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PubMed2026

Chemoradiotherapy versus short-course radiotherapy for response-adapted organ preservation in early-stage and intermediate-stage rectal cancer (STAR-TREC): 12-month results of an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial.

BACKGROUND: Total mesorectal excision (TME) is the standard treatment for most early-stage and intermediate-stage rectal cancer but can cause substantial perioperative morbidity, functional impairment, and reduced quality of life. We assessed whether long-course chemoradiotherapy (LCCRT) or short-course radiotherapy (SCRT) could increase organ preservation and reduce surgery, toxicity, and quality-of-life harms without compromising oncological outcomes. METHODS: STAR-TREC is an international, multicentre, open-label, parallel-group, randomised, phase 2/3 trial in five European countries. Eligible patients were aged 16 years or older in the UK or aged 18 years or older elsewhere, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and rectal adenocarcinoma (≤40 mm staged as mrT1-T3bN0). In phase 2, participants were randomly assigned (1:1:1) to LCCRT-based organ preservation (LCCRT-OP; 50 Gy in 25 fractions plus oral capecitabine 825 mg/m2 twice daily), SCRT-based organ preservation (SCRT-OP; 25 Gy in five fractions), or primary TME. Phase 2 assessed feasibility, with recruitment at months 12 and 24 as the primary endpoint and feasibility thresholds of four or more and six or more randomisations per month, respectively. Phase 3 adopted a partially randomised patient-preference design, allowing participants to choose either organ preservation or TME. Participants that chose organ preservation were randomly assigned (1:1) to receive LCCRT-OP or SCRT-OP using centralised, computer-generated assignment, with stratification by country and MRI T category (≤T3a vs T3b) using minimisation. The phase 3 primary endpoint was organ-preservation 30 months after treatment initiation, defined as absence of TME, stoma, or local recurrence, which was assessed in the modified intention-to-treat population, which included participants in phase 2 and phase 3. After a planned interim analysis of unmasked phase 2 data, the trial steering committee and independent data monitoring committee recommended reporting a 12-month, modified intention-to-treat analysis of implementation outcomes for participants recruited before Aug 8, 2023. This study is registered with ISRCTN (14240288) and is closed. FINDINGS: Between June 14, 2017, and April 8, 2024, 503 participants were enrolled at 37 sites. Phase 2 enrolled 120 participants, with recruitment rates of three and six participants per month at months 12 and 24, respectively. Overall, 12-month TME-free survival was 60% (47 of 78 participants). After phase 3 recruitment ended, interim analysis of unmasked phase 2 data showed an early TME-free survival benefit with LCCRT versus SCRT (12-month median TME-free survival not reached [95% CI not reached-not reached] vs 7·6 months [95% CI 6·4-not reached]; hazard ratio [HR] 3·7 [95% CI 1·7-8·0]; posterior probability of superiority >99·5%). The trial steering committee and independent data monitoring committee therefore recommended expanded analysis of 426 participants recruited before Aug 8, 2023: 120 from phase 2 and 306 from phase 3. 17 participants withdrew before treatment, leaving 409 in the modified intention-to-treat population: 163 allocated to LCCRT, 168 to SCRT, and 78 to primary TME. 116 (28%) participants were female and 293 (72%) were male. Among participants who opted for organ preservation, 12-month TME-free survival was 78·5% (95% CI 72·4-85·1) with LCCRT and 60·6% (53·6-68·4) with SCRT (HR 1·90 [95% CI 1·29-2·81]). The most common grade 3-4 serious adverse events were gastrointestinal disorders (four [2%] with LCCRT vs six [4%] with SCRT vs six [8%] with TME) and procedural complications (three [2%] with LCCRT vs five [3%] with SCRT vs five [6%] with TME). One participant allocated to primary TME died after an anastomotic leak. INTERPRETATION: These early results support a response-adapted organ-preservation approach, with LCCRT appearing more effective than SCRT at 12 months. Organ-preservation might also reduce treatment-related toxicity compared with primary TME. Longer follow-up is needed for the prespecified 30-month endpoint and definitive functional and oncological outcomes. FUNDING: Cancer Research UK, Stand Up to Cancer, Dutch Cancer Society, Danish Cancer Society, Kom Op Tegen Kanker, Cancerfonden, ALF Region Stockholm, RCC Region Stockholm.

