Updates on CNS tumors

Background:

Central nervous system (CNS) tumors are categorized as primary or secondary, with metastatic tumors being more common. They contribute significantly to morbidity and mortality. Over the past decade, notable advances have emerged in their management.

Methods:

A comprehensive literature review was conducted using PubMed and major conference proceedings from the past 10 years.

Results:

Progress has been most evident in systemic therapies.

(A) Vorasidenib was FDA-approved for patients with Grade 2 astrocytoma or oligodendroglioma harboring IDH1 or IDH2 mutations.

(B) Tovorafenib, a type II RAF kinase inhibitor, was approved for patients ≥6 months old with relapsed or refractory pediatric low-grade glioma harboring BRAF fusions, rearrangements, or V600 mutations. In the FIREFLY-1 trial (NCT04775485), involving patients aged 6 months to 25 years, the overall response rate was 51% (95% CI, 40–63), with a median duration of response of 13.8 months (95% CI, 11.3–not estimable).

In radiotherapy:

(A) The QUARTZ trial (n=538) found that whole-brain radiotherapy (WBRT) did not improve survival versus dexamethasone alone, except in patients under 60 or with favorable Graded Prognostic Assessment (GPA ≥2.5), while increasing side effects such as drowsiness, hair loss, nausea, and scalp irritation.

(B) The Brain Metastases Velocity (BMV) score defined as the number of new brain metastases after initial stereotactic radiosurgery (SRS) divided by time (years) was found to predict survival: 12.4, 8.2, and 4.3 months for BMV ≤3, 4–13, and ≥14, respectively. Higher BMV was linked to ≥2 initial metastases (P=.004) and melanoma histology.

(C) In the NRG Oncology CC001 Phase III trial, hippocampal avoidance WBRT plus memantine (HA-WBRT+M) preserved neurocognitive function better than WBRT+M (30 Gy in 10 fractions), with patients stratified by RPA class and prior interventions.

(D) As immunotherapy evolves, systemic therapy alone may suffice for small, non-eloquent lesions; however, SRS remains essential as initial and salvage treatment.

Two additional innovations include:

(A) Tumor treating fields, FDA-approved for glioblastoma, inhibit tumor cell division.

(B) The PuMP trial investigates MVR-C5252, an oncolytic HSV-1 virus encoding IL-12 and anti-PD-1, delivered via convection-enhanced delivery (CED). A novel implanted pump enables repeated intratumoral dosing, aiming to convert immunologically "cold" gliomas into "hot" tumors, overcoming key challenges in glioblastoma therapy.

Conclusions:

Substantial advances in systemic and radiation therapies have improved CNS tumor care. Ongoing research into earlier diagnosis, personalized treatments, and quality of life optimization remains crucial.

Liburn Grabovci is a medical doctor and who graduated in the faculty of medicine in Kosovo. His interests include surgery and internal medicine, and he aims to pursue postgraduate specialization while remaining dedicated to lifelong learning, professional growth and works in scientific papers. He collaborates with his other colleagues in the cancer research team of Professor Patricia Tai in Canada who serves as a mentor for them all.