Advanced Brain tumors: What to Ask

Gliomas behave unlike most cancers. They rarely travel. NCI makes the consequence explicit. Deaths from malignant glioma are usually caused by uncontrolled disease inside the skull. They are not usually caused by spread to other organs.

So "advanced" here almost always means the tumor has grown back, or grown on, in the brain. NCI is blunt about what that implies. Recurrent central nervous system tumors are rarely curable. NCI says patients should consider enrolling in a clinical trial.

That is not a counsel of despair. It sets the frame for every question below.

NCI names three genetic findings as powerful prognostic factors in diffuse glioma, and says they may guide management:

• A change in IDH1 or, more rarely, IDH2. NCI calls this a strong prognostic factor. People with these tumors live significantly longer, independent of grade or subtype.
• Codeletion of chromosome arms 1p and 19q. This is common in oligodendroglioma. NCI calls it powerful for prognosis. It may also predict response to chemotherapy.
• Methylation of the MGMT gene promoter, a switch on a DNA repair gene.

One number is worth carrying into the appointment. NCI reports that most grade II and III diffuse gliomas carry an IDH change, but only 5 to 10 percent of glioblastomas do.

It is worth asking whether these were repeated on new tissue. Assuming them from the first operation is common. The reports also decide what is available, because biomarker testing sets trial eligibility as much as it describes biology.

A new area that lights up with contrast is not automatically the tumor.

NCI notes that after treatment, SPECT and PET scans may help. They can separate tumor regrowth from radiation necrosis, which is damage caused by the radiation itself. On an ordinary MRI the two look much the same. Getting it wrong in either direction changes the plan.

NCI lists four families of option for recurrent CNS tumors: chemotherapy, antiangiogenesis therapy, radiation therapy and surgery.

On repeat radiation it is unusually cautious. There are no randomized trials. The literature is small retrospective case series, which is hard to interpret. NCI names two specific risks. One is thinking and memory problems. The other is radiation necrosis. It also names the argument in favor. Radiosurgery can put a treating dose into a recurrence sitting in tissue that has already had its limit.

Surgery at recurrence brings a second question. Carmustine wafers can be laid into the cavity during the operation. The trial is worth knowing in detail. In 222 patients needing repeat surgery, median survival was 31 weeks with carmustine wafers. With placebo wafers it was 23 weeks. The straightforward comparison gave a hazard ratio of 0.83, which was not statistically significant. An analysis adjusted for prognostic factors gave 0.67, which was. The investigators reported the trial as positive; a Cochrane review, using the unadjusted figure, reported the same trial as negative. Both descriptions are in NCI's summary.

Chemotherapy. NCI lists temozolomide, lomustine, or the combination of procarbazine, a nitrosourea and vincristine, in people who have not already had them. It adds that this has not been tested in controlled studies. Who gets chosen for treatment probably shapes the results as much as the drugs do.

Bevacizumab. The FDA granted accelerated approval in 2009 for progressive glioblastoma. That pathway allows approval on a measure other than survival. The evidence the FDA reviewed came from 85 patients on bevacizumab alone. Of those, 26 percent responded. Responses lasted a median of 4.2 months. NCI says it has since become standard therapy for recurrent glioblastoma.

Vorasidenib. This pill is FDA-approved for grade 2 astrocytoma or oligodendroglioma with an IDH1 or IDH2 mutation, after surgery. The adult dose on the label is 40 mg once daily, stated here once so you can recognise it; the neuro-oncology team decides what you are actually prescribed and when to hold or reduce it. The label also requires liver blood tests on a set schedule, closely spaced at the start and less often later; your own clinic will tell you when each one is due.

Tumor Treating Fields. The Optune device delivers alternating electric fields through scalp arrays. It holds FDA premarket approval P100034. A 2018 supplement added long-term data from its pivotal glioblastoma study to the labeling.

Much of daily life with an advanced glioma is not about the tumor at all. It is about the swelling around it.

NCI lists dexamethasone, mannitol and furosemide as the treatments used for that swelling. It also states that anticonvulsants are mandatory for anyone who has had a seizure — not optional, not as-needed.

Steroids carry their own cost over time, which is why one finding from the bevacizumab trials in newly diagnosed disease is quoted so often. Starting steroids was delayed from a median of 3.7 months to 12.3 months. And 66 percent of people already on them were able to come off, against 47 percent on standard treatment.

• Which of the three molecular results are known, and were they repeated on the newest tissue?
• Is the new area on the scan tumor, treatment effect, or still undecided?
• Which chemotherapy drugs have already been used, and which remain untried?
• If surgery happens, would carmustine wafers be placed, and what is the case for them here?
• What dose did the previous radiation deliver, and does that leave room for more?
• Would coming down on dexamethasone change how I feel day to day?
• Which trial would be the first choice, and does eligibility depend on doing it before the next treatment?

A second opinion is worth asking for in three situations. When the subtype is unclear. When the molecular panel is incomplete. Or when a further operation is on the table. See getting a second opinion and brain tumors.

• Call 911 if a seizure lasts more than 2 to 5 minutes, if another seizure starts soon after one ends, or if the person does not wake up and behave normally afterwards. Call 911 for a first-ever seizure, and for one that looks different from that person's usual pattern.
• Call your care team the same day if a headache is new, is worst on waking, or comes with vomiting. Do the same for sudden weakness down one side, new trouble speaking, or vision that is changing fast. Swelling around the tumor is the usual reason, and the treatments for it are given quickly.
• Call your care team the same day if anticonvulsant doses have been missed or vomited back. NCI treats these drugs as mandatory, not optional, for anyone who has had a seizure.
• Call your care team within a day or two if sleepiness is deepening, or if family notice a change in personality, mood, or the ability to focus. Do not change the dexamethasone dose on your own first.

• https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq
• https://www.cancer.gov/types/brain/patient/adult-brain-treatment-pdq
• https://medlineplus.gov/ency/article/003200.htm
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31405fee-55b7-4857-987e-2724ee76be84
• https://api.fda.gov/device/pma.json?search=trade_name:%22OPTUNE%22&limit=5