Roger Stupp, MD
The National Comprehensive Cancer Network (NCCN) made history when it updated its glioblastoma treatment guidelines in March. The group became the first learned body to endorse the routine frontline use of an entirely new treatment modality known as tumor-treating fields (TTFs).
The Optune system, a wearable device that the FDA initially approved in 2011 for glioblastoma following tumor recurrence, now carries an NCCN category 1 recommendation in combination with radiotherapy and temozolomide for patients who have undergone surgery.1
The technology uses low-intensity electrical fields to disrupt tumor cell division, and it represents the biggest step forward against glioblastoma in more than a decade. A phase III trial published last December in the Journal of the American Medical Association
) found that using TTFs in addition to temozolomide extended median progression-free survival (PFS) by 2.7 months and median overall survival (OS) by 4.9 months over temozolomide alone.2
Investigators are currently exploring TTF—and at least 2 related technologies—against a wide variety of additional tumor types in hopes that this new modality may prove as broadly effective as immunotherapy, or even chemotherapy.
Novocure, the company that developed Optune, is testing the technology in approximately 30 ongoing studies, including pivotal phase III trials in patients with pancreatic cancer (PANOVA-3; NCT03377491), non-small cell lung cancer (NSCLC) with up to 10 brain metastases following radiosurgery (METIS; NCT02831959), and stage IV NSCLC (LUNAR; NCT02973789).
More than 20 cancer centers throughout the world are studying Novocure’s TTF therapy, according to the company. The technology uses electrical fields that alternate 100,000 to 300,000 times per second; electromagnetic frequencies targeted to specific tumor types are 150 kHz for pancreatic cancer and NSCLC to 200 kHz for glioblastoma and ovarian cancers.3
Those frequencies are below those used in x-rays and slightly above those in ultrasound (Figure
If effective, TTF therapy would likely complement other treatment types rather than replace them. Trials to date suggest that it would be safe to use with other modalities because its adverse events (AEs) do not mimic those of other therapies. Indeed, trials to date have found limited AEs associated with TTFs. The most prevalent AE associated with TTF in the glioblastoma trial was mild-to-moderate skin irritation from the transducer arrays that attach to the patient’s head.
Nevertheless, the use of electromagnetic currents as anticancer therapy is far from widespread adoption. Its success requires not only demonstrable efficacy against many tumor types but also eventual acceptance by skeptical oncologists.
“Chemical and electrical processes are both important to the body’s operation, but medicine has always focused so much on the chemical side that the idea of treating disease with electricity still seems vaguely crazy to most people, including a lot of doctors,” said Warsito P. Taruno, PhD, who developed an electrical field system after his sister developed breast cancer.
Taruno’s sister has survived until now, so he continued developing the technology at CTECH Laboratories, a company based in Jakarta, Indonesia, that he runs. CTECH lags market-leader Optune, but Taruno believes that the modality will be a large enough industry to support many companies.
“It actually makes more sense to treat cancer from an electrical perspective rather than a chemical perspective because cancer tends to be chemically stable and electrically instable,” Taruno said. “In theory, it should be possible to disrupt the electrical activity in many cancers and force tumors to commit suicide.”
Figure. Tumor-Treating Fields in the Radiofrequency Spectrum
A Growing Body of Research
The idea of using electromagnetic fields to treat cancer dates back at least as far as the 1920s, when investigators demonstrated that ultrashort wavelengths initially spurred rapid growth and then tumor destruction in plants.4
It wasn’t until the 1990s, however, that investigators found a practical use for electromagnetic fields in cancer treatment: radiofrequency ablations for hepatic cancers.5
In the study, a needle electrode was advanced into the tumor for the delivery of a high-frequency alternating current. Although surgical resection was still favored, the results showed radiofrequency ablation of unresectable tumors provided local disease control.