Question about GBM, spinal metastases management, and immunotherapy clinical trials.
For a 32 year old GBM patient with an inoperable tumor in the splenium and metastasis in the spinal cord. 1. Would you consider anti-PD1 or anti-CTLA-4 treatment for this condition? If so, and while I know it’s only experimental, which one (ipilimumab or nivolumab)?. What would be a potential treatment option for the metastasis in the back (near L5), besides radiotherapy?
Dr. Lee: Checkpoint inhibitors such as ipilimumab and nivolumab are available only in clinical trials for GBM patients. While there is much excitement about these treatments, it is unclear how beneficial they are in GBM. It is also unclear if an anti-CTLA-4 treatment such as ipilimumab is better than an anti-PD1 treatment such as nivolumab or vice versa. Regarding the metastasis in the spinal cord, recommendations are slightly different depending on whether the lesion is a “drop metastasis” in the spinal fluid space around the spinal cord versus a lesion in the spinal cord itself. Based on the described location of L5, I suspect this refers to a lesion in the spinal fluid space. Another option besides radiation is a chemotherapy that is able to penetrate the spinal fluid spaces. Examples might include temozolomide or lomustine.
Question about cognitive effects from inoperable temporal lobe tumor:
My spouse has an inoperable temporal lobe tumor- what can we expect as far as cognitive effects as he progresses?
Dr. Lee: This depends on whether the lesion is in the right or left temporal lobe and what side controls language function (typically language lives on the left side of the brain in right-handed individuals). He may experience symptoms not only from the tumor itself but also the treatments, particularly radiation. Some of the more common symptoms people experience with temporal lobe tumors include seizures and short-term memory dysfunction. Again, depending on the side, a temporal lobe tumor can also cause problems with language (called aphasia).
Question about anxiety, frustration, and depression following GBM diagnosis:
My husband has glioblastoma, it has affected how he is able to function cognitively (loss of words, sluggish, confusion). He has always been very social but now he is fearful of going out with our friends, afraid they will notice his ‘impairments.’ He is very frustrated, anxious, and depressed. Is there anything we can do to help his cognitive function? Or anxiety?
Dr. Lee: Unfortunately, cognitive impairments, frustration, anxiety, and depression are common symptoms in GBM patients. There are medications that can help anxiety and depression and you should seek help from your treating team. Regarding the cognitive problems, sometimes cognitive rehabilitation can be helpful.
Question about diet:
Can diet make a difference? I saw a study on ketogenic diet for end stage GBM and wondered if this is something we should be doing.
Dr. Lee: Diet can helpful with overall health but there is not one specific diet recommended. There is not enough data to recommend the ketogenic diet. This diet is also very restrictive and should only be attempted under the guidance of your treating team and a dietitian.
Question about anti-angiogenic therapies, bevacizumab-resistance and clinical trials:
Regarding antiangiogenic therapies- is Avastin the best one out there? Anything else when it becomes resistant to avastin? Any trials?
Dr. Lee: With regards to GBM, we have the most experience and best evidence with bevacizumab (Avastin). Other antiangiogenic agents that have been tested to date do not seem to work as well as bevacizumab. We think some tumors become resistant to bevacizumab because there are alternate “escape” pathways of angiogenesis that allows a tumor to grow despite bevacizumab. Some of the current clinical trials combine bevacizumab with a second agent that targets an “escape” mechanism.
Question about immunotherapy and brain tumors:
I have been reading a lot about immunotherapy and cancer. Is that only for brain metastases or for primary brain tumors? What is the difference between dendritic cell vaccines, peptide vaccines, and checkpoint inhibitors?
Dr. Lee: Immunotherapy is being tested in clinical trials for patients with brain metastases and glioblastoma. Ipilimumab is now approved by the US government for treatment of patients with melanoma. One study of ipilimumab suggested that this treatment could be helpful for management of melanoma brain metastases. For other types of cancers, there is insufficient data to know if immunotherapy is beneficial for GBM or brain metastases from other types of cancer.
In terms of immunotherapy trials for GBM, as mentioned in the question, there have been trials of dendritic cell vaccines, peptide vaccines, and checkpoint inhibitors. Treatment with checkpoint inhibitors such as ipilimumab, nivolumab, or pembrolizumab “releases the breaks” on the immune system so it can attack the tumor. Therapeutic cancer vaccines are designed to stimulate the immune system against the tumor. Some cancer vaccines are made up of cancer cells, parts of cells, or tumor antigens (hence peptide vaccine). Sometimes a patient’s own immune cells (such as dendritic cells) are removed and exposed to these substances in the lab to create the vaccine (hence a dendritic cell vaccine).
