Glioblastoma and Other Primary Brain Malignancies in Adults A Review

Lauren R. Schaff, MD^1,2; Ingo K. Mellinghoff, MD^1,2,3,4

JAMA

Published Online: February 21, 2023

2023;329;(7):574-587. doi:10.1001/jama.2023.0023

Abstract

Importance  Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%.

Observations  Approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P < .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation.

Conclusions and Relevance  The incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals, and approximately 49% of primary malignant brain tumors are glioblastomas. Most patients die from progressive disease. First-line therapy for glioblastoma is surgery followed by radiation and the alkylating chemotherapeutic agent temozolomide.

Figure 2.  Imaging Features of Malignant Brain Tumors

중요성 (Importance)

·         원발성 악성 뇌종양은 미국에서 연간 1만 5천 명 이상 사망

·         연간 발생률: 10만 명당 약 7명, 연령 증가와 함께 발생률 증가

·         5년 생존율 약 36%

역학 및 종양 종류 (Observations)

·         악성 뇌종양 구성

o    교모세포종(Glioblastoma): 약 49%

o    미만성 침윤성 저등급 교종: 약 30%

o    원발성 중추신경계 림프종: 7%

o    악성 상의세포종: 3%

o    악성 수막종: 2%

임상 증상

·         두통: 50%

·         발작: 20–50%

·         인지 기능 저하: 30–40%

·         국소 신경학적 결손: 10–40%

진단

·         가돌리늄 조영 전·후 MRI가 표준 영상검사

·         종양 생검 필수

o    조직병리학적 특징

o    분자유전학적 특성 고려

치료

·         종양 유형에 따라 다르며 수술 + 항암치료 + 방사선치료의 병합이 일반적

• 교모세포종

·         표준 치료: 수술 → 방사선치료 + 테모졸로마이드

·         방사선 단독 대비 생존율 개선

o    2년 생존율: 27.2% vs 10.9%

o    5년 생존율: 9.8% vs 1.9%

o    HR 0.6 (유의함)

• 1p/19q 공결손을 가진 역형성 희돌기교종

·         방사선치료 단독 대비 PCV 요법(프로카바진·로무스틴·빈크리스틴) 병합 시

o    20년 생존율 약 2–3배 증가

o    EORTC, RTOG 임상시험에서 일관된 생존 이득

• 원발성 CNS 림프종

·         고용량 메토트렉세이트 기반 항암요법

·         이후

o    조혈모세포 자가이식 동반 고강도 항암

o    비골수파괴적 항암

o    또는 전뇌방사선치료로 공고요법

결론

·         원발성 악성 뇌종양은 드문 질환이지만 예후가 불량

·         교모세포종이 가장 흔하며, 대부분 진행성 질환으로 사망

교모세포종의 1차 표준 치료는 수술 후 방사선치료 + 테모졸로마이드