From Small Things

How a single patient and his mother built a transformative rare-cancer research and advocacy organization.

By Misha Angrist featured image Axel Dupeux/Redux Pictures

In late 2005, while at home on Christmas break, Duke University freshman Josh Sommer started getting headaches. Really, he says, it felt more like one long, unrelenting headache that left him in nearly constant pain for weeks on end. After that winter break, he had an MRI, which revealed a one-inch tumor in the center of his head. His mother, Simone, an experienced physician, took the call from the radiologist. At that moment, she says, “My world changed.”

Josh’s formal diagnosis — clival chordoma — would come a few months later, during his surgery; he was among the fewer than one in a million American chordoma patients identified every year. Chordomas arise from remnants of the notochord, the embryonic backbone — no one knows why. They can occur anywhere along the length of the spine, from the sacrum all the way to the base of the skull. Median age at diagnosis is 60 years, but chordomas can appear at any age.

Josh’s chordoma had arisen from the clivus, a bone at the base of the skull. His tumor was pressing on his brain stem and wrapping around two critical arteries. Later he and his mother would learn that it had penetrated the dura, the tough outer membrane covering the brain and spinal cord.

Neurosurgery, like real estate, is all about location. And it was clear from Josh’s scans that his tumor was in a bad one: It would be difficult to access and remove completely without disturbing any other brain structures or their blood supply. But doing so would be essential — because with chordoma, “the best chance of surgery impacting the long-term natural history of the disease is the first operation,” says Johns Hopkins neurosurgeon and researcher Gary Gallia. Those who wind up needing multiple surgeries fare demonstrably worse. Thus, the Chordoma Foundation’s patient services manager Shannon Lozinsky says, it’s terribly important to help newly diagnosed patients with “getting it right the first time.”

In Josh Sommer’s case, getting it right the first time would be difficult.

Maternal Instincts and Smarts

But Josh had an enormous advantage and a not-so-secret weapon: his mother. Not only was Simone an experienced family physician, she had a graduate degree in public health and experience in research and clinical advocacy. She became a fierce, indefatigable advocate for her son, someone who was uniquely equipped to interrogate the relatively new world of skull-based surgery in great depth and figure out which path to take. She immediately dropped everything and focused on scouring the country to find the best treatment options for Josh.

Josh and Simone Sommer (front row, third and fourth from left) at the First International Chordoma Research Workshop in May 2007.

Josh and Simone Sommer (front row, third and fourth from left) at the First International Chordoma Research Workshop in May 2007.

To that end, she visited a number of top-tier cancer clinics. At Massachusetts General Hospital she met with Norbert Liebsch, a specialist in the burgeoning field of proton beam radiation, a more powerful and precise form of radiation than X-rays. Liebsch had already treated hundreds of chordoma patients with proton beam therapy. He told her that, in a few days, there would be an international neurosurgery conference in Arizona that would include a fair number of surgeons with experience treating chordoma. Simone drove home to North Carolina and then got on a plane to Arizona.

At the conference she was unnerved by the graphic videos of various high-risk neurosurgeries that she saw. “By day I was a professional physician,” she says, “but by night I was an emotional, worried mother.”

But then she heard a talk by the pioneering neurosurgical team at the University of Pittsburgh Medical Center (UPMC), led by Amin Kassam and Carl Snyderman. Their approach was to penetrate the nose and septum rather than to go through the skull. Impressed, Simone took Josh to Pittsburgh. There, guided by real-time MRI, the surgeons could view the tumor in three dimensions. They went in through Josh’s nose, deconstructed his sinuses, and were able to access the tumor completely from the front — without having to drill any new holes in his skull. The UPMC team was able to get all of Josh’s chordoma without causing any further neurological or vascular damage. Not all chordoma patients are so fortunate.

“By day I was a professional physician, but by night I was an emotional, worried mother.”

Despite the complete resection of his chordoma, Josh spent the next few months recovering and dealing with complications, including cerebrospinal fluid that drained into his stomach and lungs. Simone continued to look after her only child. “She was incredibly strong,” Josh says. “And she was very savvy and very thorough. She was really watching over me.”

While Josh recovered, Simone had a lot of time to read about chordoma. Although there wasn’t all that much to read, what she and Josh learned alarmed them. Many clinicians and researchers believed chordoma to be benign. At the same time, not only was median survival seven years, but both surgery and subsequent radiation came with risks. Equally disturbing, they discovered that almost no one was studying the disease. Simone learned of a familial chordoma study at the National Cancer Institute, whose investigator pointed her to the only U.S. grant-funded chordoma researcher at the time: medical oncologist Michael Kelley, who worked at the Veterans Administration in Durham, North Carolina, directly across the street from Duke University, where he is also on the faculty.

