Proton Therapy for Leptomeningeal Metastasis Could Be a Major Advance

MSK radiation oncologist Jonathan Yang, who specializes in treating metastatic cancer.

Jonathan Yang says proton therapy appears to be significantly more effective than conventional radiation at treating leptomeningeal metastasis.

Leptomeningeal metastasis (LM) is a serious condition in which cancer spreads to the fluid and tissues surrounding the brain and spinal cord. This complication can have devastating effects, causing pain, seizures, difficulty thinking, and a loss of muscle control. Treatment with chemotherapy or radiation can slow progression of LM, but most people with this condition have lived six months or less.

Now Memorial Sloan Kettering Cancer Center (MSK) radiation oncologist Jonathan Yang reports that proton therapy, an advanced form of radiation therapy, is effective in controlling LM. Proton therapy uses charged particles called protons rather than the standard X-ray approach that are used in conventional radiation therapy. Proton therapy enables doctors to direct cancer-fighting energy to precise locations within the body.

Proton Therapy for LM: Clinical Trial Results

On June 6, 2022, Dr. Yang presented encouraging results from a phase 2 clinical trial at the annual meeting of the American Society of Clinical Oncology. In LM patients who received proton therapy (also called proton craniospinal irradiation), the disease remained stable more than three times longer compared with those who got conventional radiation. (This measurement is called progression-free survival.) Those who received proton therapy also lived more than one and a half times longer than those getting standard radiation.

Results were so dramatic that the trial was closed early so that proton therapy could be made available to others with LM as soon as possible. This finding could potentially benefit a growing number of people with cancer. LM has become more commonly diagnosed due to improved imaging techniques and because people are living longer with metastatic cancer.

“It’s very exciting that we have an effective new option for a disease that is very hard to treat,” Dr. Yang says. “The choices have traditionally been limited for leptomeningeal metastasis, but this approach gives us a much better way to control the disease.”

The study involved MSK patients with lung or breast cancer whose disease had spread to the fluid and tissues around the brain and spinal cord. They were randomly assigned to receive either proton therapy or conventional radiation treatment. People who received proton therapy had a median progression-free survival of 7.5 months compared with 2.3 months for those receiving conventional radiation. Those who received proton therapy lived a median of 9.9 months, compared with just 6.0 months for those receiving conventional radiation. Side effects were similar between groups.

Breast Cancer Patient Shows Remarkable Improvement

One person in the trial receiving proton therapy was Denise Morton. In 2020, at age 56, her breast cancer appeared to be under control. But she started having trouble walking straight and experienced blurry vision, muscle weakness, and nausea. She came to MSK and learned she had LM, which had spread from the primary tumor. Dr. Yang proposed this clinical trial, and Denise received 10 proton treatments in late 2020 and early 2021 at the New York Proton Center in upper Manhattan. (The facility opened in 2019 and is operated by MSK and two other institutions.)

It's very exciting that we have an effective new option for a disease that is very hard to treat.
Jonathan Yang radiation oncologist

Almost two years later, Denise says she’s doing remarkably well and has no evidence of LM. She plays solitaire and does crossword puzzles to keep her mind sharp, and she enjoys being around family where she lives on the Shinnecock Reservation in Southampton, New York. She hopes to get back to her job as a direct care worker with developmentally disabled people.

She recommends proton therapy to anyone considering the treatment.

“I would tell anyone to go for it because I don’t see any downside,” she says. “I didn’t feel anything — there was no discomfort, no lightheadedness, no pain. And the follow-up care with the team is very good. You’re going through something difficult, but everyone is so nice and professional, and they work closely with you to support you.”

MSK Is Developing Novel Therapies for Leptomeningeal Metastasis

Dr. Yang says he and other researchers at MSK are studying molecular information gathered during the trial so they can better select who is most likely to respond to proton therapy. The next step is to validate proton therapy in a larger group. Dr. Yang has been consulting with other institutions to collaborate on a phase 3 trial.

“If these results bear out in a larger group, it really could be practice-changing for people with the condition,” he says.

Apart from testing proton therapy, MSK has been a leader in finding new ways to tackle LM. Dr. Yang says working with colleagues dedicated to solving this condition is very gratifying. He cites his close collaborator, neuro-oncologist Adrienne Boire, who has devoted her research to finding ways to block cancer cells from surviving once they enter the leptomeningeal space. Her studies in mice have already produced promising results.

“We’re very lucky to be at a center of excellence where we can develop novel therapies for patients with dire needs,” Dr. Yang says. “There are multiple treatment options in clinical trials, and there could be some really exciting things coming out in the next few years.”

Key Takeaways
  • Leptomeningeal metastasis (LM) is a complication of cancer.
  • It occurs when cancer spreads to fluid and tissues surrounding the brain or spinal cord.
  • Proton therapy is an advanced form of radiation therapy.
  • It appears to work better than conventional radiation at treating LM .

Dr. Yang discloses the following relationships and financial interests:

Stock and other ownership interests  - Nanocan Therapeutics

Consulting or advisory role - AstraZeneca; Debiopharm Group; Galera Therapeutics; Nanocan Therapeutics

Research funding - AstraZeneca; Kazia Therapeutics; X-RAD Therapeutics