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

9536 Poster Discussion Session (Board #16), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Association of chromosome complexity with age and metastasis in synovial
sarcomas: Validation of expression and genomic prognostic signatures.
Presenting Author: Fred Chibon, Bergonie Cancer Institute, Bordeaux,
France
Background: Synovial sarcoma (SS) is one of the rare sarcomas that occurs
in adolescents as well as in adults. Nevertheless, metastasis occurs with a
lowest frequency in the former, 10 vs 50% respectively. In almost all cases,
a characteristic translocation t(X;18)(p11.2;q11.2) exists and the importance
of this translocation in SS oncogenesis is well established, but the
genetic basis of SS metastasis is still poorly understood. We recently
published expression (CINSARC) and genomic (GI) signatures related to
chromosome integrity control that predict outcome in undifferentiated
sarcomas and GIST and ask whether these signatures could also predict
outcome in SS. Methods: To asses this issue we selected in the European
sarcoma database CONTICABASE 92 primary untreated SS for expression
and genomic profiling. Results: As demonstrated by metastasis-free survival,
CINSARC and GI have strong and independent prognostic values (p �
1.6x10-5 and p � 4x10-6 , respectively). Comparing expression profiles of
tumors with or without metastasis in a training series of 58 SS, a 52-genes
signature was identified and validated in an independent series of 34 SS.
Fourteen of these genes are common with CINSARC and these 52 genes are
involved the same pathways than CINSARC, mitosis checkpoints and
chromosome integrity. Comparing genomic profiles of adult versus pediatric
SS we show that in both situations metastasis is associated to genome
complexity and that the adult genome is highly more frequently rearranged.
In line with this, the pediatric good-prognosis patients, according to GI, do
not develop metastasis. Conclusions: Results clearly indicate that SS
metastasis development is strongly associated with chromosome complexity
and that CINSARC and GI are powerful prognostic factors. Data also
mean that the metastasis frequency difference between adult and children
likely is associated to the genome instability which is highly more frequent
in adults. Finally, among these tree signatures, GI is potentially the best
overall and clearly the most clinically relevant considering that CGH from
FFPE samples is already used in the daily practice of pathology.
9538 Poster Discussion Session (Board #18), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Conservative treatment of intraocular retinoblastoma: A prospective phase
II randomized trial of neoadjuvant chemotherapy followed by local treatments
and chemothermotherapy. Presenting Author: Isabelle Aerts, Institut
Curie, Pediatric Oncology Department, Paris, France
Background: intraocular retinoblastoma treatments often associate chemotherapy
and focal treatments. The protocols vary and may combine two or
three drugs, and different number of cycles associated to the local adjuvant
treatments. A first prospective protocol of conservative treatments in our
institution showed the efficacy of the use of two courses of chemoreduction
with etoposide and carboplatin, followed by chemothermotherapy using
carboplatin, as a single agent. In order to decrease the possible long term
toxicity of chemotherapy due to etoposide, a prospective randomized phase
II chemo reduction protocol was conducted, using vincristine and carboplatin
vs. etoposide carboplatin. Methods: the study was proposed when initial
tumour size or location did not allow the use of front-line local treatments.
The phase II randomized study of reduction chemotherapy used vincristin
carboplatin or etoposide carboplatin, followed by local treatment including
chemothermotherapy using the combination carboplatin and laser diode
hyperthermia. Primary endpoint was the need for secondary enucleation or
EBRT not exceeding 40% at 2 years. The new treatment was considered
sufficiently effective if 10 events or less were observed among 33 eyes.
Results: 55 children, 65 eyes were included in the study (May 2004-
August 2009).32 eyes (27 children) were treated conservatively in the arm
etoposide-carboplatin and 33 (28 children) eyes in the arm vincristin
carboplatin.At two years after treatment 23/33 (69.7%) eyes were treated
and salvaged without EBRT or enucleation in the arm vincristin-carboplatin
and 26/32 (81.3%) in the arm etoposide and carboplatin. Conclusions:
neoadjuvant chemotherapy by two cycles of vincristine and carboplatin
followed by chemothermotherapy (using the combination carboplatin, as a
single drug, and laser diode hyperthermia) does not seem to offer an
optimal local control.
