Bruton tyrosine kinase inhibitors (BTKis) have been employed in the treatment of mantle cell lymphoma (MCL). However, direct comparisons of ibrutinib, zanubrutinib, and acalabrutinib across treatment-naïve (TN) and relapsed/refractory (R/R) MCL remain limited. This meta-analysis was intended to evaluate their efficacy, addressing critical gaps in clinical decision-making. We systematically searched PubMed, Embase, and Cochrane up to January 2025 for studies (RCT/single-arm) assessing the efficacy of BTKis in MCL patients. Among 70 studies, the pooled CR rate in the TN group was higher than that in the R/R group (76.5% vs. 43.2%). Among TN patients, the CR rate of the regimen incorporating zanubrutinib (95.2% [95% CI 0.893, 1.000]) was significantly higher than that of the regimens containing acalabrutinib or ibrutinib (p = 0.0042). In the R/R group, the BTKi + anti-CD20 monoclonal antibody + small-molecular therapy group presented a better CR rate (68.3% [95% CI 0.546, 0.820]; p < 0.0001). When comparing the monotherapy efficacy of three BTKis in R/R MCL, the results indicated that acalabrutinib exhibited a higher CR rate (43.2% [95% CI 0.339, 0.525]) than zanubrutinib or ibrutinib. In addition, zanubrutinib-based therapy exhibited a lower pooled rate of haematological toxicities compared to the other two BTKi therapies. This work resolved critical uncertainties in BTKi selection for MCL, demonstrating acalabrutinib's and zanubrutinib's first-line potential, leading to a meaningful improvement in response rate and a manageable safety profile. Chemotherapy-free regimen can partially overcome the traditionally unfavourable prognosis associated with R/R MCL. These results provide a roadmap for optimizing MCL therapy. Chemotherapy-free regimens for MCL based on BTKis warrant further validation in RCTs. These findings may advocate for updated guidelines prioritizing zanubrutinib and acalabrutinib in clinical practice.

To develop an intratumor heterogeneity (ITH)-aware deep learning (DL) framework for preoperative prediction of lymph node metastasis (LNM) in laryngeal squamous cell carcinoma (LSCC).

This multi-center retrospective study, which included 381 patients, proposed a ITH-aware DL framework integrated with adaptive habitat mapping to automatically decode spatial ITH from primary tumor contrast-enhanced CT images.The predictive performance of the ITH-aware DL model was compared against conventional radiomics and 3D DL model. A stacking ensemble model combining these three methods was also constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). The prognostic value for overall survival (OS) stratification was evaluated.

The ITH-aware DL model achieved superior preoperative LNM prediction in external testing (AUC: 0.745-0.766), outperforming both radiomics (AUC: 0.682-0.694) and 3D DL models (AUC: 0.718-0.732). The stacking ensemble integrating these models attained the highest diagnostic accuracy (AUC: 0.786-0.804). Critically, both the ITH-aware DL and stacking models effectively stratified patients into distinct risk groups with significantly different OS outcomes.

The proposed ITH-aware DL framework provides a robust, automated tool for preoperative LNM prediction in LSCC. By enabling accurate risk stratification, it holds significant potential to inform personalized surgical planning and improve treatment strategies.

Deep inspiration breath-hold (DIBH) is a radiotherapy standard technique for cardiac-sparing in breast cancer, particularly for left-sided tumors. However, not all patients can successfully complete DIBH RT in clinical routine, necessitating conversion to free breathing (FB) techniques and replanning. This study aimed to identify clinical factors predictive of DIBH feasibility to optimize patient selection and resource utilization.

This retrospective study analyzed all patients (n = 1920) who underwent curative postoperative breast cancer radiotherapy at our institution between May 2020 and December 2024. All patients underwent initial DIBH feasibility assessment and were evaluated for completion of radiotherapy with DIBH or conversion to FB technique. A detailed subanalysis was performed for all patients treated in 2023 (n = 470). Patient-related factors including age, body mass index (BMI), Karnofsky Performance Status (KPS), Charlson Comorbidity Index (CCI), pulmonary comorbidities, smoking status, and geometric surface distance between DIBH and FB planning scans were collected for the subanalysis.

Across the entire cohort (years 2020-2024) of 1,920 patients, 78 replannings (4%) occurred due to conversion from DIBH to free breathing. Increasing age (cut-off of 63 years) was significantly associated with higher replanning rates (p = 0.001). In the 2023 subanalysis (n = 470), pulmonary comorbidities (p = 0.008), higher CCI (p = 0.044), and a geometric surface distance of below 1 cm between DIBH and FB CT scans (p = 0.0001) were significant predictors of replanning. The Karnofsky Performance Score, BMI, and smoking status showed no significant association with replanning.

Age, pulmonary comorbidities, overall comorbidity burden, and insufficient geometric displacement are significant predictors of DIBH failure in breast cancer radiotherapy. These readily available clinical parameters can optimize patient selection algorithms and inform decisions regarding dual CT simulation workflows. A risk-stratified approach incorporating these factors may reduce unnecessary imaging, decrease planning burden, and improve resource allocation while maintaining optimal cardiac protection for appropriate candidates.

