Neuro-oncology

Question 1

What was the survival benefit when using PCV in combination with RT for low grade gliomas (e.g. Oligodendrogliomas and astrocytomas)?

Answer 1

PCV w/RT was assoc with a OS and PFS benefit. This is a Cat 1 rec for both of these tumors

Question 2

Promoter methylation in GBM is what type of prognostic factor?

Answer 2

Those tumors that are promoter methylation have a much better prognosis than those that aren’t, they respond to chemo/RT (Temozolamide) much better, but the tx is still the same for both.

Question 3

For low grade gliomas (grade 2) that are IDH mutant (e.g. Oligodendroglioma and Astrocytoma) what is the criteria for observation if they have residual tumor after resection or biopsy?

Answer 3

You can do observation for grade 2 tumors as long as they have no neurological symptoms or are neurologically stable. If treating you give RT followed by PCV, Temozolamide (TZ can be given concurrently and aduvantly or adjuvant alone).

Question 4

What is the preferred treatment for grade 3/4 IDH mutant Astrocytoma regardless of PS? Also for patients who have a good KPS what is an option that is listed repetitively in the guidelines that you don’t think about?

Answer 4

So if you look at the NCCN guidelines they only list RT+TMZ, PCV is not listed as an option. For grade 3 and good KPS, preferred option is standard RT+adjuvant TMZ. Don’t forget that clinical trials are listed options for all of these tumors (CNS tumors).

Question 5

What is the most common histologic subtype of CNS lymphoma?

Answer 5

DLBCL is the most common. Other rare types include: Burkitt, T-cell, low grade B cell lymphoma.

Question 6

What is the preferred tx for CNS lymphoma?

Answer 6

High dose MTX combined w/ Rituximab or Rituximab+TMZ. You can also do HDMTX w/ Vincristine, Procarbazine, Ritux given w/WBRT aka R-MPV

Question 7

What is the consolidation strategy for CNS lymphoma? Just be familiar with this, you don’t have to memorize it.

Answer 7

High dose systemic therapy followed by stem cell rescue: Cytarabine, thioptea followed by carmustine and thioptea. Also have as an option Cytarabine and Etoposide (EA regimen) or Cytarabine alone. Also have TBC regimen.

Question 8

What is the tx for GBM in those with a good PS and methylation promotor positive or unknown and age less than 70?

Answer 8

Can consider these patients for a clinical trial. Standard RT w/concurrent TMZ and adjuvant TMZ and alternating electric field therapy. You can do the above option also w/o electric field therapy. Both are Cat 1 recs.

Question 9

Concurrent/adjuvant Lomustine and TMZ added to RT for GBM in those with a good PS is listed as what type of rec in NCCN for age less than 70?

Answer 9

This is listed as a Cat 2B rec

Question 10

What is the tx for unmethylated GBM in those with a good PS?

Answer 10

Its essentially the same for those that are methylated: Standard RT w/concurrent TMZ and adjuvant TMZ and alternating electric field therapy or without electric field therapy. Both are Cat 1 recs.

Question 11

What is the tx for GBM in a patient with a low PS?

Answer 11

Hypofractionated RT +/- concurrent or adjuvant TMZ or TMZ alone

Question 12

For those who are older than 70 with a good PS and have GBM with promoter methylation or that is unknown, what is the Cat 1 rec? For those with unmethylated status?

Answer 12

Hypofractionated RT w/concurrent and adjuvant TMZ or Standard RT w/concurrent and adjuvant TMZ and alternating electric fields. The recs are the same for unmethylated as well, however TMZ alone isn’t a option.

Question 13

What is the tx for GBM in patients over the age of 70 with a low PS?

Answer 13

TMZ alone or palliative care

Question 14

What is the tx if indicated for grade 2 astrocytoma who have a good PS? For those w/ a low PS?

Answer 14

If tx is indicated upfront or they progress on a IDH1 inhibitor, then you give standard RT + PCV or TMZ or you can give concurrent and adjuvant TMZ. Low PS-hypofractionated RT w/ concurrent or adjuvant TMZ, TMZ alone, Ivosidenib, Palliative care.

Question 15

What do you do for a patient with a good PS who has Astrocytoma grade 2 when tx is not indicated but they have recurrent or residual dx?

Answer 15

If tx is not indicated up front (they are asymptomatic) then you can observe or you give a IDH1 inhibitor (Ivosidenib).

Question 16

What do you do for a patient with a good PS with astrocytoma that has grade 3 pathology? Low PS?

Answer 16

Standard RT + adjuvant TMZ (preferred, standard of care) or you can do with concurrent and adjuvant TMZ. Low PS-hypofractionated RT w/concurrent or adjuvant TMZ. Can also do TMZ alone or palliative care.