Simone called Kelley. The Sommers and another patient, Johnny Nelson, met with him on a Sunday afternoon for three hours. From that meeting, they identified some of the big obstacles: funding, access to tumor tissue, and access to cell lines.

Simone vowed to find additional funding and to gather whatever tissues and cell lines she could from labs around the world. Meanwhile, despite having no experience, Josh went to work in Kelley’s lab. And he immediately had a project: Around the time of Josh’s surgery, Simone saw a paper in a pathology journal from Adrienne Flanagan’s lab in London. It identified a gene that seemed to be strongly expressed in chordomas but not in other cancers. Could this gene, called T and encoding a protein called brachyury, be a reliable diagnostic? Or maybe even a drug target?

To begin to figure that out, Kelley and his young protégé would have to examine the gene’s behavior in tumor cells: What happened if you turned the T gene off or turned it down in a chordoma cell line so as to eliminate the production of brachyury? Josh spent months on this, without success. The problem was that of five would-be chordoma cell lines, only one could actually be considered chordoma. One was not even human — it was derived from a mouse; others were not malignant.

“These were honest mistakes,” says Josh of the faux chordoma cell lines. “But they were mistakes that were made over and over and over again in lots of different tumor types.” And they made doing chordoma research almost impossible.

The Sommers made developing reliable chordoma cell lines — and tissues and animal models — an explicit goal. And there were countless other infrastructural, logistical, and resource challenges. Defeating a rare cancer was one monumental task; getting a nonprofit up and running from a standing start was another.

The Chordoma Foundation (CF) incorporated in early 2007. At the end of its first year of operation it was still based out of Simone’s house in Greensboro. It had $220,000 in revenue.

It was a start, but the Sommers were going to need a lot of help.

Building Blocks

Much of that early help would come from Sharon Terry, the president and CEO of the Genetic Alliance and the parent of children with a rare genetic disease (as well as a member of Genome’s advisory board). The Genetic Alliance is an umbrella patient advocacy organization representing more than a thousand rare-disease organizations. Terry, who had never heard of chordoma, rarely has the time to commit to helping early-stage patient advocacy groups with the nuts and bolts, but the CF struck her as an exceptional case.

“Simone was so obviously driven by immense love for her son and other [patients],” says Terry, who, along with lawyer Ron Johnson, helped the foundation get off the ground. “She was so savvy that I knew she would leverage everything I offered to the max.”

Terry introduced Simone to Francis Collins, then the director of the National Human Genome Research Institute at the National Institutes of Health; he too was not familiar with chordoma. But after Simone called him (“Chutzpah is in my genes,” she says), she and Josh met with a small group in Collins’s office in December 2006 and surveyed the chordoma landscape, which was still fairly barren. “Josh and I presented a compelling argument why studying this obscure, neglected tumor was important and necessary to save the lives of [chordoma patients],” says Simone.

“About half the people at the first workshop had not studied chordoma before. It was almost like watching the field being born.”

Simone proposed a chordoma research workshop; NIH said yes and that it would take about a year to organize. Simone pushed back. “I said that my son has a disease where median survival is seven years … so, you know, can we do it in six months?” The workshop took place less than five months later.

That first gathering, says Josh, was decisive. There was great enthusiasm from the small coterie of people already working on chordoma, but much of the agenda involved explaining what chordoma was to most everyone else. “About half the people at the first workshop had not studied chordoma before,” Josh says. “It was almost like watching the field being born.”

There were other challenges, too. Simone had invited patients and many felt blindsided. “That was the first time many of them were hearing that they had a malignant cancer rather than a benign tumor,” she says. “Some were very angry.”

The research agenda had begun to coalesce, but the CF was still finding its way. Enter Heather Lee.

In 2007, after Lee’s young son Justin Straus had his fifth recurrence, his mother was scouring the internet for information about chordoma, as she did regularly. Two organizations popped up. One was the Chordoma Research Foundation (CRF) in New Jersey, a small group run by Bruce and Lynette Nelson, whose son Johnny had chordoma. The other was the Sommers, with whom the CRF would soon throw in its lot. Lee reached out.

“I remember one day my mother and I were kind of lamenting that we really needed to find someone who’s got some nonprofit experience,” Josh says. “And then a few days later we got an email.”

In that email Lee described Justin’s situation. And by the way, said Lee, she and her husband had done a lot of nonprofit work and how could they help.

