On a sweltering July day in 2012, Sue Scott and her mother, Sharon, sat on metal chairs in a doctor’s office with no pictures on the wall, no curtains, no carpet and no sense of comfort or permanence, waiting to meet the oncologist who would tell them if Scott’s cervical cancer had returned and whether it had spread.
The 36-year-old real estate agent from Takoma Park thought she had beaten cervical cancer once, after a combination of external radiation, internal radiation and low-dose chemotherapy made her tumor undetectable by a CT scan. But she began to experience sudden abdominal pain three months later, and a doctor found suspicious-looking cells on her cervix. A PET scan was ordered to get a better look at what was happening in her body.
About a month after she was diagnosed, Scott had asked her radiation oncologist what would happen if the regimen did not work. The oncologist mentioned exenteration, a nearly medieval-sounding procedure whereby her vagina, bladder, colon and rectum would be removed — along with her reproductive organs — to rid her body of the cancer.
“So basically you would cut off my lower half and stick my legs back on?” Scott would later recall saying, punctuating her words with a contagious giggle. Her humor and affection for the absurd helped sustain her and those who cared for her through the darkest moments of her disease.
But there was no doubt her condition was serious. At first, she barely allowed herself to entertain the notion of such a surgery. As time went on and the painful cramps kept her awake at night, she began to wonder if it was her only chance.
When the doctor finally entered the room that July day, he told them the news was not good: The cancer had spread to Scott’s lymph nodes. Even exenteration would not be an option. The room fell silent.
Scott looked over at her mother, who sat frozen.
Then she looked back at the doctor. She asked him about her treatment options.
“Well,” he said. Then came a long pause. The doctor’s eyes reddened with tears.
“There have to be options,” Scott said finally. “So, I could have more radiation?” No. She had already received the maximum amount of radiation anyone could have, he told her. “So, chemo?” No. There is no chemo that can beat metastatic cervical cancer, he answered.
The silence grew heavier.
Scott is not sure how long she had cancer, but it may have started in her 20s, when she began noticing an unusual vaginal discharge. She said she saw her primary-care doctor annually, but never received a diagnosis and was not referred to a gynecologist for follow-up.
After her doctor retired, Scott put off finding a gynecologist, thinking there was nothing more to be done to diagnose her problem. About three years passed. In the summer of 2011, she began to see discharge that contained specks of blood. She was diagnosed with a 1.5-inch-long adenocarcinoma, an aggressive type of cancer, on Halloween of that year. Doctors who treated her later told her the cancer had probably been growing for years, possibly a decade or more.
Her cancer was a type caused by the human papillomavirus, the most common sexually transmitted infection. Experts say a majority of adults, both men and women, get HPV at some point. Often the body clears the infection on its own, but certain strains of HPV can linger and lead to cancers of the cervix, throat, anus, penis, vagina and vulva.
Cervical cancer infects some 12,000 women in the United States each year and kills more than 4,000. With regular screening through Pap smears and HPV tests, cases of cervical cancer have dropped considerably in recent decades, but experts say not all women get screened, and cancers are sometimes missed even in those who do.
In June 2012, eight months after Scott was diagnosed with cancer, her mother was found to have uterine cancer and had her uterus removed.
Shortly after Scott learned that her cancer had spread, she met with the surgeon who had performed her mother’s hysterectomy. He recommended a hysterectomy for Scott, said any cancerous organs or lymph nodes should also be removed, and told her about an immunotherapy trial at the National Institutes of Health Clinical Center in Bethesda. It was an experimental approach, and risky. But there was a chance — however slim — that it would work.
The idea behind immunotherapy is to use the patient’s immune system to attack tumors, in hopes of solving what until now has been an impossible medical riddle: how to kill off cancer once it has spread.
The first serious attempt at immunotherapy as a cancer treatment was described in a medical journal in 1893, but successes were minimal and doctors remained doubtful of its potential for most of the next century.
But some advances, particularly over the past decade, have begun to change the perception that metastatic cancer is a certain death sentence.
“The big breakthrough leading to all this enthusiasm is the work on checkpoint inhibitors,” said Miriam Merad, professor of oncological sciences at the Icahn School of Medicine at Mount Sinai in New York.
Checkpoint inhibitors work by eliminating the disguise that allows cancer cells to hide from the immune system, and big pharmaceutical companies are investing in these drugs to treat cancers of the brain, lungs, kidneys, skin and other organs.
The other main breakthrough has been with killer T-cells, or lymphocytes. Scientists select T-cells that had been attacking the tumor, grow more of them in the lab and give them back to the patient in huge numbers. This revamped immune system has helped some patients with melanoma or leukemia see their cancers disappear and stay gone for years.
“It is really providing phenomenal hope and enthusiasm among immunologists and also oncologists who never believed before in immunotherapy,” Merad said.
“So, for the first time, we think it is possible to cure the disease or maybe transform the disease into a chronic disease, and this is why everyone is very excited about it,” said Merad, who was not involved in Scott’s treatment.
However, the process can be toxic and the cost of treatment can be high. Even more, the outcome is anything but certain. It works in some people but not others, and doctors have yet to figure out why.
“It is definitely not mainstream,” said Stephanie Blank, an oncologist with New York University’s Women’s Cancer Program.
Blank said she has referred some of her advanced cancer patients to clinical trials for immunotherapy, with mixed results. “I can’t say I’ve had anyone have a great response in the trials,” she said, aside from one woman who lived longer than expected but eventually succumbed to ovarian cancer. That has not dulled her hope, however, in what she sees as a promising field of research.
