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Integrated single-cell and bulk transcriptomics identify autophagy-related immune-suppressive subtypes and a prognostic signature in colorectal cancer.2 weeks agoColorectal cancer still causes many cancer deaths, and patient outcomes differ a lot. The tumor microenvironment can shape tumor growth and treatment response. Autophagy is a cell recycling process linked to tumor survival and immune control, but its cell-type pattern in colorectal cancer tissue and its clinical meaning are not clear. We mapped autophagy activity across cell types, defined autophagy-based subtypes, and tested their value for risk stratification.
Single-cell RNA sequencing data from colorectal cancer tumor tissues were integrated to evaluate autophagy activity across malignant, stromal, and immune cell populations. Subsequently, autophagy-related genes were curated from multiple public databases and analyzed in bulk transcriptomic cohorts obtained from The Cancer Genome Atlas and The Gene Expression Omnibus. Additionally, unsupervised consensus clustering was applied to define autophagy-based molecular subtypes. Multiple machine learning algorithms were evaluated to construct an autophagy-related prognostic model, and feature importance was assessed using explainable modeling approaches. Furthermore, immune microenvironment characteristics, genomic alterations, and stemness features were systematically analyzed. Key genes were further validated in clinical colorectal cancer specimens and through in vitro functional experiments.
Autophagy activity varied across the tumor microenvironment. Malignant and stromal cells showed higher autophagy levels than immune cells. High-autophagy tumors showed stronger tumor-stroma interactions, weaker immune communication, and an immune-suppressive microenvironment. Using 47 prognostic autophagy-related genes, we identified four subtypes with different overall survival, genomic alteration patterns, stemness signatures, and immune landscapes. The prognostic model performed well across independent cohorts. GOLGA2 (Golgi autoantigen, golgin subfamily A member 2) was the top risk gene and was upregulated in tumor tissues. Functional assays showed that GOLGA2 promotes HCT116 cell proliferation and migration.
Autophagy is closely tied to an immune-suppressive tumor microenvironment in colorectal cancer. The autophagy-based subtypes and prognostic model support patient risk stratification. Furthermore, GOLGA2 was a top-ranked gene in the signature and showed tumor-promoting effects in vitro, so it may warrant further study as a potential target.CancerCare/ManagementPolicy -
Sebaceous adenoma of the eyelid: A clinical, histopathological, and immunohistochemical perspective.2 weeks agoSebaceous adenoma (SA) is a rare, slow-growing benign tumor arising from sebaceous glands, accounting for less than 0.5% of all cutaneous neoplasms and approximately 1-2% of eyelid tumors. The eyelid is an uncommon site for this lesion. Histologically, SA shows well-circumscribed lobules composed of mature sebocytes with vacuolated cytoplasm and a peripheral rim of basaloid cells, without nuclear atypia or mitotic activity. We report a case of an 81-year-old man with a unilateral papillomatous lesion in the left lower eyelid, diagnosed as sebaceous adenoma on histopathology. Immunohistochemistry revealed EMA positivity and a low Ki-67 proliferative index, confirming its benign nature. The rarity of its pseudopapillomatous presentation and its need for differentiation from sebaceous carcinoma highlight the diagnostic importance of this case.CancerCare/Management
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Reported drug spectrum and disproportionality signals for malignant neoplasm progression in FAERS: a real-world pharmacovigilance study.2 weeks agoUsing malignant neoplasm/tumour progression as the endpoint, we screened FAERS for disproportionate reporting signals, characterized the drug spectrum represented in progression-related reports, and prioritized drug-event pairs for further evaluation rather than causal inference.
Publicly available reports from FAERS (2004Q1-2024Q4) and JADER (2004-2024) were analyzed. After FDA-recommended deduplication, malignant tumor progression was identified using the MedDRA Preferred Terms "Malignant neoplasm progression" and "Tumour progression" (version 26.1). Primary and secondary suspect drugs were standardized to generic names using MedEx. Signals were detected by disproportionality analysis using the reporting odds ratio (ROR), with positive signals defined as a report count ≥3 and a lower 95% confidence interval bound >1. The same analytical pipeline was applied to JADER for external validation.
