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SOCIÉTÉ INTERNATIONALE
rvniunni nRIF DÉrUATQinilF
SIOP ASIA
CONGRESS
INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY
LATE EFFECTS
ABSTRACT NO.: 0-130
Musculoskeletal sequelae of childhood solid tumours survivors, treated with intensive chemotherapy, surgery and radiation therapy
A. Petrichenko, E. Bukreeva, N. Ivanova
Applied Research Center for Specialized Medical Care of Children named after V.F. Voyno-Yasenetsky, Russia
Key words: solid tumours survivors, musculoskeletal late effects
Introduction. Advances in diagnosis and treatment of childhood cancer have dramatically increased long-term survival and it is now evident that the disease and its treatment can significantly impair long-term health. Childhood solid tumours survivors are known to be at risk for the serious musculoskeletal late effects that may result in disability Aim. Recommendations for screening, prevention, and management of survivors and the evaluation of efficiency of cancer rehabilitation of children, treated with intensive chemotherapy, surgery and radiation therapy.
Materials and methods. 102 children and adolescents with solid tumours were treated between 1987 and 2014 years. The mean age at the date of orthopedic diagnosis was 13.25 ± 0.43 years (from 2 till 24 years). Common sites of primary disease include the thorax, abdomen, trunk and extremities. Most often the affected area was the area of the lower extremity - 48.0 % ofthe cases. According to the histological variation ofthe tumor40.2 % ofthe patients had morphologically confirmed diagnoses of Ewing sarcoma, 28.4 % - osteosarcoma, 31.4 % - other solid tumours. 31.0 % patients had primary distant metastases. Among them, 46.9 % patients had solitary metastases, 53.1 % patients had multiple metastases. Treatment consisted of neoadjuvant chemotherapy, the radiotherapy of the initial tumor and metastasis left after the induction and/or oncologic surgery and adjuvant chemotherapy. The local control of the tumor consisting of the surgical ablation of the primary lesion and metastases, if the technical opportunity of this stage is available, including limb-sparing procedures. The most common late effects we had observed were: scoliosis - in 78.4 % cases, muscular hypoplasia - 74.5 %, osteopenia - 55.9%, limb-length discrepancy in spite of usage of growing endoprosthesis - 45.1%, poor joint movement - 66.7%, musculoskeletal deformity - 39.2%. 77.5% patients had from 1 till 5 late effects, 22.5% - 6 till 11. We used the NCI Common Terminology Criteria for Adverse Events (CTCAE) for reporting. We have not observed serious Adverse Events, like Grade 4: life-threatening consequences and Grade 5: death related to Adverse Events. Among the children who developed the largest number of effects, children who received CT and radiotherapy were 17.4 %, in the group with major surgery - 56.5 %, CT, surgery and radiotherapy - 26.1 %. This indicate, that some researchers revaluate the role of radiation therapy in the development of musculoskeletal sequelae. All long-term survivors of childhood cancer should attend rehabilitation therapy, because it is dramatically increase the quality of life. An individual rehabilitation program consist with combined early mobilization, physical exercise, kinesiotherapy, aquatic rehabilitation and orthopaedic correction, laser therapy, massage, gait training. Results. Currently 90 patients are alive without disease, following up of 12 to 343 months. We have observed Grade 2 Adverse Events (CTCAE) in 43.3 % cases. The lowest grade by Musculoskeletal Tumor Rating Scale we have observed in cases with distal leg localization - 51.4 %.
Conclusion. Interdisciplinary team, provide services that enable patients to achieve their highest functional status to permit them to return to their role in society. We suggest that the usage an individual rehabilitation program can dramatically increase the quality of life. Long-term survival is possible, even for patients with metastatic disease.
