Annual Meeting Proceedings Part 1 - American Society of Clinical ...

9528 Poster Discussion Session (Board #8), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Renal carcinoma following therapy for cancer in childhood: A report from
the Childhood Cancer Survivor Study. Presenting Author: Carmen Louise
Wilson, St. Jude Children’s Research Hospital, Memphis, TN
Background: Limited data exists describing the incidence of and risk factors
for subsequent renal carcinoma among long-term survivors of childhood
cancer. Methods: The study included 14,351 five-year survivors of childhood
cancer diagnosed between 1970 and 1986 who participated in the
Childhood Cancer Survivor Study. Chemotherapy and radiotherapy exposures
were abstracted from medical records; total dose of radiation to the
renal beds was estimated by a radiation physicist. Standardized incidence
ratios (SIRs) were calculated using age-, sex-, and calendar-specific
incidence data from the Surveillance, Epidemiology and End Results
(SEER) program. Cumulative incidence was calculated treating death as a
competing risk. Poisson regression analyses were used to assess associations
between diagnosis and treatment characteristics and the risk of
subsequent renal carcinoma while adjusting for changes in risk due to age.
Results: Twenty-six survivors were diagnosed with a renal carcinoma at a
median follow-up of 19.3 years (range: 1 month to 34.3 years) from study
entry at 5 years post diagnosis. Eight patients received �5Gy radiotherapy
to a renal bed, 16 received chemotherapy, seven of whom seven received
both radiotherapy �5Gy and chemotherapy. Cumulative incidence of renal
carcinoma at 20 years was 0.16% (95% CI 0.12-0.20). The SIR was 8.1
(95% CI 5.3-11.8) comparing survivors to the general population. Highest
risk for renal carcinoma was observed among survivors of neuroblastoma
(SIR 87.1, 95% CI 38.4-175.2), non-Hodgkin lymphoma (SIR 9.3, 95%
CI 1.9-27.4), and bone tumors (SIR 7.0, 95% CI 1.4-20.4). In multivariable
analyses, the risk of subsequent renal carcinoma was elevated among
survivors exposed to platinum-based chemotherapy (Rate Ratio 3.1, 95%
CI 0.9-10.6) or renal bed radiotherapy �5Gy (RR 3.6, 95% CI 1.5-8.4).
Conclusions: While cumulative incidence is low, survivors of childhood
cancer are at an eight-fold increased risk for subsequent renal carcinoma
compared to the general population. In addition to a primary diagnosis of
neuroblastoma, radiotherapy directed to the renal bed increased the risk for
renal carcinoma.
9530 Poster Discussion Session (Board #10), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Effect of dexraoxane on impaired mitochondrial structure and function in
doxorubicin-treated childhood ALL survivors. Presenting Author: Steven E.
Lipshultz, Department of Pediatrics, University of Miami Miller School of
Medicine, Miami, FL
Background: Cardiotoxicity in doxorubicin (DOX)-treated long-term childhood
cancer survivors is characterized by impaired cardiac function which
is partly mediated by mitochondrial (mt) energy production. Preclinical
studies show irreversible DOX-associated cardiac mt dysfunction. A response
to impaired mt function is to increase the mtDNA copies/cell
(mtDNA). We examined mtDNA and function in peripheral blood mononuclear
cells (PBMCs) in childhood survivors of high-risk ALL who received
DOX alone or DOX plus dexrazoxane (DOX/DEX). Methods: Patients with HR
ALL treated on DFCI Childhood ALL protocols from 1987-2005 were
eligible for this study. PBMCs mtDNA and oxidative phosphorylation
(OXPHOS) NADH dehydrogenase (CI) and cytochrome c oxidase (CIV)
activities were measured by RT-PCR and immunoassays respectively. A
Wilcoxon rank-sum test was used to compare continuous measures between
groups. Models for mitochondrial parameters were based on maximum
likelihood variance component estimation and were adjusted for
patient characteristics. Results: 64 patients provided samples at a median
follow-up of 7.8 (2.9-30.2) years. 58% received DOX/DEX. Median
cumulative DOX dose was 300 mg/m2 . A significant difference was
detected between groups for mtDNA (p�0.001, adjusted p�0.015).
MtDNA medians for the DOX and DOX/DEX groups were 1106.3 and 310.5.
No significant differences were found between groups for CI or CIV
activities. Conclusions: DOX-treated survivors have increased mtDNA consistent
with impaired mt function, which is abrogated by concurrent use of
DEX. The use of DOX/DEX is associated with lower mtDNA. Due to a
compensatory increase in mtDNA to augment mt function, overall mt
function is not different between groups. This compensatory mechanism in
7.8-year survivors at risk for cardiac dysfunction is concerning over their
subsequent lifespan.
