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

1504 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Dexrazoxane exposure and risk of secondary acute myeloid leukemia in
pediatric cancer patients. Presenting Author: Dana Marie Walker, Children’s
Hospital of Philadelphia, Philadelphia, PA
Background: Dexrazoxane (DXZ) is an effective cardioprotectant in children
with leukemia and solid tumors. However, the potential risk of secondary
acute myeloid leukemia (AML) limits DXZ use. We compared the incidence
of secondary AML in pediatric cancer patients with and without DXZ
exposure to estimate the risk of DXZ-associated secondary AML. Methods:
We conducted a retrospective cohort study of anthracycline exposed
pediatric cancer patients (excluding de novo AML) hospitalized from
January 1999 to March 2011 in 43 freestanding children’s hospitals in the
Pediatric Health Information System (PHIS) database. Secondary AML was
defined as an ICD9 code for AML that occurred at least 90 days after first
anthracycline exposure. Proportions of patients with secondary AML were
compared between patients with and without an exposure to DXZ after the
initial anthracycline exposure. Results: During the study period of interest,
15,532 pediatric cancer patients were exposed to anthracycline, of which
1404 (9.04%) subsequently received DXZ. Secondary AML was identified
in 235 (1.51%) patients. Patients � 10 years of age, black patients,
patients in New England and the Midatlantic regions, and those with bone
tumors were significantly more likely to have received DXZ. The unadjusted
incidence of secondary AML in the DXZ exposed and unexposed patients
did not differ significantly (1.21% v. 1.54%, p�0.3308). After adjusting
for these variations in demographics, the incidence of secondary AML still
did not significantly differ between DXZ exposed and unexposed patients
(p�0.6224). Conclusions: Our findings suggest that DXZ exposure does not
lead to an increased risk of secondary AML in children. These data are
important given the conflicting results from individual clinical trials about
the risk of DXZ-associated secondary AML. While subject to well-known
limitations of administrative database analyses, these data represent the
largest cohort of DXZ exposed patients with available data on the occurrence
of secondary AML. Additional multivariate analyses of chemotherapeutic
covariates and time to secondary AML are ongoing.
1506 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Sensitivity of clinical BRCA1 testing compared with linkage analysis.
Presenting Author: Payal D. Shah, University of Pennsylvania, Philadelphia,
PA
Background: Specific clinical interventions in BRCA mutation carriers
reduces the risk of breast and ovarian cancers and may improve survival;
thus,identification of mutation carriers is important. The sensitivity of
current BRCA mutation testing is unclear as a “gold standard” test is
lacking. We assessed the BRCA1 mutation detection rate with current
comprehensive clinical testing using linkage analysis as the comparator.
Methods: 26 families with linkage analyses results available were included
in this analysis. BRCAPRO, BOADICEA, and other risk estimation models
were applied. Maximum-likelihood linkage analyses were performed to
compute two-point and multipoint LOD scores using previously described
BRCA1 –linked genetic markers; scores were classified as linked, not
linked, or suggestive. At least one individual from each family underwent
comprehensive testing. Results: Of 26 families analyzed, 9 demonstrated
linkage and 4 demonstrated suggestive linkage to BRCA1. Of these 13
families, 12 were found to have BRCA1 mutations: a detection rate of
92.3%. In 3 of these 12 families, genetic mutation testing performed prior
to large genomic rearrangement (LGR) testing was negative, demonstrating
an improved detection rate with LGR testing which in this series was 23%.
The 12 families with higher LOD scores and positive mutation testing had
high mean prior probabilities by all models. Families which were not linked
and who tested negative for mutations had lower mean prior probabilities.
In one family, disease demonstrated linkage with a two-point LOD score of
1.59 and multipoint LOD of 0.85 and all risk estimation models yielded
high prior probabilities. Despite this, mutation testing was negative by full
sequencing and MLPA analysis. Conclusions: When evaluated in a sample
of families from high-risk clinics, current comprehensive testing compares
well to linkage data. The inclusion of LGR testing has improved the
mutation detection capability of clinical testing; however, some mutations
may still be missed. Negative mutation testing results should be interpreted
in the context of family history and prior probability during
counseling. Despite recent advances, further improvements in genetic
testing are warranted.
Cancer Prevention/Epidemiology
87s
CRA1505 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Quality of cancer family history and referral for genetic counseling and
testing among oncology practices: A pilot test of quality measures as part of
the ASCO Quality Oncology Practice Initiative (QOPI). Presenting Author:
Marie Wood, University of Vermont, Burlington, VT
The full, final text of this abstract will be available at
abstract.asco.org at 12:01 AM (EDT) on Monday, June 4,
2012, and in the Annual Meeting Proceedings online
supplement to the June 20, 2012, issue of Journal of
Clinical Oncology. Onsite at the Meeting, this abstract will
be printed in the Monday edition of ASCO Daily News.
1507 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
The APC I1307K polymorphism as a significant risk factor for CRC in
average-risk Ashkenazi Jews. Presenting Author: Ben Boursi, Sheba Medical
Center, Ramat Gan, Israel
Background: The I1307K adenomatous polyposis coli gene variant, prevalent
among Ashkenazi Jews, may increase risk for colorectal neoplasia. We
studied the clinical importance of screening for this polymorphism in 3305
Israelis undergoing colonoscopic assessment. Methods: Blood samples and
risk factor information were collected from individuals undergoing colonoscopic
examination at our medical center. Germline genetic analysis for the
APC I1307K variant was performed using real-time PCR for DNA extracted
from peripheral mononuclear cells. Results: The overall prevalence of the
I1307K polymorphism was 8.0% (10.1% among Ashkenazi while only
2.7% among Sephardic Jews, p�0.001). The overall adjusted odds ratio
(OR) for CR neoplasia among carriers was 1.51(95% CI, 1.16 –1.98).
Among average risk Ashkenazi Jews, the OR was 1.76 (95% CI 1.26-2.45).
On the contrary, among Sephardi subjects the OR was 0.996 (95% CI,
0.51-1.93). A multiplicative interaction was identified between Ashkenazi
ethnicity and APC I1307K carrier status (PINTERACTION�0.055). The
histopathological features of adenomas and cancers did not differ between
carriers and non-carriers. Conclusions: The APC I1307K gene variant is an
important risk factor for CRC in average risk Ashkenazi jews and should be
considered for screening in this population.
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