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

9520 Clinical Science Symposium, Mon, 11:30 AM-1:00 PM
Real-time dynamic and sequential tracking of tumor propagation and
associated immune responses in the CNS microenvironment. Presenting
Author: Alex Yee-Chen Huang, Case Western Reserve University, Cleveland,
OH
Background: Ex vivo experimental systems are often unable to fully capture
complex intercellular communication between tumor cells and surrounding
tissues - a critical feature in understanding cancer development and
immune evasion. Imaging modality such as bioluminescence lacks the
resolution necessary to discern subtle structural differences and heterogeneity
in the tumor niche. Microscopic examination of fixed specimens is
devoid of the 3-dimensional context or evolution of tumor progression
within the same host. Methods: New insights have come from studies
involving the use of intravital 2-photon laser scanning microscopy (2P-
LSM), which allows deep visualization (�300um) with single-cell resolution
(�1um), thus enables direct observation of cellular behavior in intact
tissues at a suitable dynamic spatial-time resolution. We study the role of
tumor niche in shaping immune repertoire and develop strategies to modify
tumor niche to enhance anti-tumor immunity. Results: One example is our
study of glioblastoma multiforme (GBM), which contains a cellular hierarchy
with a CD133� sub-population representing self-renewing and tumorigenic
GBM stem cells (GSCs). In a xeno-transplant model, GSC was
capable of tumor initiation in the mouse brain. To directly test the relative
tumorigenic potential of GSCs (CD133�) and non-GSCs (CD133- ), we
inoculated paired tumor populations from the same primary GBM tumor
cells and monitored tumor competition by serial 2P-LSM through implanted
cranial windows. Serial 2P-LSM imaging shows that after 35 days,
GBM formation was driven exclusively by GSCs but not non-GSCs. To
interrogate tumor-associated immune responses, we inoculated syngeneic
mouse glioma tumors into C57BL/6 mice. Using this and CNS-inflammatory
models, we have begun to undercover the role of perivascular
antigen-presenting cells and microglia in guiding the recruitment of
CNS-bound lymphocytes. Conclusions: Our data provide the first direct
functional evidence that CSCs are responsible for tumor propagation in
GBM, and represent an in vivo experimental platform to monitor immunotherapeutic
interventions.
9522 Poster Discussion Session (Board #2), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Outcome of 116 cases of pleuropulmonary blastoma type I and type Ir
(regressed): A report from the International PPB Registry (IPPBR). Presenting
Author: Yoav H. Messinger, Children’s Hospitals and Clinics of
Minnesota, Minneapolis, MN
Background: Pleuropulmonary blastoma (PPB) is a rare dysembryonic lung
neoplasm of early childhood with progression from a purely cystic Type I
(T-I) lesion to cystic solid and solid high grade sarcoma (Type II and Type
III). A regressed form of PPB (T-Ir) has been recognized pathologically. The
outcome of both T-I and T-Ir has been only partially described. Methods:
Retrospective analysis of 345 IPPBR cases showed 116 T-I or T-Ir. In all
cases the PPB diagnosis was made on surgically removed cysts. The
treating physician decided whether to use chemotherapy after surgery.
Results: The pathologic diagnosis of the 91 PPB T-I and 25 T-Ir is now
confirmed by central review (LPD and DAH). Patients with T-I were younger
than T-Ir (median: 8 months vs. 48 months).Diagnosis after age 6 years
included only one T-I compared to 10 T-Ir patients. Therapy is not known
for 28 T-I and 2 T-Ir. Surgery was followed by chemotherapy in 31 T-I and 2
T-Ir. Six (5%) recurred with the same type, all were alive at last follow-up: 5
(5.5%) T-I, 1 (4%) T-Ir. Progression to high-grade Type II or III occurred in
9/91 (10%) T-I and 2/25 (8%) T-Ir. The addition of chemotherapy did not
significantly reduce progressions (Fisher’s exact test). All of the tumor
progressions were seen by 75 months of age; this finding is similar to
broader IPPBR data: � 95% of patients are diagnosed with Type II/III by
72 months of age. Of the 9 patients with T-I who progressed, 5 ultimately
died, whereas the 2 T-Ir who progressed were alive. At last follow-up
111/116 (95.6%) were alive. Conclusions: A cyst in an older individual
most likely will be Type Ir. Type I and Type Ir are clinically similar with a
small risk of progression to the advanced Type II/III up to 6 years of age.
Outcome for those whose cystic PPBs progressed is poor. The role of
chemotherapy remains uncertain for the prevention of progression in the
pure cystic PPB Type I or Ir.
Upfront chemotherapy and progression.