Humans↗

PubMed2026

Symptom Networks and Core Symptoms in Patients with Solid Tumors Undergoing Chemotherapy: A Systematic Review.

OBJECTIVES: To summarize symptom network characteristics in patients with solid tumors undergoing chemotherapy and synthesize evidence on core symptoms, bridge symptoms, and temporal associations. METHODS: We systematically searched eight databases through October 2025 to identify studies that applied symptom network analysis to adults with solid tumors receiving chemotherapy. Eligible studies assessed symptoms using cross-sectional, longitudinal, or interventional designs. Two reviewers independently screened articles and extracted data on study characteristics, symptom assessment, and network outcomes. Methodological quality was assessed using the National Institutes of Health Study Quality Assessment Tool. RESULTS: Twenty-seven studies involving 13,452 participants were included, yielding 79 symptom networks. Fatigue was the most frequently identified core symptom (10/20, 50%), whereas sadness, lack of appetite, and nausea each occurred in 10% of studies, with variation across cancer types, treatment phases, and latent classes. Bridge symptoms included disturbed sleep, lack of appetite, and dry mouth (2/7, 28.6%). Studies evaluating temporal associations found that symptoms such as sadness, dyspnea, somnolence, and dry mouth predicted subsequent changes in appetite, distress, nausea, and other outcomes. Strength metrics showed acceptable stability (correlation stability coefficients: 0.28-0.83). CONCLUSIONS: Fatigue was frequently identified as a central symptom across studies, largely reflecting evidence from breast cancer studies. Core symptoms varied across cancer types, treatment phases, and latent classes, suggesting heterogeneity. IMPLICATIONS FOR NURSING PRACTICE: These findings highlight the importance of considering relationships among symptoms in clinical care. Focusing on key symptoms such as fatigue, while tailoring management strategies to cancer-specific symptom patterns, may support more effective symptom management.

Humans↗

PubMed2026

Hope is linked with more favorable tumor molecular signatures in serous ovarian cancer.

INTRODUCTION: Hope has been associated with improved quality of life and lower mortality in cancer, but the underlying biological mechanisms are poorly characterized. We previously reported that hope was associated with less inflammation and more normalized diurnal cortisol pre-treatment among women with ovarian cancer. We also reported associations of socio-environmental factors with pro-metastatic processes. Here, we used genome-wide transcriptional profiling to quantify associations between hope and tumor molecular signatures reflecting invasiveness, inflammation, and cellular immunity. METHOD: Participants were 74 women with serous ovarian cancer who provided demographic information and completed surveys pre-surgery. Hope was assessed using a face-valid item from the Center for Epidemiological Studies Depression Scale (CES-D). Depression was assessed using the full CES-D without the hope item. Illumina HT12 microarrays were used to assay tumor RNA, and associations between hope and tumor gene expression were quantified, adjusting for depression, age, BMI, grade, and stage. RESULTS: Adjusting for covariates, hope was associated with multiple favorable differences in RNA expression, including lower levels of mesenchymal differentiation (p = 0.008) and pro-inflammatory gene regulation (NF-κB: p < 0.001; IRF1: p = 0.024; STAT: p = 0.018), elevated epithelial differentiation (p = 0.011), and elevated activity of the IRF7 transcription factor which promotes cellular immunity (p = 0.016). CONCLUSIONS: These data suggest that hope is associated with an ovarian tumor gene expression profile characterized by reduced epithelial-mesenchymal transition (EMT) and inflammatory activity, and increased activity of a transcription factor promoting cellular immunity. These findings highlight potential biological implications of a resilience factor such as hope, but need replication with more robust assessments of hope.

Epithelial mesenchymal transition↗

PubMed2026

Obstructive sleep apnea and long-term risk of site-specific cancers: A population-based cohort study.

