New Technologies, Holistic Treatment Approaches for Brain Cancer Emerging

Glioblastoma accounts for 49.1% of all primary brain tumors in adult patients, with a 5-year survival rate of 6.8%.¹ Treatment developments had remained mostly rigid in this space, but new technologies and holistic approaches to treatments have allowed physicians to take incremental steps toward better outcomes for these patients.

For Brain Cancer Awareness Month, Targeted Oncology^TM sat down with Charles Redfern, MD, for a discussion on recent changes to the field and how helping patients navigating their treatment, ideally in one location, can make a huge difference in tackling toxicities that arrive with treatment.

Redfern, medical director of the Laurel Amtower Cancer Institute and Neuro-Oncology Center at SHARP Healthcare, also highlighted the continued and improved use of tumor treating fields, such as the FDA approved wearable and portable device Optune.² By using low frequency electrical fields emitted from pads on the patient’s head, patients can get continuous treatment while continuing to be active. This is given alongside temozolomide chemotherapy after surgery and radiation are completed in patients. However, Redfern highlights the potential for this device at different points of treatment.

Charles Redfern, MD

Medical Director

Laurel Amtower Cancer Institute

Neuro-Oncology Center at SHARP Healthcare

While the growing use of immunotherapies and identifying genomic alterations in these patients are showing more promise, institutions like SHARP are also looking at approaches to holistic treatment. Redfern discusses how giving patients the ability to have all their needs addressed at a single cancer center can be just as impactful as the treatment decisions a physician has to make.

Targeted Oncology: What are some of the biggest changes to the treatment landscape in the past few years?

REDFERN: I mainly only see adult patients [with brain cancer], and I'm fortunate enough to work in a neuro-oncology center where we have great surgeons, great radiation oncologists, and a great support staff. Probably the main change over the past few years that I have [observed has] been surgical techniques. I'm not a surgeon, but surgical techniques [have improved] with the wide availability of pre-operation MRI and MRI guided surgery, and Optune—also called tumor treating fields [TTF], which are low frequency electrical fields placed in padded arrays on patient’s heads—[being used more]. Those are probably the biggest changes in treatment of adults with glioblastoma in the past several years, which is the main brain tumor in adults. Optune has become a standard of care, and it's a new technology that doesn't exist for any other type of cancer.

Are there any studies looking at these new technologies?

In adults with aggressive brain tumors, typically surgery, radiation, and a type of chemotherapy [are the standard treatments] and then TTF is probably the newest change. There have been 2 randomized studies that show survival benefits [for these patients],^3,4 which is why the FDA approved it. Now, the current study is looking at [the use of TTF] upfront in conjunction with radiation and chemotherapy.⁵

What emerging targets are there in the brain cancer population?

[One of the targets] being investigated that has not been proven yet [includes] EGFR because it is heavily overexpressed and heavily amplified in many adults with aggressive brain tumors. We have drugs that target it in the rest of the body, but whether it can be effectively targeted in the brain is unclear.⁵ And if you can target in the brain, can you really change the behavior of brain tumors? That's been the subject of many previous studies and there are more ongoing studies.

How has immunotherapy impacted treatment decisions for patients with a glioblastoma?

Probably the biggest growth field in oncology is immunotherapy, which has so far [had] a single, very large, randomized licensing study in patients with glioblastoma multiforme [GBM] that did not show a benefit of immunotherapy [in this patient population]. People are still pursuing this, I think with good reason, but there are a lot of studies of immunotherapy and trying to [use it in] different ways in the brain. And in the brain, specifically with primary brain tumors, you always have the extra added issue of whether the drug really gets to where you want it to be.

Is there a role for next-generation sequencing (NGS) in this patient population?

The other huge field in oncology is molecular diagnostics and personalized therapy...for certain patients with brain tumors. It's not on the National Comprehensive Cancer Network [NCCN] guidelines, and I always go back to guidelines because I think that's important as those are vetted by a lot of agencies. So, it’s not currently on guidelines, but I get NGS in most adults with an aggressive brain tumor. I get that from the time of diagnosis, because...we may need to know that information in 6 months, or in 2 to 3 years. Is there a driver mutation? Is there a DNA change in that GBM specimen we wouldn't have expected? And is there a drug available in an intravenous or oral form that can potentially target that?

We're fortunate enough [at my institution] to have a study through a [third-party] company that gets patients to a basket trial. [For example, if] the patient has a DNA change, like a BRCA mutation in their brain tumor, then we can get a PARP inhibitor on study in that basket trial to the patient, when they need it. Both parts of that have been big changes—the NGS is a big change, and then getting access to a drug to target [the mutation] because most of these drugs are not approved in patients with brain tumors, and you need to be able to get your hands on it easily for the patient.

