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47
CNS TUMOURS
ABSTRACT NO.: PP-110
A case of hepatic veno-occlussive disease (VOD) presented as huge hemothorax after the first chemotherapy for childhood medulloblastoma
Chueh Hee Won, Lee Mi Ji, Joe Sun Young
Dong-A University Hospital
Key words: medulloblastoma, VOD, standard chemotherapy
Introduction. Hepatic veno-occlusive disease (VOD) is a serious toxic complication occurring after autologous and allogeneic hematopoietic stem cell transplant (HSCT). Also, there were many reports on VOD associated with certain chemotherapeutic agents, such as actinomycin-D for the treatment ofWilms tumor and rhabdomyosarcoma, and 6-thioguanine for acute lymphoblastic leukemia. However, VOD occurrence associated with regular chemotherapy is rare, and it has been regarded as "transplantation-related complication". Aim. We report a 21-months-old boy with high-risk medulloblastoma, who developed severe hepatic VOD presenting huge hemopthorax and ascites during his second cycle of chemotherapy, and recovered after PGE1 treatment.
Materials and methods. Case report. 21-months-old boy was arrived to Dong-A University Hospital for the complaints of decreased mentality and seizure. Brain-imaging study revealed large mass located in cerebellar area with severe hydrocephalus, and he received total resection of tumor operation. Biopsy confirmed medulloblastoma, but he couldn't receive chemotherapy due to recurrent aggrevation of hydrocephalus. After receiving other two EVD insertion operation and V-P shunt operation, his mentality didn't improved through the hydrocephalus improved, and the MRI showed progression of the tumor with increased metastatic seeding through the ventricle and spine. Chemotherapy was started according to the protocol of KSPNO-S1102, which was developed by Korean Society of Pediatric neurosurgery and oncology for the patients under 3 year with high-risk medulloblastoma. His plan was receiving two different chemotherapy regimens alternatively for 6 months, and receiving tandem high-dose chemotherapy with autologous stem cell transplantation. Radiation therapy was planned to start after his age reach 3-year-old.
Results. He received chemotherapy with cisplatin, cyclophosphamide, etoposide and vincristine. On chemoday he showed high-grade fever with grade 5 neutropenia. When the WBC counts recovered, he suddenly showed desaturation with haziness on both lung fields. Chest CT showed the large volume of effusion - suspected hemorrhage. Chest tube was inserted, and the large volume of blood got out continuously through the chest tube. He also showed large amount of ascites and bloody diarrhea. Blood test revealed that he was in the state of hepatic VOD. FFP and albumin transfusion, continuous heparin and PGE1 infusion started. After 20 days later, VOD was completely recovered, and he could undergo next cycle of chemotherapy. After that, the VOD didn't relapse during the treatment course.
Conclusion. Our patients presented severe hepatic VOD with huge hemothorax after the single course of chemotherapy, which is not so intensive, and rarely considered to induce VOD. There are a few reports of VOD occurred in standard chemotherapy setting, and all patients didn't receive the chemotherapy agents which are known to be related to VOD. But this is the second report ofVOD occurred after the 1st chemotherapy in the patient with medulloblastoma. Therefore, VOD also should be considered as important complication during the induction chemotherapy.
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topicract DISEASE ORIENTED
SIOP ASIA CONGRESS
ABSTRACT NO.: OP-114
Low-grade gliomas in children, associated with neurofibromatosis type I
R.R. Bayramgulov1, A.R. Bayramgulova1, A.A. Gumerov2, R.A. Gumerov1, V.B. Makhonin1, I.I. Badrtdinova1
Republican Children's Clinical Hospital, Ufa, Republic of Bashkortostan; 2Bashkirian State Medical University, Ufa, Republic of Bashkortostan
Key words: low-grade gliomas, astrocytoma, children, neurofibromatosis, chemotherapy
Introduction. Low-grade gliomas (LGG) are the most common brain tumors in pediatric population comprising 30 % of primary central nervous system (CNS) tumors in children. Neurofibromatosis type I (NF-I) is a hereditary syndrome of which predisposition to the development of peripheral nervous system (PNS) and central nervous system (CNS) tumors is typical. Low-grade gliomas (LGG) with optic nerve, chiasm and hypothalamus involvement develop in 10-12 % of children with NF-I. Aim. To evaluate the results of treatment for low-grade gliomas (LGG) associated with NF-I in children who received treatment at our centre.
Materials and methods. 79 patients with low-grade gliomas (LGG), 8 of which (10.1 %) were associated with NF-I received treatment at SBHI RCCH (State Budgetary Healthcare Institution "Republican Children's Clinical Hospital") from 12.05.2008 till 25.12.2015. All patients irrespective of age received chemotherapy (CT) with vincristine and carboplatin after neurovisualization and surgery.
Results. Female patients prevailed (ratio 6:2). Distribution according to the age was the following: 1-4 years old - 3 (37.5 %) cases, 5-10 years - 2 (25 %) cases, older than 11 years old - 3 (37.5 %) cases. Tumour localization in all patients is presented with visual pathways and hypothalamus. According to the Dodge classification stage I was determined in 2 cases, stage II was observed in 5 cases, stage III was determined in 1 case. Neurovisualization was performed in all patients after the manifestation of symptoms: ophthalmological in 8 cases, neurologic - in 6 cases, general cerebral - in 3 cases, diencephalic syndrome - in 2 cases, endocrinological disorders - in 2 cases. In 1 (12.5 %) patient with chiasmatic-hypothalamic tumor, diencephalic syndrome, endocrinopathy there was performed partial resection of diffuse astrocytoma of WHO grade II followed with chemotherapy that was complicated by lethal toxicity. Chemotherapy (CH) was performed after neurovisualization in 7 patients. Stabilization of the disease after chemotherapy was achieved in 6 cases, partial remission was achieved in 1 case. 7-year overall survival and progression-free survival were 87.5 %.
Conclusion. The results of treatment for low-grade gliomas (LGG) associated with NF-I are favorable. The main indication to the administration of chemotherapy (CH) in case of low-grade gliomas (LGG) and NF-I were ophthalmological symptoms, diencephalic syndrome. Factors of unfavorable prognosis in case of low-grade gliomas (LGG) associated with NF-I are age above 5 years, chiasmatic-hypothalamic localization, diencephalic syndrome.
ABSTRACT NO.: OP-115
Epidemiology of low-grade gliomas in children
R.R. Bayramgulov1, A.R. Bayramgulova1, A.A. Gumerov2, R.A. Gumerov1, V.B. Makhonin1, I.I. Badrtdinova1
Republican Children's Clinical Hospital, Ufa, Republic of Bashkortostan; 2Bashkirian State Medical University, Ufa, Republic of Bashkortostan
Key words: low-grade gliomas, astrocytoma, children, epidemiology
Introduction. Low-grade gliomas (LGG) represent a heterogenous group of central nervous system (CNS) tumours in children that comprises 30-50 %. There is a suggestion that the number of these tumours is understated in children's cancer registers that is partially due to the limited referral of patients to specialized centres. Aim. To investigate epidemiological peculiarities of low-grade gliomas (LGG) in children by the experience of our centre.
Materials and methods. We have carried out the analysis of the patients who received treatment for low-grade gliomas (LGG) at the SBHI RCCH (State Budgetary Healthcare Institution "Republican Children's Clinical Hospital") during 12.05.2008 - 25.12.2015. Data about the patients was obtained from medical documents with identification of patients with the histologically proved diagnosis of low-grade gliomas (LGG). Data analysis included age, sex, association with neurofibromatosis type I (NF-I). Moreover data of neurovisualization was analyzed in order to specify the tumour localization and define involved brain structures.
Results. During the stated period 79 children with low-grade gliomas (LGG) remained under observation at SBHI RCCH. 49 male patients, 30 female patients (ratio was 1.6:2) were registered. 8 (10.1 %) of 79 patients with low-grade gliomas (LGG) were associated with NF-I. Age distribution among the patients with NF-I was the following: 1-4 years old - 3 (37.5 %) cases, 5-10 years old - 2 (25 %) cases, older that 11 years old - 3 (37.5 %) cases. Brain hemispheres were involved in 10 (12.2 %) cases, of which the tumour localization in temporal lobe was in 6 children, in frontal lobe in 2 children, in occipital lobe in 1 child, there was 1 case with the involvement of several lobes. Supratentorial medial localization was presented in 30 (36.6 %) patients, optic nerves were involved in 2 cases of them, chiasm was involved in 6 cases of them, optic nerves/chiasm -in 3 cases of them, optic nerves/chiasm/ hypothalamus - in 4 cases of them, chiasm/ thalamus/ hypothalamus - in 3 cases of them, chiasm/ III ventricle - 1 observation, chiasm/ III ventricle/ hypothalamus - 2, thalamus - 5, thalamus/ III ventricle - 1, other medial structures - 3 observations. The involvement of cerebellum was observed in 30 (36.6 %) cases, of them the involvement of the right hemisphere was noted in 5 observations, the left hemisphere - in 4, vermis - in 10 cases, the right hemisphere/vermis - in 4, the left hemisphere/ vermis - in 3, both hemispheres/vermis - in 4. Brainstem was involved in 3 children, spinal cord - in 2 (2.4 %) at the level of C2-Th9, C1-Th10. Other brain structures were involved in 10 (12.2 %) patients. 3 children had several tumours of different localizations. Tumour localization in all patients with NF-I was presented with visual pathways, hypothalamus. Histology is verified in 71 patients: pilocytic astrocytoma (Ac) I - 30 cases, desmoplastic infantile ganglioglioma I - 1, pleomorphic xanthoastrocytoma II - 1, diffuse astrocytoma (Ac) II - 27, other - 10. In 8 cases with low-grade gliomas (LGG), associated with NF-I verification was not necessary.
