Frontline therapy for advanced-stage classical Hodgkin lymphoma (cHL) has entered a new era. Two phase III trials have established highly effective but conceptually different strategies: nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) in SWOG S1826 and PET-adapted BrECADD in GHSG HD21. Because these regimens were tested against different comparators and in different populations, their outcomes should not be interpreted as a head-to-head comparison. This review focuses on translating both trials into individualized treatment selection. N-AVD combines excellent disease control with relatively low hematologic toxicity, minimal use of radiotherapy, operational simplicity, and direct evidence across a broad age range, including patients older than 60 years. BrECADD provides mature disease-control data, PET2-guided treatment duration, potentially only 4 cycles in patients with complete metabolic response, lower anthracycline exposure in PET2-negative patients, and substantially improved gonadal recovery compared with eBEACOPP. The relevant trade-offs differ: hematologic and infectious toxicity, immune-related adverse events, fertility, long-term toxicity, radiotherapy exposure, PET availability, and health-system logistics may each influence regimen selection. Rather than identifying a universal winner, contemporary practice should define which patient is best suited to each strategy and incorporate shared decision-making into frontline treatment.

Glioblastoma remains one of the most aggressive primary brain tumors, characterized by rapid progression, therapeutic resistance, and poor prognosis. Dexamethasone is routinely administered to patients with glioblastoma to reduce peritumoral edema and improve neurological symptoms. However, its broader molecular effects on tumor-cell biology and treatment response remain incompletely understood. This study examined the effects of dexamethasone alone and in combination with temozolomide, valproic acid, or metformin on glioblastoma cell viability, real-time proliferation, senescence-associated β-galactosidase activity, cell-cycle distribution, global DNA methylation, and oxidative DNA damage. Dexamethasone induced concentration- and time-dependent changes in global DNA methylation in glioma cells. In T98G cells, shorter exposure increased 5-methylcytosine, whereas longer incubation or selected combined treatment conditions reduced methylation, suggesting dynamic epigenetic remodeling. Low dexamethasone concentrations were associated with increased 5-methylcytosine content, also in temozolomide-containing conditions. In contrast, higher dexamethasone concentrations reduced global methylation. That effect was cell-line dependent. In SW1783 cells, high-dose dexamethasone caused a reduction in 5-methylcytosine amount as well as an increase in 8-oxo-2'-deoxyguanosine level. Dexamethasone also reduced real-time T98G cell proliferation after prolonged exposure, while temozolomide was the main compound associated with cell-cycle changes in T98G cells. Metformin displayed comparatively limited cytotoxicity under the tested conditions. Beyond dexamethasone's well-established anti-edematous and anti-inflammatory role, it may also modify glioma redox and epigenetic states and influence cellular responses to temozolomide, valproic acid, and metformin. When considering these findings it is necessary to take into account a number of limitations. The upper limits of the DEX, TMZ, and MF concentration ranges were one to three orders of magnitude higher than the brain or CSF exposure levels that have been reported, and the experiments were carried out at standard culture oxygen concentrations (about 18-21% O2), which are much higher than the oxygen levels found in brain tissue (about 2-6% O2). Furthermore, the conclusions drawn from the T98G experiments only apply to this cell line and cannot be applied to glioblastoma without first being verified in other models.

Glioblastoma (GBM) remains an aggressive primary brain tumor with limited therapeutic options after recurrence. Cytokine-induced killer (CIK) cells are ex vivo-expanded cytotoxic lymphocytes with T-cell and natural killer-like properties. We evaluated CIK-cell-based therapy using an orthotopic LN229-luciferase GBM model and a retrospective cohort of patients with recurrent GBM.

Older adults (OA, ≥60 years) with classic Hodgkin lymphoma (cHL) have historically experienced inferior outcomes compared to younger patients. Nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (NAVD) has demonstrated high efficacy in clinical trials, but real-world data in OA are limited. We conducted a multicenter retrospective study across 20 centers in patients with newly diagnosed advanced stage cHL treated with NAVD and analyzed outcomes in OA across the aging spectrum. Among 327 total patients, 81 (25%) were ≥60 years, with most OA presenting with stage IV disease (58%) and B symptoms (57%). Anygrade and ≥grade 3 AEs occurred in 88% and 67% of OA, respectively. Prophylactic growth factors were used in most OA (82%) which led to low rates of febrile neutropenia (12%) and infection (12%) despite 52% ≥grade 3 neutropenia. Immune-related AEs occurred in 29% (12% ≥grade 3) and treatment was discontinued due to toxicity in 10% of OA. Interim overall (ORR) and complete response rates (CRR) were 100% and 81.6%, end-of-treatment rates were 88% and 82.6%, respectively. At a median follow-up of 12.6 months, 1-year progression-free survival (PFS) and overall survival (OS) in OA were 91.5% and 98.6%, respectively. OS was inferior in OA compared with patients.

Glioblastoma (GBM) is the most aggressive primary malignant tumor of the central nervous system and is characterized by rapid progression, frequent recurrence, and poor survival outcomes. The current standard of care, comprising maximal safe surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ), has improved clinical management; however, the therapeutic benefit remains limited by both intrinsic and acquired resistance to TMZ. O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein that removes TMZ-induced O6-methylguanine adducts, is a major determinant of TMZ responsiveness. In particular, methylation of the MGMT promoter is associated with reduced MGMT expression and improved sensitivity to TMZ, although this molecular marker alone does not fully explain interpatient variability in treatment response, which is further modulated by the immunosuppressive tumor microenvironment. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in the regulatory network controlling MGMT expression. These ncRNAs may regulate MGMT directly at the posttranscriptional level or indirectly through competing endogenous RNA networks, epigenetic mechanisms, and signaling pathways associated with DNA repair and chemoresistance. Consequently, dysregulated ncRNA expression may contribute to TMZ resistance and GBM progression. Moreover, ncRNAs have potential clinical value as biomarkers for molecular stratification and prognostic assessment, as well as therapeutic targets for restoring TMZ sensitivity. This narrative review summarizes current evidence regarding ncRNA-mediated regulation of MGMT in GBM and discusses the potential implications of targeting these regulatory mechanisms to overcome TMZ resistance.