It Takes a Lifetime to Survive Childhood Cancer

One night in 1981, in the middle of bath time, Marty Gonzalez noticed a strange glow that seemed to emanate from inside one of the eyes of her 9-month-old daughter, Marissa.

“It was really bizarre,” Gonzalez recalls. “It looked like a cat’s eye — like I could see all the way through.”

Though Marissa’s pediatrician in Long Beach, Calif., assured Gonzalez it was nothing, she sought another opinion.

While teaching her sixth-grade class, Gonzalez anxiously awaited news from her mother, who had taken Marissa to see a pediatric ophthalmologist. By lunchtime, with still no word from her mom, Gonzalez called the doctor directly. “I think it’s cancer,” the doctor told her.

Marissa, it turned out, had retinoblastoma, or Rb, a rare but aggressive cancer that almost exclusively affects children. Rb makes up only 3 percent of all pediatric cancer cases, which translates into about 300 children in the United States a year. Marissa had tumors in both eyes and needed immediate treatment: cryotherapy to freeze the malignancies and radiation to destroy them. Two days later, Marissa and her mother were on a flight across the country to see a specialist in retinoblastoma at Columbia University.

For Gonzalez, it all happened so fast. She was given no information on survival rates. She had no idea what would happen to Marissa’s vision if she lived. She didn’t know what the radiation, which would need to be administered every day for a month, might do to Marissa’s developing brain. She just wanted her daughter to live.

Childhood portraits of Marissa Gonzalez, right, and her mother, Marty, at the family home.

‘A Murderous Time’

Cancer is understood essentially as a disease of aging. Our body makes its own toxins, oxidants that damage our DNA. With every bite of food, every breath of air, each cell that divides, come tiny mutations that then accumulate. While most mutated cells are eliminated, at some point, a key cell continues to multiply uncontrollably and cancer develops. We essentially poison ourselves over time.

But childhood cancer, which often originates in utero, is fundamentally different in that it can progress before a child even begins to age. For most fetuses, the process of rapid growth doesn’t lead to cancer. But with all that cell division going on, occasionally there are mistakes. When those mistakes take place in certain cells, they’re like a ticking bomb hidden away in the fetus, often somewhere in the immune system. Those cells may stay hidden for years. Leukemia, the most common childhood cancer, manifests most frequently when children are about 3 or 4 years old and their immune system becomes more developed. But the originating cancer cell has been there all along.

For decades, a diagnosis of cancer in a child was a death sentence of the worst kind. Fewer than half of children diagnosed in the 1960s were still alive five years later.

Too many children still die of cancer, which is the second leading cause of death in kids ages 1 to 14. But the treatment of pediatric cancer is also considered one of modern medicine’s success stories. Over 85 percent of children diagnosed with cancer survive. There are currently about 500,000 survivors of childhood cancer — approximately one in every 750 people — alive in America today. These statistics may give comfort to the parents of the roughly 15,000 children who face a cancer diagnosis each year.

But the progress masks tough realities. That 85 percent survival rate for cancer is measured at five years. For a 76-year-old woman diagnosed with breast cancer, five years can feel like a reprieve. But what does a five-year survival rate mean for a toddler? And what are the long-term effects of cancer treatment — which can include radiation, chemotherapy, surgery, amputation and reconstruction — on the developing body and mind?

Fending off early death is a victory. What the next four or five decades are like remains a challenge, for patients and families and for doctors. Childhood cancer is rare, and research into its treatment remains underfunded; only 4 percent of federal funding of cancer research goes to pediatric oncology. Surviving cancer can affect a child’s entire developmental trajectory — physically and psychologically. There’s risk for hormone dysregulation and infertility, uneven limb length and lost muscle mass, hearing loss and brain damage.

A boy treated with radiation to the pelvis might retain a child-size pelvis and penis even as a grown man. A girl might have normal development in one breast and nothing in the other. Dr. Christopher Recklitis, the director of research and support services at the Perini Family Survivors’ Center at the Dana-Faber Cancer Institute in Boston, said some young women are surprised to be told at age 25 to “check their ovarian function because they may only have a few more years of fertility left. And they’re like ‘What are you talking about?’”