Conclusion. The predominance of male patients was observed. Typically low-grade gliomas (LGG) are diagnosed at the age of 1-10 years old. The association with NF-I is noted in 10.1 %. Main localizations of low-grade gliomas (LGG) are medial supratentorial and cerebellum. In most cases tumour histology was presented with pilocytic astrocytoma (Ac) and diffuse astrocytomas (Ac).
|df pediatric hematology
and oncology
ABSTRACT NO.: Q-127
Placement of the Ommaya reservoir in narrow and slit-like ventricles using a neuronavigation system
S.S. Ozerov1, A.E. Samarin1, A.V. Melnikov2, E.V. Kumirova1
1Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia; 2Research Institute of Emergency Children's Surgery and Traumatology, Moscow, Russia
Key words: Ommaya reservoir, intraventricular chemotherapy, methotrexate, medulloblastoma
Introduction. Recently, a remarkable progress has been achieved in the treatment of patients with malignant tumors of the central nervous system (CNS) and oncohematological diseases. An important part of treatment protocols is intraventricular administration of methotrexate and other chemotherapy agents. An essential requirement for the conduction of intraventricular chemotherapy is availability of an Ommaya reservoir, a special port that enables physicians to perform multiple and painless sampling of ventricular liquor and deliver chemotherapy agents into the ventricular system of the brain. In most cases the placement of Ommaya reservoir is obstructed by the small sizes of the ventricles of the brain. Nowadays, the insertion of Ommaya reservoir in patients with narrow ventricles of the brain is performed either with the use of stereotactic frame or neuronavigation. In order to simplify and reduce the price of catheterization of narrow ventricles of the brain for the placement of an Ommaya reservoir and shunt systems, the method of stereotactic placement of Ommaya reservoir and catheterization of narrow ventricles of the brain with the use of special ventricular guide (Thomale-guide) was studied and implemented in our Centre for the first time in Russia. This method make it possible to insert Ommaya reservoirs and ventricular catheters into narrow ventricles of the brain without the use of stereotactic frame and expensive navigation systems.
Aim. To simplify and optimize the method of Ommaya reservoir placement, to achieve a high precision of reservoir placement in patients with narrow and slit-like ventricles without the use of expensive navigation and stereotactic systems.
Materials and methods. An Ommaya reservoir is a convenient and safe port for intraventricular delivery of chemotherapy agents in patients with oncohematological and neurooncological diseases. From 2012 until 2016 at the FRC PHOI n.a. Dmitry Rogachev 56 Ommaya reservoirs were inserted in 56 patients.
The reservoir was inserted without the use of any devices in 3 cases. However, in most cases the procedure was performed with the help of stereotactic techniques owing to small sizes of the ventricular system of the brain. The reservoir was inserted by means of neuronavigator in 47 patients. In 6 patients stereotactic procedure was carried out based on a new technology with the use of Thomale-guide, that makes it possible to simplify and accelerate the intervention while maintaining necessary precision. Results. In all the cases a catheter was inserted into the anterior horn of lateral ventricle on the first attempt, that was confirmed by successful functioning of Ommaya reservoir as well as by the results of postoperative computed tomography or magnetic resonance imaging. In 1 patient the placement of Ommaya reservoir was performed along with a stereotactic biopsy. We did not observe any complications described in the literature such as infectious complications, hemorrhage, improper placement of a ventricular catheter. In 2 patients a few months after operation we registered the dysfunction of the reservoir caused by the displacement of a pump in the subcutaneous pocket that resulted in constriction of a ventricular catheter. In both cases normal functioning of the system was restored after the revision of the pump.
Conclusion. An Ommaya reservoir is a convenient and safe port for intraventricular delivery of chemotherapy agents in patients with oncohematological and neurooncological diseases. A Thomale-guide enables us to achieve high precision during the insertion of Ommaya reservoir and can substitute navigation stereotactic systems.
ABSTRACT NO.: OP-148
The role of adjuvant chemotherapy for radiation therapy of diffusely growing tumors
of the brain stem in children
Key words: children, brain stem tumors, radiation therapy, chemotherapy
Introduction. The poor results of radiation therapy of diffuse brain stem tumors are forced to combine the irradiation with the use of chemotherapy Aim. To evaluate the contribution of chemotherapy to the radiation treatment results
Materials and methods. We carried out the analysis of immediate and long-term results of radiotherapy or chemoradiotherapy in 120 children and adolescents with inoperable diffusely growing tumors of the brain stem, treated in the Children's Department of RSCRR in 1998-2013. Age of patients ranged from 2 to 18 years, median age was 8 years. In 22 patients biopsy of the tumor was performed: 8 cases were glioblastomas, 5 patients had pilocytic astrocytomas, 4 cases were anaplastic astrocytomas, 4 - fibrillary astrocytomas and one patient had a diffuse astrocytoma. In 93 patients radiotherapy was combined with adjuvant chemotherapy: Temozolomide (41), the combination ofVincristine and Lomustine (19), Ftorafur (11), Oncofer (16), Teralok (6). 27 children received only radiation therapy.
Results. Treatment was completed in 117 patients, the treatment of three patients was interrupted due to worsening of their condition. The main toxic effects in the form
the myelodepression and neuropathy was observed in some patients receiving chemotherapy. 110 of 117 patients, who underwent the whole course of irradiation (94 %), achieved
complete or partial regression of neurological disorders. Upon further observation 113 children died. In all cases the cause of death was tumor progression. 7 patients have been
observed for the period from 29 months to 152 months. Average life expectancy for the entire group was 13.5 ± 11.3 month: 13.7 ± 10.2 months after chemoradiation treatment
and 13.2 ± 11.1 months after only radiation therapy. Six of ten 2-year survivors had morphological confirmation: 4 cases had pilocytic astrocytoma, one had fibrillar astrocytoma ^
and one had diffuse astrocytoma. All glioblastoma patients died within the first 6 months.
Conclusion. The prognosis in the diffuse growing brain stem tumors completely depends on the degree of malignancy. Adjuvant chemotherapy in several variants used by us did not improve the results of radiation therapy, but led to an increase of economic costs and in some patients to the development of toxic complications.
O.I. Shcherbenko, R. Parhomenko, N. Zelinskaya, F. Antonenko
Russian Scientific Center of Roentgenology and Radiology, Moscow, Russia
SIOP ASIA CONGRESS
abstract topic
ABSTRACT NO.: PP-168
The responsiveness of pediatric brain tumor patients with poor prognostic factors to combination treatment with oral temozolomide and radiotherapy
Tamami Yano, Michihiro Yano, Miwa Hebiguchi, Koya Kodama, Tsutomu Takahashi
Akita University Hospital
Key words: recurrent brain tumor, temozolomide, radiotherapy
Introduction. Some trials are being performed with the aim of improving the treatment outcomes of pediatric patients with brain tumors and poor prognostic factors. Temozolomide (TMZ) is a candidate drug that is expected to affect these tumors.
Aim. We observed the clinical course and results of patients with unresectable pontine gliomas or recurrent brain tumors who received combination treatment with oral TMZ and radiotherapy.
Materials and methods. TMZ was administered orally with radiotherapy to the pontine glioma patients. The patients with other recurrent brain tumors were first managed in the same manner as the patients with pontine gliomas; TMZ then was administered alone.
Results. Case 1. A six-year-old female with a pontine glioma. TMZ was administered with local radiotherapy (54 Gy). She died of the disease at 8 months after her diagnosis. Glioblastoma was positively identified at autopsy. Case 2. A nine-year-old male with a pontine glioma. TMZ was administered with local radiotherapy (56 Gy). The patient died of the disease at 21 months after his diagnosis. Case 3. A four-month-old female who was initially diagnosed with a glioblastoma of the left parietal lobe. The patient's tumor was persistent, despite the administration of two courses of combined chemotherapy after tumor resection. TMZ and radiotherapy were administered, followed by TMZ alone for approximately 3 years. Five years after the termination of TMZ, she has shown no signs of disease reprogression. Case 4. A one-year-old male who was initially diagnosed with a medulloblastoma of the fourth ventricle and disseminated spinal metastases. According to the study protocol of a Japanese group, he underwent six courses of combined chemotherapy, several courses of intrathecal chemotherapies, and two courses of high-dose chemotherapy with autologous bone marrow transplantation. Multiple relapsed nodules were found in his cerebral ventricle and on the surface of his spine at one year after treatment. TMZ and radiotherapy were administered, followed by TMZ alone for approximately 6 months. Five and a half years after the termination of TMZ, he has shown no signs of disease reprogression.