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HEMATOLOGY and ONCOLOGY
ABSTRACT NO.: P-149
Secondary tumours in children of the Nizhny Novgorod region
L. Bogdanova, L. Privalova, V. Alexeeva, K. Isaev, E. Abramova, O. Kozhakova, L. Karaseva, A. Alekseev
Nizhny Novgorod Regional Children Clinical Hospital, Russia
Key words: secondary tumours, children, haematological malignancies, Hodgkin lymphoma, radiotherapy
Introduction. In recent years there has increased a number of follow up reports on children, who received complex therapy of malignancies and were cured. The problem has an important social aspect, since the therapy has a significant effect on the life quality of both: the patient himself, and his offspring. Secondary tumour (ST) development in such patients is a new burning problem, and according to different authors, the frequency of ST varies from 2 to 12 %. There are synchronous tumours, which occur promptly after the first lesion detection, and ST induced by chemoradiotherapy. ST risk depends significantly on specific therapy intensity, patient's age at the moment of treatment, gender, as well as the time period passed after the treatment termination
Aim. The investigation aimed at studying the frequency and peculiarities of the course of ST in children in Nizhny Novgorod region.
Materials and methods. During the period from 1989 to 2015, 12 patients with ST were treated in the Oncology Department of Nizhny Novgorod Regional Children Clinical Hospital. Results. 1) ST occur more frequently in children over 9 years old (92 % observations), and only one child aged 6 years; while primary tumours develop mainly in children under 10 years (70 %); 2) boys prevailed among the patients (60 %); 3) solid ST developed in two children having been treated for solid tumours; 4) most frequently, ST are recorded in patients with haematological malignancies (total 80 % observations), among them, 40 % patients had had Hodgkin's lymphoma (HL), and 30 % patients - acute lymphoblastic leukemia (ALL). It is interesting to note that all children treated for ALL appeared to have ST, and three children with HL had haematological malignancies (non-Hodgkin lymphoma or leukemia), and one child - gastric cancer; 5) tumour response in patients under study was from 2 months to 16 years. The younger a child was at the moment of primary tumour detection, the longer the latent period was before the ST developed: in our study in the children under 7 years (50 %) it was from 6 to 16 years; and in children over 7 years (50 %) it varied from 2 months to 2 years, and only in one case the patient was a 6-year-old child; 6) radiotherapy is of great importance in the development of ST: among the patients treated, only one appeared to have had no radiotherapy during the first disease due to an early onset of the ST (when the first disease had not yet been treated completely). There can be traced the dependence of the remission period on a dose and the number of radiation areas during the first disease: the higher the dose and more the number of areas, the shorter the latent period of the ST; 7) the therapy intensity of the first tumours influences the growth of ST: 50 % children received therapy for lymphoma and ALL; 8) a latent period for secondary hemoblastoses lasted, mainly, from two months to 6 years (median 2 years 3 months), while for solid ST it was from two to 16 years (median 7 years). Conclusion. 1. Most frequently, ST are recorded in patients with haematological malignancies, among them 40 % patients are those with HL. 2. ST are induced mainly by radiotherapy, the doses and the number of radiation areas being of importance. 3. There is the dependence of a latent period time before the ST development on the primary tumour type. 4. Currently, outcomes are significantly better: in our study, 50 % children with ST have survived, the tumour response in all children being over 5 years.
A.V. Baerbakh, E.V. Zhukovskaya, V.N. Kasatkin
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: rehabilitation
Introduction. For the last 40 years in Russia, the survival of children with cancer has increased at 60 % (V.G. Polyakov, 2015). This fact enhances considerably the relevance of improvement of rehabilitation technologies for patients with oncohematological diseases. Many cancer survivors who had musculoskeletal disorders (soft tissue tumours, bone sarcomas) require integrated/complex/comprehensive rehabilitation including recovery of movement/motor skills. Aim. To develop and implement a protocol for diagnostics and correction of movement disorders in cancer survivors.
