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SOCI&Tt INTERNATIONALE D'ONCOLOGIE PEHATRIQUE
SIOP ASIA CONGRESS
ABSTRACT TOPIC
DISEASE ORIENTED
BONE TUMOURS
ABSTRACT NO.: PP-104
Level of the TFPI-2 mRNA expression and VEGF-A165/VEGF-A189 ratio in pretreatment tumour tissue is an independent predictor of poor prognosis for pediatric patients with nonmetastatic Ewing's sarcoma
L. Kisialeu, T. Savitskaya, N. Lipay, O. Aleinikova
National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus
en
Key words: angiogenesis, pediatric patients, Ewing's sarcoma, prognostic marcers
Introduction. The improvement of Ewing sarcoma (ES) therapy is currently linked to the selection of patients who are likely to develop disease recurrence and of modified treatment regimens for them. Vascular endothelial growth factor (VEGF) as well as tissue factor pathway inhibitor (TFPI) are known marker of carcinogenesis. We have previously shown that TFPI-2 mRNA (messenger ribonucleic acid) expression and VEGF-A165/VEGF-A189 mRNA ratio were significantly different in the metastatic versus nonmetastatic forms for children with malignant diseases of bones and soft tissues. We hypothesized that these biological markers may have prognostic value exclusively for patients with nonmetastatic ES. Aim. In this study we analyzed the ability to predict the response of ES to systemic therapy based on molecular markers.
Materials and methods. The mRNA expression level of TFPI-2 and ratio of VEGF-A165/VEGF-A189 isoforms in pretreatment tumour tissues from 20 nonmetastatic ES pediatric patients were studied by quantitative reverse transcriptase-polymerase chain reaction. The value P < 0.05 was regarded as statistically significant. Kaplan-Meier and log-rank methods were used, respectively, to draw and evaluate the significance of survival curves in patients with ES.
Results. It was identified molecular combination that reflect tumor resistance to conventional drugs before systemic treatment. We observed that low mRNA expression level TFPI-2 (< 0.8) and VEGF-A165/VEGF-A189 ratio (< 1) was a significant independent negative prognostic indicator of event-free survival (EFS) rate. For patients with nonmetastatic ES and molecular combination of poor prognosis 5-year EFS rate was 27 %, while for other patients it was 89 % (P < 0.05).
Conclusion. Discriminating patients with nonmetastatic ES into poor- and standard-risk groups possible to carry before systemic treatment based on angiogenesis markers: the mRNA expression level of TFPI-2 and ratio of VEGF-A165/ VEGF-A189 isoforms. This will provide an opportunity to intensify treatment for patients with poor prognosis.
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May 2016, Moscow, Russia
OF PEDIATRIC HEMATOLOGY and ONCOLOGY
ABSTRACT NO.: P-134
Endoprosthetic reconstruction of knee joint in children and adolescents with primary bone tumors in Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev
A.I. Karachunskiy, N.A. Bolshakov, N.S. Grachev, M.V. Tikhonova, K.S. Tsilenko
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: endoprosthetic reconstruction, primary bone tumors, knee joint, children, adolescents
Introduction. Endoprosthetic reconstruction is the most common method of limb-sparing surgery in oncology, including practical pediatrics. Primary bone tumors localized in metaphyseal areas require joint arthroplasty. Bone tumors in patients with sceletal immaturity occur in the metaphyseal region, close to the growth plate, so that sacrifice of a major plate often is necessary when tumor is excised. These patients need expandable prostheses.
Aim. Show own experience of endoprosthetic reconstruction of knee joint in children and adolescents with primary bone tumors.
Materials and methods. Since June 2012 in our surgery department 38 endoprosthetic reconstructions of knee joints have been performed. Among them 27 endoprosthetic reconstructions of the distal femur, including 10 cases with the use of "growing" non-invasive endoprosthesis; 11 endoprosthetic reconstructions of proximal tibia, including 5 cases using "growing" noninvasive endoprosthesis. The youngest patient was 7 years old, the oldest - 17 years old. The MSTS scale was used for evaluation of functional results in 3 months after operation. Results. During endoprosthetic reconstruction in the case of distal femur sarcomas in 25 patients range of volume replacement ranged from 160 to 315 mm. proximal. Range of proximal tibia replacement was 140-160 mm. In all cases, the results of histological examination of the resection margins showed no tumor cells, but 4 patients were diagnosed with progressive disease. 1 patient after 12 months was diagnosed with local relapse and required rotation plasty. All patients have started rehabilitation from the first days after surgery. The worst functional outcome scale MSTS after 3 months was - 50 %, the best - 93 %. Average - 76 %. At present time, just 6 patients with "growing" endoprosthesis have require extension, which was performed without any problems.
