LGG-17. IMPACT OF STROKE AND STROKE RECURRENCE ON LATE MORTALITY AS WELL AS PSYCHOLOGICAL AND SOCIOECONOMIC OUTCOMES IN CHILDHOOD CANCER SURVIVORS

10546 Background: Childhood cancer survivors are at risk for neuromuscular dysfunction. We estimated the prevalence and cumulative incidence of neuromuscular dysfunction in a cohort of childhood cancer survivors and examined associations with treatment exposures and health/socioeconomic outcomes. Methods: CCSS participants ≥5 years from cancer diagnosed between 1970-1999 (n = 25,583, 46.5% female, median [range] age 54.4 [15.1-57.6] years) and siblings (n = 5,044, 52.3% female, median [range] age 54.1 [32.5-57.0] years) were included. Neuromuscular dysfunction was identified by self-report of 1) motor dysfunction: impaired balance, tremor, or extremity weakness; 2) sensory dysfunction: impaired touch sensation. Multivariable analyses examined predictors of dysfunction by diagnosis. Results: Cumulative incidence of neuromuscular dysfunction was elevated at 20 years from diagnosis in survivors (24.3%, 95% CI 23.8-24.8; motor 18.2%, sensory 13.5%) versus siblings (8.9%, 95% CI 8.1-9.7). In survivors five years from diagnosis, motor dysfunction was associated with exposure to cytarabine (OR = 1.39, 95% CI 1.10-1.77) and spinal radiation (OR = 2.11, 95% CI 1.31-3.41) in acute lymphoblastic leukemia/non-hodgkin lymphoma (ALL/NHL), vinca alkaloids (OR 1.29, 95% CI 1.03-1.60) and brain radiation (OR = 1.58, 95% CI 1.35-1.85) in central nervous system tumors, and cytarabine (OR = 3.73, 95% CI 1.62-8.57) and non-brain/spine radiation (OR = 1.84, 95% CI 1.42-2.40) in bone/soft tissue tumors. Sensory dysfunction was associated with exposure to vinca alkaloids (OR = 3.45, 95% CI 1.06-11.22) in ALL/NHL, and platinum agents (OR = 1.31, 95% CI 1.03-1.67) and spinal radiation (OR = 3.71, 95% CI 1.24-11.11) in bone/soft tissue tumors. Survivors with neuromuscular dysfunction were at increased risk for adverse health/socioeconomic outcomes (Table). Conclusions: Neuromuscular dysfunction is a prevalent morbidity in childhood cancer survivors, associated with specific therapies within a particular diagnosis. Interventions are needed to identify and improve neuromuscular dysfunction given its association with adverse health/socioeconomic outcomes. [Table: see text]

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Abstract 9: Risk of Stroke and Stroke Recurrence in Pediatric Cancer Survivors treated with Cranial Radiation Therapy

Stroke ◽

10.1161/str.43.suppl_1.a9 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Sabine Mueller ◽

Katherine Sear ◽

Nancy K Hills ◽

Nassim Chettout ◽

Shervin Afghani ◽

...

Keyword(s):

Radiation Therapy ◽

Cancer Survivors ◽

Childhood Cancer ◽

Cumulative Incidence ◽

Recurrent Stroke ◽

Dose Range ◽

Childhood Cancer Survivors ◽

Dose Effect ◽

Stroke Recurrence ◽

Cranial Radiation

Background: Among childhood cancer survivors, cranial radiation therapy (CRT) increases risk of self-reported first-stroke; there are no published estimates of recurrent stroke. Objective: To assess rates and predictors of first and recurrent stroke in childhood cancer survivors treated with CRT. Methods: In a retrospective cohort study of all children who received CRT at one institution,1980-2009, we performed chart abstraction (n=321) and phone interviews (n=101) to measure first and recurrent stroke; we confirmed stroke through imaging review. Incidence of first-stroke was calculated as the number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determine the cumulative incidence of first stroke after radiation, and recurrent stroke after first stroke; we used Cox proportional hazards models to examine potential predictors of first stroke. Results: Median age of children at the time of CRT treatment was 8 years (IQR 4-13 years). A total of 17 first-strokes (12 ischemic, 2 hemorrhagic, 3 unknown sub-type) were identified at a median age of 25 years (IQR 17-34 years): 6 from chart review, 8 from interview, 3 from both. Imaging was available in 12 cases and consistent with stroke in all. The overall rate of first-stroke was 594 (95% CI 346 - 949) per 100,000 person-years. The risk of stroke persists for decades after treatment (see Figure ). Males had a 4-fold hazard of first stroke compared to females (95% CI 1.1 - 14; P =0.034). Race and treatment with chemotherapy did not affect the stroke risk; dose effect of CRT could not be assessed due to a narrow dose range in our cohort. There were 5 recurrent strokes (2 ischemic, 2 hemorrhagic, 1 unknown) at a median of 6 months after first stroke (range 5.6 months to 8.9 years); brain imaging was available in 4 cases and consistent with stroke in all. The cumulative incidence of recurrent stroke was 21% (95% CI 7.5-53) at 1 year post first-stroke, 29% (95% CI 12-61) at 5 years, and 43% (95% CI 19-78) at 10 years. Conclusion: Survivors of childhood cancer who received CRT are at high risk for first and recurrent stroke. Larger studies are needed to identify predictors of recurrence to design secondary stroke prevention strategies.