Materials and methods. During 2015, a computer force plate with biofeedback was analyzed. A study group included 9 patients from LRNC "Russkoe pole": 3 patients with CNS tumours, 4 children with acute leukemia, 2 children with bone sarcomas. The mean age of the patients was 9.6 ± 1.3 years old. All the children have been in remission for 2 years and more. Children with bone sarcomas underwent treatment for malignant neoplasms: patient with osteogenic sarcoma, 1 patient with Ewing sarcoma, without amputation and endoprosthesis replacement. A testing was performed before the therapy start as well as after the completion of training period, with multiple repetition of trainings with biofeedback. The dynamics of functional impairment recovery was assessed separately for osteoarticular, muscular and nervous system. The improvement of the ability to keep balance and the coordination of movement was accepted as the measure of treatment efficiency.
Results. A total amount of trainings varied from 8 to 12. On average, the duration of training was 12-15 minutes. The maximal duration of training (20 minutes) was achieved in the patients of senior age group without serious neurologic impairment. The main difficulties while executing the protocol were observed in patients of the younger age group. Conclusion. Stabilometrics improves dynamic and postural stability of a patient in an upright position; owing to multiple repetitions and biofeedback, the walking stereotype and walking rhythm are formed. Rehabilitation events should be active and should be performed as early as possible. Timely multimodal rehabilitation for children offers the possibility to correct the consequences of disease and antitumour treatment, that would further reduce the disability status of patients. Use of robot-assisted gait training with biofeedback is a promising trend in comprehensive rehabilitation of children and adolescents with CNS tumors and malignant neoplasms of other location.
ABSTRACT NO.: P-175
Recovery of motor skills in patients with malignant neoplasms
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topicact TRANSVERSAL THEMES
SOCIÉTÉ INTERNATIONALE D'ONCOLOGIE PÉHATRIQUE
SIOP ASIA CONGRESS
ABSTRACT NO.: P-259
Application of cosmetics in the rehabilitation of children with skin manifestations of chronic GVHD
O. Rassokhina1, P. Trakhtman2, N. Potekaev1
1Pirogov Russian National Research Medical University, Moscow, Russia; 2Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: skin manifestations of chronic GVHD, rehabilitation
Introduction. Brisk growth of Hematology has led to survivability enhancement after transplantation of hematopoietic stem cells, which warrants an increase in the number of patients with chronic graft-versus-host disease (GVHD). Cutaneous manifestations of chronic GVHD has an additional negative impact on the physical, social and psychological rehabilitation of the patient.
Aim. To perform assessment of capability for cosmetics to achieve normalization of the skin.
Materials and methods. 15 patients aged from 3 to 24 years with chronic GVHD was examed: 6 (40 %) females and 9 (60 %) males, 6 patients (40 %) aged 3-5 y. 1 (6 %) 6-12y., 5 (33 %) 13-17 y and 3 (20 %) 18-24 y.o. The morphological changes of the skin was performed using dermoscopy and ultrasound, the functional state of the skin by sebumetry and corneometry. To determine changes in quality of life there was calculated a dermatological life quality index,estimation of the psycho-emotional status of patients was evaluated based on: Hamilton and Beck scales for depression and Covi, Spielberger scales-for anxiety. The general condition of the patients was evaluated based on the scales of Lansky and of Karnovsky. Assessment of the state was carried out before and during treatment. Primary survey of patients with chronic GVHD: decrease in the thickness of the epidermis for all patients, an increase in the thickness and density of the dermis by ultrasound skin with 80 % of patients, changes in blood vessels in the nail bed dermoscopy with 30 % and reduced moisture and greasiness of the skin for all patients.Patients examined with the help of psychotherapy scales had mild depressive disorder (8-10 points for Hamilton), anxiety (1-2 points on a scale Covey). Dermatological quality of life index was (9-14.6 points).The general condition of patients according to the Lansky scale was 50 for 29 % of all patients, 80 for the remaining 71 %, under the Karnovsky scale 25 % of patients had 70, 12.5 % had 80 and 62.5 % had 90.To correct the dryness of skin emollients were used 2-5 times a day, depending on the condition; hyaluronic acid was used as dermatoprotektor in combination with mucopolysaccharides. In order to accelerate epithelialization crack, reduce inflammation there was topically applied cosmetics containing panthenol, copper, zinc, manganese, thermal water.
