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

628s Pediatric Oncology
9590 General Poster Session (Board #45D), Sun, 8:00 AM-12:00 PM
Trends in survival of childhood solid tumors diagnosed 1985-2008 in the
Nordic countries. Presenting Author: Milada Cvancarova, Cancer Registry
of Norway and University of Oslo, Oslo, Norway
Background: Classification of childhood solid tumors differs greatly from
tumors diagnosed in adults. Thus establishment of childhood cancer
registries is essential to monitor changes and progress in cancer care.
Methods: All individuals born in the Nordic countries are allocated a unique
ID number and have access to comprehensive health care services. Further,
it is required by law that all new cases of cancer are reported to cancer
registries. This makes it possible to achieve almost complete registration of
all cancer cases and their status together with information regarding the
cancer tumour and its treatment. Status registrations were made partly
from national population registries and partly from death registries only, as
conditions differ between countries. Crude survival was modelled using the
Kaplan-Meier method stratified by selected diagnostic groups, age groups
and diagnostic period. The crude estimates were compared with log-rank
tests. Results: In total, 12,343 children �15 yrs of age were diagnosed with
cancer during 1986-2010 in the Nordic regions (Denmark, Finland,
Iceland, Norway, Sweden) and classified according to Birch & Marsden
classification. Data were collected at the NOPHO solid tumour registry
located at the Cancer Registry of Norway. The overall incidence for the
whole period was 11.2 per 100,000 children per year. The overall 5-year
survival for all solid tumours reached 80.0 %, 95% CI [79.3 to 80.7] %.
There was a significant increase in survival for those diagnosed after 1991,
p � 0.001. Children diagnosed when older than 10 years reached higher
5-yrs survival than those diagnosed �5 yrs, 82.4% and 78.3%, respectively.
The highest 5-yrs survival was seen for retinoblastoma (97.0%),
germ.cell neoplasm (90.8%), renal tumours (88.3%) and lymphomas
(88.2%). The lowest 5-yrs survival was observed for sympathetic nervous
system (65.4%). The highest increase in survival was seen for non-Hodgkin
lymphoma pts, 77.2% diagnosed 1986-1990 vs. 85.9% diagnosed
2001-05. Conclusions: There has been some improvement in survival in
recent time periods, especially for some diagnoses. However, there were no
changes in overall survival wrt sex and only very limited changes in overall
survival by age groups.
9592 General Poster Session (Board #45F), Sun, 8:00 AM-12:00 PM
Effectiveness of using cardiac biomarkers to detect late anthracycline
cardiotoxicity in childhood leukemia survivors. Presenting Author: Beata
Mladosievicova, Comenius University, School of Medicine, Bratislava,
Slovakia
Background: Cardiotoxicity is usually detected only when clinical symptoms
or progressive cardiac dysfunction has already occurred. Cardiac biomarkers
(troponin T and N-terminal fragment brain natriuretic peptide precursor)
have been hypothesized to reflect subclinical anthracycline
cardiotoxicity earlier than echocardiography. This study aims to assess the
effectiveness of using cTNT and NTproBNP in asymptomatic long-term
survivors of childhood leukemia treated with and without antracyclines
(ANT). Methods: Sixty-nine childhood leukemia survivors 5-25years after
completion of therapy were evaluated with immunochemical analysis of
cTnT and NT-proBNP and echocardiography. Patients from group I (n �
36) received combined therapy with anthracyclines (ANT) with total
cumulative dose 95-600 (median 221) mg/m2 , patients from group II (n �
33) received therapy without anthracyclines (nonANT). Control group
consisted from 44 age- and gender-matched apparently healthy subjects.
Results: Levels of NTproBNP were significantly higher in ANT group than in
controls (median 51,52 vs 17,37 pg/ml; p�0.0026). Patients treated with
ANT had significantly increased median values of NTproBNP compared
with patients in non ANT group (51,52 vs 12,24 pg/ml; p�0.0002). CTnT
levels remained below the diagnostic cut-off levels in all groups. No patient
had echocardiographic abnormalities, but significant differences were
found in mean values of left ventricular ejection fraction and deceleration
time between patients treated with and without ANT. Conclusions: Assessment
of plasma NTproBNP concentrations may be an effective tool for
detection of late subclinical cardiac damage in survivors of childhood
leukemia previously treated with low ANT doses. Higher NTproBNP levels
in patients after ANT therapy might reflect an initial stage of cardiotoxicity
before the development of echocardiographic abnormalities. This study
was supported by a grant from Ministry of Health 2007/42-UK-18,
Slovakia.
9591 General Poster Session (Board #45E), Sun, 8:00 AM-12:00 PM
Bleomycin-associated lung toxicity in childhood cancer survivors. Presenting
Author: Alexandra Patricia Zorzi, The Hospital for Sick Children,
Toronto, ON, Canada
Background: Bleomycin has been established as a pulmonary toxin, but the
risk for toxicity in survivors of childhood cancer is poorly characterized.