Conclusion. In the cases of pontine glioma (cases 1 and 2), the prognosis was considered to be poor because tumor resection was impossible. Bevacizumab, which is an antivascular endothelial growth factor (VEGF) monoclonal antibody, is expected to improve the prognosis of pontine glioma. The treatment outcomes of cases 3 and 4 show the potential of TMZ in improving the prognosis of patients with recurrent pediatric brain tumors. However, the contribution of radiotherapy should not be ignored. Furthermore, physicians should be vigilant for secondary malignancies, which may be induced by the long-term administration of TMZ and careful care should be taken in the long-term follow up.
ABSTRACT NO.: PP-169
An effective stereotactic radiotherapy for recurrent pilomyxoid astrocytoma in the medulla oblongata of pediatric patient
Tamami Yano, Michihiro Yano, Miwa Hebiguchi, Koya Kodama, Tsutomu Takahashi
Akita University Hospital
Key words: pilomyxoid astrocytoma, medulla oblongata, recurrent tumor, combination chemotherapy, stereotactic radiotherapy
Introduction. Pilomyxoid astrocytoma (PMA), which mainly arises within the hypothalamic-chiasmatic region, was classified as a WHO grade II disease in 2007. PMA is associated with a poor prognosis in comparison to pilocytic astrocytoma (PA, WHO grade I). It is necessary to search for a recommended treatment strategy for PMA. Aim. Stereotactic radiotherapy (SRT) was administered to a pediatric patient with recurrent PMA in the medulla oblongata.
Materials and methods. Case. A ten-month-old female presented with hoarseness, torticollis, difficulty of swallowing and poor body weight gain. MRI revealed that a heterogeneously enhanced mass projected from her medulla oblongata toward the left cerebellar hemispheres. The tumor was removed to the maximum possible extent. A histopathological examination revealed characteristics of PMA. Following surgery, four courses of combination chemotherapy consisting of cisplatin, etoposide, cyclophosphamide and vincristine were administered, and her neurological symptoms gradually disappeared. About two years after the completion of chemotherapy, the remaining tumor, that had initially been unresectable, began to slowly grow in size without any symptoms.
Results. We administered SRT (36 Gy, 9 Fr) because chemotherapy was not expected to have further effects. None of side effects of SRT occurred. Now, 4 years after SRT, the tumor is gradually becoming smaller and the patient is able to attend elementary school.
Conclusion. At present, the treatment strategies for PMA remain controversial, and are more controversial in patients with recurrent disease. The effectiveness of radiotherapy remains to be elucidated in both PA and PMA. As seen in this PMA case, SRT is an effective management strategy when a relapse occurs in spite of a good response to the initial chemotherapy.
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ABSTRACT NO.: 0P-170
Surgical treatment of low-grade gliomas (LGG) in children
R.R. Bayramgulov1, A.R. Bayramgulova1, A.A. Gumerov2, R.A. Gumerov1, I.I. Badrtdinova1, V.B. Makhonin1
Republican Children Clinical Hospital, Ufa, Republic of Bashkortostan; 2Bashkirian State Medical University, Ufa, Republic of Bashkortostan
Key words: low-grade gliomas (LGG), astrocytoma, children, surgery, extent of resection
Introduction. Low-grade gliomas (LGG) are the most common brain tumors in pediatric population comprising 30 % of primary central nervous system tumours in children. The main treatment method is surgery but it is not always feasible due to anatomical localization of the tumour that in some cases requires non-surgical treatment. Aim. To evaluate the results of surgical treatment for LGG in children who received treatment at our centre.
Materials and methods. There was carried out the analysis of medical documents of the patients with LGG who received treatment at our centre during the period from 12.05.2008 till 25.12.2015. Neurovisualization prior to the surgery defined tumour localization, involved structures, tumour volume. Neurovisualization was performed after the surgery within 24-72 hours in order to evaluate the extent of resection. Moreover, the analysis of the response to the treatment, overall survival and progression-free survival were carried out. Results. During the stated period 79 patients with LGG were enrolled, tumour resection was performed in case of 72 (91.1 %) of them. 47 (65.3 %) patients were male, 25 (34.7 %) patients were female. Age distribution: < 1 year old (n = 8), 1-4 years old (n = 23), 5-10 years old (n = 22), older than 11 years old (n = 9). After surgery 55 (76.4 %) children were referred to the observation group, 14 (19.4 %) patients required non-surgical treatment (chemotherapy (n = 8), radiotherapy (n = 7), both methods (n = 1)), there was a refusal of treatment in 3 cases. Tumour localization: brain hemispheres (n = 10), supratentorial medial structures (n = 23), cerebellum (n = 30), spinal cord (n = 2), other structures (n = 10). Tumour volume prior to an operation was evaluated in 55 children: less than 50 cm3 (n = 35), 50-100 cm3 (n = 12), more than 100 cm3 (n = 8). The extent of resection: total resection 31.9 % (n = 23), subtotal resection 25 % (n = 18), partial resection 33.4 % (n = 24), biopsy 9.7 % (n = 7). Histology was verified in 71 patients: pilocytic astrocytoma (Ac) I - 30 cases (42.2 %), desmoplastic infantile ganglioglioma I - 1 (2.8 %), pleomorphic xanthoastrocytoma II - 1, diffuse Ac II - 27 (38.1 %), others - 10 (14.1 %). In 8 cases of low grade gliomas (LGG) associated with NF-1 verification was not required. The disease progression was observed in 3 children (4.2 %), the disease stabilization was registered in 9 (12.5 %) cases, partial response - 18 (25 %) cases, complete response - 37 (51.4 %) observations. 5 (6.9 %) children died: of complications from surgery (n = 3), of complications from chemotherapy (n = 1), of disease progression (n = 1). Overall survival comprised 93 %, progression-free survival - 90.3 %.
Conclusion. Surgery remains the basis of therapy for LGG in children. Total and subtotal resection are the most consistent prognostic factor defining overall survival and progressionfree survival.
ABSTRACT N0.: P-184
Reirradiation treatment of diffuse brain stem tumors in children
O.I. Shcherbenko, O. Geludkova, R. Parhomenko, N. Zelinskaya, F. Antonenko
Russian Scientific Center of Roentgenology and Radiology, Moscow, Russia
Key words: Tumors of the brain stem, repeated radiation therapy, children.
Introduction. A local relapse of tumour of brainstem is principal reason of failures after conservative treatment. In practice such patients usually fall into a category incurable and undergo only to symptomatic therapy.
Aim. To evaluate the possibility and effectiveness of the reirradiation treatment of diffuse brain stem tumors in children.
Materials and methods. For 2001-2011 repeated radiation treatment was performed in 20 children with diffuse brain stem tumors. All the children had previously received radiation therapy with irradiation of the tumor in a total dose of 50-55 Gy and 7 in combine with chemotherapy by temozolomide . The reason for conducting the re-treatment was the resumed tumor growth, proven by clinical and radiological data. The interval between the end of the initial treatment and the beginning of reirradiation ranged from 5 to 32 months, the median interval was 12 months. Re-radiation therapy was combined with adjuvant chemotherapy: temozolomide in 10 patients and bevazisumab in three. Total dose of re-irradiation was less than 30 Gy in 10 patients, 31-45 Gy in 9 and 50 Gy in 1.
Results. In the process of treatment the condition of the 5 patients, who had radiological signs of the destruction of the tumor, worsened, and therapy was discontinued. Their median survival was 3.5 months. In all others, who had no MRI signs of the tumor destruction, a positive subjective effects were noted in the form of full or partial regression of neurological disorders. In this group 93 % survived 6 months from the beginning of the second course, 53 % survived one year, 40 % - 1.5 years, 20 % - 2 years. One patient survived over five-year period, he has lived for 13 years. In one case, 5 months after the re-irradiation at a dose of 50 Gy, symmetric foci of necrosis in the cerebellar hemispheres were identified, combined with persistent tumor growth.
Conclusion. Repeated radiation therapy for the regrowth of diffuse brain stem tumors without signs of destruction can improve quality of life and increase survival in most cases.