Pediatric Oncology
615s
9537 Poster Discussion Session (Board #17), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Evaluation of local control strategies in patients with localized Ewing
sarcoma of bone: A report from the Children’s Oncology Group. Presenting
Author: Steven G. DuBois, University of California, San Francisco, San
Francisco, CA
Background: Patients (pts) with Ewing sarcoma (EWS) require local control,
either with surgery alone (S), radiation alone (R), or a combination of
surgery � radiation (S�R). Optimal choice of local control for disease
control remains unclear. Our primary aim was to determine the mode of
local control associated with the highest event-free survival (EFS). Methods:
Pts with localized EWS of bone treated on INT0091, INT0154, or
AEWS0031 phase III trials were included if they had complete local control
data, did not have cranial tumors, received local control starting 2-6
months after enrollment, and were randomized to receive standard dose
5-drug chemotherapy every 3 weeks. We used propensity scores to control
for differences in age, tumor site, and year of diagnosis between local
control groups. We constructed Cox models controlling for local control
propensity scores to assess the impact of local control type on EFS and
overall survival (OS) from the start of local control. Results: 465 pts were
included. Pts selected for S were treated more recently (p � 0.001), more
likely to have appendicular tumors (p � 0.001), and younger (p � 0.02).
Pts treated with R, compared to S, had higher unadjusted risk of any event
(HR 1.70; 95% CI 1.18 - 2.44; p � 0.004) or death (HR 1.84; 95% CI
1.18 – 2.85; p � 0.006). Pts treated with S�R, compared to S, had higher
unadjusted risk of death (HR 1.75; 95% CI 1.10 – 2.76; p � 0.02). After
adjusting for propensity scores, there was a trend of higher risk of any event
for pts treated with R (HR 1.42; 95% CI 0.94 – 2.14; p � 0.10) compared
to S, though this was not statistically significant. No other differences in
adjusted risk of event or death between local control groups were statistically
significant. We confirmed these results with standard Cox models
using age, tumor site, and year of diagnosis as covariates. Conclusions: In
this large group of uniformly treated pts, investigator choice of local control
approach was not significantly related to EFS. These data support current
practice of surgical resection when feasible, while validating radiotherapy
as a reasonable alternative in selected pts.
9539 Poster Discussion Session (Board #19), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Carboplatin (CBP) versus cisplatin (CP) within prognostic groups in
pediatric extracranial malignant germ cell tumors (MGCTs). Presenting
Author: Juliet Hale, Newcastle upon Tyne Hospitals Trust, Newcastle upon
Tyne, United Kingdom
Background: It is established that CBP is inferior to CP in adult MGCTs
when used at AUC 5 or 400mg/m2 . There are no randomised data for
paediatric MGCTs, so conclusions from adult MGCTs have been generalised
despite differences in site, histology and biology. A database, pooling
patients from US and UK paediatric MGCT studies, was established to
determine prognostic factors in paediatric MGCTs. We examined the effect
of CBP and CP in identified prognostic groups. Methods: A dataset of 1110
paediatric MGCTs was created, treated 1983 to 2009. Treatment was CBP
(JEB, AUC 7.9) in the UK and CP (PEB) in the US. After excluding patients
with surgery only, pure germinoma or immature teratoma , 697 patients
remained. The cure model was used to assess the prognostic significance of
chemotherapy regimen after adjustment for patient characteristics. Results:
Analysis stratified prognosis according to age (0-10 v 11�yrs) and stage
(1-3 v 4) at diagnosis by site (testis: ovary: extragonadal). Outcome for CBP
and CP in these prognostic groups is shown in the table. Conclusions:
Interpretation of the results of this nonrandomised comparison requires
caution. However, after adjustment for other prognostic factors, the risks of
failure for JEB and PEB were not statistically different . This is particularly
true for 0-10yrs. At AUC7.9 CBP is tolerable in paediatric patients, with
potentially fewer late toxicities than CP.
Prognostic group 4-year EFS JEB (95% CI) 4-year EFS PEB (95% CI) P value
Testis 0-10 stage 1-3 0.94 (0.63-0.99) 0.92 (0.83-0.96) 0.79
Testis 0 –10 stage 4 0.82 (0.45-0.95) 0.94 (0.67-0.99) 0.31
Ovary 0-10 stage 1-3 1.00 (0.80-1.00) 1.00 (0.92-1.00) n/a
Ovary 0 -10 stage 4 0.67 (0.05-0.95) 0.80 (0.20-0.97) 0.78
Extragonadal 0-10 stage 1-3 0.92 (0.81-0.97) 0.90 (0.82-0.94) 0.90
Extragonadal 0-10 Stage 4 0.76 (0.60-0.86) 0.83 (0.74-0.90) 0.38
Testis 11� stage 1-3 1.00 (0.54-1.00) 0.95 (0.68-0.99) 0.57
Testis 11� stage 4 1.00 (0.16-1.00) 0.81 (0.59-0.91) 0.52
Ovary 11� stage 1-3 0.82 (0.62-0.92) 0.90 (0.80-0.95) 0.25
Ovary 11� stage 4 0.71 (0.26-0.92) 1.00 (0.29-1.00) 0.85
Extragonadal 11� stage 1-3 0.50 (0.01-0.91) 0.68 (0.44-0.83) 0.55
Extragonadal 11� stage 4 Not assessable 0.45 (0.17-0.71) 0.45
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.