CNS Lymphoma
Low Grade Gliomas
High Grade Gliomas
Meningioma
Miscellaneous
100
The use of which medication may complicate the diagnosis of a suspected primary CNS lymphoma?
(A) Mannitol
(B) Sodium
(C) Albumin
(D) Corticosteroids
D
Corticosteroids are cytotoxic to lymphoma, interfering with pathologic diagnosis.
100
Regarding EORTC 22845 "Non-Believers", which randomized patients with low grade glioma to 54 Gy vs. observation, what outcome was improved by the use of early radiation therapy?
a. Cognitive function
b. Quality of life
c. Progression free survival
d. Overall survival
C
The EORTC 22845 trial randomized patients to 54 Gy vs observation. The median progression free survival was statistically different, 5.3 years vs 3.4 years and the 5 year PFS was 55% vs 35%. However the median overall survival was not statistically different at 7.4 years vs 7.2 years.
100
For patients with glioblastoma, the addition of temozolomide to radiation is associated with improved OS and increased:
(A) chemotherapy induced diarrhea.
(B) methylation of the promoter region of MGMT gene.
(C) incidence of pseudoprogression following chemoRT.
(D) degradation of the protein product of the MDR1 (multi-drug resistance) gene.
C
In the Stupp study, the addition of concurrent and adjuvant temozolomide improved overall survival. In cultured glioblastoma cells, temozolomide treatment induces expression of the MGMT gene product. Methylation of the MGMT promoter region would be associated with lower MGMT expression. Increased expression of the MDR gene product would be expected to induce chemotherapy resistance following exposure. While temozolomide is not associated with diarrhea, the incidence of pseudoprogression following combined chemoradiation is increased.
100
What pathological feature is frequently present in meningioma?
A. Psammoma bodies
B. Rosenthal fibers
C. Pseudorosettes
D. Gemistocytes
A.
Psammoma bodies are frequently found in meningioma.
Rosenthal fibers and gemistocytes are seen in astrocytomas.
Pseudorosettes are a hallmark pathological feature of ependymomas.
100
Acoustic neuromas most commonly affect which cranial nerve?
A. Cranial nerve V
B. Cranial nerve VII
C. Cranial nerve VIII
D. Cranial nerve IX
C.
Acoustic neuromas, commonly seen in neurofibromatosis 2, most commonly affect the vestibular division of CN VIII.
200
What is the most common histology of primary CNS lymphoma?
a. Hodgkin lymphoma
b. Burkitt lymphoma
c. Follicular lymphoma
d. Diffuse large B-cell lymphoma
D
200
What was the chemotherapy used in RTOG 9802 (RT alone vs RT followed by chemotherapy for low grade glioma)?
(A) Paclitaxel, Lomustine, and Vinblastine
(B) Procarbazine, Lomustine, and Vincristine
(C) Procarbazine, Irinotecan, and Carboplatin
(D) Temozolomide, Irinotecan, and Vinblastine
B
RTOG 9802 randomized patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor to RT alone vs RT followed by 6 cycles of Procarbazine, Lomustine (CCNU) and Vincristine chemotherapy.
Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P = 0.003).
200
All of the following regarding temozolomide are true except:
A. It is an alkylating agent with a half-life of minutes.
B. Hypermethylation of the MGMT promoter leads to increased sensitivity to temozolomide.
C. It was first approved as a single agent in recurrent glioma.
D. Concurrent with radiation for newly diagnosed glioblastoma, it is given daily at 150mg/m2 .
D.
Temozolomide is an alkylating agent with a half- life of minutes that leads to methylation of the O-6 position of guanine. Unrepaired, this will lead to double-strand breaks. Although now the standard of care in newly diagnosed glioblastoma multiforme due to the overall survival benefit seen in Stupp’s landmark trial, it was first studied and FDA approved in recurrent glioma.
In Stupp’s study, temozolomide was given concurrently with radiation (60 Gy), at a daily dose of 75 mg/m2, and adjuvantly for 6 cycles at 150–200 mg/m2 . The latest update published in 2009 in The Lancet showed that the overall survival benefit persisted
MGMT is a DNA repair enzyme that repairs this damage induced by temozolomide. Methylation of the MGMT promoters results in epigenetic silencing and thus decreased MGMT expression. After determining the methylation status of glioblastoma patients randomized to radiation +/− temozolomide, Hegi et al. found MGMT promoter methylation to be associated with improved survival.
200
Which is the most typical appearance of meningioma on magnetic resonance imaging?
A. Isointense on pre-contrast T1, no enhancement with gadolinium contrast
B. Isointense on pre-contrast T1, uniform enhancement with gadolinium contrast
C. Hyperintense on pre-contrast T1, no enhancement with gadolinium contrast
D. Hyperintense on pre-contrast T1, uniform enhancement with gadolinium contrast
B.
Meningiomas tend to be hypointense or isointense on pre-contrast T1-weighted images and uniformly enhance with gadolinium contrast.
