certainty of evidence was very low to low across the included studies. Future prospective studies are needed to overcome the clinical heterogeneity and possible selection bias.

Humans↗

PubMed2026

Evidence Gap in Managing Lateral Pelvic Lymph Nodes in Rectal Cancer: a Systematic Review of Radiation Boost Strategies.

PURPOSE: Lateral pelvic lymph node (LPLN) involvement is a significant predictor of local recurrence in patients with locally advanced rectal cancer (LARC). While lateral pelvic lymph node dissection (LPLND) is routinely used in some countries to manage suspicious nodes, it is associated with increased morbidity and is not widely adopted in Western practice. Radiation boost (dose escalation) to involved LPLNs during neoadjuvant chemoradiotherapy (nCRT) has emerged as a potential non-surgical alternative. Despite increasing adoption of radiation boost to clinically involved LPLNs, there remains limited evidence defining its safety, oncologic benefit, and role relative to LPLND. METHODS: A systematic search of MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane databases was conducted following PRISMA guidelines. Studies were included if they reported outcomes of radiation dose escalation specifically targeting radiologically suspicious LPLNs in the context of nCRT. RESULTS: Ten retrospective cohort studies encompassing 482 radiation boosted patients were included. Boost doses ranged from 35.0 to 60.2 Gy. Rates of Grade 2-3 toxicity ranged from 28.0% to 39.3% across individual studies, with only one study reporting a single Grade 4 adverse event. Across individual studies, reported nodal response rates ranged from 62.3% to 100%. Comparative studies suggest that radiation boost may improve local control and reduce LPLN recurrence. CONCLUSION: Current retrospective evidence suggests that radiation dose escalation to involved LPLNs is a promising treatment strategy; however, the available data are limited by retrospective study designs and substantial clinical heterogeneity. Given the absence of prospective evidence and lack of consensus in current guidelines, an important evidence gap remains. Well-designed prospective trials are warranted to define the role of LPLN boost relative to LPLND.

Humans↗

PubMed2026

Enhancing Self Care Among Oral Cancer Survivors Using a Digital Approach: The Empowered Survivor Trial.

BACKGROUND: Oral and oropharyngeal cancer survivors experience debilitating physical and psychosocial challenges. Little knowledge exists on the efficacy of interventions to enhance self-efficacy in managing these challenges, increase survivorship preparedness, and improve health-related quality of life (HRQoL). METHODS: Individuals (n = 643) diagnosed with oral or oropharyngeal cancer diagnosed within past 3 years were randomized to a digital intervention, Empowered Survivor (ES) or a Generic Online Intervention (GO). Primary (self-efficacy, preparedness, HRQoL) and secondary outcomes (self-care activities) were measured at Baseline, 2-months, and 6-months. RESULTS: Participants assigned to ES reported greater self-efficacy and increased self-care activities of oral self-exams, swallowing, and mobility exercises than those assigned to GO (self-efficacy: 2 months, p = 0.003, 6-months, p < 0.001; self-care activities). CONCLUSIONS: The ES enhanced self-efficacy and increased self-care activities. Further examinations of survivorship preparedness and HRQoL in oral and oropharyngeal cancer are warranted. TRIAL REGISTRATION: Registered on clinicaltrials. gov as NCT04713449.

Humans↗

PubMed2026

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans↗

PubMed2026

Sarcomas: Research on Ultrarare Subtypes Gains Ground.

Rare cancers account for almost one fourth of all cancers. Sarcomas belong to the group of cancerous diseases with an incidence of less than 6 cases per 100,000 inhabitants. Over the past decade, activities were launched worldwide to elucidate the peculiarities of many of the more than 100 sarcoma subtypes described in the World Health Organization handbook. The major contributor to exact diagnosis is molecular pathology. The subgroup of ultrarare sarcomas (URS) poses a significant problem as each URS type has its own morphology, biology, natural history, and prognosis. In 2020, 35 international sarcoma centers agreed to standards of evaluating URS. The threshold was set to an incidence of less than 1 case per 1,000,000 inhabitants, and 77 URS subtypes were defined. Also quality criteria for centers to be selected for retrieving data to registries were consented. This issue of Cancer Epidemiology, Biomarkers & Prevention contains the first article to validate these principles of URS using the data from a nationwide cancer database. The authors from Taiwan also pointed out limitations of the approach. Combination with the national death database allowed to calculate overall survival (OS) and identified age as a significant factor for OS per URS type. These new data might foster future research on diagnosis and treatment of URS. See related article by Lee et al., p. 1654.