The study was registered in the German Clinical Trials Register (DRKS; registration number: DRKS00038550) on 22 December 2025 ( https://www.drks.de/ ).

The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations.

A combined retrospective (2015-2023, n = 114: 43 AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n = 28: 13 AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS).

The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR = 3.223, p = 0.0450; PFS: HR = 2.374, p = 0.0476); reduced EOR (AC: 74.3% ± 5.3%; standard craniotomy: 86.9% ± 12.3%, p = 0.0470); and better motor recovery.

Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution.

Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

The optimal timing for initiating bone-modifying agents (BMAs) after the diagnosis of bone metastasis remains unclear. We evaluated the association between the timing of BMA initiation and the subsequent risk of skeletal-related events (SREs).

Patients with solid tumors who received BMA therapy for bone metastasis at a single institution between 2010 and 2024 were retrospectively analyzed. To minimize immortal time bias, a landmark analysis was performed at 6 months after the diagnosis of bone metastasis. Patients who remained under follow-up and had not experienced an SRE by the landmark were classified into the Early group if BMA therapy was initiated by the landmark; otherwise, they were assigned to the Delayed group. One-to-one propensity score matching (PSM) was performed to balance baseline characteristics between the groups. The primary endpoint was the time from the landmark to the first SRE.

Following PSM, 134 patients were included in each group. SREs were observed in 86 patients during follow-up after the landmark. The Delayed group had a significantly higher subsequent risk of SREs than the Early group (hazard ratio (HR), 1.82; 95% confidence interval (CI), 1.16-2.84; P < 0.01).

Among patients who remained under follow-up and SRE-free at the 6-month landmark, delayed BMA initiation was associated with a higher subsequent risk of SREs than early initiation. Thus, prolonged delay in BMA initiation after the diagnosis of bone metastasis may be clinically relevant to subsequent SRE risk.

To evaluate indications, safety, and early outcomes of MRI-guided laser interstitial thermal therapy (LITT) in a nationwide prospective pediatric cohort and to assess the feasibility of same-session stereotactic biopsy.

All consecutive pediatric patients (≤ 18 years) who underwent LITT at the Danish National Referral Center between June 2021 and October 2025 were prospectively enrolled. Demographic, clinical, radiological, and surgical variables were recorded. Safety outcomes included complications, neurological deficits, length of stay, and 30-day readmission. Seizure outcomes were assessed by Engel classification and tumor response on follow-up MRI.

A total of 27 children (mean age 11.6 ± 4.3 years) underwent LITT, including 18 treated for drug-resistant epilepsy and 9 for tumor indications. Same-session stereotactic biopsy was performed in 10 patients without biopsy-related complications or interference with ablation. Transient neurological deficits were observed in 5 patients and persistent deficits in 3. Hospital stay was 1-2 days in 23 patients, and no 30-day readmissions occurred. Seizure freedom (Engel class I) was achieved in 67% and 50% at 12 and 24 months, respectively. In tumor patients, clinical and MRI follow-up were available in all 9 patients, with one radiographic recurrence during follow-up.

In this nationwide prospective cohort of 27 consecutively treated children, LITT demonstrated a favorable safety profile across epilepsy and tumor indications. Same-session stereotactic biopsy was feasible and safe, supporting LITT as a minimally invasive option in carefully selected pediatric patients.

The rising incidence of cancer diagnoses alongside improving survival rates in low- and middle-income countries (LMICs) has substantially increased the demand for comprehensive supportive care. This study aimed to assess the supportive care needs of patients diagnosed with breast or cervical cancer at Hawassa University Comprehensive Specialized Hospital Cancer Treatment Center, Ethiopia. A hospital-based cross-sectional study was conducted among 349 patients with breast or cervical cancer between December 2023 and May 2024. Data were collected using three validated instruments: the Supportive Care Needs Survey Short Form (SCNS-SF34), the Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being scale (FACIT-Sp-12), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). All instruments were scored according to their respective guidelines. Multivariable linear regression was performed to identify factors independently associated with supportive care needs. Patients were relatively young, with a mean age of 42.5 ± 12 years for breast cancer and 49.5 ± 12 years for cervical cancer. The majority reported cancer-related symptoms, and nearly all patients indicated unmet supportive care needs in at least one domain. Greater supportive care needs were significantly associated with the use of traditional or spiritual healing practices (mean difference [MD] 9.15, 95% CI: 3.51-14.59), lower functional performance status (MD 5.53, 95% CI: 3.11-7.96), higher number of children (MD 1.95, 95% CI: 0.90-3.01), and higher educational attainment (MD 2.58, 95% CI: 1.22-3.94). Conversely, having health insurance was associated with significantly lower supportive care needs (MD - 3.78, 95% CI: -7.36 to - 0.19). Unmet supportive care needs were prevalent across all assessed domains: physical and daily living, psychological, sexual health, patient care, and health information underscoring a substantial gap in comprehensive cancer care in this setting. To address these needs, healthcare systems should prioritize patient-provider communication, strengthen social support networks for high-need patients, integrate spiritual well-being into care planning, and develop context-sensitive, multidisciplinary supportive care strategies.