Clearly, a five-year goal post isn’t enough. Success in pediatric cancer must be rethought not as a short-term cure but as a lifelong recovery. “Our goal should be the next 10, 20, 30, 40 years,” said Dr. Douglas Hawkins, a professor of pediatrics at the University of Washington and chair of the Children’s Oncology Group, a coalition that unites the work of over 10,000 experts.

It’s taken decades to get to that challenge.

In 1956, Dr. David Nathan, president emeritus of the Dana-Farber Cancer Institute, began his oncology career at the National Cancer Institute. He administered chemotherapy to some of the earliest pediatric patients to receive the treatment. In the first test group, Nathan treated 50 children without a single survivor. It was, Nathan recalls, “a murderous time.”

“We made the kids so sick that most of the kids died from the therapy,” Nathan told me. “They died of infection, they died of bleeding, they fell apart.”

For Nathan, it was extremely difficult to cope. By his own admission, he lacked what he described as the “will” necessary to handle the trauma. “It took a certain personality that I just didn’t have,” he told me. He would go home and say to his wife, “I just killed another kid.” He went into adult hematology for 10 years to escape. “I didn’t want to have anything to do with it,” he said.

In the early days of chemotherapy, knowing just how toxic chemotherapy agents were, doctors hesitated to treat patients with more than one agent simultaneously. How could you cause so much damage to a person who was already so sick? The answer was that you had to: If patients got only a single form of chemo, the cancer would mutate past it; only attacking the cancer with multiple agents at the same time prevented it from adapting. This multi-agent assault on the system is what causes people to suffer so palpably during treatment — the vomiting, the hair loss, the systemic illness we’ve come to recognize in cancer patients.

Dr. Sidney Farber, the famed pathologist and pioneer in childhood oncology, found it especially hard to give such harsh toxins to children, instead arguing that single agents be administered sequentially. Nathan and Farber, working in the field at the time, fought each other terribly over the best approach. Farber could not bear the idea of being responsible for killing children in an attempt to treat them. “I will never injure seven children to save three,” Nathan recalled Farber saying. “But right now you’re saving none,” Nathan replied. “He would look at me savagely,” Nathan said.

Dr. David Nathan administered chemotherapy to some of the earliest pediatric patients to receive the treatment.Credit…Damon Winter/The New York Times

Once multi-agent chemotherapy was shown to work in children, the feat of keeping the child alive was in itself considered a success, no matter how intense or traumatizing the treatment. For a long time, the guiding principle was, the more you could do to save the child, the better. Anything for a cure.

Often this meant radiation in addition to chemotherapy. Any parent today knows that you should limit your child’s exposure to radiation. But in the early days of pediatric cancer treatment, radiation was often considered vital to survival. What this radiation did to a growing body and brain was unknown.

Unfortunately, we now know what the toll of radiation can look like, which is one reason it’s used much less often. Dr. Lisa Diller, director of the David B. Perini Jr. Quality of Life Clinic for Childhood Cancer Survivors at Dana-Farber, recalled that when she was a young doctor in the early 1980s, she saw a child who had been treated for leukemia at age 2. “She had three separate secondary tumors, two different cancers as well as skin cancer, all from the radiation. I had this feeling of, ‘What the heck? What did we do here? Did we cure this child?’”

But while certain cancers, notably neuroblastomas, which develop in nerve cells, remain stubbornly difficult to treat, it’s hard to deny the efficacy of these more aggressive protocols in curing children of their primary cancer. In the early 1960s, for example, 5 percent to 10 percent of children with acute lymphoblasticleukemia were successfully treated. Today, that figure is around 90 percent. Over time, doctors refined their protocols. When a number of leukemia patients later developed brain injury, doctors cut back on radiation in areas that could reach the developing brain.

Marissa Gonzalez began treatment in 1982, when radiation was still commonly used to treat retinoblastoma. Initially, each time her eyes were radiated, she had to be carried onto a table and forcibly immobilized so that the radiation could precisely target the tumors growing inside her eyes. By the end of the month, Marissa was so accustomed to it, she was climbing onto the table herself.

But a month’s worth of treatment failed to stop the more aggressive tumor growing in Marissa’s left eye. This meant the worst-case scenario: Her eye would need to be removed. Afterward, a pathologist would determine whether cancer had reached the optic nerve, threatening the brain; the family would have to wait several weeks for the results.

“I remember just wailing,” Gonzalez said. It was a month before Marissa’s second birthday.

