Trials · Topics · CNS

CNS clinical trials

69 CNS trials (Medical Oncology and Radiation Oncology) summarized for fellows and board review, newest first within each disease. Each summary covers design, results, toxicity and what changed in practice.

Jump to: Others · SRS · GBM · Glioma · Brain metastases · WBRT

Others (25)

• ROAM/EORTC-1308 Lancet 2026
  Adjuvant RT after complete resection of atypical meningioma reduced recurrence and improved DFS vs observation. RT should be considered when recurrence prevention is...
• RTOG 0539 Int J Radiat Oncol Biol Phys 2020
  RTOG 0539 established risk-stratified RT benchmarks for meningioma. Intermediate-risk tumors achieved 3-year PFS of 93.8% with 54 Gy; high-risk tumors achieved 3-year...
• NOA-09 / CeTeG Lancet 2019
  Lomustine+TMZ significantly improved OS vs standard TMZ in newly diagnosed MGMT-methylated GBM (48.1 vs 31.4 months; HR 0.60). The combination is now considered a...
• EORTC 22042-26042 Radiother Oncol 2018
  Adjuvant RT to 60 Gy after GTR of WHO grade II meningioma achieved 5-year PFS of 87.9%, substantially exceeding historical surgery-alone rates of ~60-75%, supporting...
• Proton RT Quality of Life Review JNCI 2018
  Proton therapy is associated with better HRQOL outcomes compared to photon RT in HNC, pediatric CNS, and thoracic malignancies. For prostate cancer, no HRQOL...
• CATNON Lancet 2017
  Adjuvant TMZ (12 cycles after RT) significantly improved OS (HR 0.65) in non-1p/19q codeleted anaplastic glioma, establishing RT + adjuvant TMZ as standard of care...
• EF-14 (TTFields) JAMA 2017
  Adding TTFields to maintenance TMZ improved OS (20.9 vs 16.0mo) and PFS (6.7 vs 4.0mo) in patients with newly diagnosed GBM after chemoRT, with no significant...
• EORTC 26062 (Perry 2017) NEJM 2017
  Adding temozolomide to hypofractionated RT (40 Gy/15fr) significantly improved OS (9.3 vs 7.6mo) and PFS in elderly GBM patients ≥65yr. Benefit was strongest in...
• EORTC 22033-26033 Lancet Oncol 2016
  TMZ monotherapy did not improve PFS vs RT in high-risk LGG overall. Molecular subgroup analysis showed 1p/19q codeleted patients did better with RT than TMZ (possibly...
• NOA-04 Long-Term Update Neuro Oncol 2016
  Long-term NOA-04 follow-up confirms that treatment sequence (RT vs chemotherapy first) does not affect final outcomes in anaplastic gliomas with combined sequential...
• IAEA Trial (Roa 2015) JCO 2015
  The ultra-short 25 Gy/5fr regimen was non-inferior to 40 Gy/15fr in elderly/frail GBM patients, with similar OS and toxicity profile. The 1-week schedule is...
• Suzuki 2015 (Mutational Landscape LGG) Nat Genet 2015
  Grade II and III gliomas comprise three distinct molecular subtypes defined by IDH status, 1p/19q codeletion, ATRX mutation, and TERT promoter mutation, with discrete...
