Peripheral T-cell lymphoma (PTCL) remains a formidable challenge in clinical management. Histone deacetylase inhibitor chidamide has demonstrated its anti-tumor effects in real-world studies in relapsed or refractory PTCL. To evaluate the efficacy of real-world utilization of chidamide combined with chemotherapy for untreated PTCL and explore relative prognostic factors, a cohort of 151 PTCL patients treated with chidamide combined with chemotherapy as front-line treatment in our center were enrolled. The overall response rate (ORR) and complete remission rate (CRR) at the end of treatment were 81.5% and 67.5%. The 7-year overall survival (OS) rate and progression-free survival (PFS) rate were 67.6% and 49.7%, with a median follow-up period of 21 months, showing its satisfactory efficacy and survival advantage. Most of adverse events were transient and reversible. Furthermore, several baseline characteristics of patients were relevant to prognosis. The study identified gene mutations in TET2 (30.9%), STAT (22.7%), RHOA (17.5%), TP53 (14.4%), DNMT3A (12.4%), with TP53 and DNMT3A mutations correlating with worse clinical outcomes. The identification of gene mutations contributed to personalizing treatment strategies and predicting patient outcomes. This study raised the preliminary hypothesis that chidamide-containing front-line therapy might be promising for PTCL patients, which warranted further investigation.

IntroductionLow- and middle-income countries (LMICs) like Nigeria face rising cancer incidence and mortality, with late-stage presentation and limited resources. Only eight government-funded radiotherapy centres serve a population of 223.8 million-far below the estimated 280 radiotherapy machines required. To increase patient throughput we evaluated integration of AI auto-contouring tools to expedite treatment planning, specifically target and organ-at-risk delineation.Materials and MethodsWe performed an observational, survey-based study of radiation oncology staff at our Cancer Centre. Participants were consultant and resident oncologists and medical physicists. The survey compared time spent using AI auto-contouring versus manual contouring and collected perceptions of impact, benefits, and limitations.ResultsThirty-one staff responded: 20 (64.5%) oncologists and 11 (35.5%) medical physicists. Experience with AI varied (33% ≤ 6 months; 13% ≈2 years). Respondents reported increased confidence in planning: 11 (35%) moderate, 12 (39%) moderate-high, and 8 (26%) high. Common limitations were licence availability (20, 64.5%) and technical expertise (19, 61.3%). Most respondents (20, 65%) would recommend the tool. The principal benefit was improved workflow efficiency (25, 81%). AI-assisted planning significantly reduced planning time for most tumour sites; sites with complex anatomy showed no time benefit, reflecting the need for intensive manual correction.ConclusionDeployment of AI auto-contouring at a Nigerian cancer centre reduced planning time for most sites and improved clinician confidence, but complex anatomical regions still require detailed manual oversight and additional AI training. AI tools can increase throughput in LMIC radiotherapy services, though licensing, infrastructure, and training barriers exist and must be addressed to ensure safe implementation. Future work should include multi-centre validation, formal inter-rater reliability assessment, and prospective patient-level outcome evaluation and cost-effectiveness analyses.