Unfortunately, treatment didn’t end with the removal of her left eye. Marissa’s earliest memory is of sitting in a hospital waiting room, her eyes dilated, filled with dread. She was around 4 years old, waiting for yet another procedure; she vomited from anxiety before and afterward.

From an early age, Marissa taught herself not to cry because she could see that it upset her mother. When she blew out the candles on her seventh birthday, “I wished for no more tumors,” Marissa told me. “How sad is that?”

On the bright side, Marissa’s vision remained pretty decent, roughly 20/40 in her remaining eye. Because her left eye was removed at such an early age, her brain was malleable enough to compensate. Despite wearing a prosthetic eye, she learned to ride a bike and, inspired by Nancy Kerrigan at the 1992 Olympics, took up competitive ice skating. For the next seven years, she woke up at 5 a.m. every day for practice. Out on the rink, vision and cancer never came up. “Ice skating was a sanctuary — nobody teased me because my eye and face looked different,” she said.

For Marissa at age 9, ice skating was a sanctuary.

But as she got older, the bones in her face near her temples, where radiation had beamed its rays, stopped growing along with the rest of her face. Her eyelid drooped over the prosthetic eye. By middle school, she said, she was often called One-Eyed Willie. It wasn’t until she switched schools in high school that she made a group of close friends. At 17, Marissa enrolled at the University of Southern California, where she majored in communications, hoping to become a journalist.

Retinoblastoma is “like a microcosm of cancer treatment over the last 150 years,” said Dr. Michael Dyer, chair of developmental neurobiology at St. Jude. In 1809, doctors realized this kind of tumor was starting in the eye. Shortly thereafter, the first surgeries were attempted, well before the development of anesthesia and the earliest attempts at radiation in 1903. In the 1950s, a derivative of mustard gas from World War II was used as one of the first chemotherapeutic agents to treat eye cancer, as it had been for other cancers, in children.

In 1971, a cancer geneticist named Alfred Knudson proposed that people with retinoblastoma carried a mutation in a gene that suppressed tumors. The existence of these tumor-suppressor genes was a new concept, and it transformed the field of cancer genetics. In 1986, when researchers were able to identify the precise gene in question, it became the first tumor-suppressor gene to be identified.

Retinoblastoma also shows us what the future of cancer treatment may look like. Today, survivors can have their children tested for the gene, and scientists can screen for the 30 percent to 40 percent of kids who are likely to get it because they carry the mutation from their parents. Doctors could identify it early enough to treat it with laser therapy. Of course, telling parents their newborn has a 90 percent chance of developing an eye tumor is complicated.

To avoid the side effects of systemic chemotherapy, chemo can now be injected into the femoral artery in the leg through a long tube that goes directly into the vessels of the eye. Other new techniques involve injecting the drugs into the tissue surrounding the eye or directly into the eye. At St. Jude, doctors are trying to save at least some vision in patients with the most aggressive forms of Rb. In their most recent trial, 23 out of 25 children ended up with 20/70 vision in at least one eye. But these new treatments are extremely challenging. A few tumor cells can break off and become vitreous seeds, which float around and are difficult to target.

“The major challenge is you just don’t know what the consequences later on will be,” Dyer said. “Is this going to cause vision loss or other problems in 45 years? It just isn’t known.”

‘They Look Like 50- and 60-Year-Olds’

Doctors are trying to fill in that knowledge gap, not just for Rb but for all childhood cancers. Beginning in the early 1980s, once more childhood cancer patients were surviving past five years, researchers began focusing on the psychosocial impact of childhood cancer survival.

Initially, survivors of pediatric cancer may feel invincible. They are thrilled to be healthy again. But often, as they hit adolescence, they become newly vulnerable. A number of studies show that though most survivors do quite well, as a group they have higher levels of anxiety and depression and suicidal ideation. The school years can be especially tough on cancer survivors, many of whom look markedly different from their peers — shorter, weaker, occasionally slower. They often have prostheses or bear visible marks of their illness.

As one patient told his doctor, “I’m 24, but I’m five feet tall and I look like I’m 14.” Another said he didn’t bother dating women because “They will want a baby and I can’t have a baby.” Some are hit with a version of survivor’s guilt, comparable to making it out of a war zone: Why me? Why did I survive and so many of my peers on the cancer ward didn’t? What did I put my parents through? How must my sisters and brothers feel about the sacrifices they had to make?