200
A glioma has IDH mutation, p53 mutation, ATRX loss, 1p deletion, and 19q intact. How should this tumor be classified according to the 2016 WHO classification?
a. Medulloblastoma
b. Astrocytoma
c. Oligodendroglioma
d. Pilocytic astrocytoma
B
In the 2016 WHO Classification of Brain Tumors, some of the molecular characteristics of an astrocytoma are: IDH mutation, p53 mutation, ATRX mutation leading to loss, and lack of co-deletion of 1p19q. A single deletion in 1p or 19q is not sufficient to make an oligodendroglioma diagnosis; they must be co-deleted. Furthermore, p53 mutation and ATRX loss together denote an astrocytoma and are largely mutually exclusive from 1p19q co-deletion.
300
What is the recommended radiation treatment after chemotherapy for primary CNS lymphoma?
(A) 45 Gy WBRT if partial response to chemotherapy
(B) 45 Gy WBRT regardless of response to chemotherapy
(C) 23.4 Gy WBRT if partial response followed by a cone-down to 45 Gy to residual disease
(D) 36 Gy WBRT if partial response followed by a cone-down to 45 Gy to residual disease
D
From 2018 NCCN CNS guidelines: WBRT may be withheld in the primary setting in patients treated with chemotherapy. When used, WBRT doses should be limited to 23.4 Gy in 1.8 Gy fractions following a CR to chemotherapy. For less than a CR, consider WBRT to 30-36 Gy followed by a limited field to gross disease to 45 Gy or focal radiation to residual disease only.
300
A grade III glioma is histologically consistent with an astrocytoma and has 1p19q co-deletion and IDH mutation. How should this tumor be classified according to the 2016 WHO classification?
a. Anaplastic astrocytoma
b. Anaplastic oligodendroglioma
c. Anaplastic ependymoma
d. Glioblastoma
B
In the 2016 WHO Classification of Brain Tumors, at times molecular type determines the diagnosis rather than classic histology on H&E.
A histologic astrocytoma, but a molecular oligodendroglioma (with IDH mutation and 1p19q co-deletions), is an oligodendroglioma. Similarly, a histologic oligodendroglioma but without 1p19q co-deletion is not an oligodendroglioma, assuming the molecular testing is accurate. A glioblastoma (GBM) is not a grade III tumor.
300
In the NCIC/EORTC randomized trial of glioblastoma patients > 65 years, what resulted from the addition of concurrent and adjuvant temozolomide to 40 Gy in 15 fractions?
a. Improved OS
b. Worsened OS
c. Improved QoL
d. Worsened QoL
A
The NCIC CE.6/EORTC 26062-22061 trial randomized 562 patients older than 65 years, with ECOG performance status 0-2, who were not deemed candidates for standard 60 Gy with temozolomide (TMZ) chemotherapy, to: 40 Gy in 15 fractions alone vs. 40 Gy in 15 fractions with concurrent and adjuvant TMZ.
The addition of TMZ improved OS (9.3 vs. 7.6 months) and PFS (5.3 vs. 3.9 months). Quality of life was similar in the two groups.
300
The Daily Double wager may be as high as the team's total points at the time that the Daily Double is chosen or 500 points, whichever is greater.
What is an appropriate fractionated EBRT dose for a grade I meningioma recurrent after surgery?
a. 14 Gy
b. 36 Gy
c. 54 Gy
d. 60 Gy
C
Fractionated radiation doses range from 50 to 54Gy in 1.8’s to 2’s. RTOG 0539 used dose of 54Gy for intermediate risk meningiomas.
300
What is an appropriate dose (Gy) for single fraction SRS to a functioning pituitary adenoma?
What is an appropriate conventionally fractionated dose (Gy) to a functioning pituitary adenoma?
(A) 10; 45
(B) 14; 39.6
(C) 16; 59.4
(D) 20; 54
D
SRS: Non functioning pituitary adenomas; 14-16Gy. Functioning; 18-20 Gy.
Fractionated radiation therapy: For nonfunctioning pituitary adenomas, 45–50.4 Gy delivered at 1.8 Gy daily fractions; for functioning pituitary adenomas, 50.4 –54 Gy delivered in 1.8 Gy daily fractions.
400
According to NCCN guidelines, what is the preferred induction therapy for CNS lymphoma?
(A) Methotrexate
(B) Rituximab
(C) 18 Gy WBRT
(D) 45 Gy WBRT
A
Methotrexate is the most effective agent against primary CNS lymphoma. After a CR to chemotherapy, low dose WBRT to 23.4 Gy may be considered. For patients who are not candidates for chemotherapy, WBRT to 24 to 36 Gy is followed by a boost to 45 Gy.
400
All of the following are true regarding the EORTC 22844 “Believer’s Trial” in low-grade glioma except:
A. Only 25% of patients underwent gross total resection.
B. 45 Gy was the radiation dose of one arm in the study.
C. 50.4 Gy was the radiation dose of one arm in the study.
D. Overall survival did not improve with dose escalation.
C. In EORTC 22844, the “Believer’s Trial,” patients with low-grade glioma were randomized to immediate postoperative RT with either 45 Gy or 59.4 Gy. Only 25 % underwent gross total resection prior to radiation.
Dose escalation did not result in improved survival, nor progression-free survival.