Conclusion. Limb-sparing surgery in children with oncological diseases of the musculoskeletal system is the preferred method of treatment. Endoprosthesis secures good oncological and functional results, as well as favors the most adequate social adaptation of a child. The use of modern oncological systems for arthroplasty in pediatric and adolescent surgical practice may achieve good oncological and functional results.
ABSTRACT NO.: PP-304
The role of radiation therapy in treatment of pediatric and young adult patients
with Ewing sarcoma family tumors
T. Jukhta1, Yu. Punanov1, I. Kazantsev1, A. Malinin2, S. Safonova1, G. Gafton2, A. Gevorgyan1, E. Morozova1, L. Zubarovskaya1, B. Afanasyev1
1Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Russia; 2N.N. Petrov Research Institute of Oncology, St-Petersburg, Russia
Key words: Ewing sarcoma, radiation therapy
Introduction. Ewing sarcoma family tumors (ESFT) have aggressive clinical course and tend to disseminate early, which is the reason for many advanced or metastatic
primary cases (about one third of patients). ESFT treatment programs combine dose-intensive systemic therapy with aggressive local control possibly sparing the limb function
(surgery and/or irradiation). ^
Aim. In this study, we evaluated radiation therapy effectiveness based on total dose (TD) and time-dose-fractionation (TDF) values. ^
Materials and methods. A total of 115 children (a median age of 10.5, range 2-17 years) with ESFT received treatment during the period of April 1985 - August 2013. 3
These patients are divided into two groups based on therapy intensity. The 1st group patients (n = 64) received therapy according to modi-fied T9 protocol, to 2nd group belong
51 patients receiving treatment according to EICESS-92 and Euro-EWING 99 protocols. Sixty-four (56 %) patients underwent primary lesion irradia-tion, 27 (23 %) surgical resection ^
and 21 (18 %) patients received a combination of both. The target TD was achieved by megavoltage external beam therapy in 5-6 weeks (by daily fractions of 1.8-2.0 Gy given 5 days co
a week). A median TDF value on the whole bone and soft tissue component was similar in the 1st (82.3, range 52-103 Gy) and the 2nd (825, range 59-108 Gy) group. In patients with
axial tumor the doze was conducted to the whole bone. If the lesion was limited to metaphysis or metadiaphysis, the non-involved epymetaphyses with epiphysial plate was excluded
after reaching TD of 30 Gy to longitudinal axis with boost to the lesion up to 50-55 Gy. All patients with metastatic disease (n = 11) received radiation therapy to all visible lesions.
Results. The most important factors for long-term survival were disease stage, therapy regimen used and disease recurrence (local or systemic). Although there was no difference
in event-free survival (EFS) between the groups (37.9 % and 39.5 %, P=0.25), the overall survival (OS) was better in the 2nd group, than in the 1st one (55 % and 25 % accordingly,
P = 0.03) due to better results in primarily disseminated disease patients. While there was no significant difference localized tumor treatment results (OS 49.5 % and 69.9 %,
P = 0.11; EFS 48.6 % and 48.8 %, P = 0.6 for 1st and 2nd groups patients accordingly), all patients with metastases from the 1st group died 45 months after the end of therapy, while
in the 2nd group OS and DFS are 45.8 % and 28.9 %, accordingly. Local and systemic relapse rate in localized disease patients was similar for both groups (30 % and 25 %, 52 %
and 58 %, accordingly), better result were generally observed in patients with most intensive local control combining surgery and irradiation (18.2% of local relapses).
The local control rate in patients receiving only irradiation was also evaluated based on TD and TDF values. Local relapse cumulative incidence in patients with TD values of
Conclusion. Unlike TD, TDF values showed direct correlation to local relapse rate with a minimal of 12.6 % reached in > 80 TDF group. This method of biologically equivalent dose
calculation may prove valuable for local control planning in ESFT patients.