But Recklitis, at Dana-Farber, also points to their tremendous resilience. “These are people who have had to work through huge challenges and find meaning in it,” he told me.

From the earliest days, specialists in pediatric oncology made a concerted effort to track their patients’ physical health over time and to work collaboratively. Because the patient population is relatively small — only 1 percent of cancer patients are children — and there are 16 major types of pediatric cancer, it’s difficult for any one research center to have enough data to make conclusions meaningful. But because the stakes are so high, a spirit of shared mission imbues the field.

Funded by the National Cancer Institute since 1994, the Childhood Cancer Survivor Study is the world’s largest resource for survivorship research. The C.C.S.S. has been tracking a cohort of 25,735 survivors diagnosed and treated between 1970 and 1999 across 31 member institutions. Those patients are showing the world what survival looks like over the long term. “What we’ve learned from them has absolutely changed how we treat new cohorts of children,” said Dr. Greg Armstrong, the principal investigator of the C.C.S.S. and the chair of the department of epidemiology and cancer control at St. Jude.

Since its inception, data from the C.C.S.S. has helped doctors fine-tune treatment. Children who had been initially treated at early ages with radiation suffered from cognitive impairment and I.Q. loss that became more pronounced as they aged. Their executive function was compromised; they found it harder to live independently and achieve employment goals. They were growth-hormone deficient, leading to decreased growth. Many were obese for reasons doctors couldn’t determine. Worst of all, the radiation caused secondary cancers; many would ultimately die of brain tumors.

It also became apparent that chemotherapy had certain delayed side effects. A common class of chemotherapeutic agents, anthracyclines, ultimately led to heart disease and heart failure. “I had 50 years of experience with this drug for leukemias and solid tumors,” said Dr. Stephen Sallen, a pediatric hematologist and oncologist at Dana-Farber. “But each dose kills some heart muscle cells. It’s inconsequential at the time, but with children, by the time they’re 35 or 45, some are going into heart failure. It’s horrible.” Among patients diagnosed in the 1970s and 1980s who passed the five-year survival mark, for example, 18 percent died of various complications in the 25 years that followed.

As the research on the physical and social effects of treatment accumulated in the 1980s and 1990s, doctors realized they were over-treating some cancers at the expense of the child with the cancer. They largely eliminated whole-brain radiation. Whenever possible, they avoided the administration of anthracyclines. They also found that a new heart-protectant drug, dexrazoxane spared the heart muscle when prescribed with anthracyclines. They started to view treatment not just as curing the cancer that was present but as preventing more problems down the road.

Coping with late-onset issues is a challenge not only for patients but also for doctors. Five or 10 years ago doctors begin to notice that when some patients hit their 30s and 40s, they looked 20 to 30 years older than they should, Dr. Kevin Krull, who studies the brain and cognitive development of pediatric cancer survivors at St. Jude, told me. Their skin and hair looked older. Their heart and lung function was that of an older person. They seemed to be aging more quickly. “We wondered, what is going on here?” Krull said. “These people were having health complications we’d expect in a 70-year-old when they’re only 40.” The medical community is now encountering survivors in their 50s and 60s for the very first time. No one knows what old age will look like for them.

Untangling these myriad factors is challenging because it’s not simply a straight line from radiation to accelerated aging. Late-onset health problems may have to do with epigenetic changes in the DNA or with physical consequences that alter behavior — leg weakness that leads to less exercise that leads to lowered cardiovascular function, for example.

Longitudinal studies like the C.C.S.S. and the St. Jude Lifetime Cohort, as well as survivorship programs, can help doctors distill those sequences of events. They also help doctors alter treatment or modify post-treatment care in order to minimize their adverse long-term effects. And they may also help isolate genetic predispositions to certain late-life complications, enabling doctors to work preemptively to lower those risks.

Sometimes it’s these late-life complications that have the greatest impact on survivors.

Marissa with her mother at the home in Long Beach, Calif., where she grew up.Credit…Damon Winter/The New York Times

By the time Marissa enrolled at U.S.C. in 1998, a radiation-induced cataract, which had begun to develop when she was 9, got so bad she could no longer see the blackboard. By junior year, she had to have it removed. Though it was a simple procedure, Marissa was terrified. After all, she had only one eye left. But the surgery went smoothly, and her vision improved to 20/25. She thought her future was clear.