400
What is one rationale for inclusion of concurrent bevacizumab with re-irradiation of recurrent glioblastoma?
(A) Treatment of radiation necrosis
(B) Alters MGMT methylation status
(C) Reduces HIF-1 metabolic signaling
(D) Induces transition from a mesenchymal to pro-neuronal phenotype
A
Bevacizumab has not been shown to improve overall survival outcomes in the treatment of newly diagnosed glioblastoma. However, both animal and clinical studies have shown that bevacizumab is effective in the treatment of radiation necrosis. For re-irradiation, the incidence of radiation necrosis is higher than with primary radiation and thus it may be expected that bevacizumab will reduce the incidence of radiation necrosis. Bevacizumab, an angiogenesis inhibitor, does not alter MGM methylation status or glioblastoma phenotype.
400
What is the appropriate marginal dose (Gy) for single fraction SRS to a 1.0 cm WHO grade 1 meningioma?
(A) 10
(B) 14
(C) 18
(D) 22
B
Per NCCN 2018: WHO Grade I meningiomas may be treated with SRS doses 12-16 Gy in a single fraction when appropriate.
400
What was the median overall survival (in months) found for TTF-TMZ vs TMZ alone respectively in Stupp et al (2017)?
A) 22.5 vs 18.0
B) 20.9 vs 16.0
C) 18.5 vs 15.3
D) 6.7 vs 4.0
B
Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]),637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95%CI, 0.52-0.76; P < .001).
Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63;95%CI, 0.53-0.76; P < .001).
500
For treatment of primary CNS lymphoma, what is the minimum dose of methotrexate needed to cross the blood-brain barrier?
a. 0.5 g/m2
b. 1.0 g/m2
c. 3.5 g/m2
d. 8.0 g/m2
C
Per NCCN 2018: Systemic Induction Chemo may consist of
1) High dose MTX (8 g/m2) combined with Rituximab or Rituximab + temozolomide (TMZ)
2) High dose MTX (3.5 g/m2) combined with the following, and consider WBRT
- Vincristine, procarbazine and rituximab (R-MPV)
- TMZ + rituximab followed by post-RT TMZ
500
The Daily Double wager may be as high as the team's total points at the time that the Daily Double is chosen or 500 points, whichever is greater.
According to RTOG 9802, which patient with gross total resection of a low grade glioma would benefit from the addition of chemotherapy after radiation?
a. 48 year old woman
b. 37 year old man
c. 26 year old woman
d. 19 year old man
A
RTOG 9802 randomized high risk low grade glioma patients, defined as either >40 years after biopsy/resection or patients age 18 – 39 years after subtotal resection, to either radiation versus radiation followed by PCV. The updated analysis found both a progression free survival benefit and overall survival benefit
500
What were the 5-year overall survival rates with and without temozolomide, respectively, reported in the latest (2009) update of the Stupp trial?
A. 10%, 2%
B. 2%, 10%
C. 27%, 10%
D. 10%, 27%
A.
In Stupp’s study the initial report in 2005 showed an improvement in median survival with the addition of temozolomide: 14.6 versus 12.1 months. Two year survival was also improved (26.5 % vs. 10.4 %). The latest update published in 2009 in The Lancet showed that the overall survival benefit persisted:5-year survival 9.8 % versus 1.9 %.
500
Which targeted agent has been shown in a phase II study to have efficacy in the treatment of recurrent/progressive atypical or anaplastic meningioma?
(A) Sunitinib
(B) Imatinib
(C) Erlotinib
(D) Nivolumab
A
Platelet-derived growth factor receptors (PDGFRs; imatinib) and epidermal growth factor receptor (gefitinib and erlotinib) have not shown efficacy. A phase II study of imatinib in recurrent meningioma demonstrated a PFS of 0% in the atypical/anaplastic cohort. In a phase II trial of sunitinib, median PFS in this cohort was 5.2 months (95% CI: 2.8–8.3 mo), and median OS was 24.6 months (95% CI: 16.5–38.4 mo)
500
What system is used to grade arteriovenous malformations (AVMs)
A. House-Brackmann
B. Koos
C. Spetzler-Martin
D. Simpson
C. Spetzler-Martin
The Spetzler Martin Grading Scale estimates the risk of open neurosurgery for a patient with AVM, by evaluating AVM size, pattern of venous drainage, and eloquence of brain location. A Grade 1 AVM would be considered as small, superficial, and located in non-eloquent brain, and low risk for surgery. Grade 4 or 5 AVM are large, deep, and adjacent to eloquent brain. Grade 6 AVM is considered not operable.
Note however, that this scale does not necessarily correlate with risk of treatment by embolization or radiosurgery.
Size of AVM
Small (<3 cm) 1
Medium (3-6 cm) 2
Large (>6 cm) 3
Location
Noneloquent site 0
Eloquent site* 1
Venous drainage
Superficial 0
Deep 1
*Sensorimotor, language, visual cortex, hypothalamus, thalamus, brainstem, cerebellar nuclei, or regions directly adjacent to these structures.
House-Brackmann - Degree of nerve damage in facial nerve palsy
Koos - Extent of vestibular schwannoma
Simpson - Predict risk of recurrence following resection of meningioma