• RTOG 9402 IDH Analysis J Clin Oncol 2014
  IDH mutation identified patients with anaplastic oligodendroglial tumors who benefit from PCV+RT - including non-1p/19q codeleted patients with IDH mutations. IDH...
• Kim 2013 (Pituitary Adenoma FSRT) Int J Radiat Oncol Biol Phys 2013
  FSRT achieves 97.5% 5-yr tumor control for pituitary adenomas of varied size/histology, with hormone normalization in 44% of functioning tumors and lower...
• Proton RT Cost-Effectiveness Cancer 2013
  Proton therapy is most cost-effective for pediatric malignancies (medulloblastoma, ependymoma) where long life expectancy makes late effects prevention most valuable....
• RTOG 9402 Long-Term J Clin Oncol 2013
  With 10-year follow-up, PCV+RT dramatically improved OS in 1p/19q codeleted anaplastic oligodendroglioma (14.7 vs 7.3yr) - a benefit invisible at 3-year follow-up....
• Maniakas 2012 (VS Microsurgery vs SRT Meta-Analysis) Otol Neurotol 2012
  For small vestibular schwannomas, SRT achieves equivalent/superior local control with significantly better facial nerve preservation vs microsurgery and comparable...
• Nordic Trial Lancet Oncol 2012
  In elderly GBM patients (≥60yr), TMZ monotherapy improved OS vs standard RT (8.3 vs 6.0mo; HR 0.70), especially in patients >70yr. Both TMZ and hypofractionated RT...
• RANO Criteria J Clin Oncol 2010
  RANO updated the Macdonald framework to account for pseudoprogression, antiangiogenic radiographic effects, and non-enhancing tumor, becoming the standard response...
• EORTC 26981 5-yr Update Lancet Oncol 2009
  The survival benefit of TMZ+RT was durable at 5 years, with 9.8% vs 1.9% alive at 5 years - confirming that a meaningful subset of patients achieve long-term...
• NOA-04 J Clin Oncol 2009
  Initial RT vs initial chemotherapy (PCV or TMZ) achieved comparable TTF, PFS, and OS in anaplastic gliomas when used sequentially with crossover at progression...
• EORTC 26981/22981 (Stupp 2005) NEJM 2005
  Radiotherapy plus concomitant and adjuvant temozolomide significantly improved OS (14.6 vs 12.1 months; 2-yr OS 26.5% vs 10.4%), establishing TMZ+RT as the standard...
• Roa 2004 J Clin Oncol 2004
  Abbreviated 40 Gy/15fr and standard 60 Gy/30fr had equivalent overall survival in elderly GBM patients (≥60 years), with less corticosteroid requirement in the...
• NCCTG/RTOG/ECOG Low vs High Dose RT J Clin Oncol 2002
  High-dose RT (64.8 Gy) provided no survival benefit over standard-dose RT (50.4 Gy) for LGG, while causing more radiation necrosis. Established 50.4-54 Gy as the...
• Goldsmith 1994 (UCSF Meningioma RT) J Neurosurg 1994
  Post-surgical EBRT with doses >52 Gy produced 5-year PFS of 93% for meningioma, establishing the minimum effective dose threshold. Subtotally resected meningioma...

