As Emerald Cromwell battles a rare adrenal cancer, she learns two close friends have the same disease.
As Emerald Cromwell battles a rare adrenal cancer, she learns two close friends have the same disease.
Emerald Cromwell kept repeating the statistic in her head – one in a million. Her family had joined her for this first-ever trip to Moffitt Cancer Center, each unwilling to believe that Emerald — their wife, daughter, sister — could possibly be that “one.”
But the nurse in her knew something was seriously wrong.
For months, she'd written off the added pounds to approaching 40; the shortness of breath to the stress of being laid off at work. For her first job interview in years, she'd put on a pair of heels and soon noticed the swelling in her ankles and feet.
"Being a nurse," she said, "I kind of freaked out" thinking of potential cardiac issues. It would take two ER visits and the persistence of a physician (and former colleague) to obtain CT images of a mass above one of her kidneys in the adrenal gland. Friends of friends sent those images to Moffitt. Her brother went online searching for information on adrenal masses. More common than you might think, he told her, but the odds of being cancerous? Slightly less than one in a million.
Five days later – the day after her 40th birthday – Cromwell and her family crowded into an exam room, waiting to meet Ricardo Gonzalez, a surgical oncologist at Moffitt.
"He immediately said, 'I'm sorry this is happening to you,' " she recalled with a catch in her voice. "That's when I knew this was bigger than I thought."
As he sat across from her with her hands in his, Gonzalez explained how the mass – nearly 4 inches by 5 inches – was compressing organs and creating a large blood clot in the inferior vena cava, the vein that carries blood from the legs and lower body to the heart. Its sheer size and location could only mean it was adrenocortical carcinoma, or ACC.
"There's no cure for this cancer. That's the first thing I need you to know," he said. "We're going to try to shrink this by hitting it with the 'big guns.' "
All Cromwell could think was, "I'm 40! I can’t have cancer. I have two kids to raise!"
Moffitt is the only National Cancer Institute-designated comprehensive cancer center based in Florida, attracting patients from all over the country to be treated for such "one-in-a-million" cancers.
As the leader of Moffitt's Endocrine Oncology Program, Julie Hallanger-Johnson, MD, knows just how rare and devastating that diagnosis can be. "These people stay in your mind," she said. "They are special patients."
Asked how many she currently treats, the doctor ticks through a list of names in her head to tally seven patients in recent months.
Julie Hallanger-Johnson, MD
As Cromwell would learn through the course of her care, she was not as alone as she thought. Two friends from her St. Petersburg neighborhood received treatment at Moffitt for the same cancer, and all three women were diagnosed in the past six years.
"It's just very strange," said Hallanger-Johnson. "There has to be something. There has to be a reason for this, and I think they all feel that way, too."
Cromwell is not content to write this off as a coincidence or statistical quirk. "We may never get the answer," she said. "But my goal is to raise awareness. There's something making us sick."
From October 2015 through April 2016, Cromwell soldiered through chemotherapy, knowing the odds were roughly 50/50 that her tumor would respond to a chemotherapy regimen of powerful drugs called etoposide, doxorubicin and cisplatin. Not a cure, the chemo's only benefit would be to shrink her tumor. Six rounds of the stuff was no picnic, but the encouraging scans kept her going. As the tumor shrank, the goal of surgical removal inched closer to reality.
Surgery with Gonzalez was scheduled for Good Friday 2016, a good omen to Cromwell's Greek Orthodox family. The complex operation went well – the mass was excised along with one kidney. And though internal bleeding landed her back in the OR the following day and in ICU for a week, she progressed to the next step in her care plan: radiation therapy, five days a week for six weeks ("worse than chemo") followed by three years on an adrenal-suppressing drug called mitotane, a derivative of the banned pesticide DDT, to blast any remaining cancer cells.
Cromwell endured it all with the goal of beating one last set of odds: Overall five-year survival rates for those with ACC are just over 50/50.
One of the perverse quirks of having a cancer diagnosis is how suddenly everyone you know wants to share their cancer experience. "You get all these texts and phone calls," Cromwell explained, "and it's very hard to respond." She opted to reveal her diagnosis to friends on Facebook, counting on posts to reduce retelling her story over and over.
Little did she realize the surprising posts she'd get in return. "A girl from high school that I was friends with reached out to me and said 'Hey, my sister Elisa has the same cancer and she was treated at Moffitt. Here's her number. Please call her.' But I just couldn't. I knew her. I was friends with her sister. But I just wasn't ready – it was too close to home."
