Making Rare Cancer Treatments Not So Rare

The Cancer Institute of Greenville Health System (GHS) is on the leading edge in nationwide clinical trials for new cancer treatment therapies focused on treating rare cancers.

The tumors in Lisa Smith’s lungs disappeared when she participated in a clinical trial through the GHS Cancer Institute.

Twenty years ago, Lisa Smith of Travelers Rest never dreamed the little girl she was teaching at her church would one day play a key role in her survival.

Smith, a 53-year-old wife and mother of two, had a lump on her jaw for years, but when it started growing in 2015, she sought medical help. The tumor was successfully removed at Duke University Hospital, but later scans showed the cancer had spread to her lungs. After she was told by the Duke doctor nothing else could be done for her, a series of events unfolded that would result in remission of her cancer.

That journey began with a conversation with Kelsey Tallon, who works at GHS Cancer Institute. The exchange led to Smith’s participation in a clinical trial of a new type of cancer treatment called immunotherapy, which uses the human immune system to find and attack cancer cells.

Calling on the Defense

In 1893, William B. Coley, MD, observed cases of cancer that went away after a patient contracted a bacterial infection. While he wrongly concluded that the bacteria destroyed the tumors, his lifetime of research paved the way for modern immunotherapies that are inspiring clinicians and researchers today.

Human beings begin life as a single cell. Through the process of cell division, we have around 37 trillion cells by adulthood. Cells divide for various reasons, including the replacement of old or damaged cells and growth. In the typical adult, nearly two trillion cells undergo division every day.

All cancers begin as normal cells. But something happens that causes these particular cells to grow out of control.

Historically, cancers have been treated with chemotherapy agents based on where they begin. More recently, the way cancer treatment is determined has undergone a paradigm shift. Now, rather than looking at where the cancer started, treatment is based on an individual tumor’s unique characteristics through a test called molecular profiling.

“GHS’ Rare Tumor Center is using molecular profiling to identify targets that can direct a physician to a specific treatment that may have more benefit than a general chemotherapy approach,” said Julie Martin, DNP, director of Cancer Research at the Cancer Institute.

Immunotherapy trials at the institute started in 2004 in the Phase 1 Clinical Research Unit with vaccine testing through an affiliation with the National Cancer institute. “We have become experts at managing patients for toxicity and side effects because of our experience with these trials,” Martin noted.

The immune system tracks substances normally found in the body and goes on the attack when it finds something that doesn’t belong there. That response can kill foreign substances such as germs—or cancer cells.

The problem is that the system doesn’t always recognize cancer cells as foreign. Immunotherapy works by helping the system identify the intruders, so they can be sought out and destroyed.

Immunotherapy can be used by itself or administered in combination with chemotherapy and/or radiation therapy. Because it does not affect all cells, it may cause fewer side effects than other treatments. Unlike chemotherapy, immunotherapy often is able to penetrate the shield that cancer cells sometimes hide under.

Something Better

Smith had a type of cancer called adenoid cystic cancer, found in her salivary glands in the left side of her mouth and neck. Salivary cancer is rare and usually associated with slow growth over years or even decades. With the spread of the cancer to her lungs, though, her oncologist at Duke had given her six months to live.

“When the doctor walks in and won’t look at you, you know you’re in trouble,” recalled husband Mark. “It was like there was an expiration date. You don’t want the sun to go down because you strike that day off. You have just spent another day from your precious finite number.”

Lisa was scheduled for a course of chemotherapy at Duke but was not offered much hope for a change in her prognosis. After repeatedly making the 580-mile round trip to Durham and paying for living expenses there, Lisa and Mark were relieved to find she could receive the chemo treatment in Greenville instead.

Just after their return to Greenville, the Smiths shared their story with their church family at Berea First Baptist Church and were overwhelmed with the response.

“We wanted to make sure that where God led we followed,” Mark said. “We were praying and, as we got up, I felt a hand on my shoulder. Surrounding us were 500 people, praying.”

