2ⁿᵈ Edition of the Cancer R&D World Conference 2026

Abstract

Background:
Tumors of the central nervous system (CNS) are classified as primary or secondary, with metastatic (secondary) tumors being more common. These tumors contribute significantly to morbidity and mortality. Numerous advances have been made in the past decade.

Methods:
A literature review was conducted using PubMed and recent conference proceedings over the past 10 years.

Results:
Most recent progress has occurred in systemic therapies:                                                                       
(A) Vorasidenib, approved by the U.S. Food and Drug Administration (FDA) for patients with Grade 2 astrocytoma or oligodendroglioma harboring isocitrate dehydrogenase (IDH)1 or IDH2 mutations.                                                                                                                                               
(B) Tovorafenib, approved by FDA, It is a type II RAF kinase inhibitor for patients of 6 months or older, with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion, rearrangement, or V600 mutation. Approval was based on the FIREFLY-1 trial (NCT04775485), a single-arm, open-label, multicenter study in patients aged 6 months to 25 years. Among 76 patients, 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).

For radiotherapy:                                                                                                                                            
(A) the QUARTZ trial (total 538 patients) laid important groundwork for future research. Whole-brain radiotherapy (WBRT) was associated with significantly more drowsiness, hair loss, nausea and scalp irritation compared to dexamethasone alone, and showed no survival benefit for most patients—except those younger than 60 or in favorable Graded Prognostic Assessment (GPA) categories (score ≥2.5).                                                                                                       
(B) Another important concept has developed: the Brain Metastases Velocity (BMV) score, defined as the cumulative number of new brain metastases after initial stereotactic radiosurgery (SRS) divided by time (in years), predicts survival: 12.4, 8.2, 4.3 months for BMV ≤3, 4-13 and ≥14, respectively. A lower BMV correlated with reduced salvage WBRT (P=.02) and neurologic death (P=.008). Predictors of higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology. This metric has been validated after subsequent SRS courses.                                                                                                                               
(C) Radiotherapy technique for brain metastases in the NRG Oncology CC001, a Phase III trial, hippocampal avoidance (HA) in combination with WBRT and memantine (M). This combined treatment was found to better preserve neurocognitive function in patients with brain metastases. They were stratified by Recursive Partitioning Analysis (RPA) class and prior radiosurgery or surgery, then randomized to WBRT+M or HA-WBRT+M (30 Gy in 10 fractions).                                                                                        (D) With the expanding role of immunotherapy, questions remain about the necessity of radiotherapy for brain metastases. For small lesions not located in critical areas (e.g., brainstem, motor cortex), systemic therapy—with or without local intervention—may suffice. Nonetheless, stereotactic radiosurgery continues to play an important role both as initial and salvage therapy.

Another two noteworthy innovations are:                                                                                              
(A) the FDA approval of tumor treating fields, which are now used to slow or halt glioblastoma cell division.                                                                                                         (B) MVR-C5252 - the PuMP Trial is a phase 1, open-label study of the oncolytic herpes simplex virus type 1 for recurrent high-grade glioma. Delivered directly into tumors via convection-enhanced delivery (CED), the virus carries genes for IL-12 (immune activation) and anti-PD-1 (immune checkpoint blockade. This dual mechanism is intended to convert "cold" tumours (immune-suppressive) into "hot" (immune-active) tumours, a significant challenge in glioblastoma treatment. Second, while many CED trials have been conducted before, the implantation of a pump that enables repeated doses, allowing both priming and boosting doses of the immunotherapeutic agent, is new.

Conclusions:
Significant advances in both systemic and radiation therapies have occurred in CNS oncology. However, continued research into early diagnosis and treatment strategies that improve quality of life and survival remains essential.