FAERS contained 321,020 progression-related reports; 84,977 unique cases remained after deduplication, rising over time (notably after 2018) with severe outcomes (death 27.63%, hospitalization 13.66%). Among the top 50 drugs, 92% were antineoplastic/immunomodulating agents; nivolumab, pembrolizumab, enzalutamide, everolimus, and osimertinib were most frequently reported. 49 drugs showed positive ROR signals (highest: afatinib, gefitinib, osimertinib); 35/49 were replicated in JADER (8,929 cases).
Progression-related reporting signals were concentrated mainly in immunotherapies and targeted agents. Although disproportionality analysis does not establish causality, these findings may help prioritize drug-event pairs for further investigation and highlight the need for more standardized reporting, as well as confirmatory epidemiologic and mechanistic studies.CancerCare/Management -
Narrative and arts-based interventions in oncology supportive care: a narrative review of evidence and implications for bridging the distress screening-response gap.2 weeks agoPsychological distress is a core dimension of oncology care and has long been described as the "sixth vital sign". Although distress screening is widely recommended and increasingly embedded in oncology services, translation of screening results into structured supportive responses remains inconsistent. The aim of the study is to synthesize the literature on narrative and arts-based interventions in adult oncology supportive care and to examine how implementation science can clarify the persistent gap between distress screening and timely supportive action. This manuscript was developed as a targeted narrative review. PubMed and Scopus were searched for systematic reviews, meta-analyses, landmark randomized trials, and implementation science papers relevant to distress screening, narrative medicine, art therapy, creative arts therapy, music interventions, dignity therapy, meaning-centered psychotherapy, and participatory visual methods in oncology. Priority was given to high-quality secondary evidence, seminal conceptual papers, and practice guidelines. Across visual art therapy, creative arts therapy, music interventions, dignity therapy, meaning-centered psychotherapy, and participatory visual approaches, the literature generally shows modest but consistent improvements in anxiety, emotional well-being, quality of life, existential outcomes, and patient experience. However, the same literature repeatedly reveals structural limitations: specialist dependency, multi-session intensity, heterogeneous outcome measurement, short follow-up, and sparse reporting of adoption, fidelity, penetration, cost, and sustainability. These constraints help explain why many psychosocial and arts-based interventions remain peripheral to routine oncology pathways despite favorable therapeutic signals. The central challenge in supportive oncology is no longer only whether distress can be detected, but whether detected distress is followed by a visible, scalable, and person-centered response. The literature supports renewed attention to brief, identity-centered conceptual models that can complement specialist psycho-oncology services and strengthen the connection between screening and supportive care within multidisciplinary cancer systems.CancerCare/ManagementAdvocacy
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Multidisciplinary oral rehabilitation after head and neck radiotherapy.2 weeks agoRadiotherapy for head and neck cancer is associated with adverse oral effects, including salivary gland hypofunction, radiation-related caries, and periodontal tissue alterations, which negatively impact oral health and quality of life.
A 56-year-old male previously treated with surgery, radiotherapy, and chemotherapy for oropharyngeal cancer presented with dentin hypersensitivity, gingival recession, and reduced keratinized tissue. A multidisciplinary rehabilitation was performed, including non-surgical periodontal therapy, free gingival grafting, restorative treatment of cervical lesions, prosthetic rehabilitation, and individualized preventive maintenance.
Uneventful healing was observed at all surgical sites. The free gingival grafts resulted in increased keratinized tissue and vestibular depth, with stable periodontal conditions and resolution of dentin hypersensitivity. Clinical stability was maintained throughout a 24-month follow-up period, with no adverse radiation-related effects.
Multidisciplinary oral rehabilitation, including mucogingival surgery and preventive care, can be safely and effectively performed in irradiated patients, improving periodontal stability, oral comfort, and quality of life.