Progression No progression Total
Type I:
Surgery � chemotherapy 2 29 31*
Surgery only 6 25 31
Unknown
Type Ir:
1 27 28
Surgery � chemotherapy 1 1 2**
Surgery only 1 19 20
Unknown 0 2 2
Excluding 2 chemotherapy treated patients: for 2nd malignancy*, and for concurrent rhabdomyosarcoma**
Pediatric Oncology
611s
9521 Poster Discussion Session (Board #1), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Effect of radiation on outcome of types II and III PPB: A report from the
International Pleuropulmonary Blastoma Registry. Presenting Author:
Gretchen M. Williams, Children’s Hospitals and Clinics of Minnesota,
Minneapolis, MN
Background: Pleuropulmonary blastoma (PPB) is a rare dysembryonic lung
neoplasm of early childhood with progression from a purely cystic (Type I)
lesion to a solid high-grade sarcoma Type III (T-III), or a mixed solid/cystic
stage Type II (T-II). Surgery and chemotherapy are required for T-II and
T-III PPB, but the benefit of radiation therapy for T-II and T-III PPB is
debated and is being evaluated in this study. Methods: This is a retrospective
analysis of central pathology-reviewed Types II and III PPB from the
IPPBR. Treatments were chosen by physician, were not randomized, and
included surgery and chemotherapy. The outcome of patients treated with
upfront radiation (before progression or relapse) was compared to patients
who did not receive radiation. Event-free survival (EFS) and overall survival
(OS) were determined to last follow-up, using the Kaplan-Meier analysis,
with log-rank test. Results: Outcome for 212 patients (117 Type-II and 95
Type III) was significantly better for T-II than T-III: EFS for T-II was 68.1%
vs. T-III 45.7% (P�0.002), and OS for T-II was 75.2% vs. T-III 57.9%
(p�0.01). Excluding patients with incomplete therapy information, 174
were treated with surgery and chemotherapy. Of these 44 (25%) also
received radiation therapy; 130 patients did not. The table below shows
comparison of radiated vs. non-radiated. Radiation provided no additional
survival benefit, overall or by tumor Type. Multivariate analysis showed that
gender and extent of primary tumor resection (biopsy vs. gross total
resection) had no effect on outcome, however T-II vs. T-III retained
prognostic significance. Conclusions: For this collection of advanced-type
PPB, outcome is significantly better for T-II than T-III. For patients treated
initially with surgery and chemotherapy, adding radiation therapy offered
no improvement in event-free or overall survival. Limitations of this study
include its retrospective nature and non-uniform treatment regimens.
Non-radiated Radiated P (log-rank)
All patients (n�174) EFS 55.5% 46.1% 0.312
OS 63.1% 63.6% 0.952
Type II (n�90) EFS 65.8% 46.7% 0.096
OS 70.7% 66.7% 0.651
Type III (n�84) EFS 41.8% 46.4% 0.452
OS 52.7% 62.1% 0.405
9523 Poster Discussion Session (Board #3), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Increase in the incidence of differentiated thyroid carcinoma in children,
adolescents, and young adults (AYA): A population-based study. Presenting
Author: Lucas B. Vergamini, Faculdade de Ciencias Medicas da Santa Casa
de Sao Paulo, Sao Paulo, Brazil
Background: Studies have shown an increase in thyroid cancer incidence
among adults since the 1990s. However, few studies have evaluated this
occurrence among children and AYA. Increases resulting from enhanced
detection are most likely to involve small tumors. The objective of this study
is to investigate trends in incidence of differentiated thyroid carcinomas in
children and AYA by size and sex. Methods: This is an ecological time-trend
study. Cases of differentiated thyroid cancer (1984-2008) in patients
younger than 30 years old were selected from SEER 9 cancer registries
using International Classification of Diseases for Oncology 3rd edition
(ICD-O-3) codes for papillary and follicular cancers (codes 8050/3,
8052/3, 8130/3, 8260/3, 8290/3, 8330-8332/3, 8335/3, 8340-
8344/3, 8450/3 and 8452/3). Patients who had multiple primary tumors
were excluded from the study. SEER*Stat software was used to calculate
age-standardized rates (estimated per 1,000,000 persons; World Standard
Population) and annual percentage changes (APC) were calculated using
Joinpoint model. Results: Rates ranged from 2.77 (1990) to 7.45 (2002)
for males and from 17.19 (1987) to 41.3 (2008) for females. Overall, a
significant increasing trend in incidence was observed for females
(APC�3.20, 95%CI 2.80, 3.60). When a stratified analysis based on
tumor size was performed, significant increasing trends were noted for the
following categories: 0.5-0.9 cm (Males: APC�3.50, 95%CI 1.50, 5.40;
Females: APC�7.30, 95%CI 5.90, 8.80), 1.0-1.9 cm (Males: APC�3.20,
95%CI 1.00, 5.40; Females: APC�2.90, 95%CI 2.20, 3.70), and � 2cm
(Males: APC�1.30, 95%CI 0.30, 2.40; Females: APC�2.50, 95%CI
1.70, 3.20). However, no statistically significant trends were noted for
tumors �0.5 cm (Males: APC�2.50, 95%CI -0.30, 5.40; Females:
APC�2.0, 95%CI -6.90, 11.80). Conclusions: Incidence rates for differentiated
thyroid carcinoma are also increasing among children and AYA in the
United States. The absence of increasing trends for small tumors (� 0.5cm)
rules out diagnostic scrutiny as the only explanation for the observed
results. Environmental, dietary and genetic factors should be investigated.
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