Over the course of 12 years, she’d had a series of reconstructive surgeries to improve her appearance. Stem cells and fat were transplanted into the concave areas along the sides of her face, making her look almost normal. She felt better than she ever had. She got a hugely rewarding job at U.S.C., her alma mater, working in special events.

But in 2018, one of the reconstructive surgeries went devastatingly wrong. Shortly afterward, still loopy from anesthesia, Marissa noticed floaters in her field of vision. Two days later, she went for a slow walk around the block with her mother, puzzling over what felt like nighttime descending.

“It was like someone had turned the lights out,” Marissa recalled. Returning to the hospital, she had what felt like an endless series of tests: MRIs, CT scans, a spinal tap. She’d suffered an optic nerve stroke. After over 100 hours in a hyperbaric oxygen tank and strong steroids, she asked a doctor, “How can I get back the vision I had?” and the doctor told her she would never get it back. Marissa sank to the floor and vomited. She now had one eye with 20/800 vision. She was 37 years old, and she was blind.

‘It’s Going to Take an Army’

How might a doctor modify a patient’s medical treatment as the person ages in order to decrease some of the known risks of long-term cancer survival?

“Curing isn’t enough anymore,” said Armstrong, the principal investigator for the Childhood Cancer Survivor Study. “Now we have to dial back, not dial up.” This can be a tough sell to parents, particularly when it involves protocols that are still experimental. Imagine, Armstrong said, sitting down with a family and saying, “We’re going to beat this, but we want you to enroll in a study where you’re not going to use the strongest therapy.” Few parents may want to take that risk when they are laser focused on saving their child’s life. Yet decades later, data proves the payoff for children with certain cancers: More survivors from the 1990s have a longer life span because they received less treatment.

Dr. Greg Armstrong with Tyler Jones, a former patient and cancer survivor.Credit…Damon Winter/The New York Times

Some parents are calling for this change too — or at least for better ways to navigate treatment decision-making. A group of parents wrote a 2022 paper in the journal Pediatric Blood and Cancer essentially asking if, given the suffering, medicine has gone too far in aggressively fighting neuroblastoma, one of the most lethal cancers. Often, this involves multiple bone marrow or what are also called hematopoietic stem cell transplants, which are extremely tough — even on adults — and fraught with risks, including life-threatening infection. The arduous process of putting a child through such a painful and dangerous treatment is considered by many parents to be “an emotional nadir” in their child’s illness. Parents want to do anything they can to save their child; then they get a glimpse at what “anything” actually involves, especially when the chances of survival remain piteously low.

“To transplant or not to transplant is an enduring question in neuroblastoma parent forums,” the authors wrote. “Nothing instills more fear, turmoil, and regret” than the high-dose chemotherapy that comes with a stem cell transplant.

One study found that among 145 neuroblastoma survivors who underwent stem cell transplants, there was a 19-fold increase in mortality compared with the general population and a catalog of adverse effects, including at least one severe health event in over 70 percent of survivors. Parent forums teem with “a mixture of reassuring accounts and horror stories, the prevailing sense being that it is a roll of the dice,” the authors wrote.

Current research is focusing on identifying genetic markers that will help pediatric oncologists anticipate which patients might be especially susceptible to serious health complications later on in order to better determine the initial course of treatment. It will also identify high-risk patients who may need more frequent echocardiograms as a preventive measure. Dr. Smita Bhatia, director of the Institute for Cancer Outcomes and Survivorship at the School of Medicine at the University of Alabama at Birmingham, is trying to develop risk-prediction tools to help make that determination. “This is like a million-piece puzzle,” she said. “I don’t know if we will get there in my lifetime.”

As it turns out, a lifetime is precisely the right unit of time to use when studying cancer survival. The expected life span of childhood cancer survivors treated before 2000 is at least 10 years shorter and perhaps 20 years shorter than average, and that isn’t good enough, Bhatia said: “We want to make sure our survivors live as long and as healthy a life as someone who has never had cancer.”

When you treat a child for cancer, Nathan of Dana-Farber said, you’re going to need doctors and social workers and others who are prepared to help that child for life: “You can’t just treat them and say, ‘Go take care of yourself.’ It’s going to take an army.”

