NCCN CNS tumor guidelines update for 2023

The National Comprehensive Cancer Network^® (NCCN^®) is a not-for-profit alliance of 33 National Cancer Institute designated Comprehensive Cancer Centers dedicated to patient care, research, and education. The NCCN is best known for the establishment of tumor-specific clinical practice guidelines. These are based on the evaluation of evidence and formulation of recommendations by a panel of experts for each type of cancer. The impact has been far-reaching: in 2022, the CNS Guidelines were downloaded 177 296 times, including 25 944 from sites outside the United States.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers¹ are formed by the efforts of a committee of 34 members compromised of 12 neurologists, 7 radiation oncologists, 5 neurosurgeons, 7 medical oncologists, 1 neuropathologist, and 1 patient advocate. Each year, the Guidelines are reviewed and updated by the committee members. During the review period, member institutions, industry representatives, and individuals outside the NCCN can submit comments, which are then collated and discussed at the annual committee meeting held at the NCCN Headquarters in Plymouth Meeting, PA. The data supporting these comments are analyzed by the committee to decide whether to add to or revise the guideline algorithms using the NCCN Categories of Evidence (1, 2A, 2B, 3) as shown in Table 1. The committee votes on assigning category recommendations based on the quality of the data (randomized controlled trials [RCTs], non-RCTS, meta-analyses, systematic review of the literature, or clinical experience), the amount of evidence (extensive, less extensive, little, or anecdotal clinical experience), and reproducibility of the evidence (highly consistent, single trial, or variable).

Table 1.

(A) The categories of evidence and consensus. (B) The categories of preference.

A.Categories of evidence and consensus
Recommendations are based on level of clinical evidence available and degree of consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate;
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate;
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate;
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
B.Categories of preference
Preferred intervention: Interventions that are based on superior efficacy, safety, and evidence, and, when appropriate, affordability.
Other recommended intervention: Other interventions that may be somewhat less efficacious, more toxic, or based on less mature data; or significantly less affordable for similar outcomes.
Useful in certain circumstances: Other interventions that may be used for selected populations (defined with recommendation).

Updates to the 2023 NCCN Clinical Practice Guidelines for CNS Cancers

General

• The NCCN Guidelines^® for Central Nervous System Cancers Version 1.2023 continues to incorporate and clarify treatment recommendations in relation to the World Health Organization (WHO) 2021 neuropathology updates.²

• Information about chemotherapy options previously contained in section BRAIN-D (formerly titled Principles of Brain and Spinal Cord Tumor Systemic Therapy) has been reorganized and now follows directly after the treatment algorithms for the specific tumor type. NCCN Categories of Preference (Table 1) and references have been updated throughout.

GLIO

• GLIO-1 has been renamed for better specificity as Adult Glioma: Circumscribed Glioma, which includes pilocytic astrocytoma, subependymal giant cell astrocytoma, ganglioglioma, and pleomorphic xanthoastrocytoma WHO grade 2.

• GLIO-3 IDH-mutant astrocytoma: To be consistent with the WHO 2021 updated classification of gliomas, high-grade IDH-mutant astrocytomas have been separated into their own treatment guidelines. The recommendations for managing Grade 3 IDH-mutant astrocytomas follow the results of the CATNON study: radiation therapy followed by 12 months of adjuvant temozolomide.³ For Grade 4 treatments, reasonable options include those listed for Grade 3, among others.

• GLIO-7 glioblastoma: Indeterminate methylguanine methyltransferase (MGMT) status has been moved to the branch for MGMT promoter methylated glioblastoma, as the committee favored the use of temozolomide in this circumstance.

• GLIO-9 H3-mutated high-grade glioma: A separate algorithm was added for this molecular category. These tumors often behave more aggressively than glioblastoma and tend to be less sensitive to temozolomide; however, due to a lack of other effective therapies for H3-mutated high-grade gliomas, the current treatment recommendations are the same as options for glioblastoma.

BRAIN-C Principles of Radiation Therapy for Brain and Spinal Cord Tumors

• Adult low-grade glioma: Added the recommendation to consider radiotherapy (RT) dose escalation to 59.4–60 Gy for IDH wild-type diffuse low-grade glioma or CDKN2A/B deleted, IDH-mutated low-grade glioma. These should be treated as high-grade glioma, as these patients have a more aggressive course of disease.⁴

• Re-irradiation of gliomas: The recommendations have been modified to address target volume delineation, suggested RT dose, consideration of different focal RT techniques, and the role of image-guided radiotherapy for recurrent low-grade gliomas.

• Meningiomas: For WHO grade 2 meningiomas, a new emphasis is placed on using higher RT doses (59.4–60 Gy) for patients with subtotally resected disease or recurrent tumors.

• Brain metastases: Additional recommendations for when to consider a fractionated SRS approach have been included. The role of preoperative SRS was addressed: Consider preoperative SRS in select cases when logistically feasible to potentially reduce the risk of post-treatment meningeal recurrence (Category 2B). For postoperative SRS, a multifraction approach is preferred for larger surgical cavities, with specific dose and fractionation recommendations provided. More details regarding whole-brain radiation were added, such as cognitive sparing techniques, indications, and dose and fractionation recommendations.

BRAIN-D Principles of Brain and Spine Tumor Management

• The Medical Management section about corticosteroid use now contains a specific recommendation for twice or once-daily dosing of dexamethasone.⁵

BRAIN-E Principles of Brain Tumor Pathology

• This section underwent extensive updating and reorganization in keeping with recommendations from the 5th edition of WHO Classification of Tumors of the Central Nervous System.²

• The panel continues to support and encourage molecular testing of glioblastoma given the potential therapeutic impact of driver mutation discovery.

• The Molecular Characterization section provides a high-yield list of molecular alterations deemed essential for the correct diagnosis of all gliomas. The list includes mutations of IDH1 R132 and IDH2 R172, TERT promoter, ATRX, EGFR, BRAF V600E, and H3-3A mutation (K27 or G34). The copy number alterations required include 1p19q codeletion, EGFR amplification, gain of chromosome 7, loss of chromosome 10, and CDKN2A/B deletion.² While this list is not comprehensive, it covers the majority of primary gliomas seen in the community. In cases where histopathology and molecular characterization are equivocal, referral to centers that have advanced molecular diagnostic expertise, including genomic DNA methylation profiling, is strongly recommended.

Summary

The 2023 NCCN Clinical Practice Guidelines for Central Nervous System Cancers continue to predicate its recommendations on the best data available. The glioma algorithms have been substantially reorganized based on recently revised molecular-based diagnostic classifications and are in need of more subtype-specific clinical trials to foster new recommendations. These revised guidelines are intended to be more user friendly, with the inclusion of the Categories of Preference for chemotherapy choices. BRAIN-C Principles of Radiation for Brain and Spinal Cord Tumors now provides more specific details relative to clinical context and radiation dose and fraction number. The committee has also made progress in incorporating and clarifying the importance of molecular testing in the diagnosis and treatment of primary brain cancers.

Conflict of interest statement

None declared.