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AoSTcACT disease oriented
SOCltTt INTERNATIONALE D'ONCOLOGIE PEHATRIQUE
SIOP ASIA CONGRESS
ABSTRACT NO.: PP-331
Preliminary treatment results of patients with malignant bone in Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev
M.V. Tikhonova, D.V. Rogozhin, A.S. Slinin, N.V. Zhukov, D.V. Litvinov, N.A. Bolshakov, K.S.Tsilenko, M.V. Teleshova, A.N. Remizov, A.V. Nechesnyuk, A.I. Karachunskiy
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: osteosarcoma, Ewing's sarcoma
Introduction. In Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev a scientific clinical group for bone tumors is formed and works. The infrastructure of the Centre allows to perform a full complex of examinations, treatment and rehabilitation of patients with malignant locomotor system tumors including all types of imaging, molecular genetic studies, different types of chemotherapy, targeted, high dose and radiation therapy, as well as all current methods of surgical treatment. A therapy study of patients with bone tumors within EURO EWING 2008 and EURAMOS-1 protocols begun from September 2012. Aim. To evaluate a programmed therapy efficiency in patients with osteosacoma and Ewing's sarcoma.
Materials and methods. From September 2012 79 patients with bone tumors were included in the study (Ewing's sarcoma - 30, osteosarcoma - 49) aged from 5 to 19. Exclusionary criteria: previous treatment according to other therapy regimens, timing breach, age of patients under 5 years, treamtent refusal of patients or their parents, osteosarcoma and Ewing's sarcoma of non-born localization. From the patients with osteosarcoma enrolled to the study, 41 (84 %) patients had conventional osteoblastic osteosarcoma, conventional chondroblstic - 4, fibroblatic - 1, teleangiectasic - 2, parosteal - 1 among osteosarcoma patients enrolled in the study. All histological diagnoses were verificated in Federal Research Center of Pediatric Hematology, Oncology and Immunology as a reference centre. Stage distribution: I stage - 1 , IIA - 9, IVB - 13, III - 3, IVA - 14, IVB - 8. Histologically 28 patients have Ewing's sarcoma among patients with Ewing's sarcoma. Primitive neuroectodermal tumor is in 2 patients. Accordign to stage: I - 2 patients, IIA - 7, IIB - 8, III - 1, IVA - 4, IVB - 8. Patients received a therapy within EURAMOS, EURO EWING 2008 protocols, respectively.
Results. At the moment 3-year event-free survival is 55 % in the osteosarcoma group and 25 % - in the Ewing's sarcoma group. All deaths resulted from main disease progression. No patient died as a result of acute treatment toxicity, severe late effects were not reported.
Conclusion. Current methods and approaches to malignant bone tumor therapy in children are available in Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, that allows the Centre to participate in international studies.
ABSTRACT NO.: OP-403
Experience in the treatment of Ewing's sarcoma of the pelvis in children.
East-European Sarcoma Group
D. Nisichenko, A. Dzampaev, O. Nisichenko, V. Khayrullova, D. Hestanov, M. Aliev
N.N. Blokhin Russian Cancer Research Centre, Moscow, Russia
Key words: Ewing' sarcoma, pelvis, VAC, IE
Introduction. Ewing sarcoma of the pelvis is one of the worst locations for treatment in children
Aim. The aim of our study was to determine treatment outcomes in two protocols: 1) using high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) and 2) protocol with decreasing doses of chemotherapy in pediatric patients with Ewing's sarcoma of pelvis treated at the East-European Sarcoma Group cc (N.N. Blokhin Russian Cancer Research Centre).
q Materials and methods. We retrospectively analyzed the data of patients with Ewing's sarcoma of pelvis between 1997-2011. All patients receive the same mode neoadjuvant
^ chemotherapy regimens 5 courses (VAC and IE).
Results. The first group included 31 children. Metastatic disease was found in 42 % of patients. The average tumor volume was 345 ml. Middle age was 11.5 y.o. lu The second group included 21 patients with a reduction in drug dosage. Metastatic disease was found in 33 % of patients. The average tumor volume was 298 ml. Middle age was 12.7 y.o.
Overall 1-, 3-, 5-y survival after HDCT/autoPBSCT were 70 %, 39 %, 39 %. Median was 17.2 months in first group. With metastatic disease overall 1-, 3-, 5-y survival were 46 %, 7 %, 7 %. Median was 10.2 months. With non metastatic disease overall 1-, 3-, 5-y survival were 88 %, 64 %, 64 %. Median not reached.
Overall 1-, 3-, 5-y survival in the second group were 100 %, 70.5 %, 58.8 %. With metastatic disease overall 1-, 3-, 5-y survival were 100 %, 68.5 %, 34.2 %. Median not reached. With non metastatic disease overall 1-, 3-, 5-y survival were 100 %, 71.4 %, 71.4 %. Median not reached. Data is valid (P = 0.008).
Conclusion. Although we obtained the best survival data in the second group than the first using HDCT/autoPBSCT, are different by selection the data volume of the primary tumor and rate of metastatic disease. Requires further study and monitoring of patients undergoing treatment for Ewing's sarcoma of the pelvis.
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