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SIOP ASIA CONGRESS
abstract topic
ABSTRACT NO.: PP-186
High-dose chemotherapy with autologous bone marrow transplantation in the treatment of pediatric brain tumors
A. Gevorgian1, E. Morozova1, I. Kazantsev1, T. lukhta1, S. Safonova1, P. Tolkunova1, Yu. Punanov1, L. Zubarovskaya1, O. Zheludkova2, B. Afanasyev1
1First Pavlov State Medical University of St.Petersburg, Saint Petersburg, Russia; 2Russian Scientific Center of Roentgenology and Radiology, Moscow, Russia
Key words: pediatric brain tumors, high-dose chemotherapy, autologous hematopoietic stem cell transplantation, medulloblastoma, PNET, germ cell tumors, ATRT Introduction. Central nervous system (CNS) tumors are the second most common pediatric malignancies with an about 30 % 5-year overall survival rate in high-risk group. Aim. The aim of this study was to assess the effectiveness of high-dose chemotherapy (HDCT) with autologous hematopoietic stem-cell transplantation (auto-HSCT) in this patient group. Materials and methods. From 2008 to 2015, 54 pediatric patients with high-risk or relapsed medulloblastoma (n = 32), supratentorial PNET (n = 8), germinoma (n = 6), pineoblastoma (n = 3), atypical teratoid rhabdoid tumor (n = 3), choriocarcinoma (n = 1), ETANTR (n = 1) received single or tandem HDCT with auto-HSCT after induction chemotherapy, radiotherapy and surgical treatment. At the moment of HDCT 25 patients were in complete remission (CR), 24 patients were in partial remission (PR) and 5 patients had stable disease (SD). The conditioning regimen for single auto-HDCT (n=47) consisted of cisplatin, etoposide, and ifosfamide, or carboplatin, etoposide and thiotepa ± intraventricular etoposide, or thiotepa and temozolomide. In tandem HDCT (n = 7), the first conditioning regimen was carboplatin and etoposide, the second was thiotepa and cyclophosphamide, both with intraventricular/intrathecal metotrexat.
Results. The median follow-up is 48 months (range, 5-173). The median time to engraftment was day +17 (range, 8-86) after auto-HSCT. Four of 5 patients with SD at the moment of auto-HSCT had disease progression within 8 months after HDCT. Twenty-two of 49 patients with CR or PR relapsed 1-24 months after HDCT, the other 27 patients are currently in CR or PR on the maintenance therapy. Cumulative incidence of relapse in 4 years accounted 45 % (95 % CI: 21-60 %). The conditioning regimens had acceptable toxicity. Complications grade 4 (COMMON TOXICITY CRITERIA 2014) were observed in 14 % of cases. Four-year overall survival (OS) in all patient's group was 67 % and disease free survival (DFS) was 55 %. MB and germ cell tumors had better survival rate (DFS 65 % and 64 %, respectively) in compared to other embrional tumors (DFS 40 %, P = 0.05). DFS was significantly better among patients > 4year in compared to children.
Conclusion. HDCT with auto-HSCT in pediatric patients with high-risk CNS tumors may be a feasible option for patients in CR or PR after induction chemotherapy. It is ineffective as a salvage therapy in refractory patients.
ABSTRACT NO.: P-191
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Epidemiological characteristics of cerebral tumours in children in Nizhny Novgorod region
L. Karaseva1, L. Privalova1, O. Zheludkova2
Nizhny Novgorod Regional Children Clinical Hospital, Russia; 2Russian Scientific Center of Roentgenology and Radiology, Moscow, Russia
Key words: epidemiological characteristics cerebral tumours
Introduction. Central nervous system tumours steadily rank next to haematological malignancies among children in Nizhny Novgorod region. During the period from 2006 to 2010 there have been recorded 5-7 primary cerebral tumours, while within the period from 2011 to 2014, 12 tumours have been diagnosed. The highest incidence rate usually fell within the autumn months (October, November). Currently, the number of patients with primary disseminated tumour forms is progressively increasing that has significantly complicated the capabilities of complex therapy and influenced the prognosis.
Aim. The aim of the investigation was to study the epidemiological characteristics of central nervous system malignancies in children in Nizhny Novgorod region.
Materials and methods. During the last 9 years (2006-2014), 77 patients with brain tumours were receiving complex therapy in the Oncology Department of Nizhny Novgorod
Regional Children Clinical Hospital.
Results. Among them, 38 patients were the citizens of Nizhny Novgorod and Dzerzhinsk: large industrial centres with urban highway networks, and packed with automobile, chemical plants and oil refineries. The analysis of diseased children in Nizhny Novgorod showed that more than half of the patients were from Zarechnaya part of the city (Avtozavodsky, Sormovsky, Moskovsky districts), where township-forming enterprises are situated, the children population density being the highest. Three patients were under 3 years at the moment when the diagnosis was made. In 60 % cases, at birth, the mothers of the children under study aged over 30. Some mothers had burdened gynaecological and obstetric history. Five women had had previous missed miscarriages before the birth of children with CNS tumours. Five women had suffered from recurrent miscarriages, and five mothers had been receiving the therapy for infertility of mixed genesis for 2 years. One child was born after ICSI (intracytoplasmic sperm injection) procedure. The mothers of all the patients (77) were found to have had severe gestational toxicosis of the first trimester of pregnancy. Two mothers had previous dead births. In 90 % cases the mothers had bad habits (smoking), and they had kept smoking during pregnancy. The study of the anatomical structure of CNS tumours showed the growing number of patients with primary lesions of the brain stem: 13 patients (16.8 %).
Conclusion. Thus, environmental conditions have a significant effect on CNS cancer morbidity rate in children in Nizhny Novgorod region. Burdened gynaecological and obstetric history, age, and bad habits of mothers have a significant impact on the increase in the number of patients with brain tumours. Fertility specialists should be concerned with the fact and show oncologic suspicion under the present situation. The causes of an increased number of patients with brain stem tumours require further investigations.
ABSTRACT NO.: PP-207
Neurocognitive disorders in children with post cranial fossa tumour
I.D. Borodina, R.B. Miroshkin, E.V. Fisun, A.S. Pchelinceva
Treatment and Rehabilitation Scientific Centre "Russkoe pole" of Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: brain tumors, neurocognitive disorders, children
Introduction. Neurocognitive disorders are among the most common treatment complications in patients with brain tumors which do not receive due consideration owing to the difficulties connected with their identification and assessment during the standard consultation of oncologist, neurologist or psychologist. At present, the test battery CANTAB (Cambridge Neuropsychologic Test Automated Battery) designed to provide solutions of this problem meets international requirements optimally. Aim. To estimate neurocognitive disorders in patients with post cranial fossa tumours.
Materials and methods. In the framework of the study of neurocognitive disorders in children with post cranial fossa tumours with the CANTAB we have examined 26 patients aged 6-17 years old (median age at examination - 11.5 years old), among them were 14 boys (53.83 %) and 12 girls (46.15 %). Twenty-three patients (88.47 %) had medulloblastoma (MB) diagnosis, 2 (7.69 %) patients had pilocytic astrocytoma (PA), 1 (3.84 %) patient - anaplastic ependymoma (AE). All the patients (100.00 %) had underwent surgical treatment. After surgery, twenty-four patients with malignant neoplasms (MB and AE) received radiochemotherapy or/and polychemotherapy according to the HIT 2000-2008 protocol depending on their hystological diagnosis, age and the extent of tumour process (7 patients with stage M0 tumours, 3 patients with stage M1 tumours, 8 patients with stage M3 tumours, 6 patients with stage Mx). One of 2 patients with benign tumours (PA) received surgery alone, the other one underwent surgery and radiotherapy. Median age at the beginning of therapy was 6.5 (3-16) years old. After the end of antitumour therapy, 5 (19.23 %) patients had tumour progression (relapses, metastases and continued tumour growth) and underwent repeated surgical treatment, radiochemotherapy and/or anti-relapse chemotherapy. By the time of examination, all the patients have completed the treatment of main disease: 23 (88.47 %) patients demonstrated complete response, 3 (11.53 %) patients showed disease stabilization without treatment (median time after the completion of treatment and before the start of the CANTAB testing is 15 (1-102) months.
Results. The study of cognitive functions in children with post cranial fossa tumours as compared to normal ranges for healthy child population revealed the following details: 100 % of patients have visual, motor and conceptual difficulties of various degree; 82 % of the examined children demonstrate the degradation of intelligence, educability and refocusing; 63 % of children were found to have a decrease in visuospatial memory span; 33 % of patients did not manage spatial tasks and motor control, 48 % of subjects experienced difficulties in the solution of this kind of tasks; 12 % of children demonstrate signs of impulsivity, 21 % - signs of retardation.
Conclusion. Neurocognitive disorders are detected in all patients with post cranial fossa tumours despite tumour grade, extent of treatment, age and timing of treatment.
ABSTRACT NO.: PP-210
Brain tumors infant, experience of pediatric oncology unit in Algiers
Cherifa Louni1, Fatiha Gachi1, Souad Bakhti2, Fella Terkmani2
'Centre Pierre & Marie Curie, Algeria;2CHU Mustapha, Alger, Algeria
Key words: infant, brain tumors, chemotherapy, radiotherapy
Introduction. 10-20 % of childhood brain tumors occur before the age of 3 years. Treatment is often aggressive consisting of surgery followed by radiation source neurological damage, endocrine and neuropsychological . The goal of chemotherapy is to delay or avoid irradiation in these young children.