Results. Rational use of cosmetics on background of standard immunosuppressive therapy resulted in a reduction of the subjective discomfort (regression feeling of tightness and itching) for 80 % of patients, an increase in the level of moisture and greasiness for 93.3 % of patients. With the reduction of skin manifestations of chronic GVHD and improvement of general condition, confirmed by clinical, laboratory and instrumental data, psychoemotional state of patients has improved. Points on a scale of Hamilton decreased to 5, and on a scale of Covey-0, which corresponds to the rules. DILQ decreased to 3 to 80 % of patients. The general condition of patients according to Lansky Scale was 50 for 14 %, 86 for 80 % of patients, according to Karnovsky scale the results were 70 for 12.5 % of patients, 80 for 25 % of patients and 90 for 62.5 % of patients.
Conclusion. Applying cosmetics makes it possible to reduce skin manifestations of chronic GVHD, which improves the emotional state of patients and has a positive impact on rehabilitation.
ABSTRACT NO.: PP-273
Assessment of gonadal function in girls after allogeneic transplant with treosulfan-based conditioning regimens
L.I. Papusha, Yu.V. Skvortsova, E.Yu. Ilina, L.N. Shelikhova, M.A. Maschan, D.N. Balashov, G.A. Novichkova, A.A. Maschan
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: ovarian function, treosulfan
Introduction. Gonadal damage occurs in about 100 % of recipient of allogeneic transplants with classic high dose busulfan - containing conditioning regimens. However, little is known about gonadal function in recipients of new myeloablative regimens containing other alkylators. Treosulfan exerts powerful immunosuppressive and myeloablative action when used in cumulative doses > 36 g/m2 while its visceral toxicity is modest, leading to its wide use as a backbone of conditioning regimens in wide range of hematological malignancies as well as non-malignant conditions.
Aim. To evaluate ovarian function in girls who received treosulfan-based conditioning regimen.
Materials and methods. Gonadal function (puberty staging by Tanner, blood tests for luteinizing hormone, follicle stimulating hormone and anti mullerian hormone (AMH) was evaluated in 20 females recipients of treosulfan-based conditioning regimens. The conditioning regimen consisted of treosulfan 42 g/m2, fludarabine 150 mg/m2, melphalan 140 mg/m2. Mean age at HSCT was 14.5 years (range 10-20), median age at time of the study 16 years (13-22).
Results. Eight patients, initially diagnosed with ovarian failure, showed recovery of ovarian function 6-12 months after HSCT. These girls had regular menstrual cycle, but serum AMH levels were significantly decreased (AMH 0.5 ± 0.2 ng/ml) comparing with the standart levels in all but two patients in this group. Spontaneous puberty and menarche occurred ^ in seven girls, who were prepubertal at the time of HSCT. Five patients developed hypergonadotropic hypogonadism (LH 35.55 ± 18.19 UI/l, FSH 98.65 ± 52.06 UI/l, estradiol
¡^ 12.14 ± 6.85 pmol/l, AMH 0.13 ng/ml) and required hormone replacement therapy.
Conclusion. High dose treosulfan conditioning may allow prompt gonadal function recovery. Young women with diminished ovarian reserve should be informed about the risk of premature menopause. Effective fertility preservation methods should be discussed with these patients.
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OF PEDIATRIC HEMATOLOGY and ONCOLOGY
ABSTRACT NO.: PP-277
Study on late effects of treatment of oncological diseases in children: the experience of a specialized clinic
M.E. Lokhmatova, A.E. Rudneva, E.E. Ilyina
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: children, acute leukemia, lymphomas, late effects, therapy program
Introduction. Modern therapy of oncological diseases in children is highly effective but remains quite toxic and has late side-effects. Children cured of oncological diseases need a long-term systematic follow-up the aim of which is the control of disease remission maintenance and maximal early detection of the therapy late effects. The study on incidence and expressiveness of late effects of the treatment is eased if a large cohorts of patients are formed that remain in contact with the specialized clinic and are thus available for systematic examinations.
