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

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622s Pediatric Oncology<br />

9565 General Poster Session (Board #42D), Sun, 8:00 AM-12:00 PM<br />

Circulating myeloid-derived suppressor cells in pediatric solid tumor<br />

patients. Presenting Author: John M. Goldberg, University <strong>of</strong> Miami Miller<br />

School <strong>of</strong> Medicine, Miami, FL<br />

Background: Cure rates have reached a plateau for many pediatric solid<br />

tumors. Identifying new therapeutic targets, biomarkers <strong>of</strong> response and<br />

prognostic indicators should improve clinical outcomes. Accumulation <strong>of</strong><br />

myeloid derived suppressor cells (MDSCs) is an important mechanism <strong>of</strong><br />

tumor mediated immune evasion. Increased levels <strong>of</strong> MDSCs in adult<br />

cancer patients correlate with a worse prognosis, and decrease in levels<br />

with treatment is associated with benefit. Little is known about MDSCs in<br />

childhood, or in children with cancer. This pilot measured levels <strong>of</strong> MDSCs<br />

in pediatric patients with cancer and healthy children. Methods: We<br />

enrolled subjects using an Institutional Review Board approved protocol<br />

after obtaining informed consent. Blood was obtained from 14 children<br />

with newly diagnosed or recurrent solid tumors at start <strong>of</strong> therapy. In 10 <strong>of</strong><br />

these patients, levels were also drawn after therapy. Blood was obtained<br />

once from 6 healthy children in a primary care <strong>of</strong>fice. Samples were<br />

obtained concurrently with complete blood counts. MDSCs were measured<br />

on fresh whole blood and were defined as Lin-1�/HLADR-/CD 33�/<br />

CD11b�/ by flow. Total MDSC numbers were then calculated. Results: The<br />

mean total number <strong>of</strong> MDSCs was 596 cells/ul at diagnosis for the 14<br />

children with cancer and 170 cells/ul for the 6 healthy children (t(18) �<br />

3.02, p � .0073). For the 10 children with cancer who had repeat values<br />

measured after treatment, MDSCs decreased in 4 and increased in 6. The<br />

mean initial MDSC count for these children was 494 cells/ul, and the mean<br />

post treatment count was 1716 cells/ul (t(9) � 1.81, p � .1036). Larger<br />

change scores tended to be associated with children treated with alkylator<br />

therapy followed by G-CSF. The results for percent MDSC in white cells<br />

mirrored those <strong>of</strong> total number. Conclusions: Circulating MDSCs were<br />

higher in pediatric cancer patients than healthy controls. Cancer treatment<br />

did not reliably reduce MDSC levels. After some treatments, the levels<br />

increased, potentially increasing immune tolerance. Further research is<br />

needed to determine if circulating MDSCs are a reliable predictive or<br />

prognostic marker in pediatric cancer, and whether they represent a<br />

potential target for therapeutic intervention.<br />

9567 General Poster Session (Board #42F), Sun, 8:00 AM-12:00 PM<br />

Diffuse pontine gliomas in children: Do changing strategies change results?<br />

Presenting Author: Rejin Kebudi, Istanbul University, Cerrahpasa Medical<br />

Faculty and Oncology Institute, Istanbul, Turkey<br />

Background: The prognosis <strong>of</strong> children with diffuse intrinsic pontine<br />

gliomas (DIPG) is dismal. Despite various studies undertaken to improve<br />

outcome, radiotherapy (RT) remains the standard treatment, which is<br />

mostly palliative. This study aims to evaluate characteristics and treatment<br />

outcome <strong>of</strong> children with DIPG in a single center. Methods: We retrospectively<br />

reviewed the demographic, clinical characteristics and treatment<br />

outcome <strong>of</strong> children with DIPG treated at Istanbul University, Oncology<br />

Institute from 1999 to 2011. We also evaluated the group that prospectively<br />

recieved RT with concurrent and adjuvant temozolamide after 2004.<br />

Results: 47 children (24 female, 23 male) with the median age <strong>of</strong> 7 years (6<br />

months-16 years) were analyzed. The median duration <strong>of</strong> symptoms was 30<br />

days (2-630 days). The frequent clinical findings were ataxia, strabismus<br />

and motor weakness. All patients received RT, 54-60 Gy to the tumor site.<br />

12 recieved only RT. 35 had concomitant and/or adjuvant chemotherapy<br />

with RT. 8 recieved cisplatinum, 7 vincristine. Since 2004, 20 patients<br />

recieved the institutional protocol consisting <strong>of</strong> temozolomide (TMZ) (75<br />

mg/m2/day) for 6 weeks concurrent with RT, followed by TMZ (200<br />

mg/m2/day) for 5 days every 28 days for 12 cycles or until progression.<br />

There was no major side effect due to TMZ, thrombocytopenia being the<br />

most frequent, but managable side effect. The median overall survival after<br />

diagnosis was 13 months (3-132 mo.) for the whole group. The median<br />

overall survival in 20 patients that received RT and TMZ [ 17 months<br />

(3-132 months)], was significantly superior than that in 12 patients that<br />

recieved only RT [ 12 months (3-20 months)] ( (p�0.03). Nimotuzumab<br />

was given to 4 patients that progressed after RT and TMZ. There was no<br />

major side effect due to nimotuzumab. One was stable for 1 year with<br />

significant clinical improvement, the others were stable for 5, 2 and 2<br />

months after nimotuzumab. Conclusions: In our series, the median survival<br />

was significantly superior in patients who received RT with concurrent and<br />

adjuvant temozolamide in comparison to patients that recieved RT alone.<br />

Nimotuzumab may be promising in some progressive patients, its role as<br />

upfront treatment needs further investigation.<br />

9566 General Poster Session (Board #42E), Sun, 8:00 AM-12:00 PM<br />

Intensive alternating 6-drug chemotherapy for high-risk nonmetastatic<br />

rhabdomyosarcoma in children and adolescents: Impact on survival.<br />

Presenting Author: Gerges Attia Demian, National Cancer Institute, Cairo<br />

University, Cairo, Egypt<br />

Background: Both 5-year overall survival (OS) and event free survival (EFS)<br />