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Impact of Cancer Therapy-Related Exposures on Late Mortality in Childhood Cancer Survivors

Chemical Research in Toxicology ◽

10.1021/tx500374k ◽

2014 ◽

Vol 28 (1) ◽

pp. 31-37 ◽

Cited By ~ 9

Author(s):

Todd M. Gibson ◽

Leslie L. Robison

Keyword(s):

Cancer Therapy ◽

Cancer Survivors ◽

Childhood Cancer ◽

Childhood Cancer Survivors ◽

Late Mortality

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Late mortality and second cancers in an Australian cohort of childhood cancer survivors

The Medical Journal of Australia ◽

10.5694/j.1326-5377.2010.tb03902.x ◽

2010 ◽

Vol 193 (5) ◽

pp. 258-261 ◽

Cited By ~ 18

Author(s):

Carmen L Wilson ◽

Richard J Cohn ◽

Karen A Johnston ◽

Lesley J Ashton

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Childhood Cancer Survivors ◽

Late Mortality ◽

Second Cancers ◽

Australian Cohort

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Increased late mortality in underweight survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.5_suppl.110 ◽

2017 ◽

Vol 35 (5_suppl) ◽

pp. 110-110

Author(s):

Emily S. Tonorezos ◽

Lillian R. Meacham ◽

Joanne F. Chou ◽

Chaya S. Moskowitz ◽

Wendy M. Leisenring ◽

...

Keyword(s):

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Survivor ◽

Childhood Cancer Survivors ◽

Normal Weight ◽

Late Mortality ◽

History Of ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer

110 Background: Approximately one-in-ten adult survivors of childhood cancer are underweight. While the consequences of being overweight or obese have been well-described, outcomes among underweight childhood cancer survivors are unknown. Methods: Underweight was defined as a body mass index (BMI)< 18.5 kg/m2, calculated from self-reported height and weight on either the baseline or the first follow-up questionnaire from the Childhood Cancer Survivor Study (CCSS). National Death Index provided death data and self-reported subsequent malignant neoplasm were validated by pathology report. Chi-square test was used to examine the association between underweight status (< 8.5 kg/m2 vs ≥ 18.5 kg/m2) and baseline demographic characteristics. Marginal models with generalized estimating equations were used to evaluate the associations between BMI and outcomes. Results: Of 9454 survivors (median age 35 years old, range 17-58, with an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline and had at least two years of additional follow-up. 29 of 184 deaths were among underweight survivors. In univariate analysis, underweight status was more common among females (9.1% vs 4.5 %, p<0.01) and participants with younger age (8.2% for <5 yrs vs. 6.1% for >=5yr, p<.01), lower household income (8.9% for <$20,000 vs. 6.0% for >=$20,000, p<0.01), and a history of a grade 3 to 4 chronic condition (p = 0.05). After adjustment for these factors, in addition to race/ethnicity, prior smoking, and a history of radiation therapy, the odds of all-cause mortality within two years of BMI report was 2.82 (95% CI: 1.64-2.2; p<0.01) for underweight survivors, compared to normal weight survivors. The risk of subsequent malignant neoplasms within two years of BMI report among underweight survivors compared to normal weight survivors was not significantly increased (OR 1.31; 95% CI: 0.60-2.85; p = 0.49). Conclusions: Childhood cancer survivors who are underweight are at significant risk for late mortality that is unrelated to smoking status, chronic illness, or second malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

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