SRS (17)

• ROADS JCO 2026
  Resection plus Cs-131 tile brachytherapy met non-inferiority and superiority for surgical-bed control vs post-operative SRT, with comparable overall adverse-event...
• Alliance N107C Lancet Oncol 2017
  Post-operative SRS to the surgical cavity preserved cognition significantly better than WBRT (52% vs 85% cognitive failure at 6 months) without compromising OS. The...
• MD Anderson Post-op SRS Lancet Oncol 2017
  SRS to the surgical cavity reduced 12-month local recurrence by 68% (HR 0.31, P<.001) compared with observation alone, without improving OS or functional outcomes....
• Alliance N0574 JAMA 2016
  SRS + WBRT produced significantly more cognitive deterioration than SRS alone at 3 months (91.7% vs 63.5%). OS was equivalent. Although WBRT reduced intracranial...
• Combs 2015 (VS Long-Term SRS/FSRT Pooled) Radiother Oncol 2015
  Both SRS (≤13 Gy) and FSRT (57.6 Gy) achieve equivalent, excellent local control exceeding 94% at 10 years for vestibular schwannoma, with no clinically meaningful...
• Grant 2014 (High-Dose SRS Pituitary Adenoma) World Neurosurg 2014
  High-dose SRS at 35 Gy for secretory pituitary adenomas achieved 70% initial hormone normalization with faster time to remission than historical 20-24 Gy series....
• JLGK0901 Lancet Oncol 2014
  OS after SRS alone for patients with 5-10 brain metastases was non-inferior to OS after SRS for 2-4 metastases (both medians ~10.8 months), suggesting that the number...
• Sheehan 2013 (Cushing's Disease SRS) J Neurosurg 2013
  SRS achieves ~70% 5-yr endocrine remission in Cushing's disease with persistent/recurrent disease after transsphenoidal surgery, median time to remission 16.5 mo. New...
• Sheehan 2011 (Nonfunctioning Pituitary Adenoma SRS) J Neurosurg 2011
  SRS achieves 93% 5-yr tumor control for residual/recurrent NFPA after transsphenoidal surgery, with new hypopituitarism in 27% and visual deficit in 4.7%. Larger...
• Combs 2010 (VS LINAC SRS vs FSRT) Int J Radiat Oncol Biol Phys 2010
  LINAC SRS and FSRT achieved equivalent 5-yr local control (97.5%) for vestibular schwannoma. Hearing preservation comparable, numerically favoring FSRT (80% vs 73%)...
• MD Anderson SRS±WBRT Lancet Oncol 2009
  SRS + WBRT caused significantly greater cognitive decline at 4 months compared with SRS alone, as measured by Hopkins Verbal Learning Test. Although WBRT markedly...
• JROSG 99-1 JAMA 2006
  Adding WBRT to SRS did not improve survival for patients with 1-4 brain metastases. However, WBRT significantly improved intracranial control and reduced need for...
• Sheehan 2005 (Pituitary Adenoma SRS Meta-Analysis) J Neurosurg 2005
  SRS achieves ~90% tumor control across pituitary adenoma types with acceptable toxicity. Risks of hypopituitarism, neoplasia, and vasculopathy appear lower than...
• RTOG 9508 Lancet 2004
  Adding an SRS boost to WBRT improved OS for patients with single unresectable brain metastasis (6.5 vs 4.9 months) and improved functional autonomy (KPS) for all...
• Flickinger 2003 (Meningioma SRS Complications) Int J Radiat Oncol Biol Phys 2003
  SRS achieves 5-year local control of 96% for benign meningioma with acceptable overall complication rates of ~10%. Tumor location (parasagittal highest risk due to...
• Pollock 2003 (Meningioma SRS Tumor Control) Int J Radiat Oncol Biol Phys 2003
  SRS and microsurgery achieved equivalent 5-year tumor control for small to medium benign meningiomas, with comparable complication-free survival. SRS was particularly...
• Andrews 2001 (VS SRS Outcomes) Int J Radiat Oncol Biol Phys 2001
  SRS achieved 94% 5-yr local control for small-to-medium VS with complete facial nerve preservation and 75% hearing preservation, establishing SRS as a safe...

GBM (10)

• INTRAGO-II trial Lancet Oncol 2026
  Intraoperative radiotherapy dose escalation added to standard care did not improve progression-free survival and increased radiation necrosis and seizures. The...
• CheckMate 498 Neuro Oncol 2023
  Nivolumab plus radiotherapy was inferior to temozolomide plus radiotherapy in newly diagnosed MGMT-unmethylated GBM (mOS 13.4 vs 14.9 months, HR 1.31), definitively...
• DCVax-L JAMA Oncol 2023
  DCVax-L produced an mOS of 19.3 months across all treated newly diagnosed GBM patients and 34.7 months in MGMT-methylated patients, with a notable proportion of...
• CheckMate 548 Neuro Oncol 2022
  Nivolumab added to standard temozolomide chemoradiation did not improve PFS or OS compared to placebo in newly diagnosed MGMT-methylated GBM (mOS 21.2 vs 20.0 months...
• CeTeG/NOA-09 Lancet 2019
  Lomustine plus temozolomide with radiation significantly improved OS (48.1 vs 31.4 months, HR 0.60) compared to the standard temozolomide-based Stupp regimen in...
• CheckMate 143 JAMA Oncol 2020
  Nivolumab did not improve OS compared to bevacizumab in recurrent GBM (mOS 9.8 vs 10.0 months, HR 1.04), with lower response rates and shorter PFS, establishing that...
• EF-14 JAMA 2017
  TTFields plus temozolomide significantly improved OS (20.9 vs 16.0 months, HR 0.63) and PFS compared to temozolomide alone in newly diagnosed GBM following standard...
• AVAGLIO NEJM 2014
  Bevacizumab improved PFS but not OS when added to the standard Stupp protocol in newly diagnosed GBM. RTOG 0825 independently confirmed these findings, definitively...
• RTOG 0825 NEJM 2014
  Bevacizumab added to standard first-line chemoradiation significantly improved PFS (10.7 vs 7.3 months) but did not improve OS in newly diagnosed GBM, and was...
• STUPP NEJM 2005
  Concurrent and adjuvant temozolomide added to radiotherapy significantly improved OS in newly diagnosed GBM, establishing the Stupp protocol as the global standard of...