for pediatric rhabdomyosarcoma (RMS) has increased in the last 3 decades<br />

through multimodality, risk-adapted management. The reported EFS for<br />

high risk RMS in children treated at the NCI in Egypt during the 1990s was<br />

50%. Using an intensive 6 drug alternating chemotherapy regimen in<br />

addition to local control measures was our aim to improve the outcome for<br />

this group <strong>of</strong> patients. Methods: Forty-six previously untreated patients,<br />

younger than 21 years <strong>of</strong> age, with localized high risk RMS received this<br />

regimen. High risk criteria included: (1) Localized tumors (T1) biopsied or<br />

incompletely resected, ortumors extending beyond the tissue or organ <strong>of</strong><br />

origin (T2) completely or incompletely resected at any site (excluding orbit,<br />

uterus, vagina, and paratestis); (2)All node positive patients with primary<br />

tumor at any site; and (3) All RMS with alveolar histology at any site.<br />

Chemotherapy regimen comprised 27 weeks <strong>of</strong> alternating 6 drugs (carboplatin,<br />

doxorubicin hydrochloride, ifosfamide, actinomycin D, etoposide,<br />

vincristine). Local therapy (surgery, radiotherapy, or both) was <strong>of</strong>fered at<br />

week 9. Results: Forty-six patients meeting high-risk criteria were recruited<br />

from September 2000 to November 2005. Median follow-up <strong>of</strong> survivors<br />

was 62 months. The 5-year OS and EFS for the whole group was 64% �<br />

10% and 47% � 8% respectively. The EFS was significantly affected by:<br />

the size <strong>of</strong> the tumor (�5 cmvs.� 5 cm, p� 0.03), SIOP UICC clinical<br />

stage (p � 0.004), IRS stage (p � 0.01), lymph node status (p � 0.02),<br />

surgery vs. incisional biopsy (p�0.01) and overall duration <strong>of</strong> time in which<br />

therapy was delivered (p � 0.04). There was significant toxicity, mainly<br />

hematologic, but only one treatment related fatality. Conclusions: The use<br />

<strong>of</strong> intensified alternating 6-drug CT did not improve the EFS compared with<br />

historical control although it was feasible to be delivered safely in a variety<br />

<strong>of</strong> outpatient settings. Surgical resection <strong>of</strong> the tumor is essential.<br />

Delivering therapy in a timely fashion appears to impact outcome and<br />

future investigations will focus on impediments to administering chemotherapy<br />

as scheduled.<br />

9568 General Poster Session (Board #42G), Sun, 8:00 AM-12:00 PM<br />

Demographics, treatment, and outcome <strong>of</strong> retinoblastoma: A large series<br />

with protocol-based management. Presenting Author: Vijay Anand Palkonda<br />

Reddy, Apollo Hospitals, Hyderabad, India<br />

Background: Retinoblastoma is the most common primary intraocular<br />

malignancy <strong>of</strong> childhood with incidence <strong>of</strong> 1 in 20,000 and the third most<br />

common pediatric cancer. In the previous decades, early diagnosis and<br />

treatment <strong>of</strong> retinoblastoma have improved survival rates in developed<br />

countries. Nevertheless, protocol based management help reduce the<br />

mortality rate associated with advanced tumors. The purpose <strong>of</strong> the study is<br />

to report demographics, management, and outcome <strong>of</strong> retinoblastoma in<br />

the Ocular oncology centre <strong>of</strong> South India. Methods: Consecutive case<br />

series <strong>of</strong> 1,543 eyes <strong>of</strong> 1,067 patients with 22 years <strong>of</strong> follow-up.<br />

Demographics, clinical features, treatment and outcome (survival, organ<br />

salvage and function salvage) were analyzed. Management comprised <strong>of</strong><br />

focal therapy for small tumors, standard triple drug chemoreduction for<br />

larger (�4mm) tumors, high dose chemoreduction and periocular chemotherapy<br />

for vitreous seeds, and enucleation for advanced tumors. Adjuvant<br />

therapy was provided in patients with histopathologic high-risk factors for<br />

systemic metastasis. Orbital retinoblastoma was managed with a multimodal<br />

treatment protocol. Results: Sixty-six percent were �3 years <strong>of</strong> age.<br />

Forty-five percent were bilateral. Symptoms were leucocoria (33%), vision<br />

loss (10%), proptosis (6%), and squint (6%). The tumor was intraocular in<br />

94% and orbital in 6%. Management was by protocol and included<br />

enucleation (52%), chemoreduction (26%), focal therapy (11%), and<br />

external beam radiation (5%). Fifty-five percent <strong>of</strong> enucleated patients had<br />

histopathologic risk factors for metastasis and received adjuvant chemotherapy.<br />

Chemoreduction with focal therapy resulted in eye and vision<br />

salvage in 92%. Overall, 94% survived. Conclusions: Protocol-based<br />

management <strong>of</strong> retinoblastoma provides excellent prognosis for survival,<br />

eye salvage and vision salvage.<br />

Visit abstract.asco.org and search by abstract for the full list <strong>of</strong> abstract authors and their disclosure information.

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