Question 17

With astrocytoma with a good PS and grade 4 pathology how do you treat these patients? What about low PS?

Answer 17

RT+adjuvant TMZ or you can do w/concurrent and adjuvant TMZ +/- electric field therapy. Low PS-hypofractionated RT w/concurrent or adjuvant TMZ. Can also do TMZ alone or palliative care.

Question 18

What is the tx of Oligodendroglioma grade 2 in those with a good PS?

Answer 18

If no residual dx-observation
For residual or recurrent dx where upfront tx is not indicated you can do observation or Ivosidenib.

Question 19

For oligodendrogliomas that are grade 2 and the patient has a good PS where upfront tx is indicated (they are symptomatic) what do you do?

Answer 19

Always consider a clinical trial. RT w/adjuvant PCV (Cat 1 rec). Can also consider RT w/ adjuvant TMZ or w/concurrent and adjuvant TMZ

Question 20

For those with oligodendrogliomas grade 2 and the patient has a poor PS what is the tx?

Answer 20

Hypofractionated RT + concurrent and/or adjuvant TMZ. Can also consider Ivosidenib or TMZ alone. Of course palliative care is always an option.

Question 21

What is the tx for Grade 3 Oligodendroglioma in those with a good PS?

Answer 21

Clinical trial, standard RT w/ neoadjuvant or adjuvant PCV (Cat 1 rec), standard RT with concurrent and adjuvant TMZ, standard RT

Question 22

What is the tx for Grade 3 Oligodendroglioma in those with a poor PS?

Answer 22

Hypofractionated RT (can always consider standard RT) w/concurrent and/or adjuvant TMZ. TMZ alone (Cat 2B). Palliative care.

Question 23

What is the molecular profile of Oligodendroglioma? What is the overall prognosis and grade? For Astrocytomas that are positive for CDKN2A/B what is the clinical significance?

Answer 23

IDH mutant, 1p19q co-deleted. Generally these are very slow growing tumors and grade 2/3 and are associated with a good prognosis. Astrocytoma-this deletion denotes Grade 4 pathology.

Question 24

What are the key molecular signatures that help identify a GBM tumor according to the new WHO classification? What histology might you see?

Answer 24

IDH-WT is a must. They also may have: TERT mutation, EGFR, 7 gain/10 loss. Look for microvascular proliferation and tumor necrosis. However, this may not be present but look for the molecular signature to identify it as GBM.

Question 25

What are the key molecular features of astrocytomas? What is the overall prognosis compared to oligodendrogliomas?

Answer 25

They are IDH mutant. They can either have the presence of CDKN2A/B (Grade 4 if this is present) or the absence of this. Grade 2/3 if absent). They are more aggressive than Oligodendrogliomas, they have Grades 2-4. So the prognosis is slightly worse.

Question 26

What is the molecular signature for Diffuse Hemispheric Glioma? What is the grade and prognosis? What is the tx?

Answer 26

IDH-WT. Harbors the H3-G34 mutation. High grade-Grade 4, poor prognosis! Tx-Standard RT w/concurrent and adjuvant TMZ (for methylated and unknown status) OR clinical trial or RT alone for those that are unmethylated. Can do chemo/RT for unmethylated, but Cat 2B rec.

Question 27

In general after resection of a medulloblastoma what is the tx? Which patient can just get RT alone?

Answer 27

Craniospinal RT w +/- Vincristine followed by adjuvant chemo. Those w/low risk of recurrent dx can get RT alone (small volume residual dx, classic or desmoplastic histology, no mets). Refer to other flash card for chemo regiments.

Question 28

What chemo is given in the adjuvant setting for medulloblastoma?

Answer 28

Cisplatin, Cyclophosphamide, Vincristine. Also can do Cisplatin, Lomustine, and Vincristine.

Question 29

Vismodegib can be used in medulloblastoma in which setting?

Answer 29

In the recurrent setting after prior systemic therapy if they have a SHH mutation

Question 30

When can be high dose chemo followed by stem cell rescue be used in medulloblastoma?

Answer 30

This can be done in recurrent dx if they achieve a CR after surgery or systemic chemo. You can review the available chemo options for recurrent dx in NCCN pg 43.

Question 31

What is the tx of VHL associated CNS hemangioblastoma?

Answer 31

Belzutifan

Question 32

In general for meningioma suspected based off of imaging if they are asymptomatic what do you do?

Answer 32

Just observe

Question 33

For patients with meningioma that undergo resection what are the tx options depending on grade?

Answer 33

Grade 1-observation, consider RT for those with symptoms
Grade 2 w/complete resection-RT
Grade 2 w/incomplete resection-consider RT or observe in those with low PS
Grade 3-RT