Question about the latest in targeted therapy for GBM:
Do we know what genes are responsible for GBM yet? Are we making progress in targeted therapy?
Dr. Lee: GBM was the first cancer to be sequenced by the Cancer Genome Atlas (TCGA), funded by the US government. What we have learned is that several molecular abnormalities are responsible for GBMs. No one single genetic mutation is responsible for GBM. There is also some variation from person to person as to what molecular abnormalities are responsible for the GBM in that patient. Now, many trials of targeted therapy in GBM select patients for the molecular abnormality the therapy targets. We hope this will prove more successful than our prior trials of targeted agents in unselected GBM patients.
Question about tumor metabolism in brain tumors and clinical trials.
I have read that tumor metabolism is important in brain tumors—is this still an area of research? Any active clinical trials?
Dr. Lee: Tumor metabolism is an active area of research in brain tumors. For example, IDH1 is an enzyme important in cellular metabolism. Some gliomas have mutations in the IDH1 gene. There are now clinical trials of drugs which target IDH1.
Question about tumor or cancer stem cells: What are tumor stem cells? Is this the same as glioma stem cells?
Dr. Lee: Tumor or cancer stem cells (which can also be called glioma stem cells in glioma patients) are cancer cells within the tumor that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample.
Questions about radiation therapy for brain metastases and primary brain tumors.
It seems like there are lots of different ways to deliver radiation to the brain; which is the best? My doctor talked about hypofractionated IMRT. Are there any radiosensitizing drugs?
Dr. Lee: The “best” way to deliver radiation depends on the type of tumor. Gliomas are generally treated with focal radiation. IMRT is a way to deliver focal radiation. Other types of brain tumors such as brain metastases might be treated with whole brain radiation or a highly focused type of radiation called stereotactic radiosurgery. In trials of brain metastases, none of the radiosensitizing drugs tested to date have proven beneficial. For glioma, the chemotherapy temozolomide can be radiosensitizing.
Question about pleomorphic xanthoastrocytoma.
Just diagnosed with pleomorphic xanthoastrocytoma, should I see a specialist or is treatment fairly standard?
Dr. Lee: I would recommend seeing a neuro-oncologist as this is a rare type of brain tumor. Treatment typically involves surgical resection. Radiation and/or chemotherapy are sometimes considered for tumors that recur or that cannot be completely resected.
Question about stage 3 anaplastic astrocytoma.
Initially diagnosed with stage 3 anaplastic astrocytoma over a year ago. 80% of the tumor was removed followed by radiation and chemo pills. MRI two months ago found no sign of the tumor. The oncologist seems surprised. How common is it that the tumor is not able to be located after treatment and does this affect the initial prognosis?
Dr. Lee: Most anaplastic astrocytomas stabilize with treatment. It is uncommon to have a “complete response” to treatment. This suggests that your tumor may be more responsive to treatment and I suspect you will continue to do well but it is hard to quantify exactly how this changes prognosis.
Question about the latest in effectively crossing the blood brain barrier for brain metastases.
Are there any advances in designing drugs that cross the blood brain barrier for brain metastases? Engineering?
Dr. Lee: Engineering drugs with better brain penetration is an active area of research. Two examples of drugs designed to cross the blood brain barrier and that have been tested in patients with brain metastases from breast cancer include TPI-287 and GRN1005. TPI-287 is a chemotherapy that can cross the blood brain barrier and is designed to circumvent a protein on the surface of cancer cells that pumps foreign substances out of cells (including chemotherapy). GRN1005 is a chemotherapy attached to a special protein which allows it to cross the blood barrier more readily.
What are some of the earliest symptoms of brain metastases?
Dr. Lee: Symptoms depend on the locations of the brain metastases. Some patients present with nonspecific symptoms like headache or confusion. Other patients will present with focal neurologic deficits (such as weakness) or seizures.
Prophylactic cranial irradiation for small cell lung cancer.
I have small cell lung cancer; radiation to prevent spread to the brain has been recommended but from what I have read this seems questionable? Should radiation be used to prevent spread of lung cancer to the brain?
Dr. Lee: There have been several studies examining the role of prophylactic cranial irradiation (PCI) in small cell lung cancer. For patients with limited stage small cell lung cancer, PCI can decrease the incidence of brain metastases and prolong survival and is therefore recommended. For patients with extensive stage small cell lung cancer, PCI can decrease the incidence of brain metastases although whether it prolongs survival is uncertain. Therefore, PCI might be recommended in select patients with extensive stage small cell lung cancer, such as those who have had a complete or very good response to their initial chemotherapy.
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