It was about to get much closer.
On the one-year anniversary of her surgery, Cromwell's cellphone rang with a familiar number. It was her best friend, Shannon Jager. Inseparable since kindergarten, the two had attended the same schools, married best friends, got pregnant at the same time and watched each other raise their children from houses four blocks apart.
Cromwell could tell immediately something serious was up. Jager, the picture of health, sounded winded. "She said, 'Hey, I'm supposed to jump on a plane for a work trip tomorrow and I just want to run something by you. I'm having these symptoms and I'm really short of breath. My doctor said it's OK to fly, but I just don't feel right.' "
"And in my head, I thought, well that sounds like everything I had," recalled Cromwell. "But there's no way. There's just no way." Ever the nurse, she advised her friend not to board that flight. Fearing a pulmonary embolism – a blood clot in the lung – that is easily discounted in healthy, young adults, Cromwell knew a long flight could be dangerous, even deadly.
Jager heeded her friend's advice, cancelling the trip and instead heading back to her doctor's office for an ultrasound the next day. Sure enough, it showed the clot – and more. An adrenal mass. When Jager called to relay this news, Cromwell immediately headed to the hospital to meet her friend.
"I was scared they were going to biopsy her," she said. You have to be careful about puncturing a gland that produces adrenaline. And since these masses often are not truly solid (more like the consistency of an egg yolk), puncturing with a needle can potentially disseminate tumor cells throughout the abdomen.
"Just as I walked in, the doctor arrived and said, 'We're going to get a biopsy,' " she recalled. "And I politely said, 'Let's send her to Moffitt.' "
Jager was added to Hallanger-Johnson's mental list of ACC patients and began the same protocol her best friend knew so well.
By the time she'd reconnected with Cromwell, Elisa Hughes was already coming off the medication for her ACC. They'd grown up in the same neighborhood. Elisa's younger sister had been in the same class as Cromwell and Jager throughout school. As kids, Hughes and Jager had even taken dance classes from the same instructor.
It was Cromwell's Facebook post about her own diagnosis that had prompted the phone call from Elisa Hughes' younger sister and eventually brought the women back together.
Hughes was diagnosed at age 42 after years of debilitating migraines, leg cramps, heart palpitations and feeling like she couldn't eat because she was always full.
"Clearly, there was no room," she said, "because I had a tumor the size of a basketball in my belly."
PLAY ELISA'S AUDIO
She remembered the day she finally got the CT scan that led to her diagnosis. "You know when you walk out and the staff is sitting at a computer looking at the image? I happened to turn around and I saw this big black thing in my abdomen," said Hughes. "I don't know anything about anatomy, but I figured that's not good."
It took two surgeons and hours in an operating room at St. Anthony's Hospital in St. Petersburg to remove the 22-centimeter, 5-pound mass from Hughes' adrenal gland in January of 2013. "It was all encapsulated, thank God," said Hughes. Initially, her St. Petersburg physicians thought the mass was an adrenal tumor called a pheochromocytoma, which is usually benign. It wasn't until the pathology report came back days later that they learned it was this one-in-a-million cancer called ACC.
When Hughes wound up at Moffitt for her first appointment, the seriousness of it all hit her. She and her mom had visited Moffitt often enough – Hughes' father underwent a stem cell transplant at the cancer center for multiple myeloma. "But when I walked in and saw all those people, I looked at my mom and my face just went white," said Hughes. "It hit me – I really have cancer."
Her scans have been clear ever since the tumor was removed. But to be sure no malignant cells had escaped the encapsulated mass, Hughes went through nearly three years of treatment with mitotane and steroids, up to 20 pills a day. She returned to work, her refuge, five months after surgery.
"For me, cancer was the thing that I didn't want to talk about a lot," she said. "I wanted to be at work so I didn't have to think about it."
While Hughes pulled in, Cromwell seemed bent on finding answers. "I'm glad she's the type of person who can take this on," Hughes said of her friend. "If it's not some extremely random universal coincidence – which it seems, how could it be? – then someone needs to figure this out just so people can be mindful of their health."
Elisa Hughes, Patient #1:
Hughes grew up in the Azalea neighborhood of St. Petersburg, attending the same schools and dance classes as Emerald Cromwell and Shannon Jager. Diagnosed with ACC at age 42, Hughes had a 5-pound mass removed from her abdomen in 2013.