“Within three days, Simone and Josh were at my house for dinner,” Lee says. A few months later, she was on the CF’s board, which eventually began to have regular meetings, some at her dining room table. Josh grew close to the precocious Justin, who gave a moving speech to chordoma researchers and patients in April 2008. He succumbed to his chordoma only a few months later, at the age of 13.

“He was a tough young man,” says neurosurgeon Chandranath Sen, who treated Justin. “An amazing young man.”

Meanwhile, the narrative surrounding Josh — “young man and his mother search for a treatment for his cancer” — was getting media attention. In early 2008, after seeing an article in the Chicago Tribune, producers from the Today show invited Josh and Justin to share their story. For the Sommers, this kind of exposure was key to their larger goals of raising funds to accelerate research and, they hoped, find a cure.

The Pivot

“My mother used to tell me I was one in a million,” says Bill Dorland. “Little did she know.”

After his chordoma diagnosis, Dorland, a professor of physics at the University of Maryland, took advantage of his access to the university library to read all of the chordoma papers he could find. In the early 2000s he began frequenting an online chordoma patient support group on the late Microsoft Network (MSN) and eventually became one of its moderators.

In fall 2006 Dorland and a few other members of the MSN group decided to attend the annual meeting of the National Organization for Rare Disorders (NORD). “We all came to this thing with a combination of financial resources, energy, ideas, empathy, and compassion,” says Dorland. “And then Simone showed up like a force of nature. It was clear, even then, that she was already looking up the food chain. She was ahead of the game.”

By the time of the NORD meeting Dorland had read enough painful stories on the chordoma forum to know how lucky he had been. “There were a hundred things that went well for me that didn’t go well for many other patients.” But he too had been through the ringer: an initial surgery, a relapse, a second surgery, proton beam therapy, and treatment at multiple institutions. He and his wife had experienced insurance problems firsthand: sacral chordoma surgeries were not routinely reimbursable. “I had gold-standard medical coverage but still had to pay tens of thousands of dollars for my treatment.”

Those experiences convinced Dorland that the CF’s focus should be on improving patients’ lives rather than on pursuing the dream of a cure or even researching more effective treatments, which, at the time, seemed to him to be hopelessly out of reach. “I was used to working on hard physics problems for 20 years, where everything is a dead end, so I thought it was irresponsible to focus on a cure for chordoma,” he says. “I thought the chances of us figuring out our own disease were zero.”

“Bill Dorland was the sand in the oyster,” says Heather Lee. “Many of us were so focused on the science that we didn’t prioritize a pivot to patients. Bill convinced us to pivot.”

The first Chordoma Community Conference aimed primarily at patients took place in 2008; there have been nine since.

More Models

On the research side, the CF has laid out a road map where each step is meant to move patients closer to better treatment. It begins with the same emphasis on resource development — cell lines, animal models, and genomics — that Simone and Josh first pursued in the early days, when there was but a single chordoma cell line. Today, thanks in large part to the CF’s Cell Line Prize, there are 12.

Similarly, chordoma researchers have long recognized the importance of so-called patient-derived xenografts (PDXs). These are mouse models in which patient tumor samples are implanted in immune-deficient mice. PDXs are essential, says Gary Gallia, of Johns Hopkins, because “tissue is different once it leaves the body and gets in a petri dish.” PDXs mimic the environment of a human tumor and are a more realistic proxy for drug testing than cell lines.

Gallia’s group published the first chordoma PDX in 2012; the CF then funded the Hopkins team to test drugs against it. Since 2015 CF-funded researchers have engrafted more than 20 tumors — all from samples donated by patients — in mice; Josh hopes to reach 50 by the end of 2017. Also in development is a genetically engineered mouse model that can reproduce the various genetic alterations found in chordoma.

Trial by Trial

Brachyury, the protein that Adrienne Flanagan’s lab identified in 2006 as a potent biomarker for chordoma, has continued to cast a long shadow over chordoma research — and for good reasons. Brachyury is activated in all chordomas, and chordoma cells cannot survive without it. Almost all non-Asian chordoma patients carry a variant in the brachyury gene, compared to less than half of the general population. If brachyury isn’t a smoking gun, it is at the very least a piping hot one.

And not only in chordoma, says Chris Heery, an oncologist who was a clinical trialist at the National Cancer Institute (NCI) from 2012 to 2016 (he is now chief medical officer at the Danish pharmaceutical startup Bavarian Nordic). “We know that patients with epithelial cancers — lung, colon, ovarian, breast — that have high levels of brachyury all have worse prognoses.”