Multiple approaches to immunotherapy are now being tested in clinical trials. The one Scott learned of is run by Christian Hinrichs of the National Cancer Institute and is based on an approach for melanoma developed by his boss, Steven Rosenberg, chief of the surgery branch of the institute, which is part of the NIH.
Hinrichs’s work focuses on the T-cells, white blood cells that target two specific HPV proteins and kill any tumors driven by the virus, effectively destroying the cancer as if it were a viral infection.
The process involves extracting a patient’s tumor and isolating some of the immune cells that had failed to destroy it. (Those fighter cells, called tumor-infiltrating lymphocytes, or TILs, are grown in a lab until there are billions of them that are later infused back into the patient.)
After the tumor is removed, a seven-day regimen of intense chemotherapy wipes out the patient’s immune system. “It makes immunological space for the new immune system that we grow in the lab and infuse back into the patient,” Hinrichs said.
Rosenberg’s most recently published data on 93 melanoma patients treated with TILs shows that 52 responded to the therapy. Twenty of the 52 saw their cancers disappear, though one had a recurrence after 19 months. The rest have remained cancer-free for five to nine years.
When Scott first contacted Hinrichs in October 2012, he told her his trial had had promising results in one of the four patients who had gone through his regimen. Those weren’t great odds, but they were better than no chance of survival at all.
Scott probably had less than a year to live, doctors said. At least seven tumors were growing throughout her body. One was on her liver; another, the size of a plum, was protruding from her belly. There was a tumor near her colon and another that had begun blocking off one of her ureters, which carry urine from the kidney to the bladder.
“Even if it doesn’t work for me, maybe the doctors will learn how to help the next woman who ends up here,” Scott wrote to friends and family in her Christmas letter that year, describing how she had decided to, in essence, donate her body to science.
“Maybe this is the final gift I can offer the world.”
At first, NIH refused to enroll Scott in the trial, citing the blood clots in her lungs and the multiple tumors. There was concern that she might not be able to withstand the arduous treatment.
So Scott hand-wrote a letter, filled it with confetti and addressed it “To the kind, heart-led, wise, hard-working and (I’m guessing) dashingly good-looking team of doctors in charge of my fate. From a gal who had an unfortunate string of events that led me to VBC (very bad cancer).” Since it was election season, she also wrote on the envelope: “Vote ‘yes’ on question Sue Scott!”
The personal approach was memorable, but Hinrichs said it did not influence the team’s decision. It wasn’t until January 2013, after her clots stabilized, that she was accepted into the trial.
The tumor on her liver was surgically removed so the team could isolate the fighter cells and grow them in the lab. In March, she endured the week of prescribed chemo.
Her hair fell out. She felt nauseated nearly all the time. When the lab-grown cells came, they arrived in an IV bag that looked like it contained condensed milk. It held 75 billion tumor-infiltrating lymphocytes.
“The infusion of the newly altered TILs was not painful and didn’t take very long at all,” Scott said.
The next morning, she began the second phase of the treatment, which involves doses of interleukin-2, a hormone that encourages the TILs to grow, every eight hours.
By the fifth dose, Scott had to be given oxygen day and night.
Scott’s team of supporters grew, as people from her church prayed for her and friends, relatives and others sent her cards, which soon filled the walls of her hospital room.
After a few weeks, she was able to walk out of the NIH Clinical Center, and went home with her mother to recuperate.
A month later, she went back for CT scans of her chest, abdomen and pelvis and an MRI scan of her liver. Hinrichs told her the tumors had shrunk significantly. In particular, the tumor on her abdomen was no longer visible on the scans.
Scott hadn’t felt that spot since she first realized it was there; she had not wanted to touch it. On learning it was gone, she burst into tears.
Two months after the treatment, she returned to NIH again for scans. They revealed no sign of cancer. Sue began giggling and crying, hugging everyone in the room. Sharon felt as though she could fill her lungs for the first time in years.
Hinrichs released the first results of his trial at an oncology meeting in May: Two of nine patients — Scott and a woman in the Midwest — had seen their metastatic tumors disappear. One of the nine initially responded to treatment but the improvement did not last beyond a couple of months. The others’ cancers continued to advance, and some have died.
The results have not yet been published in a scientific journal. So few patients have been treated that it’s too early to give a success rate, project a survival time or say when the experimental treatment might become widely available.
And doctors will not call this a cure, preferring to use such words as “complete and ongoing response.”
Scott’s “response is still the fastest, but both patients responded in the same way, and it is really how long that response holds up that is important,” Hinrichs said.
For Scott, the physical healing far outpaced the mental recovery. She and others in the small but growing ranks of metastatic cancer survivors must overcome post-traumatic stress and the depression that accompanies serious illness; they also must find ways to pay bills that have stacked up and grapple with a life that is not the same as before. For Scott, who is not married, that includes coming to terms with being post-menopausal while most of her friends are having babies.
“My life is very different than I thought it would be, very different from anyone my age,” Scott said. “But my gratitude for a second chance at life far exceeds any grief I have over the losses cancer cost me.”
Scott returns to the NIH Clinical Center for scans every few months. Her last appointment was in late October, almost three years to the day since she was diagnosed. Her scans showed no sign of cancer.
Sheridan is a health writer for Agence France-Presse in Washington.