Aim. To arrange the data of pediatric patients that had different oncological diseases.
Materials and methods. Since 2007 in FRSC PHOI n.a. Dmitry Rogchev the prospective data collection on health of patients after the treatment of oncological diseases is carried out. From April, 2007 to December, 2015 765 patients aged from 1.5 to 30 years were registered (acute lymphoblastic leukemia - 44 %, non-Hodgkin's lymphomas - 22 %, Hodgkin's lymphoma - 15 %, brain tumors - 4 %, soft tissue sarcomas - 3 %, neuroblastomas - 2 %, acute myeloid leukemia (AML) - 2 %, other malignant diseases - 7 %), the interval from the end of the therapy is 1.5 months to 20 years (median - 3.25 years).
Results. Over the whole period of the follow-up 3366 present and absent encounters of patients were registered. 48 adverse events were noted: 32 (4.2 %) relapses of the main disease, 13 (1.7 %) secondary tumors, 3 (0.4 %) patients died in remission at place of residence allegedly from infectious complications. The detection of relapses and secondary tumors at scheduled follow-up before complaints was observed in 15 (47 %) cases of 32 and in 3 of 13 cases, respectively. Eight (17 %) of 48 adverse events were at the period of more than 5 years after the end of the treatment: 1 relapse of anaplastic large-cell lymphoma and 7 secondary tumors. The mean term of the relapse development was 1.8 years (3 months, Burkitt lymphoma - 5.8 years, ALK-lymphoma), secondary tumor - 5.5 years: (2.5 years, thyroid cancer after Hodgkin disease - 12 years, AML after rhabdomyosarcoma). Loss-to-follow-up (the absence of information about patient for more than 12 months) was 32 % (246 patients), out of which 30 (12 % of lost and 4 % of the total number of patients) were lost in the first year after the treatment. More than 450 patients are regularly examined. The follow-up is carried out on individual plans that allow to detect such late effects as growth arrest, hypothyroidism, emmeniopathy, postradiation fibrosis, mental retardation, obesity and others. At the moment due to the lack of resources in-depth cardiological, pulmonary examinations are not carried out, reproductive health and the quality of life of patients are not studied.
Conclusion. In our country this work is the first attempt to arrange the data of pediatric patients that had different oncological diseases. With a large number of disadvantages (high percentage of losses-to-follow-up, absence of in-depth study of some organs and systems) this group of patients can be a basis for a systematic study of late therapy effects, particularly on therapeutic protocols that are unique to our country. The detection of adverse events in a later date indicates the necessity of a long-term follow-up.
ABSTRACT NO.: P-283
Functional and ultrasound diagnosis in the assessment of late toxicity in children with
oncological diseases
T.V. Kudinova, P.M. Gorbylev
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: late effects, functional and ultrasound diagnosis, leukemia, osteosarcoma, histiocytosis, hematopoietic stem cell transplantation, rehabilitation
Introduction. The problem of the development of late toxicity still remains unsolved, and timely diagnosis including ultrasound and functional methods would help to detect specific
changes as early as at the preclinical stage.
Aim. Considering the incidence rate of late complications after treatment of the above mentioned diseases, we have suggested the algorithm of functional and ultrasound studies. Materials and methods. Neurotoxicity in patients with acute lymphoblastic leukemia develops in 43.6 % of cases and manifests itself as encephalopathy (with convulsive seizures in 10 % of cases), polyneuropathy. Cardio- and hepatotoxicity develop in 20 % and 14 % of children respectively. It is recommended to place emphasis on electroencelography (EEG), electroneuromyography (ENMG), electrocardiography (ECG) with Holter monitoring, echo-cardiography (Echo-CG), ultrasonography (US) of abdominal cavity, US of intestine and lymph nodes. Brain stem tumors account for 10-20 % of all central nervous system (CNS) neoplasms. These aspects combined with the received therapy/being received, including hormonal therapy, may cause respiratory, cardiovascular, hypothalamo-pituitary-adrenal systems deficits. In addition to EEG monitoring and EKG, we recommend to estimate external respiration function, perform abdominal US, as well as evaluate visual evoked potentials in case of sight impairment.