After arriving at the NCI, Heery ran a trial for a yeast-based vaccine, manufactured by a company called GlobeImmune, targeting brachyury in epithelial cancers. The trial was predicated on the idea that heat-killed yeast, genetically modified to express brachyury and thereby play the role of Trojan horse, could safely provoke a vaccine-like immune response in cancer patients.

A few months after the trial had begun, Heery was asked to speak about immunotherapy to an NCI leadership advisory committee comprised of patient advocates. “The people there knew about immunotherapies [but when it came to brachyury] they didn’t know what I was talking about,” he says. With one notable exception.

“Josh Sommer came up to me and said, ‘I want patients on your trial.’” Heery had attended Duke as an undergraduate and was familiar with Josh’s story. “We wrote an amendment and over the next few months we enrolled 13 chordoma patients.”

Bill Dorland was one of them. Dorland had had multiple aggressive recurrences since his initial diagnosis in 2004; by late 2012 he had two new large chordoma tumors and was running out of options. While continuing to seek aggressive treatment, including radiation, which he received in March 2013, he also met with palliative care specialists. In July 2013 he enrolled in the yeast vaccine trial.

Initial expectations for the brachyury vaccine were low — it would take time to build the immune response. “Chordomas grow so slowly,” says Heery, “we thought it could take eight months or a year before we saw anything.”

By the time the trial ended, slightly more than half of the patients had had a confirmed immune response. And two patients saw their tumors shrink dramatically.

Dorland was one of the two. Within five months of his enrollment in the trial, his primary tumor shrank by more than 30 percent. Heery and the NCI team suspected that, in the case of Dorland and the other patient, the combination of the vaccine and recently administered radiation was enough of a one-two punch to have had a real effect. Unfortunately, in December 2015, Dorland learned that he had two new tumors, which meant that he was no longer eligible for the yeast vaccine trial.

Heery sought out another trial for Dorland; he found one for a so-called checkpoint inhibitor — a drug that can interfere with cancer cells’ ability to inhibit the immune system. (See “A Shot Against Cancer?” on page 44.) Dorland was on it for three months, before, as had happened in the vaccine trial, aggressive growth in one of his tumors rendered him ineligible to continue. The next several months brought an aborted surgery and lots of watching and waiting.

But in October 2016 his fortunes turned — again. In the space of just a few weeks the tumor that had been growing so aggressively shrank by more than 20 percent. He sent Josh an email: “I’m back from the brink.” Exactly why remains a mystery: Perhaps the checkpoint inhibitor had finally kicked in.

Scans at NIH and Johns Hopkins in late 2016 and early 2017, respectively, brought even better news. NIH investigators, says Dorland, found the recent results “shocking ­— in a good way.” And while he can’t say how long it will last, “it’s very welcome.”

A Life of Its Own

Last summer Heather Lee was diagnosed with gastrointestinal cancer. Ironically, she wound up getting proton radiation treatment in Boston at one of the same clinics that treated Justin. She credits her experience with the CF for helping her to manage her own care and for giving her the courage to enroll in a clinical trial. Her doctors say her prognosis is good, although some days are better than others. “No recovery is linear,” she says. “But a little more linear would be awesome.”

In July 2010, after four years of 24/7 devotion to the CF, Simone chose to step away. “I’m glad that my efforts have benefited many people and that some aspects of my vision and innovative ideas have continued,” she says.

Dorland is grateful for Simone’s early insistence on pursuing research toward better treatment. He’s also glad she didn’t shy from the word “cure.” “She saved my life twice,” he says.

“I think it’s a real testament to what she did,” says Josh, “that [the Chordoma Foundation] has a life of its own now.”

That life includes more than $3 million invested in research and, by sometime this year, 10 full-time employees. In the last two years the CF’s Patient Navigation Service has offered one-on-one assistance to some 500 chordoma patients and their loved ones. In the next 18 months it will have launched seven clinical trials. In 2016 the CF raised $4 million, which is commendable, says Josh, but he envisions $10 million worth of research in the next three years. The CF’s accomplishments so far are great, but, as he often says, “not sufficient.”

For Dorland, who is helping to spearhead a new online chordoma community, that progress reflects the efforts of many. Their work will help to sustain and grow a small but dedicated community of patients, doctors, and researchers who give patients with ultra-rare diseases hope and make them feel less alone.

“We are,” he says, “better together.”

This article has been updated to reflect new 2007 revenue numbers and new 2017 employee numbers and research revenue at the Chordoma Foundation.