ObjectiveOccupational exposure to carcinogens significantly contributes to the global burden of tracheal, bronchial, and lung (TBL) cancers. This study aims to quantify the global, regional, and national burden of TBL cancers attributable to occupational carcinogens using Global Burden of Disease (GBD) 2021 data and project trends to 2050. Additionally, we employ Mendelian Randomization (MR) to explore potential causal relationships between modifiable risk factors and TBL cancers.MethodsWe extracted mortality and Disability-Adjusted Life Year (DALY) data for TBL cancers caused by occupational carcinogens from the GBD 2021 database. Exponential smoothing and autoregressive integrated moving average (ARIMA) models projected the burden to 2050. Two-sample MR analysis utilized genome-wide association study (GWAS) data, primarily from individuals of European ancestry, to investigate causal links.ResultsIn 2021, occupational carcinogens caused 285,628 deaths and 6.12 million DALYs globally. While age-standardized mortality and DALY rates declined in some high-income countries, low- and middle-income countries (LMICs) showed rising trends. Projections indicate a potential shift, with some regions plateauing while others face increasing burdens due to persistent exposure. MR analysis confirmed significant causal relationships, identifying higher BMI, smoking, visceral adiposity, and waist circumference as risk factors, while coffee consumption, dried fruit intake, physical activity, and education were protective.ConclusionDespite progress, the burden of occupational TBL cancers remains substantial, particularly in LMICs. The discordance between declining rates in high-income nations and rising burdens elsewhere highlights the need for targeted interventions and stricter regulations. Integrating genetic evidence supports precision prevention strategies focusing on both occupational safety and modifiable lifestyle factors.

Characterisation of CT detected ovarian masses is challenging with overlapping imaging features, unreliable biomarker or clinical presentation. We proposed a two-staged CT-based radiomics model to identify early-stage ovarian carcinoma (ES-OC) and sub-classify different types of benign ovarian masses (BOM).

Patients with histologically confirmed BOM or ES-OC (FIGO I-II) were retrospectively recruited from 5 centres. Radiomics features were derived from CT images using PyRadiomics (v3.0.1), which intrinsically resampled volumes to isotropic 1 mm³ voxels. To reduce feature redundancy, features with high correlation (Spearman's ρ ≥ 0.85) were excluded. Two-staged feature selection was applied. First, elastic-net regression with repeated 5-fold stratified cross-validation (100 iterations) was performed to identify highly repeatable features, followed by Mann-Whitney U testing for statistical significance. Second, Boruta algorithm with Random Forest (RF) estimator was employed over 500 iterations to robustly select features by comparing their importance to randomized shadow features. Several machine learning (ML) classifiers were evaluated using stratified 10‑fold GridSearch cross-validation with area under the curve (AUC) as tuning metric. The optimal model from each stage with highest cross-validated AUC was then evaluated on the respective test set. The AUC, calibration plot, and decision curve analysis (DCA) were employed to assess the performance and clinical utility of models.

The study enrolled 483 patients with 529 lesions (ES-OC: 192 patients, 192 lesions; BOM: 291 patients, 337 lesions). In the first-stage, logistic regression (LR) algorithm was selected with high sensitivity (0.870), moderate specificity (0.719) and high AUC (0.859) in the test set. In the second-stage, support vector machines (SVM) had high diagnostic accuracy with sensitivity 0.750, specificity 0.839 and AUC 0.918. DCA identified the highest benefit at 0.20 risk threshold probability in determining ES-OC.

The two-staged CT-based radiomics model incorporating LR and SVM algorithms had high diagnostic efficiency in characterising ES-OC and BOM, potentially in triaging disease and personalising care.

Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality worldwide, posing a major public health challenge. Flavonoids, a large and diverse group of plant metabolites, exhibit various anticancer properties, making them promising candidates for therapeutic applications. This study evaluated the anticancer efficacy of methoxy flavonoids and elucidated their underlying mechanisms of action in A549 lung cancer cells.

A549 cells were treated with various flavonoids (AKC1-AKC5), and their effects were analyzed using an MTT assay, DAPI staining, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, colony formation, and wound scratch tests. Molecular docking was also performed to confirm the binding of AKC1 and AKC3 to EGFR, BCL-2, and CDK-2 proteins.