Late effects associated with hematopoietic stem cells transplantation are accompanied by the involvement of the liver, lungs (in the form of interstitial pneumonits/pulmonits), joints,
muscles, by the atrophy of lymphoid organs. In 40 % of cases, impairment of pancreatic function and dysfunction of reproductive system are detected, cataract is diagnosed in 20 % of
cases. Also, there is a risk of developing a brain tumor, a thyroid gland tumor and an osteosarcoma. The list of studies includes EEG, EKG, visual evoked potentials, external respiration
function (ERF), US of abdominal cavity organs, intestine, thyroid gland, all groups of lymph nodes, soft tissues. ^
In children with Langerhans cell histiocytosis, skeletal involvement is registered in 60-80 % of cases, lung changes - in 10-30 % of cases. Liver, spleen, lymph nodes pathology
is observed in 10-15 % of patients. CNS injuries exhibit local degenerative changes or mass lesion pattern. A protocol of examinations should contain EEG, evoked potentials, ERF
evaluation, ECG, Echo-CG, US of abdominal cavity organs, and peripheral lymph nodes.
According to the degree of tumor extension, 80 % of osteosarcomas in children may be divided into localized osteosarcomas, accompanied only by the involvement of bones with adjacent muscles and tendons, as well as into metastatic ones with multiple involvement of bones, lungs (85 % of cases), brain and internals. Taking into consideration different
AOSTcRACT TRANSVERSAL THEMES
SOCIÉTÉ INTERNATIONALE D'ONCOLOGIE PÉHATRIQUE
SIOP ASIA CONGRESS
incidence of neuro, ortho, nephro and cardiotoxicity, we recommend to include into a protocol such examinations as: ECG with auditory evoked potential, ENMG, densitometry, ECG, Echo-CG, ERF, US of abdominal cavity organs and kidneys, US of soft tissues and lymph nodes.
Results. Following the work that has been carried out, protocols of functional and ultrasound diagnosis of late effects in pediatric cancer survivors will be developed. Rehabilitation, oncology and hematology may be the possible fields of its application.
Conclusion. Ultrasound and functional methods may be widely used in diagnosis of late toxicity in patients with oncology diseases. After conducting a definite volume of examinations and analyzing examination findings the suggested algorithm may be reconsidered and modified.
ABSTRACT NO.: O-337
Microelemental homeostasis in patients with oncological diseases
V. Bondarenko, E.V. Zhukovskaya, Yu.A. Obukhov, L.V. Sidorenko, I.R. Minulin, B.V. Kholodov
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: microelements, rehabilitation
Introduction. The interest in microelemental homeostasis in patients with malignant neoplasms is present both on a disease diagnosis stage and at the period of remission establishment. There are many hypothesis about the applicability of the microelemental homeostasis study in patients with oncological diseases. However, none of the current theories has an essential evidential base. The problem is mostly in a planning stage.
Aim. To evaluate the content of toxic and essential microelements in different biological environments within a pilot study of patients that are on different rehabilitation stages.
Materials and methods. 35 hair and blood/serum probes, 23 saliva probes were studied in 40 patients that were on a rehabilitation in Treatment and Rehabilitation Centre "Russian
field" in 2015. Solid soft-tissue tumors were in 28 patients: nephroblastoma - 9, neuroblastoma - 6, bone sarcomas - 4, soft-tissue tumors - 3; leukemia and lymphomas were in
12 patients. The remission duration was 1 year and more. The age varied from 4 to 16 years. Probe testing was performed on 40 and more microelements with the help of an atomic
emission spectrometry with an inductively coupled argon plasma on Optima 2000 DV unit (PerkinElmer SCIEX, USA) and a mass-spectometry with the inductively coupled argon
plasma on Elan 9000 (PerkinElmer, USA) unit. A table of referential values that were developed earlier was used as comparative analysis data. (A.V. Skalnyi, 2006).