BACKGROUND: Obstructive sleep apnea is common, but its long-term association with site-specific cancers remains unclear. In this study, we examined 15-year risks of site-specific cancers in people with obstructive sleep apnea compared with the general population and to people with overweight or obesity. METHODS: We conducted a nationwide population-based cohort study using Danish registries, 1995-2021. People diagnosed with obstructive sleep apnea were compared with the general population and to people with overweight or obesity. Adjusted (weighted) 15-year risks, risk differences, and risk ratios (RRs) were estimated using the Aalen-Johansen estimator. Confounding was addressed using standardized morbidity ratio weighting. RESULTS: The study included 114,264 people with obstructive sleep apnea, 115,497 members of the general population, and 113,034 with overweight or obesity. After weighting, the distributions of sex (74% male), age (median 53 years), and comorbidities were comparable across the three cohorts. Obstructive sleep apnea was associated with an increased risk of cancers of the brain (adjusted 15-year risk: 5.78 vs. 3.61 per 1,000 persons; aRR 1.60 [95% CI 1.43-1.78]) and spinal cord (1.65 vs. 1.17 per 1,000 persons; aRR 1.41 [95% CI 1.16-1.72]) compared with the general population. Associations persisted when the obstructive sleep apnea cohort was compared with those with overweight or obesity. No associations were observed for other site-specific cancers. CONCLUSION: Obstructive sleep apnea was associated with an increased risk of brain and spinal cord cancers. These findings highlight the importance of effective prevention of obstructive sleep apnea and the need for further research on treatment.

Cohort Study↗

PubMed2026

Clinicopathological response and survival outcomes of HER2-low versus HER2-zero early breast Cancer: A systematic review and Meta-analysis.

BACKGROUND: Breast cancer is the most common malignant tumor in women. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for classification and treatment. A subgroup with HER2-low expression has been identified, but existing evidence is heterogeneous. This systematic review and meta-analysis compared pathological response and survival outcomes between HER2-low and HER2-zero early-stage breast cancer to clarify prognostic features. METHODS: This study followed PRISMA guidelines and was registered in PROSPERO (CRD420251120506). PubMed, Embase, Web of Science, ClinicalTrials.gov, and major oncology conferences were searched through September 2025. Cohort studies of early-stage breast cancer comparing HER2-low (IHC 1+/2+ and ISH-negative) vs. HER2-zero with extractable pCR, DFS, or OS data were included. Studies involving HER2-positive patients or inconsistent definitions were excluded. Meta-analyses were performed using RevMan 5.3. RESULTS: Twenty-eight studies involving 115,182 patients were included. HER2-low patients showed significantly lower pCR rates (OR = 0.58, 95% CI: 0.52-0.65). DFS favored HER2-low (multivariate HR = 0.75, 95% CI: 0.69-0.83), especially in HR+ tumors, with a weaker effect in HR- cases. OS also favored HER2-low (HR = 0.80, 95% CI: 0.72-0.89), mainly driven by the HR- subgroup; no OS difference was seen in HR+ tumors. Sensitivity analyses and funnel plots indicated robust results with no apparent publication bias. Overall study quality was high (17 high-quality, 11 moderate-quality). CONCLUSION: HER2-low early breast cancer shows lower pCR after neoadjuvant therapy but better long-term survival. These findings support the clinical relevance of HER2-low as a biologically meaningful subgroup within HER2-negative disease, while its status as a stable and independent subtype still requires further validation through prospective studies, standardized testing, and multi-omics investigation.