Materials and methods. A retrospective study by analyzing records on 50 children aged under 36 months bearers of brain tumors treated between January 2008 and December 2014. The diagnosis was made by histology after surgery or stereotactic biopsy or imaging (inaccessible tumors). The treatment consisted of first surgery unless the anatomical exposes to unacceptable effects of chemotherapy followed by SFOP BABY protocol.
Results. 30 % of patients were younger than 18 months, with a male predominance (sex ratio: 0.56). The clinical picture is dominated by a intracranian hypertension syndrome. A imaging, large tumors and surgery was often incomplete. According to the histological type (medulloblastoma 40 %, 18 % high-grade astrocytoma, 16% low grade gliomas, ependymome 14 % and 12 % neuroectodermal tumors). All received chemotherapy according to SFOP BEBE protocol. 3 children were irradiated at the age of 03 years (ependymoma). 29 children died. The 21 survivors were not irradiated but have neurologic sequel of surgery.
Conclusion. Diagnosis is often delayed at the stage or tumors are very large making it difficult and incomplete surgery. The prognosis of brain tumors in children under three years is worse compared to older. Conventional chemotherapy is not always effective, the use of intensive chemotherapy, conformal radiotherapy and the development of specific protocols each tumor will improve outcomes for these children.
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INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY
ABSTRACT NO.: OP-276
Review on the management & outcome of childhood cerebral or cerebellar low grade glioma
Godfrey Chi-Fung Chan1, Matthew Ming-Kong Shing2, Kai-On Chang3, Dennis Tak-Noi Ku4, Alvin Siu-Cheung Ling5, Anthony Pak-Yin Liu1
'The University of Hong Kong; 2Prince of Wales Hospital; 3Queen Elizabeth Hospital; 4Tuen Mun Hospital; 5Princess Margaret Hospital
Key words: low grade glioma
Introduction. Astrocytoma is the commonest type of brain tumors in childhood and low grade (WHO Gr I & II) accounted for almost half of them. Despite having good prognosis, the management approach remains quite variable in different parts of the world. Aim. We reviewed our experience on this group of patients.
Materials and methods. This is a retrospective review of a population based cohort from Jan-1999 to Dec-2014. The patients underwent treatment in 5 local hospitals which captured almost all children with cancers locally. The patients' data were recorded prospectively by 2 full time data managers. The data was verified annually with the respective centers and HK Cancer registry.
Results. Within this 16 yrs period, there were 157 children with astrocytoma diagnosed. They were distributed as following: Cerebral & Cerebellar: n = 107 (Gr I n = 44, Gr II n = 21, Gr III n = 14, Gr IV n = 28); Brainstem: n = 50; Spinal: n = 9 (Gr I n = 4, Gr II n = 1, Gr III n = 1, Gr IV n = 4); Other types of glioma: n = 20 (Oligodendroglioma n = 10, PXA n = 2, Ganglioglioma n = 7, SEGA n = 1). Excluding the spinal astrocytoma and other types of glioma, we identified 65 patients with cerebral or cerebellar low grade astrocytoma as mentioned above. Their median age was 7.95yrs (range 0.15 to 17.81yrs) and M:F = 35:30. Cerebellum is the most common location (n = 28) followed by suprasellar region (n = 10). Surgery was the main form of treatment (n = 57) and 18 received additional low intensity chemotherapy. The choice of different regimens depended on different era, including carboplatin + vincristine, temozolomide alone, vinblastine alone, TPGV, PCV, etc. Patients often received more than one course of chemotherapy. Two patients underwent RT in the early 2000 era. Only 3 patients died of disease progression (all WHO Gr I). The 5-year event free survival was 93.3 % and 100 % for Gr I & Gr II patients respectively. Conclusion. Childhood low grade astrocytoma has relatively good prognosis even if unresectable. Low intensive chemotherapy could suppress the progression of a significant proportion of these low grade tumors and achieve long term survival. Even if it recurred, we could utilize chemotherapy again and avoid using RT on this group of patients.
E.V. Mironova1, I.B. Mironov2, I.D. Borodina1
'Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia;
2Morozov Children's City Clinical Hospital, Moscow, Russia
Key words: medulloblastoma, rehabilitation, CNS tumors
Introduction. Central nervous system (CNS) tumors are the most frequent solid neoplasms in childhood, CNS neoplasms incidence in children aged from 0 to 18 years is 3.5-4.0 per 100 000 children. The quality of life of patients with CNS neoplasms is defined both by pathogen itself and by a complex of complications that occur in the course of this disease. Also the current cancer treatment methods themselves adversely affect patients' organs and systems. Nervous system responds very sensitively to any problems of an organism, therefore highly expressed neurological disorders immediately occur in the human body which prevent patients' recovery even after the end of the therapy. Aim. Detection and management of neurological disorders in patients with CNS tumors.
Materials and methods. Considering that 60 % of CNS tumors in children older than 3 years are localized infratentorially in posterior cranial fossa (PCF), the investigation of 75 patients with the diagnosis "medulloblastoma" was undertaken with the use of a standard neurological examination, neurological status assessment on EDSS, ATAXIA scales. Along with this, the possibilities of disorder management were defined.
Results. During examination and dynamic follow-up of 75 patients with the diagnosis "medulloblastoma" it was noted that 92 % of them have such coordination disorders as ataxia, dysmetria and intention during coordination test; motor disorders (paresis, paralysis) were reported in 81.3 % of cases; such peripheral nervous system involvements as polyneuropathies are detected in 41 % of patients and behavioural and neurocognitive disorders form in 89 % of children. After complex (motor, neurocognitive) rehabilitation a positive dynamics was reported in a motor sphere in the form of intensity reduction of disorders during coordination tests, ataxia, muscular strength increase; in neurocognitive sphere - in the form of the improvement of the results during the performance of applicable tasks - an increase of productivity, attention concentration were observed . Conclusion. A timely detection of nervous system disorders and their complex management are an essential part of complex rehabilitation of children with CNS tumors.
ABSTRACT NO.: P-284
Neurological disorders in case of central nervous system (CNS) tumors
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ABSTRACT NO.: OP-298
Preliminary results of treatment according to HIT-MED-Study Guideline 2014
in Russian cohort of patients
E. Kumirova1, S. Oserov1, L. Papusha1, E. Salnikova1, I. Borodina1, A. Samarin1, V. Yemtsova1, A. Ektova1, A. Kislyakov1, M. Ryzhova2, A. Panfyorova1, A. Nechesnyuk1, D. Kobyzeva1, A. Usychkina1, A. Artemov1, L. Zemtsova1, A. Kazakova1, S. Homyakova1, M. Dubrovina1, A. Pshonkin1, M. Tihonova1, A. Spirin1, S. Gorelishev2, E. Shorikov3, M. Mushinskaya4, I. Gerbek5, E. Erega6, A. Shapochnik7, M. Belogurova8, G. Novichkova1, A. Karachunskiy1, A. Valiakhmetova2,
M. Andrianov1, G. Tereshchenko1 1Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia; 2Scientific Research Neurosurgery Institute named after the academician N.N. Burdenko, Moscow, Russia; 3Children's Regional Clinical Hospital № 1, Yekaterinburg, Russia; 4Perm Regional Children's Clinical Hospital, Russia; 5Regional Children's Hospital, Tomsk, Russia; 6Regional Children's Clinical Hospital named after A.K. Piotrovich, Khabarovsk, Russia;7Orenburg Regional Clinical Oncology Center, Russia; 8City Clinical Hospital № 31 of Saint-Petersburg, Russia
Key words: brain tumors, children, chemotherapy, radiation therapy
Introduction. Federal Research Clinical Centre for Pediatric Hematology, Oncology and Immunology named after D. Rogachev (Rogachev's Center) observe 1000-1200 children per year with tumors of the central nervous system from all regions of Russia. Infrastructure of the center has all modern facilities of diagnosis, treatment and rehabilitation for children with tumors of the central nervous system including standard molecular biological studies, such as MYC-amplification (FISH/CISH), CTNNB1 gene mutation (Sanger sequencing). On February 2015 after formal permission of the office of HIT-MED-Study (Hamburg, Germany) the Guideline 2014 was adopted to use it in our Centre and other oncohematological centers/departments of Russia.