In an ideal world, a survivor’s general practitioner would continue follow-up care. A specialist could employ cognitive behavioral techniques to help with cognitive impairment. Efforts could include preventive care against hypertension and diabetes.

“After 10 years, you would think you’re out of the woods, but that’s not the case,” said Dr. Nicholas Phillips, a cancer-survivorship physician at St. Jude.

Many survivors of childhood cancer move on from their oncology team to their pediatrician or general practitioner once they’ve passed the five-year survival mark. Many of those doctors aren’t as well versed in the long-term physical and emotional consequences of pediatric cancer treatment.

The patients “get lost,” Phillips said. They miss out on potential screenings, preventive medicine, early warning signs. Oncologists hope their survivorship studies can help inform the wider medical community.

In interviews with oncologists around the country, the subject of the C.C.S.S.’s future came up repeatedly. A number of new methods for treating childhood cancer have been introduced since the last patients enrolled were diagnosed in 1999, and doctors have made significant improvements in survival rates for more types of cancer in the short term. But this is a new cohort of patients; we don’t know how these protocols will affect children treated in 20 or 30 years’ time. Patients, parents and doctors need updated data that reflect the long-term prospects of those patients who are being treated today, not just those who were treated 24 years ago.

The issue is money, which comes from the National Institutes of Health and its National Cancer Institute. There is currently no funding to track a new cohort of patients treated after the year 2000. The C.C.S.S. also needs money to continue tracking and studying the initial cohorts. Those patients, like the rest of the American population, are now entering old age; it’s incumbent upon all of us to know what to expect and how best to support them.

Beginning in the 1970s, Western medicine went through a phase of reimagining its specialty-dominated approach to illness toward a more holistic one — thinking big in the moment of crisis. In subsequent decades, we’ve also moved toward being more thoughtful about preventive medicine — thinking big about how to avoid the crisis to begin with. The next big shift should be a greater emphasis on recovery over the long term — what we do after the initial crisis passes.

Large-scale survivorship studies could also expand into other childhood diseases, as well into areas of adult medicine. The highly collaborative and long-term approach to the field of pediatric oncology could be a model. And we could think even bigger.Given that we now have electronic data records, we could have a national registry that tracks all diseases, not just pediatric cancer, or even cancer, but all medical issues over the course of a lifetime.


For now and for many survivors, there isn’t always a road map. Marissa Gonzalez knew she could expect visual challenges over time. But blindness was unimaginable. How was she going to run high-profile events for U.S.C.? How was she going to read? What if her roommate moved a chair or left a book on the floor where Marissa wasn’t expecting it and she tripped? She felt like she was stumbling around her own life, and it filled her with rage. She took a nine-month leave from work and started drinking heavily. “I was trying to be drunk so I didn’t have to face reality,” she told me, years of therapy later.

When her mother suggested Marissa sell her car, Marissa was outraged. Though she couldn’t drive, it symbolized yet another loss of freedom. Hearing the car pull out of the driveway for the last time, Marissa dissolved into tears.

Eventually, Marissa pulled herself back together. She stopped drinking away her pain. She started using adaptive technology for her phone and computer, signed up for Audible, mastered the walking stick. U.S.C. offered her a new job, and she threw herself into volunteering with World Eye Cancer Hope, a community organization for retinoblastoma survivors and their families. Because she is part of a survivorship program at U.S.C., her health is carefully monitored. With a 17 percent chance of developing breast cancer, she makes sure to get an annual mammogram. She sees a dermatologist twice a year; even a case of melanoma, which Marissa knew she was at high risk of developing, this past summer didn’t slow her down.

Marissa, whose first treatment for retinoblastoma was in 1982, has faced a lifetime of challenges.Credit…Damon Winter/The New York Times

In a 2022 essay celebrating her 30th anniversary of being cancer free, an occasion she used to fund-raise for Rb survivors, Marissa wrote, “I find it both overwhelming and encouraging to look back on the life that retinoblastoma set forth for me. I have no idea what my life would look like had I not been a baby with cancer.” Given her druthers, she would have been born without cancer, she went on, but that was never an option. “That is why I choose instead to focus on what I can control, and what I can do with a cancer-filled life.”

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