Humans↗

PubMed2026

Efficacy of Mindfulness-Based Interventions on Anxiety and Sleep Quality in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Patients with breast cancer commonly experience anxiety and sleep disturbance during and after treatment, and these symptoms are closely interrelated, negatively affecting the quality of life. Mindfulness-based interventions (MBIs) have been increasingly used as a nonpharmacological supportive approach. This systematic review and meta-analysis aimed to evaluate the effects of MBIs on anxiety and sleep quality in patients with breast cancer. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, CINAHL, and Embase was conducted up to May 15, 2025. Random-effects meta-analysis was used to estimate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2.0, and the certainty of evidence was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Twenty-four randomized controlled trials (RCTs) including 3,212 participants were analyzed. MBIs significantly reduced anxiety compared with control groups receiving usual care, no intervention, or wait-list conditions (SMD: -0.47, 95% CI: -0.62 to -0.32), whereas no significant effect was observed for sleep quality. Subgroup analysis indicated that intervention duration accounted for 55.5% of the heterogeneity in anxiety outcomes. All studies were rated as having some concerns regarding risk of bias, primarily due to self-reported outcomes and lack of blinding. Certainty of evidence was moderate for anxiety and low for sleep quality. DISCUSSION: MBIs appear to be effective in reducing anxiety among patients with breast cancer; however, no significant effect was observed for sleep quality. All included studies were rated as having some concerns regarding risk of bias, and the limited reporting of adverse events represents a limitation of the evidence. In addition, substantial heterogeneity in sleep quality outcomes and the limited number of included RCTs restrict exploration of heterogeneity sources and limit generalizability. Further high-quality well-designed RCTs are needed to strengthen and confirm the evidence.

Female↗

PubMed2026

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans↗

PubMed2026

Reduced Length of ADT and ARTA With XRT in High-Risk Prostate Cancer (RELAX): A Randomised Controlled Trial.

AIM: To assess the efficacy of a short, intensified regimen of androgen deprivation therapy (ADT) and androgen receptor-targeted agent (ARTA) with curative-intent external beam radiotherapy (XRT) for high-risk prostate cancer (HRPCa) staged with prostate specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: The RELAX (Reduced Length of ADT and ARTA with XRT in high-risk prostate cancer) trial is a multicentre, phase II randomised non-inferiority trial comparing 9 months of ADT and 6 months of ARTA against the standard 24-month ADT, with definitive dose-escalated hypofractionated pelvic radiotherapy for PSMA-staged non-metastatic HRPCa. The primary endpoint is 5-year disease-free survival (DFS), defined from randomisation to first biochemical or clinico-radiological recurrence or any-cause death. Secondary endpoints include biochemical failure-free survival, metastasis-free survival, overall survival, testosterone recovery, treatment-related adverse effects, and patient-reported outcomes. Participants are monitored with serial serum PSA and testosterone levels, CTCAE and PRO-CTCAE assessments, and PSMA-PETCT at recurrence. The non-inferiority margin is set at 10% absolute difference from an expected 5-year DFS of 85% in the standard arm, with intention-to-treat analysis. The trial is ethics board approved and funded by institutional intramural grant, and registered on clinicaltrials.gov (NCT06818682). RESULTS: The planned accrual of 206 participants commenced in February 2025, with nearly a third of enrolment completed till date. CONCLUSION: The RELAX trial incorporates contemporary standards of PSMA-based staging, dose-escalated hypofractionated radiotherapy, and ARTA for HRPCa. The results are expected to inform the efficacy of a shorter, intensified androgen suppression strategy against the prevailing standard of long-term ADT for these patients.

Humans↗

PubMed2026

Sustained effects of auricular point acupressure on chemotherapy-induced neuropathy: a randomized controlled trial follow-up study.

PURPOSE: Chemotherapy-induced neuropathy (CIN) is a persistent condition that impairs function and quality of life. Auricular point acupressure (APA) has shown short-term benefit for CIN, but the durability of these effects after treatment completion is unknown. This study evaluated the sustainability of symptom improvements for 3 months following a 4-week APA intervention. METHODS: This prespecified secondary analysis of a randomized wait-list controlled trial compared mobile-supported APA (mAPA) and virtual APA (vAPA) in adults with moderate or greater CIN who received APA during the initial treatment phase (mAPA, n = 80; vAPA, n = 75). Outcomes at 1, 2, and 3 months post-intervention were analyzed using generalized estimating equations with multiple imputation. The primary outcome was CIN severity, measured with an individualized composite outcome (ICO); the secondary outcome was CIN interference. RESULTS: Reductions in CIN severity and interference were maintained throughout follow-up in both groups (all p < .001). ICO scores decreased by 3.10, 3.36, and 3.61 points in mAPA and by 2.88, 2.90, and 3.21 points in vAPA at 1, 2, and 3 months, respectively. Benefits were maintained post-treatment, with higher retention in the mAPA group. CONCLUSIONS: Improvements in CIN severity and interference after APA were sustained for up to 3 months post-treatment, suggesting a durable benefit as a self-management strategy. Larger studies with longer follow-up and untreated comparison groups are needed. IMPLICATIONS FOR CANCER SURVIVORS: APA may offer survivors a durable, self-administered, nonpharmacologic option for managing CIN well beyond active treatment, without requiring ongoing clinical visits. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT04920097 registered on 3 June 2021.