Glioma (7)

• EORTC 22033-26033 trial J Clin Oncol 2026
  Choice of initial single-modality therapy (dose-dense TMZ vs RT alone) did not affect PFS or OS in any molecular subtype of high-risk grade 2 glioma. The OS signal...
• INDIGO NEJM 2023
  Vorasidenib significantly extended PFS and delayed time to next intervention in IDH-mutant grade 2 glioma managed with watchful waiting, establishing targeted therapy...
• CATNON/EORTC 26053-22054 Lancet Oncol 2021
  Adjuvant temozolomide, but not concurrent temozolomide, improved OS in 1p/19q non-codeleted anaplastic glioma. Benefit was IDH-mutation dependent, establishing...
• CODEL/N0577 Neuro Oncol 2021
  In 1p/19q-codeleted oligodendroglioma, omitting radiotherapy in favor of TMZ alone produced significantly shorter PFS and more frequent salvage interventions. These...
• RTOG 9802 NEJM 2016
  Radiotherapy plus PCV chemotherapy significantly prolonged both OS (13.3 vs 7.8 years, HR 0.59) and PFS (10.4 vs 4.0 years, HR 0.50) compared to RT alone in high-risk...
• EORTC 26951 JCO 2013
  Adjuvant PCV after radiotherapy significantly improved OS in anaplastic oligodendroglioma/oligoastrocytoma (42.3 vs 30.6 months, HR 0.75), with the most dramatic and...
• RTOG 9402 JCO 2013
  Neoadjuvant PCV followed by radiotherapy significantly prolonged OS in 1p/19q-codeleted anaplastic oligodendroglioma (14.7 vs 7.3 years, HR 0.59), confirming and...

Brain metastases (6)

• Brain Metastases SRS vs HA-WBRT in TNBC: Review Cancers 2026
  TNBC-BM management evolving toward selective local approaches (SRS, HA-WBRT) with CNS-penetrant systemic therapy; multimodal strategy superior to monotherapy.
• CheckMate 204 Lancet Oncol 2021
  Nivolumab + ipilimumab achieved a 54% intracranial ORR and 52% 3-year OS in asymptomatic untreated melanoma brain metastases, establishing dual checkpoint blockade as...
• HER2CLIMB BM Analysis JCO 2020
  Adding tucatinib reduced CNS progression risk by 68% (HR 0.32) and improved OS by 6.1 months (HR 0.58, P=.005) in HER2+ MBC with brain metastases, the first systemic...
• ALEX CNS Analysis Ann Oncol 2018
  Alectinib achieved dramatically superior CNS activity versus crizotinib in ALK+ NSCLC with brain metastases - 81% intracranial ORR (vs 50%), 38% CNS CR (vs 7%), and...
• FLAURA CNS Analysis JCO 2018
  Osimertinib demonstrated superior CNS activity over 1st-gen EGFR TKI in EGFR-mutant NSCLC (91% vs 68% intracranial ORR; 52% reduction in CNS progression risk)...
• COMBI-MB Lancet Oncol 2017
  Dabrafenib plus trametinib achieved a 58% intracranial response rate with a 22% complete response rate in BRAF V600E-mutant asymptomatic untreated melanoma brain...

WBRT (4)

• EORTC 22952-26001 (QoL) JCO 2013
  Among patients without intracranial recurrence at 9 months, adjuvant WBRT was associated with significantly worse QoL and physical functioning compared with...
• EORTC 22952-26001 JCO 2011
  Adjuvant WBRT after complete resection or SRS of 1-3 brain metastases substantially reduced intracranial relapse but did not improve OS or preservation of functional...
• Gondi 2010 (HA-WBRT technique) IJROBP 2010
  Hippocampal-sparing WBRT is technically feasible using IMRT, markedly reducing hippocampal dose and thus theoretically reducing radiation-induced neurocognitive...
• Patchell II JAMA 1998
  Postoperative WBRT after complete resection of a single brain metastasis reduces brain recurrence and neurologic death compared with observation, but does not improve...