Head and neck radiotherapy can cause long-lasting oral complications that require careful and individualized dental management. Periodontal surgery, restorative treatment, and prosthetic rehabilitation can be safely performed in irradiated patients when properly planned and followed. Long-term preventive maintenance is essential to maintain oral health and minimize complications in head and neck cancer survivors.CancerCare/Management -
Early Detection of Biochemical Recurrence in Prostate Cancer Patients with PSA Levels ≤0.5 ng/mL; Comparison Study between [¹⁸F]PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11 PET/CT.2 weeks agoThis study compared the correct detection rates (CDR) of [¹⁸F]PSMA-1007 and [⁶⁸Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in patients with prostate-specific antigen (PSA) ≤0.5 ng/mL after radical prostatectomy.
This retrospective study included 88 patients who underwent [¹⁸F]PSMA-1007 (n=41) or [⁶⁸Ga]Ga-PSMA-11 PET/CT (n=47) for PSA ≤0.5 ng/mL after radical prostatectomy. Patients were stratified into ultra-low biochemical recurrence (u-BCR, <0.2 ng/mL) and early BCR (e-BCR, 0.2-0.5 ng/mL) groups. CDRs, defined as the proportion of patients with true positive findings for each imaging modality, and positive predictive values (PPVs) were compared between radiotracers.
The overall CDR of [¹⁸F]PSMA-1007 was significantly higher than [⁶⁸Ga]Ga-PSMA-11 (70.7% vs. 23.4%, p<0.001) in both u-BCR (60.0% [9/15] vs. 19.0% [4/21], p=0.017) and e-BCR groups (76.9% [20/26] vs. 26.9% [7/26], p<0.001). Local recurrence was more frequently detected with [¹⁸F]PSMA-1007, particularly in the e-BCR group (46.2% vs. 3.8%, p<0.001), while lymph node (LN) and distant metastases detection was comparable. In the u-BCR group, the recurrence sites identified by [¹⁸F]PSMA-1007 included local (n=3), LN (n=3), bone (n=2), and local plus LN (n=1), whereas [⁶⁸Ga]Ga-PSMA-11 identified local (n=1), LN (n=1), bone (n=1), and lung (n=1). In [¹⁸F]PSMA-1007, CDR was higher in high/very high-risk than in low/intermediate-risk patients in the u-BCR group (p=0.011). No such difference was observed with [⁶⁸Ga]Ga-PSMA-11. PPVs did not differ significantly between radiotracers (p=0.333).
[¹⁸F]PSMA-1007 PET/CT showed higher CDR than [⁶⁸Ga]Ga-PSMA-11 PET/CT in patients at PSA ≤0.5 ng/mL after radical prostatectomy. Given the high detection performance, these findings support consideration of [¹⁸F]PSMA-1007 PET/CT for detection at PSA ≤0.5 ng/mL, particularly for prostate bed assessment in high/very high-risk patients.CancerCare/Management -
Does Everyone Need CEA? A Case for Selective Omission After Colorectal Cancer Resection.2 weeks agoCancerCare/Management
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Impact of Physical Frailty on Early Intolerance to CAPOX Chemotherapy in Patients With Colon, Rectal, and Gastric Cancer.2 weeks agoPatients with gastrointestinal cancer often present reduction in functional capacity and develop frailty, which increases the risk of chemotherapy intolerance. We investigated whether physical frailty is associated with early intolerance to CAPOX (capecitabine+oxaliplatin) in patients with colon, rectal, or gastric cancer.
This single-center observational study included patients from the Oncogeriatrics Outpatient Clinic at Clinical Hospital at UNICAMP between October 2021 and July 2024. Data included physical, clinical, and anthropometric measures. Frailty was assessed using the Fried criteria, along with planned and modified chemotherapy regimens. Early chemotherapy intolerance was defined as dose reduction, cycle delay, regimen change, or treatment discontinuation due to toxicity within the first three CAPOX cycles. Patients were classified as with or without early chemotherapy-related intolerance.
Of 82 patients, 47 (57%) showed early intolerance to treatment. These patients were older, more frequently female, and smokers; no significant differences were observed in anthropometric and oncological variables, or in frailty criteria classification. The number of frailty criteria was associated with increased risk of intolerance (OR = 2.07; CI: 1.14-3.75; p = 0.01). Among individual components, self-reported exhaustion and reduced gait speed independently predicted higher risk (OR = 6.04; CI: 1.62-22.55; p = 0.007), while higher gait speed was protective (OR = 0.05; CI: 0.005-0.61; p = 0.01).