Aim. To demonstrate the capabilities of Russian clinics to participate in international studies on the diagnosis and treatment of tumors of the central nervous system in children. Materials and methods. From February 2015 to January 2016 38 patients (pts) with the first time verified primary brain tumors with the age at diagnosis from 1,9 to 14 y.o. (median 6 y.o) were included to database according to guideline's requirements. The male:female ratio was 25:13. Resection was performed: in federal centers in 18 pts, in regional - 20. Hystologycal type was: medulloblastoma (MB) - 21 (13 - classical MB, 5 - desmoplastic MB, 2 - MBEN, 1 - anaplastic MB), ependymoma (EP) - 10 (Grade II - 2, Grade III - 8), PNET - 6, pineoblastoma - 1. Histology was confirmed in all patients in reference centers (Rogachev's Center and Burdenko Institute) M0 stage of disease was in 25 pts, M1 - 3 pts, M2 - 3 pts, M3 - 5 pts, Mx - 2 pts. Among MB-patients MYC amplification was performed in 11 pts (52 %) and was positive in 1. Sanger sequencing analysis was performed in 2 MB pts with M0R0 stage of disease and positive nuclear expression of b-cathenin, CTNNB1 mutation was detected in 1 of them. All pts received different arms of therapy according HIT-MED-Guideline 2014, among them 2 pts with MB - tandem HDCT (in Rogachev's Center). Hyperfractionated Radiation Therapy (HFRT) and Intensive Modulated RT (IMRT) planning and delivery techniques, which available in Rogachev's Center, were used in 4 pts and in 27 pts respectively.
Results. All patients are alive. Finished all course of the therapy - 8 pts with total response. 1 pt with AE recurred locally. All points of the protocol requirements are fulfillment. There were no any SAE during the treatment.
Conclusion. The modern standard approaches of diagnosis and treatment for children with high grade neuroepithelial brain tumors including molecular biological studies are available in Russia which can allowed taking part in international trials.
ABSTRACT NO.: PP-349
Results of medulloblastomas treatment in children under 5 years
E.V. Kumirova1, E.A. Salnikova1, I.D. Borodina1, L.I. Papusha1, S.S. Ozerov1, A.E. Samarin1, A.P. Ektova1, M.V. Ryzhova2,
A. Korshunov3, A.V. Nechesnyuk1, D.A. Kobyzeva1, O.G. Zheludkova4, O.I. Shcherbenko4, M.B. Belogurova5, S.V. Gorbatykh6, M.V. Mushinskaya7, R.Z. Shammasov8, E.P. Erega9, A.P. Shapochnik10, E.V. Shorikov11, I.E. Gerbek12, E.V. Inyushkina13, S.A. Kulyova14, N.A. Filatova15, E.P. Matseha16
1Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia;
2 Scientific Research Neurosurgery Institute named after the academician N.N. Burdenko, Moscow, Russia; 3German Cancer Research Center, Heidelberg; 4Russian Scientific Center of Radiology and Nuclear Medicine, Moscow, Russia; 5Municipal Clinical Hospital № 31, Saint-Petersburg, Russia; 6Morozov Children's City Clinical Hospital, Moscow, Russia; 7Perm Regional Children's Clinical Hospital, Russia; Children's Republican Clinical Hospital, Kazan, Republic of Tatarstan; 9Regional Children's Clinical Hospital named after A.K. Piotrovich, Khabarovsk, Russia; 10Orenburg Regional Clinical Oncological Dispensary, Russia;11Regional Children's Clinical Hospital № 1, Ekaterinburg, Russia;12Regional Children's Hospital, Tomsk, Russia; "Moscow Regional Oncological Dispensary, Balashikha, Russia; 14N.N. Petrov Research Institute of Oncology, St-Petersburg, Russia; 15Arkhangelsk Regional Children's Clinical Hospital named after P.G. Vyzhlezov, Russia; 16Trans-Baikal Regional Oncological Dispensary, Chita, Russia
Key words: children, medulloblastomas, chemotherapy, radiotherapy
Introduction. Medulloblastomas (MB) in children of younger age are one of unsolved issues in pediatric neurooncology. Prognostic-factors-based risk group stratification is needed, which will probably allow to individualize such patients treatment in the future.
Aim. To evaluate treatment results of 86 patients under 5 years (median age of 21 months) with primarily diagnosed MB. pB
Materials and methods. The ratio of boys and girls was 1.5:1 (60 % and 40 %, respectively). Depending on the age: in 31 follow-up - tumor resection (R0), in 49 (57 %) cases - non radical surgery, in 3 (3.5 %) - biopsy, in 3 (3.5 %) patients the volume is unknown. Histologically: classic (class) - 43 (50 %) patients, desmoplastic (desmo) - 21 (24.4 %), large
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cell/anaplastic (anapl) - 7 (8.1 %), MBEN - 1 (1.2 %), in 14 (16.3 %) patients the variant is unknown (MB NOS). Molecular genetic analysis undertaken in 31 patient: 10 - SHH group, 5 - group 3, C-MYC-amplification was in 2 cases. Depending on a disease stage: M0 - 30 (35 %) patients, M1 - 15 (17.4 %), M2 - 4 (4.6 %), M3 - 25 (29 %), M4 - 1 (1.2 %), Mx - 11 (12.8 %). R0M0 reported in 14 (16.3 %) children. On the first stage 64 (74.4 %) patients received polychemotherapy, 22 (25.6 %) patients - radiotherapy (RT). Treatment under HIT SKK protocol was received by 77 (90 %) patients, under M-2000 protocol - by 3 patients, unprogrammed therapy - by 6 patients. Intraventricular methotrexate (MTX) injection was received by 30 (33%) patients, intrathecal - 9 (10.5 %). High-dose chemotherapy with auto-HSCT undertaken in 15 (17.4 %) patients. RT was received by 59 (68.6 %) patients. Positive responce to RT was achieved in 54 (91.5 %) patients, DP was reported in 5 (8.5 %) patients. On different therapy stages DP was observed in 34 (40 %) patients, 14 (41 %) of which are alive. 64 (74.4 %) /86 patients are alive, 17 % continue the therapy, the rest (83 %) completed specific treatment
Results. Five year overall survival is a 0.42 ± 0.06 (median - 39.5 months, follow up period - from 2 to 271 months), 5-year progression free survival (PFS) - 0.60 ± 0.05 (median - 27.5 months, follow up - from 2 to 235 months). PFS in boys and girls is 0.7 and 0.49, respectively (P = 0.13). PFS depending on age: 0.2 (36 months) (P = 0,03). PFS depending on M-stage: M0/M1/M3 - 0.62/0.59/0.53 (P = 0.25), M2/M4 - 0. PFS depending on histology: class/desmo/MBNOS/anapl = 0.7/0.55/0.58/0.29 (P = 0.15). PFS in patients with SHH was 0.50. Depending on resection volume: PFS - 0.53 (in patients with R+) and 0.66 (R0), P = 0.28. In SHH-group patients survival without RT was 0.33, with RT - 0.75 (P = 0.29). PFS in patients that received and did not receive intraventricular/intrathecal MTX was 0.52 and 0.50, respectively (P=0.3). Conclusion. Adverse prognostic factors were age (under 12 months), histological MB variant (large cell/anapl), M+ stage, presence of residual tumour, absence of RT in SHH-group patients. For further verification of treatment strategy additional studies are needed.
ABSTRACT NO.: OP-351
Effect therapy for medulloblastoma within protocol HIT-2000/2008 among children under
the age of four years
O. Zheludkova1, M. Ryzhova2, A. Melikian2, Yu. Kushel2, S. Ozerov3, E. Kumirova3, I. Borodina3, V. Ozerova2, S. Gorbatykh4, O. Polushkina4, L. Olhova4, A. Nechesnyuk3, O. Shcherbenko1, E. Shorikov5, A. Beznoshchenko6, R. Shammasov7, S. Kovalenko8, N. Yudina9, M. Mushinskaya10, E. Inyushkina11, L. Privalova12, A. Matytsyn13, A. Korshunov2
1 Russian Scientific Center for Roentgenology and Radiology; 2Scientific Research Neurosurgery Institute named after the academician N.N. Burdenko, Moscow, Russia; 3Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia; 4Morozov Children's City Clinical Hospital, Moscow, Russia; 5Regional Children's Clinical Hospital № ', Ekaterinburg, Russia;6Ryazan Regional Children's Clinical Hospital named after N.V. Dmitrieva, Russia; 7Children's Republican Clinical Hospital, Kazan, Republic of Tatarstan;8Chelyabinsk Regional Children's Hospital, Russia; 9Voronezh Regional Children's Hospital, Russia;10Perm Regional Children's Clinical Hospital, Russia;11 Moscow Regional Oncological Dispensary, Balashikha, Russia; ™Nizhny Novgorod Regional Children Clinical Hospital, Russia;13Tambov Regional Children Clinical Hospital, Russia
Key words: medulloblastoma, young children, chemotherapy
Introduction. Medulloblasma is the most common malignant brain tumor occuring in children. Standart treatment of medulloblastoma in older children consists of surgery, craniospinal irradiation and chemotherapy, with overall survival approaching 85 % at 5 years for children with non-metastatic and near totally resected medulloblastoma. The prognosis for infants and young children with medulloblastoma treated with a similar approach remains poor. The use of cranial irradiation in young children has been implicated in learning, attention and processing speed deficits, problems with hearing, endocrine disfunction, leukoencephalopathy and deficits in theur physical growth. Aim. To estimate the efficiency of chemotherapy and chemoradiotherapy in patients with medulloblastoma under the age of four and to determine the prognostic factors. Materials and methods. From 2009 to 2014, we analyzed 36 patients who got therapy within protocol HIT-2000/2008 after tumor resection. There were 19 (53 %) girls and 17 (47 %) boys. The age of 5 (14 %) patients was 3-12 months, 18 (50 %) - 13-24 months, 13 (36 %) - 25-48 months. The histological variant of the tumor was: 16/3 (53 %) DMB/MBEN, 15 (41.5 %) CMB, and 2 (5.5 %) LCA. Stage M0 was in 25 (69.5 %) patients M+ in 11 (30.5 %). In 26 cases (72 %) underwent total resection; a residual tumor was found in 10 patients (28 %). Chemotherapy + radiotherapy was used on 19 (53 %) patients; 17 (47 %) got only chemotherapy. Intrathecal/intraventricular Methotrexate used to 22 (61 %) patients.