Have there been survival improvements for patients on these targeted treatments?

In EGFR targeting, not yet, but there's a lot of studies still for EGFR targeting. With immunotherapy, not yet, but there are hints of that. There are more studies looking at immunotherapy in the brain and that's because...it's hard to get drugs [to affect the brain], and it's an immune privileged area where the immune system is not the same there as it is in the rest of the body.⁷

With NGS, we've certainly seen that with disease that has spread to the brain these drugs are very active, but that's a different kind of disease state than a primary aggressive glioblastoma in the brain. [Ultimately,] we don't know yet. I have patients I've put on treatments based on NGS, and I think they're working, but those are only case studies.

How do you handle toxicities in adult patients with cancer?

Our neuro-oncology center was set up to treat patients with state-of-the-art care at their regional or community hospital. We help with care at 3 large community hospitals, so everybody can get the right neurosurgery at their hospital, the right radiation, chemotherapy, and TTF at their regional hospital near their home. This allows patients to stay at home and not travel, as many of these patients have disabilities. They have disabilities from the brain tumor and from surgery and radiation, so it allows them more time at home.

If we get them on a clinical trial, we're trying to do it in that community hospital setting, and not make those patients travel 50 miles or more for that. That was one of the reasons our neuro-oncology center was started as a lot of patients have full-time care needs that land on their spouse, their brother, their sister, or their child. We think that they get better...access because it's easier [to get to treatment]. That's important because a lot of these patients have fragmented care in the past [where they get] surgery in 1 place, radiation in another place, and then their brain scans someplace else. Those places are all good, but they're not talking to each other, and there's nobody who knows what's going on, and there's nobody in charge of their [case], so that's what we've tried to fix.

We think that's a hugely important issue, and now you're starting to see...[in other disease states] that patients are getting their care scattered all over the place and no one knows what's going on, which is probably a bigger impact than the newest drug you can get for the patient. We're big believers in treatment [near] home…. But that takes a huge commitment from your hospital too, patients need a nurse navigator, a social worker, and you have to have the radiation, surgery, and everything else there.

Do you have any advice for community oncologists that may treat patients with brain cancer?

My advice [would be] not so much for the radiation oncologist, but for the medical oncologist because they may see 1 or 2 patients [like this] per year. It's not a very complicated treatment from our part. We know the medications that are available, and other aspects are pretty much provided by radiation oncology. So, you need to know current therapy and be able to provide a lot of supportive care...and it's helpful if the hospital can assist or manage a lot of those supportive care services.

Do you need that at every hospital? No, but it's nice to have that in any medium-sized city, because for a patient who travels back and forth for an hour or 2 hours for [apointments], it's hard. They have physical disabilities, mental disabilities, and financial issues to have to do that, so removing the travel issues is a big assist. Some of these patients can do well; we know from all these therapies and good supportive care, the prognosis in general is not great, but patients are doing better. That's the history of oncology, is not a wonder drug but it's incremental improvements in everything, that's true for almost every cancer.

^References:

^{1. About glioblastoma. National Brain Tumor Society. 2023. Accessed May 10, 2023. https://bit.ly/44VOqMe}

^{2. Treating GBM: what are the treatment options for GBM. Novccure. 2023. Accessed May 10, 2023. https://bit.ly/42K0heg}

^{3. Guzauskas GF, Salzberg M, Wang BC. Estimated lifetime survival benefit of tumor treating fields and temozolomide for newly diagnosed glioblastoma patients. CNS Oncol. 2018 Jul 1;7(3):CNS23. doi: 10.2217/cns-2018-0010}

^{4. Rominiyi O, Vanderlinden A, Clenton SJ, et al. Tumour treating fields therapy for glioblastoma: current advances and future directions. Br J Cancer. 2021 Feb;124(4):697-709. doi: 10.1038/s41416-020-01136-5}

^{5. In recurrent GBM, the efficacy and safety of Optune monotherapy were compared with physician's choice of chemotherapy. Novccure. 2023. Accessed May 10, 2023. https://bit.ly/3nLQBkJ}

^{6. Hatanpaa KJ, Burma S, Zhao D, Habib AA. Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance. Neoplasia. 2010;12(9):675-84. doi:10.1593/neo.10688}

^{7. Sampson JH, Gunn MD, Fecci PE, Ashley DM. Brain immunology and immunotherapy in brain tumours. Nat Rev Cancer. 2020;20(1):12-25. doi:10.1038/s41568-019-0224-7}