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Chronic health conditions prevalent among childhood cancer survivors

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September 7, 2017

Nickhill Bhakta

More than 99% of childhood cancer survivors experienced an average of 17 chronic health conditions by age 50 years, suggesting a high burden of health complications during adulthood, according to a retrospective analysis of the St. Jude Lifetime Cohort Study.

“By age 45 to 50, survivors continue to have two times more life threatening chronic health conditions compared with the standard population,” Nickhill Bhakta, MD, assistant member in the department of global pediatric medicine at St. Jude Children’s Hospital, told HemOnc Today. “We now know merely applying the screening guidelines currently in place for the general male and female populations that are 50 years or older, to a 30-year survivor, is not appropriate because the types of diseases they are having are substantially different and in some cases more morbid. We have to highlight the survivorship guidelines in place and continue to adjust and modify them based on this data.”

The number of survivors of pediatric cancer continues to increase, with 10-year survival rates at more than 80%.

“Fifty or 60 years ago only a handful of pediatric cancer patients were survivors, but as a result of collaborative efforts, we’ve boosted that survival,” Bhakta said. “It really is incremental progress that has been made by learning how to use fundamentally older drugs — developed in the 1950s and 1960s — and using them more efficiently and effectively.

“Between population growth and curative treatments, we are now getting a fairly large pediatric cancer survivor population in the United States alone,” Bhakta said.

However, curative treatment-related exposures, morbidities and risk for chronic health conditions remain. Few studies have measured the burden of disease among childhood cancer survivors and compared survivor morbidities to a community of controls.

Researchers retrospectively collected data on chronic health conditions of 5,522 patients treated for cancer at St. Jude Children’s Research Hospital (median age at diagnosis, 7.6 years) that survived 10 years or longer postdiagnosis and were aged at least 18 years at the time of the study. Researchers matched patients by age and sex frequency to a community of controls (n = 272) for comparison. At the time of enrollment, 54.5% remained alive (n = 3,010) and underwent prospective clinical assessments for comparison of all medical conditions — except hearing loss, glaucoma, cataracts and retinopathy — with controls.

The cumulative incidence of chronic health conditions at age 50 years was 99.9% (95% CI, 99.9-99.9) for grade 1 to 5 and 96% (95% CI, 95.3-96.8) for grade 3 to 5.

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The cumulative burden in the total study population was 17.1 (95% CI, 16.2-18.1) chronic health conditions of any grade per individual. An average 4.7 (95% CI, 4.6-4.9) chronic health conditions were grade 3 to grade 5 conditions.

The cumulative burden in matched controls was 9.2 (95% CI, 7.9-10.6) for grade 1 to 5 and 2.3 (95% CI, 1.9-2.7) for grade 3 to 5.

The highest cumulative incidences and burdens at age 50 years for the total population affected the cardiovascular (incidence: 93.2%; burden: 4); endocrine (incidence: 91.6%; burden: 2.6); and musculoskeletal (incidence: 83.6%; burden: 1.7) systems.

The cumulative burden of chronic conditions at age 50 years appeared highest among survivors of central nervous system malignancies (24.2%; 95% CI 20.9-27.5) and lowest among survivors of germ cell tumors (14; 95% CI, 11.5-16.6).

Researchers found total cumulative burden to second neoplasms, spinal disorders and pulmonary disease to be major contributors to burden.

Thirty-seven percent of survivors had a second neoplasm by age 50 years.

Researchers observed two kinds of chronic conditions: growth conditions associated with older age, such as cardiovascular disease and neoplasms; and acute toxicity conditions, such as neurological damage, which were linked to previous cancer therapy, Bhakta said.

“There has been a lot of work in this area over the last 30 years, describing the amount and number of chronic health conditions survivors of this group experience,” Bhakta said. “Our study goes beyond just what the common conditions are. It highlights that there are substantially different patterns of chronic health conditions between different survival groups — they vary by age and type.”

After adjusting for demographic differences and treatment exposures, multivariate analyses showed older age at diagnosis, higher doses of brain and chest radiation and treatment era held a significant association with higher cumulative burden and severity of chronic conditions.

“This is a vulnerable and growing population and we need to have a larger conversation about this,” Bhakta said. “How will we handle these adults who survive and age beyond 26 years is still an open question.”

The findings by Bhakta and colleagues highlight the diversity of survivors of childhood cancer and how long-term follow-up is crucial, according to Miranda M. Fidler, postdoctoral fellow in the section of cancer surveillance at International Agency for Research on Cancer, in Lyons, France, and Michael M. Hawkins, DPhil, professor of epidemiology and director of the Centre for Childhood Cancer Survivors Studies at University of Birmingham in the United Kingdom.

“The authors provide a clear hierarchy of health-related concerns for each subgroup that will be very useful for clinical follow-up, developing guidelines and designing future clinical trials,” Fidler and Hawkins wrote in a related editorial. “These results also emphasize the need for continued follow-up of childhood cancer survivors, and raise the question of the extent to which specialized health delivery services could benefit these individuals.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.

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Perspective

In the last several decades we have seen survival rates for childhood cancer steadily increase, from being nearly universally fatal to an impressive 10-year survival rate of 80%. Even as we celebrate the increasing number of children who survive cancer, we continue to learn the price to be paid by the now adults who live with the health consequences of their cure.

Bhatkta and colleagues present a comprehensive and sobering look at what life is like for survivors as they age. As a clinician who has cared for this population for more than 2 decades, it confirms to me that we do not have time to pat ourselves on the back for curing childhood cancer until we address the life-long consequences of the cure.

Upon reading the paper, I came away with two important issues that the pediatric oncology and health care community at large need to address. First, how do we best provide care for this vulnerable population? Is it realistic to think that the primary care community has the resources to stay abreast of the special health care needs of survivors in a climate of ever increasing demands on their time and expertise? Can we reach and provide specialized health care to survivors across the nation, or will we be limited to those who live close to survivorship programs (eg, SJLIFE of St. Jude) or have the means to seek out similar expert care? Will the future of health care in our nation embrace or exclude childhood cancer survivors?

Secondly, how do we improve health outcomes for childhood cancer survivors? Are we doing enough with intervention research to improve or ameliorate the complications that have or may occur in those already treated? How do we continue to design therapies with fewer long-term complications without compromising the cure rates we have achieved? Will the newer targeted therapies improve survival and minimize long-term complications?

The childhood cancer survivorship community has accomplished much, including evidence-based screening guidelines and provision of treatment summaries and care plans for survivors. However, even with these achievements, we have only scratched the surface of what is needed to adequately serve these heroes and the generations of survivors to follow.

Reference:

Children’s Oncology Group. Survivorship guidelines. Available at: survivorshipguidelines.org/. Accessed on Sept. 22, 2017.

Kathy Ruble, CRNP, PhD

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Disclosure: Ruble reports no relevant financial disclosures.