Acupressure↗

PubMed2026

Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.

PURPOSE: Transforming growth factor β (TGFβ) plays a dual role in cancer, acting as a tumor suppressor early in the disease but promoting progression and immune evasion when dysregulated. In pancreatic ductal adenocarcinoma (PDAC), TGFβ-driven desmoplasia fosters chemoresistance and immunosuppression, limiting therapeutic efficacy. NIS793, a fully human mAb targeting TGFβ, demonstrated antifibrotic and immunomodulatory activity in preclinical models and early-phase trials. PATIENTS AND METHODS: We conducted a randomized, open-label, phase II study in treatment-naïve patients with metastatic PDAC (mPDAC) to evaluate NIS793 ± spartalizumab (anti-PD-1) combined with nab-paclitaxel (or Abraxane)/gemcitabine (ABRA/GEM) versus ABRA/GEM alone. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, pharmacokinetics, and biomarker analyses. Exploratory assessments included paired tumor RNA sequencing, cell-free DNA profiling, and plasma proteomics. RESULTS: NIS793 demonstrated target engagement and suppression of TGFβ signaling, confirmed by transcriptomic and proteomic analyses. Stromal remodeling was evident, with significant downregulation of cancer-associated fibroblast markers (Acta2, Fap) and collagen-related signatures. Despite proof of mechanism, clinical efficacy was not observed: Median PFS and OS were comparable or numerically worse in the NIS793 arm versus control (HR for OS in NIS793 + ABRA/GEM vs. ABRA/GEM: 1.32; 95% confidence interval, 0.84-2.07). The safety profile was manageable, with no unexpected toxicities. Biomarker data revealed increased expression of neutrophil-related genes after treatment, suggesting potential induction of tumor-promoting inflammation. CONCLUSIONS: NIS793 effectively inhibited TGFβ signaling and led to stromal remodeling but failed to improve outcomes in mPDAC. These findings highlight the complexity of TGFβ biology and caution against its blockade in combination with chemotherapy for PDAC. Future strategies should consider context-dependent effects of TGFβ inhibition.

Humans↗

PubMed2026

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

PubMed2026

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (χ² = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans↗

PubMed2026

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans↗

PubMed2026

Ifebemtinib plus garsorasib in previously treated metastatic colorectal cancer with KRASG12C mutation: a multicentre, randomised, phase 1b/2 trial.

