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Childhood, young adult cancer survivors face high risk of long-term morbidity

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Cancer cure is not enough

Because adolescents and young adults have a unique pattern of cancer development, as well as different psychosocial stressors compared with younger or older patients, the late-effects burden of AYA cancers may be distinct from survivors of childhood or adult cancers. Studies involving this age group will help guide screening and treatment for AYA survivors.

The analysis by Rugbjerg et al. describes malignant neoplasms that occur frequently in AYA survivors, and these results differ from previous observations. Particularly surprising is the low prevalence of breast and thyroid cancers, two of the most common subsequent malignant neoplasms previously reported in AYA cancer survivors.

While the hospitalization rate ratios offer some insight on the risks faced by AYA survivors, early detection and intervention strategies require a comprehensive view of the cancer treatment–related sequelae, and this must come from both inpatient and outpatient information.

In examining late effects of childhood cancer, a particular area of interest is neurocognitive development, due to its far-reaching affects on education, employment, and quality of life.

The results from Edelmann and colleagues suggested that the risk of neurocognitive impairment in long-term survivors of pediatric osteosarcoma is linked to chronic health conditions and not high-dose methotrexate. However, only a longitudinal study can determine if neurocognitive deficits were present prior to the development of chronic health conditions and linked to chemotherapy exposure.

Furthermore, a genetic predisposition may increase sensitivity to chemotherapy and neurocognitive outcomes.

Given the impact of neurocognitive functioning on the lives of cancer survivors, development of interventions to improve long-term outcomes is imperative.

Dr. Karen Effinger is a pediatric oncologist and instructor in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. Dr. Michael Link is professor and pediatric oncologist in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. These remarks were part of an editorial accompanying the reports (JAMA Oncol. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4392). Dr. Effinger and Dr. Link reported having no disclosures.


 

FROM JAMA ONCOLOGY

References

Survivors of cancer diagnosed at early ages, compared with healthy controls, face higher risk of chronic medical problems, according to two independent studies.

Survivors of adolescent and young adult (AYA) cancer had an overall 38% increased risk of hospitalization, which persisted throughout life, according to a Danish Cancer Registry study. The St. Jude Lifetime Study found that long-term survivors of childhood osteosarcoma had significant neurocognitive deficits in attention, memory, processing speed, executive function, and academics. “The morbidity pattern … underscores the need for further implementation of strict evidence-based sex,-, age-, and cancer-specific follow-up plans for survivors, thereby increasing the likelihood for early detection and ultimately prevention of treatment-induced morbidities,” wrote Kathrine Rugbjerg, Ph.D., of the Danish Cancer Society Research Center, Copenhagen, and colleagues (JAMA Onc. 2015 Nov. 19 doi: 10.1001/jamaoncol.2015.4393).

Analysis of the Danish Cancer Registry from 1943 to 2009 included 33,555 5-year survivors of cancer diagnosed between age 15 and 39 years, and 228,447 matched population comparisons. During the median 14-year follow up, cancer survivors had 53,032 hospital admissions, with 38,423 expected, for a standardized hospitalization rate ratio of 1.38 (95% CI, 1.37-1.39). The absolute excess risk (difference between observed and expected hospitalization rates per 100,000 person years of follow-up) remained relatively stable, ranging from 2 to 4 disease-specific hospitalizations per 100 survivors for each year of follow-up.

Categories that carried the highest relative risk of hospitalization for cancer survivors were diseases of blood and blood-forming organs (RR men, 2.36; women, 1.85), infectious and parasitic diseases (men, 1.81; women, 1.62), and malignant neoplasms (men, 1.80; women, 1.52). Treatments for these cancers tend to be intensive and lengthy, the researchers noted.

The AYA cancers that had the highest risk of subsequent hospitalization among survivors included leukemia (RR, 2.21), brain cancer (RR, 1.93), and Hodgkin lymphoma (RR, 1.87).

The large size of the study made possible the calculation of relative risks for hospitalization according to disease category and AYA cancer type. Survivors of brain cancer had high risk of endocrine, nervous system, and sense organ diseases (RR, 5.5); leukemia survivors had high risks of diseases of blood and blood-forming organs, respiratory system diseases, and infectious and parasitic diseases (RRs, 6.3, 4.9, and 6.3, respectively): Hodgkin lymphoma survivors had high risk of malignant neoplasms (RR, 3.7).

On average, AYA survivors spent 50% more days in hospitals than did the comparison cohort.

A separate study compared neurocognitive performance of long-term survivors of childhood osteosarcoma with community controls and found lower reading scores (P = .01), more variability in sustained attention (P = .002), poorer short-term memory (P = .01), slower motor processing speed (P less than .001), and poorer cognitive fluency (P = .006), reported Michelle N. Edelmann, Ph.D., of St Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (JAMA Onc. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4398).

The St. Jude Lifetime Cohort Study evaluated 80 survivors of childhood osteosarcoma at a mean 24.7 years after diagnosis, and compared their neurocognitive function results with 39 community controls.

All osteosarcoma survivors had undergone treatment with high-dose methotrexate, but neurocognitive outcomes were not related to cumulative dose or pharmacokinetic indices of methotrexate exposure.

Chronic health conditions can affect neurocognitive functions in survivors of childhood cancers, and the study found that osteosarcoma survivors with grade 3 or 4 adverse chronic health conditions showed poorer memory and processing speeds.

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