AKC1 and AKC3 prevented the growth of A549 lung cancer cells with IC50 of 64.57 and 19.80 μM among 5 methoxy flavonoids. AKC1 and AKC3 triggered notable alterations in the shape and reduced the colony-forming potential of A549 cells. The DAPI staining experiment demonstrated that AKC1 and AKC3 impede the growth of cancer cells through activation of apoptotic cell death. Moreover, the anticancer properties of AKC1 and AKC3 were attributed to significant inhibition of MMP and a notable ROS enhancement in a dose-related pattern. The wound scratch assay demonstrated that AKC1 and AKC3 suppressed A549 lung cancer cell migration, suggesting their anti-metastatic properties. Molecular docking studies confirmed that AKC-1 and AKC-3 bind strongly to EGFR, BCL-2, and CDK2, suggesting a multi-target mechanism that underlies their anti-proliferative and pro-apoptotic effects in A549 cells.

AKC1 and AKC3 exhibited significant anticancer activity against A549 cells and may serve as promising therapeutic drugs for lung cancer treatment.

With the advent of the immunotherapy era, the combination of radiotherapy and immunotherapy has become a critical strategy to enhance patient outcomes. In addition to its direct cytotoxicity, radiotherapy modulates the immune response within the tumor and its surrounding microenvironment by stimulating the body's anti-tumor immune response. This interplay provides the rationale for combining radiotherapy with immunotherapy. This review will summarize the immunomodulatory mechanisms of radiation therapy, evaluate the clinical efficacy and safety of combining radiotherapy with immunotherapy, and outline its current applications, challenges, and future potential. In the future, the combination of radiotherapy and immunotherapy holds immense potential in esophageal cancer treatment. Through additional prospective clinical trials exploring optimal combinations, timing, and biomarkers, we can further refine treatment strategies and enhance patient survival.

Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking.

We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin.

This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.

Human papillomavirus (HPV) is a well-established oncogenic virus implicated in the development of several epithelial cancers, most notably cervical, anogenital, and oropharyngeal carcinomas. In contrast, neuroendocrine neoplasms (NENs)-a heterogeneous group of malignancies arising from neuroendocrine cells across various organ systems-have not traditionally been linked to HPV infection. In this study, we performed extensive genomic and transcriptomic profiling to compare HPV-positive NENs to HPV-positive non-NENs across anatomical sites, aiming to uncover biologically and clinically actionable differences.

HPV16- and HPV18-positive tumors were identified from 101,343 solid tumors profiled at Caris Life Sciences (Phoenix, AZ) with DNA and RNA sequencing. Prevalence of pathogenic mutations and copy number amplifications were calculated. Fisher's exact/χ² tests were applied appropriately with p-values adjusted for multiple comparisons (p < 0.05).

HPV positivity was most frequent in cervical carcinomas (70%, 1200/1716). Importantly, 6% (96/1620) of NENs from all tissues were positive for HPV16 or HPV18. Among HPV-positive NENs, 93% were high-grade compared to 54% observed in HPV-negative NENs (p < 0.001), highlighting a strong association between HPV and tumor aggressiveness in this subset. Analysis of HPV-associated sites (cervix, anorectal region, and head and neck) revealed that HPV-positive NENs possess distinct genomic and transcriptomic landscapes compared to HPV-positive non-NENs. Notably, interferon signaling was significantly suppressed in HPV-positive NENs, suggesting a unique tumor-immune microenvironment.

Our findings indicate that HPV-positive NENs form a distinct subset with unique genomic features, including reduced interferon signaling, compared to HPV-positive non-NENs. Thus, future studies focused on evaluating HPV status, along with genomic and transcriptomic characteristics, may uncover biologically and clinically actionable distinctions for this rare yet clinically significant tumor subgroup.