BACKGROUND: Ifebemtinib is a potent oral focal adhesion kinase inhibitor. Preclinical evidence supports combining ifebemtinib with the KRASG12C inhibitor garsorasib. This study aimed to evaluate this combination in KRASG12C-mutated solid tumours. METHODS: This multicentre, phase 1b/2 study had a phase 1b component to establish the recommended phase 2 dose and a phase 2 multitumour expansion component. In phase 1b, the safety and tolerability of ifebemtinib combined with garsorasib was assessed using a 3 + 3 design in KRASG12C-mutated solid tumours. No dose-limiting toxic effects were observed, and the recommended phase 2 dose was established as ifebemtinib 100 mg orally once daily plus garsorasib 600 mg orally twice daily. Here, we report the results of the cohort of previously treated KRASG12C-mutated metastatic colorectal cancer from phase 2 expansion. Eligible patients (aged ≥18 years) who had histologically confirmed locally advanced or metastatic colorectal cancer harbouring the KRASG12C mutation, an Eastern Cooperative Oncology Group performance-status score of 0 or 1, and had disease progression after previous irinotecan-based or oxaliplatin-based combination therapy, were recruited from seven of nine participating tertiary hospitals in China. On the basis of the recommended phase 2 dose, phase 2 comprised a single-arm study to evaluate the safety and efficacy of ifebemtinib combined with garsorasib and an open-label, randomised study in which patients were randomly assigned (1:1) to receive ifebemtinib plus garsorasib or garsorasib alone, by use of centralised computer-generated block randomisation with no stratification. Investigators were masked to the block size. The primary efficacy endpoint of phase 2 was investigator-assessed objective response rate (Response Evaluation Criteria in Solid Tumours, version 1.1), assessed in the safety analysis set in the single-arm study and in all randomly assigned patients (intention-to-treat population) in the randomised study. At least six objective responses (safety analysis set) were required in the single-arm study to proceed to the randomised study. This study is registered with ClinicalTrials.gov, NCT06166836 and NCT05379946, and is active but not recruiting. FINDINGS: Between April 7, 2023 and Dec 13, 2024, 51 patients were enrolled in phase 2 (15 in the single-arm study and 36 in the randomised study). In the single-arm study, the median age was 53 years (IQR 39 to 63), nine (60%) patients were female, six (40%) were male, and all were Asian. In the randomised study, the median age was 51 years (IQR 42 to 59) in the combination group and 63 years (IQR 54 to 66) in the monotherapy group, 24 (67%) were female, 12 (33%) were male, and all patients were Asian. In the single-arm part, the confirmed objective response rate was 46·7% (95% CI 21·3 to 73·4). Seven patients had partial responses, triggering progression to the randomised study. In the randomised study, the confirmed objective response rate was 38·9% (95% CI 17·3 to 64·3) with the combination therapy versus 16·7% (95% CI 3·6 to 41·4) with garsorasib alone (between-group difference 22·2%, 95% CI -7·7 to 49·1; one-sided p=0·068). In the single-arm study, grade 3 treatment-related adverse events occurred in four (27%) of 15 patients, and in the randomised study, grade 3 treatment-related adverse events occurred in six (33%) of 18 patients in the combination group and five (28%) of 18 in the garsorasib group. Grade 3 treatment-related adverse events occurring in at least two patients were diarrhoea (six [18%]), proteinuria (two [6%]), and intestinal obstruction (two [6%]) in patients treated with combination therapy (combined), and increased alanine aminotransferase and γ-glutamyltransferase (two [11%] each) in patients treated with garsorasib alone. Serious adverse events occurred in ten (30%) patients in the combination group and in four (22%) patients in the monotherapy group. One patient in the garsorasib monotherapy group died due to the underlying malignancy within 30 days after completing study treatment, which was reported as a serious adverse event. The death was assessed by the investigators as not related to garsorasib. No grade 4 treatment-related adverse events or treatment-related deaths were reported across all cohorts. INTERPRETATION: The combination of ifebemtinib and garsorasib showed promising anticancer activity and manageable safety profile in previously treated patients with KRASG12C-mutated metastatic colorectal cancer. Although the improvement in response rate did not reach statistical significance in the randomised study, these findings support further evaluation of ifebemtinib plus garsorasib in this population. FUNDING: InxMed, InventisBio, National Natural Science Foundation of China, the Jian Bing Ling Yan + X Research and Development Program of Zhejiang Province, and the Zhejiang Province Medical and Health Science and Technology Plan Project.

Humans↗

PubMed2026

Adjuvant alectinib versus chemotherapy in resected ALK-positive non-small-cell lung cancer (ALINA): health-related quality-of-life and safety outcomes from a randomised, open-label, phase 3 trial.