N
DOX
Median (range) N
DOX/DEX
Median (range) P
mtDNA 27 1106.3 (144.2-6746.8) 35 310.5 (15.3-1859.2) 0.001
CI activity (OD/mg x 10 3 ) 25 10.5 (5.0-31.3) 33 11.7 (5.0-41.4) 0.97
CIV activity (OD/mg x 10 3 ) 25 9.8 (5.0-20.1) 34 8.1 (4.7-23.4) 0.40
Pediatric Oncology
613s
9529 Poster Discussion Session (Board #9), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
A longitudinal study of anthracycline cardiotoxicity in pediatric Ewing
sarcoma. Presenting Author: Tanya Renae Brown, British Columbia Children’s
Hospital, Vancouver, BC, Canada
Background: Trends in cardiac function over time have not been previously
described in Ewing sarcoma. Our cohort is unique as all the cardiac
evaluations occurred systematically in one tertiary cardiology unit during a
28 year period. Objectives: 1.To evaluate the cardiac functional trends in
the cohort at baseline, during treatment and in surveillance. 2.To evaluate
the risk factors associated with cardiac toxicity. Design: Received ethics
approval for a retrospective chart review of all patients less than 17 years,
diagnosed with Ewing sarcoma from 1978-2006, treated initially at British
Columbia Children’s Hospital . Methods: There was complete data on 71/79
eligible patients. Echocardiograms were recorded at 5 time points: pre
treatment, worst function during treatment, on therapy completion, worst
function during surveillance and the most recent echocardiogram. Cardiac
toxicity was graded using CTCAE v 4.0. The statistical analysis with SAS
software v 9.2 calculated the chi square and odds ratios to explore a
possible association between exposure and outcome. Results: Median age
at diagnosis 11.1 yrs (2.2-16.1 yrs), 52% female, metastatic in 17, overall
survival 74% at 10yrs. A total of 397 echocardiograms were performed with
244 (61%) being normal and 153 (39%) being abnormal. The median
cumulative dose of anthracyclines was 365mg/m2 . Grade 1-5 cardiomyopathy
occurred in 42 (59%) patients. Grade 3-5 toxicity occurred in 11
(15%) patients on chemotherapy completion increasing to 23 (32%) 120
months post diagnosis. The median time to the worst cardiac function was
51months (2-183). Four of 19 (20%) deaths were cardiac related
including 2/3 cardiac transplants. Conclusions: Symptomatic cardiac
toxicity increased from 20% noted in our earlier Ewings cohort (Kakader et
al. 1997) to 32% with longitudinal evaluation assessments. Significant
and progressive cardiac toxicity occurred after completion of chemotherapy.
9531 Poster Discussion Session (Board #11), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Tumor location and neurocognitive impairment in adult survivors of
pediatric brain tumors: A report from the St. Jude Lifetime Cohort (SJLIFE).
Presenting Author: Tara M. Brinkman, St. Jude Children’s Research
Hospital, Memphis, TN
Background: Follow-up guidelines identify supratentorial tumor location as
a risk factor for poor neurocognitive outcomes during childhood; yet few
studies have systematically compared long-term cognitive outcomes between
adult survivors of childhood infratentorial and supratentorial brain
tumors. Methods: Neurocognitive functions were evaluated in 130 adult
survivors of pediatric brain tumors (58 supratentorial and 72 infratentorial,
mean [SD] current age � 27.4 years [5.2], age at diagnosis � 8.6 years
[4.6], and time since diagnosis � 18.8 years [4.8]) participating in the
SJLIFE long-term follow-up protocol. Age-adjusted standard scores for
measures of intelligence, attention, memory, processing speed, and executive
functioning were calculated, with clinical impairment defined as scores
�10th percentile. Odds ratios (OR) and 95% confidence intervals (CI) were
calculated using multivariable logistic regression models to examine
associations between neurocognitive functions and tumor location. Results:
As a group, survivors performed below average across multiple neurocognitive
domains, including full scale IQ (mean�88.1; SD�18.2), with 34%
demonstrating impaired IQ. Survivors of infratentorial tumors were more
likely to be impaired on measures of focused attention (OR�2.19, 95%
CI�1.03-4.65) and fine motor dexterity (OR�2.62, 95% CI�1.21-5.66)
compared to survivors of supratentorial tumors. After adjusting for sex, age
at diagnosis, shunt placement and cranial radiation (yes/no), infratentorial
tumor location was only associated with reduced performance on a task of
visual abstract reasoning (OR�3.76, 95% CI�1.40-10.1). Cranial radiation
therapy was independently associated with impaired short-term
memory (OR�15.6, 95% CI�1.64-147.8) and processing speed
(OR�3.86, 95% CI�1.15-13.0). Conclusions: Tumor location was not
associated with neurocognitive impairment after adjusting for treatment
exposures. To further delineate potential differences associated with tumor
location, future studies will examine factors including radiation dose/
volume, extent of surgical resection, and medical complications.
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