Categorical physical frailty status was not associated with early toxicity in our cohort. However, the accumulation of physical frailty criteria showed a significant association with early toxicity. Among these criteria, gait speed emerged as one of the most relevant predictors of early toxicity in patients with colon, rectal, or gastric cancer treated with CAPOX. Objective assessment of the physical domain should be prioritized over subjective measures to improve treatment decisions and minimize adverse effects. Further research is needed to define standardized protocols for evaluating physical frailty in cancer patients.CancerCare/Management -
Fenugreek seed extract-doxorubicin synergy against hepatocellular carcinoma in HepG2 cells: in vitro and in silico mechanistic studies.2 weeks agoHepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. The therapeutic efficacy of conventional chemotherapeutic agents such as doxorubicin (DOX) is limited by dose-dependent toxicity and the development of drug resistance. Combination strategies incorporating bioactive natural products may enhance anticancer efficacy while enabling dose reduction. The present study aimed to evaluate the potential synergistic cytotoxicity of combining Fenugreek aqueous extract (FAE) with (DOX) against the HepG2 cell line.
Phytochemical characterization was performed using UHPLC-QTOF-MS/MS Profiling and HPLC. Cell viability and selectivity were assessed using the SRB assay. Apoptosis, necrosis, autophagy, and cell cycle distribution were analysed by flow cytometry and Western blotting. Drug-drug interaction was evaluated using the Chou-Talalay method. Molecular docking was performed to explore potential interactions between selected FAE constituents and apoptosis- and autophagy-related protein targets.
FAE enhanced DOX's cytotoxicity on HepG2 cells, with the interaction ranging from synergistic to additive depending on the concentration ratio. The DOX/FAE combination enhanced cell death through sub-G1 arrest and augmented apoptotic, necrotic, and autophagic responses compared with monotherapies. Western blot analysis demonstrated modulation of the Bax/Bcl-2 ratio and increased LC3-II expression. Docking simulations suggested favourable binding of selected steroidal saponins to Bcl-2 and LC3 proteins.
These findings indicate that FAE potentiates DOX-induced cytotoxicity in vitro through modulation of multiple regulated cell death pathways. While the results support the possibility of this combination as a dose-modulating strategy, further validation in additional HCC models and in vivo systems is required.CancerCare/Management -
The 2026 American Association for Thoracic Surgery (AATS) expert consensus document: Surgical management of primary chest wall malignancies.2 weeks agoThe management of chest wall primary malignancies is challenging for thoracic surgeons due to the rarity and diversity of disease processes requiring nuanced knowledge. This document reviews the existing literature and provides multidisciplinary consensus recommendations for evaluation and treatment of chest wall primary malignancies.
The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an international, multidisciplinary panel of medical oncologists, radiation oncologists, orthopedic surgeons, plastic and reconstructive surgeons and thoracic surgeons with significant expertise in the management of chest wall malignancies. A focused literature review was performed with the assistance of a medical librarian. The panel used a modified Delphi method to develop expert consensus statements with a class of recommendations and level of evidence for 6 themes: 1) diagnosis and staging, 2) tumors treated with primary resection, 3) tumors treated with resection following induction therapy, 4) tumors not treated with primary surgical resection, 5) technical surgical principles, and 6) postoperative management.
Consensus was achieved on 34 statements based on extensive literature review and current clinical experience spanning 11 high-volume institutions. These statements provide a standard for initial evaluation of a suspected chest wall neoplasm, histology directed management of a diverse group of malignancies, surgical management principles, and postoperative management.
This multidisciplinary expert consensus document provides a framework upon which thoracic surgeons can approach the management of primary chest wall malignancies. Accurate diagnosis and staging, multidisciplinary treatment planning and careful attention to surgical techniques to achieve an R0 (microscopically negative margin) resection are all vital elements. Further, multi-institutional efforts are required to advance our understanding of chest wall malignancies.CancerCare/Management