Humans↗

PubMed2026

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer↗

PubMed2026

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of ≥ 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer↗

PubMed2026

Identifying biomarkers of accelerated ageing in cancer patients from routine clinical data.

INTRODUCTION: Cancer and ageing have a bidirectional relationship: age is the strongest risk factor for cancer, and cancer and treatments can accelerate ageing. Therefore, biological age can differ from chronological age; biomarkers are needed to stratify interventions to minimise accelerated ageing. METHODS: PhenoAge was calculated from routine blood test results of patients attending a Geriatric Oncology clinic. PhenoAgeAccel was the residual from a regression of PhenoAge against age. RESULTS: Data were available for 173 patients (62% male). Mean PhenoAge was higher than age (84.3 (12.6) vs 76.2 (7.24), p < 0.001), though the two were correlated (r = 0.579, p < 0.001). Unlike age, PhenoAge and PhenoAgeAccel were associated with one-year mortality (PhenoAge OR=1.083, 95% CI: 1.038-1.136; PhenoAgeAccel OR=1.096, 95% CI: 1.047-1.155). PhenoAge correlated with Clinical Frailty Score and Timed Up and Go (CFS: Rs=0.31, p < 0.001; TUG: Rs=0.25, p < 0.005); there were no correlations with age. PhenoAgeAccel correlated with the number of CGA interventions made (Rs=0.17, p < 0.05), unlike age and PhenoAge. Patients with diabetes mellitus had a higher PhenoAgeAccel compared to those without (3.40 vs -1.71, p = 0.002). In patients receiving systemic anti-cancer treatment, patients with PhenoAgeAccel calculated pre-treatment had less age acceleration than those with PhenoAgeAccel calculated post-treatment, both overall (2.18 vs -2.87; p = 0.048) and in matched samples (n = 21, 7.76 vs -2.87, p < 0.001). CONCLUSIONS: PhenoAgeAccel is a greater predictor of risk than chronological age in older people with cancer. This makes it a promising biomarker to stratify patients for holistic geriatric assessment, dose reductions, or future geroprotective measures which could be integrated within electronic healthcare record systems.

Humans↗

PubMed2026

Unveiling the power of TIIC: A prognostic tool for esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) remains a lethal malignancy with limited prognostic tools for guiding immunotherapy. Tumor-infiltrating immune cells (TIICs) play a critical role in EAC prognosis and treatment response. METHODS: We integrated single-cell RNA sequencing and bulk transcriptome data from TCGA and GEO databases. TIIC-specific RNAs were identified via tissue specificity index calculation combined with machine learning feature selection. Twenty machine learning algorithms were benchmarked to construct an optimal TIIC signature score (TIIC-Score) based on the comprehensive C-index. Immunotherapy response, genomic mutation, and copy number variation were analyzed. Summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (MR) were performed to explore genetic associations. Core prognostic TIIC-related genes were functionally validated in esophageal cancer cell lines through loss-of-function assays. RESULTS: The TIIC-Score demonstrated robust prognostic value for 1-, 2-, and 3-year overall survival across multiple cohorts, outperforming 22 published models. High TIIC-Score was associated with poor survival and increased chromosomal instability. Mutation profiling revealed high frequencies of TP53 (78.2%), TTN (48.7%), and SYNE1 (30.8%). MR analysis identified a significant association between gastro-oesophageal reflux and EAC risk at SNP rs8130507. Functionally, CCNI was upregulated in esophageal cancer cells, and its knockdown suppressed malignant phenotypes while promoting apoptosis, supporting its pro-tumorigenic role. CONCLUSION: The TIIC-Score provides a novel prognostic framework for EAC that effectively stratifies patient risk and may help identify individuals most likely to benefit from immunotherapy.

Esophageal adenocarcinoma↗