Results. PFS and OS were 0.71 ± 0.08 and 0.86 ± 0.06 respectively. The mean time of observation was 24 months, and the median time to progression was 17 months. 27 patients completed their treatment, 9 were diagnosed with recurrence/metastases, and 4 died of PD. PFS/OS was 0.88/1.0 for patients aged 25-48 months, 0.62/0.77 for 13-24 months and 0.60/0.80 for 3-12 months. There were no significant differences in PFS/OS depending on the histological variant of medulloblastoma: 0.61/0.85 for DMB and MBEN, 0.79/0.86 for CMB, and 1.0/1.0 for LCA. Patients with stage M0 had PFS/OS 0.74/0.95 and for M+ 0.64/0.65. PFS/OS among patients with M0R0 were 0.64/0.92; for M0R+ 0.89/1.0. PFS for patients who received intrathecal/intraventricular MTX was 0.79 and 0.63 who didn't. This was also true for DMB/MBEN: 0.75 and 0.43, respectively. PFS was 0.67 among patients who got radiotherapy and 0.76 among those who didn't.
Conclusion. Multiagent chemotherapy is efficient in MB patients under the age of 4. A low survival rate was observed among patients under 1 year and with metastases. The completeness of the surgical resection and the use of radiotherapy did not affect the results of treatment. The best survival rate was found among patients who got regional therapy with MTX, including those with DMB/MBEN.
cc
hematology and oncology
ABSTRACT NO.: P-364
Results of treatment of intracranial AT/RT in children
O. Zheludkova1, M. Ryzhova2, L. Shishkina2, A. Melikyan2, Yu. Kushel2, L. Olhova3, O. Polushkina3, S. Gorbatykh3, E. Kumirova4, I. Borodina4, E. Inyushkina5, V. Ozerova2, M. Mushinskaya6, N. Popova7, L. Privalova8, R. Shammasov9, O. Shcherbenko1, E. Abbasova1, A. Kryanev1, O. Chulkov10, N. Yudina11, A. Korshunov2, A. Matytsyn12, I. Vorotnikov13
Russian Scientific Center for Roentgenology and Radiology; 2Scientific Research Neurosurgery Institute named after the academician N.N. Burdenko, Moscow, Russia; 3Morozov Children's City Clinical Hospital, Moscow, Russia; 4Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia; 5Moscow Regional
Oncological Dispensary, Balashikha, Russia; 6Perm Regional Children's Clinical Hospital, Russia; 7Volgograd Regional Clinical Oncological Dispensary № 1, Russia; 8Nizhny Novgorod Regional Children Clinical Hospital, Russia; Children's Republican Clinical Hospital, Kazan, Republic of Tatarstan; 10Children's Regional Clinical Hospital, Krasnodar, Russia;11Voronezh Regional Children's Hospital, Russia; 12Tambov Regional Children Clinical Hospital, Russia; 13Center of New Medical Technologies, Novosibirsk, Russia
Key words: AT/RT, children, treatment, malignant tumor
Introduction. Atypical teratoid/rhabdoid tumors are highly malignant central nervous system (CNS) tumors. As compared with other malignant CNS tumors, their biological behavior is particularly aggressive, but patients may benefit from an intensified treatment. Aim. To determine prognostic factors in patients with AT/RT.
Materials and methods. We have evaluated the prognostic factors in 43 patients with AT/RT. Most patients were younger than 3 years old (28, 65 %), and 15 patients (35 %) were above 3 years. The boys and girls were 20 and 23, respectively. The tumor was infratentorial in 21 patients (48.8 %); 2 patients (4.7 %) had infratentorial and renal tumors; and 20 patients (46.5 %) had supratentorial tumors. Stage M0 was in 24 patients (55.8 %); 11 patients (25.6 %) had metastases or detected tumor cells at diagnosis; and the stage was not precisely determined for 8 patients (18.6 %).Treatment according to protocol ATRT-2006 was administered to 24 patients (55.8 %); protocol CWS, to 8 patients (18.6 %); HIT-SKK, to 4 patients (9.3 %); and 7 patients (16.3 %) got off-protocol treatment.
Results. 13 patients (30.2 %) are alive, and 30 (69.8 %) have died: 26 due to disease progression, 4 due to chemotherapy toxicity. The PFS was 30 ± 0.06%, and the OS was 38 ± 0.06%. The median survival time was 18 months; and the median observation time was 14 months (range 2 to 89 months). The survival rate was significantly higher among patients over 3 years old in comparison with younger patients: 53 % and 14 %, respectively (P=0.004); among patients after total tumor resection in comparison with subtotal or partial resection: 55 %, 31 %, and 12 %, respectively (P=0.015); among patients who got radiotherapy in comparison with those who did not: local radiotherapy, 50 %; craniospinal radiation, 35 %; no radiotherapy, 0 % (P=0.033); among patients with stage M0 in comparison with stage M+: 37 % and 0 %, respectively (P=0.007). Therapy according to the ATRT-2006 protocol led to better survival rate (43 %) in comparison with protocols CWS (12 %) and HIT-SKK (18 %), P = 0.01.
Conclusion.The factors that affected the prognosis were the patient's age, the extent ofthe surgical resection, the chemotherapy program, the use of radiotherapy, and the presence of metastases.
O. Zheludkova1, Yu. Kushel2, A. Melikyan2, S. Ozerov3, L. Shishkina2, M. Ryzhova2, A. Kislyakov3, I. Borodina3, V. Emtsova3, S. Gorbatykh4, L. Olhova4, L. Privalova5, M. Mushinskaya6, N. Yudina7, N. Popova8, V. Ozerova2, O. Shcherbenko1, E. Abbasova1, A. Kryanev1, P. Pankov1, M. Salpagarov1, A. Nechesnyuk3, E. Inyushkina9, N. Filatova10, Yu. Kozel'11, O. Chulkov12, L. Minkina13, O. Polushkina4, E. Erega14, Kh. Tsirenova15, R. Shammasov16, A. Korshunov2
Russian Scientific Center for Roentgenology and Radiology; 2Scientific Research Neurosurgery Institute named after the academician N.N. Burdenko, Moscow, Russia; 3Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia; 4Morozov Children's City Clinical Hospital, Moscow, Russia; 5Nizhny Novgorod Regional Children Clinical Hospital, Russia; 6Perm Regional Children's Clinical Hospital, Russia; 7Voronezh Regional Children's Hospital, Russia; 8Volgograd Regional Clinical Oncological Dispensary № 1, Russia;9Moscow Regional Oncological Dispensary, Balashikha, Russia; 10Arkhangelsk Regional Children's Clinical Hospital named after P.G. Vyzhlezov, Russia; 11Rostov Cancer Research Institute, Rostov-on-Don, Russia;12Children's Regional Clinical Hospital, Krasnodar, Russia;13Regional Children's Clinical Hospital № 1, Vladivostok, Russia;14Regional Children's Clinical Hospital named after A.K. Piotrovich, Khabarovsk, Russia; 15Children's Republican Clinical Hospital, Ulan-Ude, Republic of Buryatia; 16Children's Republican Clinical Hospital, Kazan, Republic of Tatarstan
Key words: anaplastic ependymoma, children, treatment, oncology
Introduction. Ependymoma is a relatively rare brain tumor which occurs about 9 % in children and 3 % in adults out of all primary brain tumors. In children 90 % of ependymomas develop in the brain. The treatment option for ependymoma is surgical resection followed by radiotherapy, although there are no randomized prospective studies available yet. Presently there are no standards treatment for ependymoma.
Aim. To evaluate the outcome of children with anaplastic ependymoma after surgery, chemotherapy and radiotherapy and to identify prognostic factors for survival.
Materials and methods. We evaluated the treatment results for 169 children with AE. Median age was 4 y.o. Most patients were over 3 y.o (119; 70.4 %). There were 104 boys
(61.5 %) and 65 girls (38.5 %). Infratentorial tumors were in 81 pts (48 %); supratentorial, in 82 (48.5 %), and 6 pts (3.5 %) had the tumor in the spinal cord. 118 pts (70 %) had stage
M0; 14 (8 %) had metastases or detected tumor cells; for 37 patients (22 %), the stage was not known. 78 pts (46 %) received chemo- and radiotherapy according to protocol HIT
2000/2008; 57 (34 %) received only radiotherapy after the surgical operation; 25 (15 %) patients got chemotherapy; and 9 (5 %) pts were treated using only surgical intervention.
