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APPs should encourage utilization of tumor treating fields for glioblastoma
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Editor’s note: HemOnc Today’s regular columns for advanced practice providers (APPs) tackle common issues APPs face, discuss day-to-day practice and regulatory concerns, and share research advances. To contribute to this column, contact Alexandra Todak at stodak@healio.com.
Advancements in the field of neuro-oncology seem to occur all too infrequently.
Perhaps the most significant contributing factor to this is the limited prognosis that comes with neuro-oncologic diagnoses — especially glioblastoma, with its median OS of just 16.7 months.
Initial standard-of-care treatment for glioblastoma is tailored to the patient and depends on several factors, including age, performance status, and size and location of the tumor.
Maximal surgical resection is ideal, as it increases PFS while decreasing mass effect and tumor burden. Surgery should be followed by 6 weeks of standard fractionated external beam radiotherapy given concurrently with adjuvant temozolomide, as this further improves PFS.
The aggressive nature and heterogeneous resistance of brain tumors, combined with the generally slow timeframe in which new clinical trials are authored and approved, does not allow much time for the development of novel treatment breakthroughs.
Although molecular sequencing, targeted agents and immunotherapy offer promise in this arena, nonconventional treatment modalities should be included in the neuro-oncology clinician’s treatment algorithms.
Tumor treating fields
Tumor treating fields (TTF) — delivered through the Optune (Novocure) device — is one such modality that interrupts mitotic cell division in glioblastoma via low-intensity alternating electric fields.
Treatment is delivered while the patient wears transducer arrays that contain numerous ceramic discs. These arrays are connected by wires to a battery pack that the patient carries in a backpack.
Researchers conducted the randomized EF-14 trial of 695 patients with newly diagnosed glioblastoma who concluded chemoradiation. The trial compared TTF plus standard-of-care maintenance temozolomide vs. temozolomide alone in a 2:1 randomization.
Results showed a statistically significant improvement in median PFS in the TTF-temozolomide group, although only by 2.7 months, from 4 months to 6.7 months. Similarly, median OS improved with the addition of TTF by 4.9 months, from 16 months to 20.9 months.
It is recommended that the patient wear the arrays at least 75% of the day to achieve maximum efficacy. Researchers derived this recommendation from a post-hoc analysis of the EF-14 trial, which showed the survival benefit increased as compliance increased (P = .031).
Patients who used the device 70% to 80% of the time achieved a median survival of 21.7 months. Patients who used the device more than 90% of the time achieved the longest survival, with a median OS of 24.9 months. However, even patients who wore the device as little as 50% of the time achieved an OS benefit (HR = 0.67; 95% CI, 0.45-0.99).
As this treatment is nonsystemic, the patient experiences no widespread systemic side effects, unlike most glioblastoma therapies. The most significant toxicity is dermatologic, with medical device-site reactions in the form of mild to moderate skin irritation occurring among about half of all patients.
The other obvious side effect is the device’s influence on patients’ daily routines. Patients must shave their heads frequently to minimize skin toxicity.
Although scarves and hats may be worn to cover the arrays, the impact on physical appearance sometimes deters patients from considering TTF as a treatment option. Further, patients are constantly tethered to the battery pack, which is still sizable despite recent design improvements.
APPs are well-suited to provide care for neuro-oncology patients utilizing TTF. Novocure — the company that manufactures the TTF device — has created a process by which APPs may prescribe TTF. APPs can capably manage side effects that patients may experience, from treating simple skin reactions to providing reassurance and support for body image issues and minimizing the negative impact on day-to-day tasks.
Disease awareness
Glioblastoma and its treatment were recently thrust into the national spotlight with the diagnosis of Sen. John McCain, who succumbed to the disease after only 13 months.
He underwent traditional therapy, including surgery and chemoradiation. Throughout his illness, Sen. McCain’s daughter, Meghan, advocated for increased funding for brain tumor research. Hopefully, the glioblastoma journey that McCain and his family so bravely shared with the world will help promote brain tumor awareness, as well as the need for continued clinical research that is so desperately needed.
We live in an era when big pharma and medical institutions are quick to tout “miracle” trial outcomes to mainstream media, sometimes without due process.
Patients with glioblastoma and their clinicians alike anxiously await any form of good news on the treatment front, and the research data showing extended OS by the addition of TTF to standard treatment is encouraging, especially given that the last therapy to show an OS improvement was temozolomide’s approval in 2005. Although a median improvement in PFS of only 2.7 months with TTF did reach statistical significance, this short benefit highlights that more work needs to be in done in this space.
Unfortunately, a stigma remains surrounding the device’s efficacy, and some in the neuro-oncology arena have been slow to adopt TTF into standard care, even with published evidence.
Although cautious, careful discernment is always prudent, we should remember that even agents such as methotrexate and cisplatin were once novel therapies. As APPs, those of us caring for neuro-oncology patients are in a unique position to promote the value of nonconventional treatments and encourage their utilization.
References:
Begley S. “John McCain has died. For brain cancers like his, ‘research is our only hope.’” STAT. Aug. 25, 2018. Available at: www.statnews.com/2018/08/25/mccain-glioblastoma-research/. Accessed on Oct. 5, 2018.
Perkins A and Liu G. Am Fam Physician. 2016;93:211-217.
Ram Z, et al. Abstract ACTR-27. Presented at: Annual Meeting and Education Day of the Society for Neuro-Oncology. Nov. 16-19, 2017; San Francisco.
Stupp R, et al. JAMA. 2017;doi:10.1001/jama.2017.18718.
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David L. Jennings II, MSN, RN, AGPCNP-BC, is a nurse practitioner at Levine Cancer Institute at Atrium Health. He also is a HemOnc Today Editorial Board Member. He can be reached at david.jennings@atriumhealth.org.
Disclosure: Jennings reports no relevant financial disclosures.