Lisa continued the story. “The very next day, I received a text from a girl I had taught in a church class years before who now works at GHS Cancer Institute asking if she could talk with me. Within a few days, I had an appointment with Dr. O’Rourke.”

Mark O’Rourke, MD, is an oncologist with GHS Cancer Institute. “Adenoid cystic cancers typically follow the pattern of spreading to the lungs and then being very difficult to eradicate,” he explained. “In Smith’s case, the cancer metastases that were found in both lungs in 2016 would normally cause the cancer to be considered incurable.”

At the appointment, Lisa told Dr. O’Rourke her story. “I expected that he was going to suggest chemotherapy,” she remarked, “but he said, ‘I have something better for you.’ ” That something better was a clinical trial.

The Cancer Institute had developed a research trial for tumors like Lisa’s to see if two types of immunotherapies together can be helpful. Two classes of drugs, CTLA-4 and PD-1, had been approved by the FDA for some cancers but not necessarily for rare cancers like hers.

“I can remember the hopes of immunotherapy in the 1980s. Those hopes are being realized by these extraordinary drugs.” – Dr. Mark O’Rourke

“There has been a dramatic change in the oncology world in the last five years,” Dr. O’Rourke stated. “At first, it was just a few cancers under specific circumstances where these immunotherapies help. Now, there are a large number of cancers that they help, and the numbers are increasing.”

In December 2016, Lisa began receiving immunotherapy treatments once every four weeks, and they continued for one year. She now receives regular checkups.

“To our wonderful surprise, the nodules in her lungs were dramatically smaller at two months and even smaller after four months,” Dr. O’Rourke emphasized. “Of the lung nodules, about 20 got smaller and one got bigger. The nodule that grew was biopsied and removed in May 2017 and, since that time, she has been free of cancer to the best of our ability to detect.”

“Immunotherapy is exciting to physicians and researchers because of the impressive and dramatic responses we have seen some patients have,” commented Martin. “Having a success like Lisa’s is what keeps us jazzed up!”

Rare But Not Forgotten

Lisa was a candidate for the immunotherapy trial because she had a rare tumor for which there is no good conventional therapy, and it was the first immunotherapy trial anywhere for her kind of tumor. While there are a number of ways to define rare cancers, tumors that are fewer than 6 per 100,000 are ultra-rare and are the subject of the GHS study. Because they don’t occur in a large group of patients, rare tumors don’t receive the research funding of more common cancers such as breast and prostate.

Research and clinical trials continue at the Cancer Institute, where a comprehensive approach means trial participants are in the care of clinicians from many disciplines. Specialists in radiology, pathology, radiation oncology, surgical oncology, endocrinology and neurology participate in ongoing discussions about immunotherapy, developing individualized treatment plans for each patient.

Patients also are cared for through lifestyle programs to help with exercise, diet and the management of stress that comes with coping with cancer. These programs help those who are living with or previously treated for cancer survive and thrive.

“What we have now is not the be-all, end-all, so researchers continue to develop smarter drugs,” said Martin. “Although we are making cancer more of a chronic disease in many cases, we want it to be something we can eradicate.”

Meanwhile, Lisa Smith has a message that she’s eager to share. “I’m an ordinary person with an extraordinary story,” she reflected, “and I think everyone deserves that—not just to have today, but to have a tomorrow.”

At Lisa Smith’s last checkup, her ENT physician discovered a small tumor in her jaw, which was removed surgically in a delicate procedure to avoid damage to the facial nerve. Her oncologists are pleased that this tumor is the extent of her cancer’s progression in over a year. They will continue to watch her closely.

In 2014, the Rare Tumor Center became a reality thanks to a generous gift by Jerry and Harriet Dempsey. If you would like to support the vital work of the center, please contact Jim Kaltenbach, (864) 797-7734 or jkaltenbach@ghs.org.