Most patients underwent total (n = 70) or subtotal (n = 91) tumor resection; for 8 (5 %) patients, the extent of the resection was not evaluated. ^
ABSTRACT NO.: P-366
Results of treatment for childhood with anaplastic ependymoma
SIOP ASIA CONGRESS
abstract topic
Results. 3-year PFS 0.47 ± 0.05, 5-year PFS 0.32 ± 0.05, median PFS 32 months (2 to 34 months). 3-year survival was better in children over 3 in comparison with younger than 3 y.o: 0.50 and 0.36, respectively. 3-year survival among girls was 0.36; among boys, 0.22 (P = 0.19). 3-year PFS were better for supratentorial tumors in comparison with infratentorial: 0.54 and 0.39, respectively (P=0.19). Survival results were better among patients with stage M0 in comparison with stage M+: 0.50 and 0.39, respectively. In the case of total tumor resection, the 3-year survival was better than in the case of subtotal resection: 0.42 and 0.22, respectively (P=0.44). PFS were the same among patients who received chemoradiotherapy or only radiotherapy: 0.53 and 0.50, respectively. Among patients who got chemotherapy after tumor resection, the 3-year PFS were 0.19; after surgery only, all patients had recurrence (P = 0.0002).
Conclusion. The patient's age, tumor location, the volume of surgical treatment and the M stage was seriously affected on the prognosis. Better survival rates observed on patients older than 3 years, with the supratentorial localization, total removal of the tumor and without metastasis. Chemotherapy does not improve the results of treatment for anaplastic ependymoma.
ABSTRACT NO.: P-378
Radiation therapy and Nimotuzumab in children and adolescents with brainstem gliomas:
a 5-year institutional experience
Migdalia Perez, Jose Alert, Jesus Reno, Mariuska Forteza
National institute of Oncology and Radiobiology of Cuba, Havana
Key words: brainstem gliomas, Nimotuzumab, children, adolescents
Introduction. Brainstem gliomas (BSG) are central nervous system (CNS) tumors with a median survival time of approximately 9 months. Up to now chemotherapy has not shown to improve survival in these patients. The outcome of radiation therapy (RT) in combination with Nimotuzumab is shown in the present report. Aim. Appoint the global over-life utilizing the monoclonal antibody was ours objective.
Materials and methods. 28 children and adolescents were included between Jan/2009 and Dec/2012 with the diagnosis of BSG and follow-up till January 2015. All patients had diffuse infiltrative pontine gliomas (DIPG) and were irradiated with a dose ranging from 54 to 59.6 Gy at the National Oncology and Radiobiology Institute in Havana, Cuba. Three patients were planned with IMRT and 25 with 3D Conformal RT. Nimotuzumab was indicated at the dose of 150 mg/m2 weekly during the time of RT treatment, then every 15 days during 8 weeks and finally
monthly for 1 year. Univariate and multivariate Cox regression models and Kaplan-Meier survival were analyzed to evaluate the survival.
Results. Median age at diagnosis was 7 years (range 3-18 years old), median overall survival was 17.3 months (95 % CI 14.0-20.5 ) since the beginning of the treatment and the accumulated survival at 5 years of treatment was 42.9 %. There was balance in sex, age and dosage of RT in the population. Addition of Nimotuzumab to RT was safe. Conclusion. The combination of radiotherapy and Nimotuzumab were well tolerated in this brainstem tumours patient's series.
ABSTRACT NO.: P-391
CNS Tumors in Children of Tatarstan Republic
V.S. Ivanov, E.F. Fatyhova, E.N. Grishina, A.G. Gazizov, D.I. Abdullin, V.V. Frolov
Children's Republican Clinical Hospital, Kazan, Republic of Tatarstan
Key words: children, CNS tumors
Introduction. CNS tumors is the second most common cancer in children.
Aim. To analyze the results of combined therapy of CNS tumors in children and adolescents younger than 18 years treated in Tatarstan during the last 10 years.
Materials and methods. From 2004 to 2015 two hundred nineteen patients aged 1 month to 17 years (24 % were children younger than 3 years) with CNS tumors underwent
surgical treatment in Neurosurgery Department. More than half (57 %) of the patients were males.
Results. At hospital admission initial neuroimaging (CT and contrast MRI) was performed in all cases. Total tumor excision was performed in 73.6 %, subtotal resection in 16.6 %, partial resection in 8.3 % and tumor biopsy in 1.4 % of cases. Post-surgical mortality was 1.01 % (both patients deceased in 2004). Since 2005 there had been no post-surgical mortality. Pathology verification of tumor was done in all cases. In more than half of the cases confirmatory review was performed in reference laboratories (NIINH named after N.N. Burdenko, FRCC named after Dmitry Rogachev). After histological verification of tumors 189 patients underwent combined treatment in Department of Oncohematology of the Children's Republican Clinical Hospital.
Conclusion. Survival after combined treatment varied in children with histologically different tumor types. In patients with low grade gliomas survival was 100 %. In patients with embryonal tumors it was 50 %. Overall survival in patients with CNS tumors after combined therapy was 66 %.
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ABSTRACT NO.: P-394
Evolution of brain tumours treatment results in childhood during 20 years
in Voronezh region
G.V. Trubnikova1, T.V. Stepanova2, A.M. Pozdniakov2, A.P. Shvyrev2
1Voronezh Regional Children's Clinical Hospital № 1, Russia; 2Voronezh State Medical University named after N.N. Burdenko, Russia
Key words: brain tumours, treatment, children, chemotherapy
Introduction. Intracranial neoplasms are the most common solid tumours in childhood. There are made up of a variety of histological subgroups, comprising embryonal tumours. Treatment strategy includes surgery, irradiation, and different chemotherapy regimens. The outcome depends on the extent of surgery, histological type of the tumours. Aim. We compare the results of the chemotherapeutic treatment in children with brain tumours during two 10-year periods since 1994.
Materials and methods. In a retrospective, longitudinal study, we reviewed patients with brain tumours, treated with craniospinal irradiation and different chemotherapeutic regimens, during two periods: from 1994 to 2003 and from 2004 till 2013 in Voronezh region. Data collection included age of diagnoses, length of follow up, extent of resection, stage of the tumours and histology.
Results. Since 1993 year 25 children (male/female - 16/9) with Brain Tumours were diagnosed in Voronezh children's centre of oncoheamatologyl. We observed 15 children with primary tumours and 10 relapsed patients. The median age was 6.5 years. Histologically there were astrocytoma, medulloblastoma, PNET, ependymoma, angioreticulosarcoma, others. All were treated with surgery, irradiation and chemotherapy according to the HIT-91 protocol. Three (20 %) patients with primary tumours survived, in one of them the second malignant disease was found. 12 (80 %) patients died. The outcome of the relapsed patients was fatal. Since 2004 the cohort includes 53 patients (male/female - 30/23) with primary brain tumours, verified in Moscow N.N.Burdenko Neurosurgery Institution. Average duration of follow up was 10 years. The median age was 7.5 years. Tumours were identified as medulloblastoma in 17 (32 %) patients (M0 stage in 12, M1, M2, M3 - in 5); anaplastic astrocytoma and glioblastoma in 8 (15 %). Low-grade astrocytomas was identified in 4 (7.6 %), anaplastic ependymoma in 5 (9.5 %), PNET in 4 (7.6 %), ATRO in 3 (5.7%) patients, pineablastoma in 1 (1.9 %), hystiocytic sarcoma in 1 (1.9 %), germinoma in 2 (3.8 %). Brain stem tumours in 8 (15%) were not verified. We used treatment regimes according to HIT-2000, HIT-SKK, M-2000, ATRO- protocol, temodal cycles, regimen avastin plus irinothecan. CR was registered in 10 (58.9 %) patients with medulloblastoma, 1 child with ATRO, in 2 (40 %) patients with anaplastic ependymoma; SD-in 1 (25 %) patient with PNET. The progression of the disease and death were in 7 (41.1 %) patients with medulloblastoma, in 6 (75 %) with anaplastic astrocytoma and glioblastoma (median of follow up was 10.6 months), in 2 (66.6 %) with ATRO (median of survival was 12 months), in 2 (50 %) patients with PNET (median of follow up is 36 months), in 1 patient with hystiocytic sarcoma, in all patients with brain stem tumours (median of follow up is 11 months).
Patients with low grade astrocytoma relapsed after the irradiation and treated with the protocol for low grade gliomas. CR was registered in 1, SD - in 3 patients (median of survival 69.5 months).
Conclusion. Treatment results of brain tumours in the last decade has nearly better evolution. The combination of RT and chemotherapy with HIT-2000 protocol in patients with medulloblastoma provided encouraging outcomes The treatment of malignant BT in children is a problem to solve.
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