Emerald Cromwell, Patient #2:
Cromwell's childhood home in the Azalea neighborhood of St. Petersburg was like a second home for friend Shannon Jager. Trained as a nurse, Cromwell was initially worried about heart issues when she was diagnosed with ACC the day after her 40th birthday.
Shannon Jager, Patient #3:
Classmate and close friend to Emerald Cromwell, Jager watched her battle through chemo, surgery and radiation for ACC. When Jager developed shortness of breath before a business flight, she reached out to her nurse friend for advice and soon found herself facing the same diagnosis.
HIGH SCHOOL CONNECTION
HIGH SCHOOL CONNECTION
In April 2017, Cromwell she set up a Facebook page centered on one element she shared with her two friends: high school.
The Boca Ciega High School Cancer Awareness Page solicits posts from alumni who've been diagnosed with any form of cancer – not just ACC.
"I initially thought it was the school because there were some renovations done in the years we were there," she said, recalling asbestos removal workers garbed in protective gear passing the kids walking through dust and debris. "Since they don't know the cause of adrenal cancer, I guess any and everything can't be ruled out."
That includes the Azalea neighborhood of St. Petersburg where all three women grew up. The area made local headlines in 2008 when Azalea residents Linda and John Swartout filed a class-action lawsuit involving a nearby site that had been home to an electronics manufacturer and a defense contractor for more than 50 years.
News organizations had reported that toxins such as lead, toluene, vinyl chloride, dioxane and trichloroethylene had seeped into the groundwater, raising questions of a "cancer cluster. " The Centers for Disease Control and Prevention (CDC) defines a cancer cluster as:
A greater-than-expected number of cancer cases that occurs within a group of people in a defined geographic area over a period of time
Suspicions are one thing. Proving a cancer cluster – and finding its cause – is a totally different issue that can take literally years to resolve, if ever.
Through her Facebook posts, Cromwell befriended Cheryl Jozsa, another cancer cluster sleuth. Jozsa's sister Terri was diagnosed with a form of leukemia, and Jozsa became her donor for a bone marrow transplant at Moffitt in 1999. After Terri died, Jozsa learned of other cancer patients in Terri's graduating class at the now-demolished site of the old Bradenton Bayshore High School in Manatee County. Several classmates, like Terri, have died from a variety of cancers. The Manatee County School Board maintains that soil tests near the site have repeatedly turned up negative for contaminants.
It's taken more than a decade of investigating and the help of epidemiologists from the University of North Carolina. But in 2017, Jozsa and her supporters were able to convince the Florida Department of Health to begin collecting data about a possible cancer cluster on the old school site. A report on that data is expected later this year.
Yet Jozsa knows even that may not yield the answers she's seeking
Start telling the story of multiple people in one location with a rare cancer, and epidemiologists like Peter Kanetsky, PhD, MPH, are liable to react with a combination of excitement and dread.
The chair of Moffitt's Cancer Epidemiology Department, Kanetsky said the excitement comes from thinking about why and how diseases occur within a given population – the essence of epidemiology.
And the dread? "It's knowing that your chances of identifying a cause are slim to none," he said.
Cromwell and her fellow ACC patients were the topic of discussion at Kanetsky's twice-monthly Cancer Epidemiology Teas several times in recent years. These informal get-togethers are open to Moffitt faculty in any clinical or research department who might want to talk through questions or ideas related to epidemiology. Hallanger-Johnson went to discuss these ACC cases despite knowing that Moffitt's epidemiology team doesn't investigate clusters.
"That type of thing is more on the level of the Centers for Disease Control and Prevention or county health departments," she explained. "But having a patient [like Cromwell] who is such an advocate to find out 'why' really gets you to pay attention."
The discussion prompted Moffitt epidemiologist Travis Gerke, ScD, to sift through data from the Florida Cancer Data System, a statewide registry of all types of cancers. At least this data could show how many ACC cases are being seen in Florida, county by county, and a spike might confirm cancer cluster suspicions.
Instead, the numbers show the limits of such data.
As Gerke explained, the state registry has a complete data table of all 3.3 million cancer diagnoses in Florida, grouped into five-year "buckets." Specific to ACC, the entire state averaged 20 new diagnoses per year in the most recent time frame – about what you'd expect for a state with 20 million residents.
