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Immunotherapy Targets Tumors’ Genetic Characteristics

Sue Hallowell hikes the Alps in July 2019. She gets immunotherapy treatments every three weeks to keep her cancer under control.

Immunotherapy Targets Tumors’ Genetic Characteristics

A photograph of Sue Hallowell in July 2019 shows her on a peak in the Alps, rolling hills and snow-capped mountains behind her, a camera strapped around her neck and her hiking poles raised triumphantly in the air. The only sign of the cancer that was once growing rapidly in her body is her mouth, asymmetrical from two surgeries to remove tumors from her gum, jaw and cheek.

Just months before the 66-year-old woman hiked Tour du Mont Blanc, a trail of about 100 miles that passes through Switzerland, Italy and France, Hallowell received chemotherapy at Sibley Memorial Hospital for an aggressive form of head and neck cancer that had metastasized in her lungs.

As chemo got the disease under control, she was concurrently placed on immunotherapy, an IV infusion regimen that activates the immune system to detect and attack tumor cells.

Earlier in her treatment, doctors tested Hallowell’s tumor and found that it expressed two predictive genetic markers that meant she would likely respond well to immunotherapy.

One was a “high tumor mutation burden,” which makes it more likely that the immune system can recognize it as a foreign body and attack it. The other was a high level of PD-L1, a protein that acts as a “brake” for immune cells that are attempting to fight the cancer, says Karim Boudadi, a medical oncologist at the Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital and an assistant professor of oncology at the Johns Hopkins University School of Medicine.

Hallowell takes an anti-PD-L1 immunotherapy drug that disables the protein’s brakes so that the immune system can fight the disease and its mutations.

After a few months on this regimen, with the cancer under control and the tumors in her lungs no longer detectable, Hallowell was taken off the chemo in April 2019. She continues to receive immunotherapy treatments every three weeks, with minimal side effects, and received one round of radiation in August 2019 to help keep her condition stable.

Studies show that immunotherapy is effective for at least two years and perhaps longer, at which point continuing the therapy is evaluated on a case-by-case basis.

“The prognosis for metastatic head and neck squamous cell cancer is definitely improving thanks to immunotherapy,” says Boudadi, one of a few clinicians in the region who specialize in this treatment.

Hallowell was first diagnosed with squamous cell carcinoma in October 2018 after a periodontist performed a biopsy on an ulcer on her gum that had doubled in size in two weeks. After learning it would take more than a month for an appointment with a doctor near her then-home in Hershey, Pennsylvania, she called Johns Hopkins at her daughter’s suggestion. Two days later, she saw Johns Hopkins head and neck surgeon Rajarsi Mandal, and surgery was scheduled within 10 days. It would be Hallowell’s first-ever surgery.

Mandal successfully removed the ulcer and reconstructed her mouth, but the tumor recurred soon after in her cheek. Even after a second surgery, the disease continued to progress, spreading to her lungs in a matter of weeks. Hallowell was put on chemo to keep the disease from spreading further.

The most common side effect of immunotherapy, which Boudadi also uses to treat other oral and throat cancers, is mild fatigue. Rare autoimmune reactions include inflammation of the skin, pancreas, bowels and lungs.

Hallowell says she gets a headache and sometimes feels tired on the night following an infusion of immunotherapy. But, she’s quick to add, those conditions are bearable.

“The side effects [of immunotherapy] are so minor that they’re unrecognizable compared to what the chemotherapy was doing to me,” Hallowell says. “It’s a night-and-day difference.”

Metastatic head and neck squamous cell cancer is the seventh most common cancer in the world, with about 50,000 new cases diagnosed annually in the United States, according to the National Institutes of Health.

Risk factors for this kind of cancer include smoking and having had human papillomavirus (HPV), although Hallowell didn’t smoke and tested negative for HPV. While she initially presented with a mouth ulcer, other symptoms can include difficulty or pain with swallowing, a hoarse voice, mouth sores, swelling or a lump in the neck, ear pain and hearing difficulty, depending on where the tumor originates.

While metastatic head and neck cancer is a serious diagnosis, Hallowell says she never worried because the doctors never gave her reason to. She also wasn’t worried about having her first surgery at age 65.

“It was more, ‘Okay, what can I do now? What do I do next? Let’s get this lined up in a hurry and get this over with,’” she says. “It wasn’t until April that it was mentioned I had a ‘scary’ cancer. It’s a good thing I didn’t know. I might have been worried.”

The avid hiker, runner and triathlete says that, since her diagnosis, she no longer puts off anything she wants to do. In addition to completing her 100-mile European hike, she recently took her kids and grandkids — a total of 11 people — on a cruise she says she booked during her “chemo fog.”

“We all had a good time,” she says. “Most of us had never been on a cruise before, so that was an experience for everyone.”

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