Adolescents with osteosarcoma face clinical and psychosocial challenges during the transition from adolescence to adulthood.

This study examined the effects of a nurse-navigated game-based intervention (N²-GBI) on transition readiness in adolescents.

Participants in the control group received usual care, whereas the intervention group received the N²-GBI programme alongside usual care. Transition readiness was assessed using the Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire as the primary outcome. Secondary outcomes included cancer worry, transition expectation and patient activation, which were measured using the Cancer Worry Scale, Transition Expectation Scale, and Patient Activation Measure, respectively. Outcomes were assessed at baseline (T0), immediately after intervention (T1) and at 12-week follow-up (T2). Generalized estimating equations were used to estimate the intervention effects.

A total of 59 adolescents were enrolled. The intervention and control groups comprised 32 and 27 adolescents, respectively, with mean ages of 15 and 13 years, respectively. A total of 19 and 15 participants were male in the intervention and control groups, respectively. Compared with the control group, the N²-GBI group showed significantly greater improvement in transition readiness at T1 (β = 8.83, p < 0.001) and T2 (β = 7.97, p = 0.001). The N²-GBI programme also significantly reduced cancer worry (p = 0.009) and increased patient activation (p = 0.001), but had no significant effect on transition expectation (p = 0.056).

The N²-GBI programme improved transition readiness, reduced cancer worry, and increased patient activation among adolescents with osteosarcoma, but did not significantly improve transition expectation. This intervention may be a useful nurse-led approach to transition preparation in pediatric oncology care. Future studies with larger sample sizes and prolonged follow-up durations are needed.

WHO5 (2022) classification of B-lymphoblastic leukemia (B-ALL) incorporates several novel entities requiring high-throughput sequencing for their accurate characterization. The clinical relevance of this classification in the context of contemporary measurable residual disease (MRD)-directed therapy is unclear.

We analyzed 533 pediatric B-ALL uniformly treated with Indian Collaborative Childhood Leukaemia group (ICiCLe)-ALL-14 protocol as defined by WHO-2016 and reclassified them as per WHO5 using targeted sequencing, FISH, and cytogenetics.

Subtype-defining genomic abnormalities were identified in 81.2% of the cohort as per the WHO5 classification. Among the new subtypes, PAX5^alt and MEF2D-r were associated with a trend toward an inferior 3-year event-free survival (EFS) of 32.8% (P = .003) and 33.7% (P = .091), respectively. We developed a three-tier genomic risk stratification model incorporating 15 genomic subtypes and the IKZF1 deletion. Children with standard (SGR), intermediate (IGR), and high genomic risk (HGR) demonstrated 3-year EFS of 80.4%, 59.3%, and 45.8% (P < .0001), and 3-year overall survival of 89.6%, 75.3%, and 62.3% (P < .0001), respectively. Genomic risk further identified heterogeneous outcomes among ICiCLe risk groups (P < .0001). SGR was associated with superior EFS irrespective of MRD status (3-year EFS 80.5% in postinduction [PI] MRD-negative v 80.8% PI-MRD-positive patients, P = .530). On multivariable analysis, genomic risk (hazard ratio [HR], 1.7 [95% CI, 1.41 to 2.01]; P < .0001), initial ICiCLe risk (HR, 1.3 [95% CI, 1.06 to 1.49]; P = .009), and PI-MRD (HR, 2.2 [95% CI, 1.66 to 2.90]; P < .0001) independently predicted EFS.

The study demonstrates the potential role of genomic risk stratification, in conjunction with MRD, in stratifying patients into clinically relevant risk categories.

Multiple myeloma (MM) is a malignant blood cancer marked by severe bone destruction and immune microenvironment disruption. Yet relapse and drug resistance remain major clinical challenges. Tanshinone IIA (TIIA) exhibits potent antitumor activity, but its molecular targets and mechanisms in MM remain unclear. Here, we systematically elucidate TIIA's pharmacological mechanisms in MM using network pharmacology, transcriptomics, molecular docking, molecular dynamics (MD) simulations, and in vitro cellular experiments. Histone deacetylase 6 (HDAC6) was identified as a key prognostic target in MM via integrative bioinformatics─combining cross-database analysis, machine learning (LASSO, SVM-RFE, random forest), and survival validation in the MMRF-CoMMpass cohort. Molecular docking and MD simulations showed stable binding of TIIA to HDAC6. In vitro, TIIA directly inhibited HDAC6 enzymatic activity and selectively killed U266 and RPMI 8226 myeloma cells in a dose-dependent manner, with minimal toxicity to normal cells. Additionally, gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) immune profiling using the LM22 signature suggested that HDAC6 participates in microenvironmental remodeling by modulating cell adhesion-mediated resistance and orchestrating an immunosuppressive niche characterized by monocyte depletion. This study highlights for the first time the critical role of HDAC6 in TIIA-mediated antimyeloma activity and provides novel mechanistic insights and potential targeted therapeutic strategies for the treatment of MM.