Break that down by county and the numbers begin to skew, showing one of the quirks inherent in the database. Cases are listed by the county where they are diagnosed. So a county like Hillsborough with the state's busiest cancer center will have higher numbers than a rural county.
To further confound matters, think of Florida's massive snowbird population – people who retire to the sunshine after decades in other states or countries. Whatever they might have been exposed to elsewhere may take years to lead to a cancer diagnosis that gets counted in Florida.
"This really speaks to the challenge of cluster-based research," said Gerke. "People are so mobile these days, moving frequently and usually not staying where they were born or grew up. Unless you have collected fine-grained information about where they've lived over decades, it's really difficult to connect cases to exposures."
Gerke said the data can be filtered to show where a particular patient was born. For instance, the data show that, from 2011 through 2015, the number of Florida-born and Florida-diagnosed ACC patients was just six.
So, while there's no compelling evidence for a cluster of ACC diagnoses in the area where Cromwell and her friends grew up, it also doesn't disprove the existence of a cluster.
"What we can say is limited by the data itself," Gerke explained. "People who lived in the same neighborhood may have moved, may have been diagnosed in other states and have had their adrenal cancer accounted for in another state's registry."
It's a more common fear than you might realize. More than 1,000 suspected cancer clusters are reported to public health agencies across the nation each year. The U.S. Centers for Disease Control and Prevention (CDC) defines a cancer cluster as "a greater-than-expected number of cancer cases that occurs within a group of people in a defined geographic area over a period of time."
Each element of that definition includes criteria that must be met before a group of cancer cases can be considered a cluster:
A greater-than-expected number occurs when the observed number of cancer cases of the same type, is higher than one would typically see in a similar setting, and is scientifically proven to have the same cause.
That occurs within a group of people — the cancer occurring in a carefully defined population, which may include factors such as race, ethnicity, age or gend
In a geographic area — the boundaries must be defined carefully. It's possible to "create" or "obscure" a cluster by selection of a specific area.
Over a period of time — the time period over which the case occured.
Sometimes, Gerke noted, those most impacted by the suspected cluster will take it upon themselves to gather more specific data, to "build a cohort of data among themselves." That's what Cromwell and a newly energized handful of colleagues are now working on: a website, complete with a tracking map and an online survey to self-report cases of ACC or other cancers among those who've lived in the Azalea neighborhood or attended Boca Ciega High School.
It seemed the least they could do, in memory of one of their own.
Shannon Bossert Jager was just 42 when she passed away on Jan. 6, 2018. She'd battled ACC for seven months. Despite all the chemo, her tumor never shrank enough to be surgically removed. It just kept growing. She left behind an adolescent daughter and two stepdaughters, a loving husband, a grief-stricken family and a huge community of friends who came to know and love her through her years of good work for a variety of nonprofit groups in Pinellas County.
Among the mourners: her best friend Emerald Cromwell.
Cromwell got the news by phone while attending a speech by Erin Brockovich, the cluster crusader whose story became a blockbuster movie of the same name. Brockovich built a legal case against Pacific Gas & Electric Company that, in 1996, resulted in a $333 million settlement for more than 600 California residents sickened by contaminated water – the largest toxic tort injury settlement in U.S. legal history.
Brockovich had just met Cromwell and Manatee County activist Jozsa and urged them to continue their efforts when the fateful phone call came. It was a sign not lost on Cromwell.
"Shannon's passing really shook up this community," said Cromwell, "and I promised her I would do this. My determination has just grown."
One in a million – From NCI: Adrenocortical carcinoma (ACC) is a rare tumor that affects only 0.72 persons per 1 million population.
EDP response rates – Combination Chemotherapy in Advanced Adrenocortical Carcinoma ... www.nejm.org/doi/full/10.1056/NEJMoa1200966
Class action lawsuit: From The Tampa Tribune – July 27, 2015 "Raytheon bought the 1950s manufacturing facility at 1501 72nd St. N. from E-Systems in 1995 and inherited a site contaminated with toxins such as lead, toluene, vinyl chloride, dioxane and trichloroethylene that had seeped into the groundwater.
Jostes [Commercial Development Company CEO Randall Jostes] said CDC's environmental consultants are satisfied the property is ready to redevelop after Raytheon's substantial remediation efforts, which have been approved by the Florida Department of Environmental Protection. Raytheon will continue to keep and monitor groundwater wells in the area."