BACKGROUND: For patients with resected, ALK-positive non-small-cell lung cancer (NSCLC), adjuvant alectinib significantly improved disease-free survival versus platinum-based chemotherapy in the global, phase 3, open-label, randomised ALINA trial. We report safety and health-related quality-of-life (HRQoL) outcomes from the ALINA trial. METHODS: Eligible patients aged 18 years or older with resected, ALK-positive, stage IB (≥4 cm)-IIIA NSCLC (per the American Joint Committee on Cancer and the Union for International Cancer Control Cancer Staging Manual 7th edition) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) via a block-stratified randomisation method to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy for four 3-week cycles. Randomisation was stratified according to disease stage and race. The primary endpoint, previously reported, was disease-free survival. Safety was a secondary endpoint and HRQoL was an exploratory endpoint. Safety was assessed by the investigator as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5·0 until 28 days after the last alectinib dose or chemotherapy cycle. HRQoL was assessed via the Short-Form 36-item health survey version 2 (SF-36v2) questionnaire at baseline, every 3 weeks to week 12, then every 12 weeks until disease recurrence, consent withdrawal, death, or week 96. Norm-based scoring was applied; clinically meaningful changes were defined using the SF-36v2 manual. Safety was assessed in the safety-evaluable population and HRQoL in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT03456076) and is ongoing. FINDINGS: Between Aug 16, 2018, and Dec 8, 2021, 257 patients were assigned to receive alectinib (n=130) or chemotherapy (n=127). 123 (48%) patients were male and 134 (52%) were female; 143 (56%) were Asian. The safety-evaluable population comprised 128 patients who received alectinib and 120 patients who received chemotherapy; median duration of safety follow-up was 24·8 months (IQR 22·0-24·9) in the alectinib group and 3·7 months (IQR 3·7-3·8) in the chemotherapy group. The safety of adjuvant alectinib was generally consistent with its known profile. The most common grade 3-4 adverse events were blood creatine phosphokinase increased (eight [6%] of 128), alanine aminotransferase increased (two [2%] of 128), and blood bilirubin increased (two [2%] of 128) in the alectinib group, and neutrophil count decreased (12 [10%] of 120), neutropenia (ten [8%] of 120), and nausea (five [4%] of 120) in the chemotherapy group. Serious treatment-related adverse events occurred in two (2%; one each with appendicitis and pneumonitis) of 128 patients in the alectinib group and eight (7%) of 120 patients in the chemotherapy group ( most common were gastrointestinal disorders in three [3%] patients). No deaths due to adverse events were reported in either group. There were fewer discontinuations due to adverse events with alectinib (seven [5%]) versus chemotherapy (15 [13%]). A clinically meaningful difference in improvement from baseline was seen at week 12 for bodily pain, role physical, mental health, social functioning, and vitality SF-36v2 domains with alectinib; improvements in physical and mental HRQoL were maintained over 2 years of active treatment (at week 96, mean Mental Component Summary score: 49·9 [SD 10·4]; mean Physical Component Summary score: 48·8 [SD 7·2]) and reached levels similar to the general population (population norm: 50). INTERPRETATION: For patients with resected ALK-positive NSCLC, adjuvant alectinib had a manageable safety profile; HRQoL improved and was maintained over 2 years of active treatment. Together with the disease-free survival benefit seen in ALINA, these data support adjuvant alectinib as an important new standard-of-care for patients with resected ALK-positive NSCLC. FUNDING: F Hoffmann-La Roche.

Adult↗

PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗

PubMed2026

The Efficacy of Pharmacotherapy Intervention on Anthropometric Outcomes in Survivors of Childhood Brain Tumors: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Many survivors of childhood brain tumors face long-term adverse health outcomes like obesity. Uncertainties surround the effect of interventions to manage obesity-related outcomes in survivors of childhood brain tumors. The goal of this updated systematic review and meta-analysis was to provide the best estimate of the treatment efficacy of pharmacotherapy intervention on anthropometric outcomes in this pediatric population. METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and ProQuest for articles published from January 1, 2015, to January 31, 2025. A meta-analysis was performed using the generic inverse-variance method in RevMan 5.4. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. We used the GRADE approach to determine the certainty of evidence. RESULTS: A total of six studies met the inclusion criteria: four newly identified studies published after January 1, 2015 (125 participants), and two from the previously published review (23 participants). The pooled estimate showed no significant change in body mass index z-score after intervention (mean difference = -0.02; 95% CI: -0.06 to 0.02, I2 = 0%; 4 studies, 94 participants; low certainty of evidence). Similar pooled effects were observed across other outcomes; however, individual studies reported significant changes in some outcomes within the treatment groups after the intervention. CONCLUSION: Pharmacological agents showed no significant change in anthropometric outcomes for survivors of childhood brain tumors. Further trials are needed to assess the efficacy of pharmacological agents and to identify subgroups most likely to benefit.

Humans↗

PubMed2026

Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans↗