Not applicable.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by progressive cytopenias, splenomegaly, and constitutional symptoms. The hallmark of MF pathophysiology is constitutive activation of JAK/STAT signaling, which, in the majority of cases, is associated with an acquired mutation in one of three driver mutations, JAK2, CALR, or MPL. Our growing understanding of the molecular biology of MPNs has resulted in regulatory approval of four JAK inhibitors (JAKi), which have demonstrated efficacy in improving symptom burden and reducing spleen size. Despite clear benefits of JAKi therapy, including evidence of improved survival, these therapeutic interventions have not established an ability to modify disease in terms of resolution of bone marrow fibrosis or molecular remissions. Therefore, recent emphasis has been on the development of novel therapies with informed targets outside of the JAK/STAT signaling pathway. Moreover, combination approaches utilizing JAK and non-JAK targeting agents underscore the potential for disease modification along with deeper and more durable clinical responses. Emerging combination strategies and their clinical development will be reviewed here, including investigations that pair JAKi therapy with BCL-2 family inhibitors, BET inhibitors, restored p53 cell death signals, telomerase inhibitors, PIM1 kinase inhibitors, and mutant CALR targeted therapies. While several combination clinical trials suggest improved spleen and symptom responses and the possibility of disease modification, toxicity profiles and optimal sequencing remain areas of active investigation.

Brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (A-AVD) improves outcomes in advanced-stage classic Hodgkin lymphoma, but patients with a positive early interim PET have inferior prognosis. We evaluated whether very early [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG)-PET-guided treatment adaptation after one cycle of A-AVD improves activity while limiting exposure to intensive chemotherapy.

This single-arm, multicentre, phase 2 trial was conducted at 16 centres in seven countries (the Netherlands, Spain, Denmark, Belgium, Portugal, Slovakia, and Poland). Adults aged 18-60 years with previously untreated advanced-stage classic Hodgkin lymphoma, WHO performance status 0-2, and adequate organ function received one cycle of A-AVD (brentuximab vedotin 1·2 mg/kg intravenously, doxorubicin 25 mg/m² intravenously, vinblastine 6 mg/m² intravenously, and dacarbazine 375 mg/m² intravenously, all on days 1 and 15), followed by centrally reviewed [¹⁸F]FDG-PET-CT (PET1). PET1-negative (Deauville score 1-3) patients received five additional A-AVD cycles; PET1-positive (Deauville score 4-5) patients switched to six cycles of BrECADD (brentuximab vedotin 1·8 mg/kg intravenously on day 1; etoposide 150 mg/m² intravenously on days 2-4; cyclophosphamide 1250 mg/m² intravenously on day 2; doxorubicin 40 mg/m² intravenously on day 2; dexamethasone 40 mg orally on days 2-5; dacarbazine 250 mg/m² intravenously on days 3-4). The primary endpoint was 2-year modified progression-free survival (mPFS), defined as the proportion of patients alive and free of progression, relapse, or death from treatment start, with initiation of new systemic therapy for persistent disease counted as an event. Analyses were prespecified and conducted in the evaluable population (registered and eligible patients, who commenced the allocated treatment according to PET1 results after 1 cycle of A-AVD). The safety population consists of all patients who started A-AVD treatment (ie, received at least one dose of study therapy). This is the primary analysis of a completed trial. This trial is registered on ClinicalTrials.gov (NCT03517137) and EudraCT 2017-000498-35).

From Aug 1, 2019, to Aug 31, 2021, we enrolled 150 patients (81 males [54%] and 69 females [46%]; median age 32 years [IQR 23-39]) who received one cycle of A-AVD, after which 90 (60%) of them had a negative PET1 and 60 (40%) a positive result. 145 were evaluable for efficacy; the median follow-up at the clinical cutoff (Sept 1, 2023; database lock Dec 11, 2023) was 30·1 months (IQR 24·6-36·4). 16 patients experienced an mPFS event. The estimated 2-year mPFS was 89·5% (80% CI 85·7-92·4). The most common grade 3-4 adverse event was neutropenia (53 [35%] of 150) followed by anaemia (18 [12%]) and peripheral sensory neuropathy (nine [6%]). Serious adverse events occurred in 45 (30%) of 150 patients. No deaths occurred.

Very early PET-guided intensification with BrECADD yields high activity in advanced-stage classic Hodgkin lymphoma while sparing most patients intensive chemotherapy.

Takeda Oncology.