Childhood Cancer Survivors at Risk for Hospitalization

Roxanne Nelson, BSN, RN

November 24, 2015

Survivors of childhood and young adult cancers are known to be at risk for late adverse effects related to treatments. Two new studies focus on specific issues they face ― an increased risk for hospitalization for survivors of various cancers, and an increased risk for neurocognitive impairment for osteosarcoma survivors.

Both studies were published online November 19 in JAMA Oncology. An accompanying editorial points out that there are now more than 9 million 5-year cancer survivors in the United States. As this number continues to grow, there is increasing focus on improved health, and quality of life becomes a priority, write the editorialists, Karen E. Effinger, MD, and Michael P. Link, MD, both from Stanford University School of Medicine, in California.

"Treatment has changed substantially in the past 3 decades, with more emphasis on quality of life and knowledge about long-term effects," Dr Effinger told Medscape Medical News. "While there are some children and young adults who are receiving less toxic therapy, there are some patients who are receiving more intensified therapy in order for cure. In addition, there are still some diseases which have poor survival rates."

 
Our goal is for these patients to have the best quality of life as they age. Dr Karen Effinger
 

Truly individualized therapy is a goal for the future, but it is not possible at this time. "We hope that as we understand the late effects of therapy better and monitor for them more closely, we will be able to detect them earlier, leading to earlier treatment and, hopefully, less impact on the patients," she explained. "Our goal is for these patients to have the best quality of life as they age."

 
It is crucial for the oncology community to continue to work with our counterparts in general pediatrics and internal medicine. Dr Karen Effinger
 

Dr Effinger pointed out that although research continues to advance in this area, it is surprising how many patients in the community do not understand their risk for late effects. "Many primary care physicians are unaware of the full extent of the late effects of cancer treatment and are unsure of the screening necessary," she said. "It is crucial for the oncology community to continue to work with our counterparts in general pediatrics and internal medicine in order to educate them and our patients about possible late effects and the screening necessary in these patients."

Increased Risk for Hospitalization

In the first study, Kathrine Rugbjerg, PhD, and Jørgen H. Olsen, MD, DMSc, of the Danish Cancer Society Research Center, Copenhagen, Denmark, found that adolescent and young adult cancer survivors had an overall increased relative risk for hospitalization as compared with those in the general population.

For this study, the Danish team surveyed 33,555 5-year survivors of adolescent or young adult cancer who were diagnosed from 1943 through 2004, when they were 15 to 39 years of age. For the sake of comparison, the researchers then incorporated data for 228,447 persons from the general population who were matched to the cancer survivors by sex and year of birth.

The cancer survivors were followed for a median of 14 years (range, 0 - 34 years), and the comparators, for a median of 18 years.

Among the cancer survivors, there were 53,032 first admissions to the hospital for treatment of diseases from one or more of 97 disease categories. The authors had expected 38,423 admissions; this resulted in an overall relative risk (RR) of 1.38.

Survivors therefore had a 38% increased risk of being hospitalized during follow-up for diseases from one or more of the defined disease categories, the authors note. This increased risk persisted throughout their life, "with 2 to 4 excess disease-specific first hospitalizations per 100 survivors each year."

The highest relative risks were observed for diseases of blood and blood-forming organs, infectious and parasitic diseases, and malignant neoplasms. In general, men appeared to be at higher risk than women.

For their analysis, the authors included survivors of the 10 most common cancers diagnosed in this age group: leukemia, brain cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, thyroid cancer, breast cancer, cervical cancer, ovarian cancer, and malignant melanoma.

At highest risk for hospitalizations were survivors of leukemia (RR, 2.21), brain cancer (RR, 1.93), and Hodgkin's lymphoma (RR, 1.87). But survivors of all 10 cancer types, they emphasize, were hospitalized at rates that were significantly higher than expected.

The risk for a new primary cancer was 1.6-fold higher for in the entire cancer survivor cohort, as compared with the control individuals. The highest risks were seen in survivors of Hodgkin's lymphoma, with a relative risk of 3.7 (95% confidence interval, 3.4 - 4.1).

"This Danish study is important, as it was the first study to look at adolescent and young adult patients, and I feel it is necessary to look more closely at these patients through a cohort study in order to determine other late effects that can be seen in an outpatient setting," commented Dr Effinger.

Nerocognitive Impairment in Osteosarcoma Survivors

In the second article, Kevin R. Krull, PhD, of St. Jude Children's Research Hospital, Memphis, Tennessee, and colleagues found that long-term survivors of osteosarcoma are at risk for neurocognitive impairment. However, this impairment is related to current chronic health conditions and not to their original treatment with high-dose methotrexate (multiple brands), they report.

The study involved 80 long-term survivors of childhood osteosarcoma. The average average age of the patients was 38.9 years, and the median time since their diagnosis was 24.7 years. These osteosarcoma survivors were recruited from the St. Jude Lifetime Cohort Study and were compared with community control persons.

Compared with the control group, the survivors demonstrated lower reading scores (P = .01), more variability in sustained attention (P = .002), poorer short-term memory (P = .01), slower motor processing speed (P < .001), and poorer cognitive fluency (P = .006).

The cancer survivors also scored significantly lower than population norms on those measures; community control persons did not differ significantly.

Performance on neurocognitive measures was related to attainment of less than a college education, having less than full-time employment, and earning less than $40,000 in annual income, adjusting for present age and sex.

The survivors also self-reported more problems with working memory in comparison with the control group (P < .001) and with national norms (P = .004).

The authors also evaluated the potential effect that treatment with high-dose methotrexate may have had on their neurocognitive functioning.

High-dose methotrexate has previously been associated with neurotoxic effects among survivors of childhood acute lymphoblastic leukemia (ALL), and the Children's Oncology Group recommends neurocognitive screening for all survivors of childhood and adolescent cancer who were exposed to it. Dr Krull and his team note that this recommendation has been applied to osteosarcoma survivors, who receive methotrexate at cumulative dosages to a degree 4- to 5-fold greater than patients with ALL.

Methotrexate pharmacokinetic studies and chemotherapy dosing data were available from the records of 68 patients. The results of these pharmacokinetic analyses showed that high-dose methotrexate maximum plasma concentration, median clearance, and median/cumulative exposure were not associated with neurocognitive outcomes in this population.

Dr Rugbjerg received an individual postdoctoral stipend from the Danish Council for Independent Research in Medical Science. Dr Olsen has disclosed no relevant financial relationships. Dr Krull's study was supported by Cancer Center Support grant CA21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities. The authors of that study and the editorialists have disclosed no relevant financial relationships.

JAMA Oncol. Published online November 19, 2015. Rugbjerg et al, abstract; Edelman et al, abstract; Editorial

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