Methods: We conducted a cross-sectional study of lung function in survivors
of childhood Hodgkin lymphoma and germ cell tumor treated with bleomycin
at our institution between 1997 and 2010. We assessed their most
recent post-therapy pulmonary function test (PFT). Spirometry and lung
volumes were categorized as normal, restrictive, obstructive or mixed.
Diffusing capacity of carbon monoxide (DLCO) was categorized as normal or
abnormal. Results: 195 patients were treated with bleomycin. Ten died of
non-pulmonary causes. Of 185 survivors, 143 (77%) had complete data
available for analysis. Median cumulative bleomycin dose was 60U/m2 (IQR 30-60). Three patients (2%) had a history of acute bleomycin toxicity.
PFTs were performed a median of 2.3 years (IQR 1.4-4.9) from completion
of therapy. Spirometry was abnormal in 58 patients (41%); of whom 5 (9%)
had respiratory symptoms. 42 (70%) had obstructive, 11 (18%) restrictive
and 5 (9%) mixed ventilatory defects. Abnormalities were mild in 53
(91%), moderate in 3 (5%) and severe in 2 (4%). DLCO was abnormal in
27 patients, 26 (96%) of whom had mildly reduced DLCO and were
asymptomatic. Univariate analysis did not demonstrate a significant
association between gender, smoking, lung metastases, lung radiation,
chemotherapy regimen, or autologous transplant and abnormal lung
function. Disease relapse was associated with abnormal lung function
(p�0.01). Smoking (p�0.04) and relapse (p�0.03) were associated with
abnormal DLCO. The odds ratio of developing abnormal spirometry for each
1unit/m2 increase in bleomycin was 1.01 (95% CI 1.00-1.02, p�0.07).
Conclusions: Childhood cancer survivors treated with bleomycin frequently
have evidence of asymptomatic abnormalities on PFT. The current recommendation
for pulmonary function testing in childhood cancer survivors
appears justified.
TPS9594 General Poster Session (Board #45G), Sun, 8:00 AM-12:00 PM
A phase II study of dasatinib therapy in children and adolescents with
newly diagnosed chronic phase chronic myelogenous leukemia (CML-CP)
or Philadelphia chromosome-positive (Ph�) leukemias resistant or intolerant
to imatinib. Presenting Author: Michel Zwaan, Erasmus University
Medical Center-Sophia Children’s Hospital, Rotterdam, Netherlands
Background: Dasatinib is a BCR-ABL inhibitor approved for treatment in
adult patients (pts) with newly diagnosed Ph� CML-CP; CML resistant/
intolerant to prior therapy, including imatinib; and Ph� acute lymphoblastic
leukemia (ALL). There are no established dasatinib treatment regimens
for children/adolescents with relapsed/refractory leukemia, but pediatric
trials are underway. A phase I dose-escalation study of dasatinib in
pediatric pts with refractory solid tumors (n�28) and imatinib-refractory,
Ph� leukemia (n�11) reported a maximum tolerated dose of 85 mg/m2 twice daily in solid-tumor pts and at least a partial cytogenetic response
(CyR) in all evaluable CML pts (n�9) (Aplenc, J Clin Oncol 2011).
Preliminary results from a phase I dose-escalation study in pediatric pts
with subtypes of relapsed/refractory leukemia (NCT00306202) indicate
that dasatinib was well tolerated up to 120 mg/m2 (Zwaan, Blood 2010
[abstr 2265]). Further study of dasatinib in pediatric pts is warranted.
Methods: To evaluate the safety and efficacy of dasatinib monotherapy in
children/adolescents with newly diagnosed CML-CP or Ph� leukemias
resistant/intolerant to imatinib, a phase II nonrandomized, global study of
dasatinib in pts birth to �18 y is ongoing (NCT00777036): Cohort 1 (C1),
Ph� CML-CP pts resistant/intolerant to imatinib; Cohort 2 (C2), Ph� ALL,
accelerated or blast phase CML pts resistant/intolerant to or relapsed after
imatinib therapy; or Cohort 3 (C3), newly diagnosed, treatment-naïve Ph�
CML-CP pts. Treatments are once daily with dasatinib 60 mg/m2 (C1/C3) or
80 mg/m2 (C2) for �24 months. Primary endpoints are major CyR (C1),
complete hematologic response (C2), and complete CyR (C3). Secondary
endpoints include safety, tolerability, best response, time to/duration of
response, survival, and molecular response rates. BCR-ABL mutations are
evaluated. First patient first visit was March 2009; estimated trial completion
is September 2016. As of January 2012, 63 pts (n�27 aged �12 y;
n�36 aged �12 y) have been treated in C1/C2 (n�41) and C3 (n�22).
Enrollment is ongoing at 79 sites.
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