Results. A less number of deviations was detected in investigational blood samples: an increase of content of toxic and conditioned toxic chemical elements Al, Cd, Ag were shown
at 1-1.3 from referential values but there is a downtrend of content of essential chemical elements Ca, I, Se, Cr. A decreased chrome content was shown in 9 of 10 patients that were
diagnosed with a metabolic syndrome, which conforms the regulation on an association of carbohydrate metabolism disorders with a chrome stress.
Main effects in saliva samples were multidirectional changes of essential elements content, their intensity both in respect of diversity and deviation values from referential values also
was defined by the severity of dental pathology.
Hair is a standard investigational substrate of microelemental structure and a relevant medical care is registered in a register of a CMI system. A content of microelements in hair reflects long-term trends of a homeostasis maintenance. Along with a silver and cadmium excesses, toxic and conditioned toxic elements excesses were not registered in patients. Deviations in the content of calcium, molybdenum, manganese, selenium, zinc in 2 or more times were reported in hair in children of an investigational group. Conclusion. Considering the fewness of investigational group and a diversity of received microelemental content changes of investigated biological environments, it is not possible to define the specificity of microelemental deviations depending on a diagnosis and a received deviation.
According to data of performed studies it is possible only to state the fact of the presence of microelemental homeostasis deviations in children that were cured from malignant neoplasms and were on a long-term remission.
At the process of data collection the significance of microelementosis in oncohematological patients in remission and the necessity of their corrections are to be specified.
ABSTRACT NO.: OP-338
The structure of the functional impairment in adolescent survivors of childhood cancer
H. Zbarouskaya
National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus Key words: functional impairment, childhood cancer survivors
Introduction. Adolescent survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status. The problems of adolescent cancer survivors appear to be distinct from both older adult and pediatric survivors. For purposes of this issue, we will address survivors as patients who have completed initial treatment for cancer and who are without evidence of disease. Functional impairment after cancer and its treatment may potentially associated with limited opportunity for participation in community or social roles.
Aim. To determine structure of functional impairment with special attention to differences between rural and urban inhabitants.
Materials and methods. Health status were assessed in 74 adolescent survivors of childhood cancer, aged 15-19 years (median 16.6 years), male/female ratio 1.55, from whom 51 were urban and 23 rural residents. The diagnoses were: hemablastosis 39 (52.7 %) cases (leukemias - 13 cases, lymphomas - 23 cases), solid tumors 35 (47.3 %) cases (CNS tumors - 7, bone tumors - 11, soft tissue sarcomas and renal tumors - 4 each, retinoblastoma - 3, other solid tumors - 6 cases). Median time after diagnosis was 6.5 years, range 1-15 years. We used International Classification of Function, Disability, and Health (ICF) to determine limitations resulting from both medical and psychosocial sequelae. Results. Among surveyed the most common consequences of childhood cancer and its treatment were endocrine, cardiopulmonary, neurocognitive and musculoskeletal dysfunctions. We revealed endocrinopathy in 15 (29.4 %) urban and 6 (26.1 %) rural inhabitants (P = 0.76) with prevalence of obesity in those who live in towns - 8 (15.7 %) vs 0 (P = 0.04). Musculoskeletal disorders were presented in 6 (11.8 %) urban and 4 (17.4 %) rural citizens (P = 0.5), sensory, cardiac and pulmonary organ system dysfunctions in 7 (13.7 %)
HEMATOLOGY and ONCOLOGY
and 3 (13 %), 4 (7.8 %) and 1 (4.3 %), 3 (5.9 %) and 1 (4.3 %) teens, respectively (P=n.s.). 9 (17.6 %) from urban residents were receiving secondary or higher education, compared with none from rural locality (P=0.03).
Conclusion. In developing rehabilitation interventions for childhood cancer survivors we must take into account their functional impairment and place of living to enhance their social participation.
ABSTRACT NO.: PP-344
Dental health of the patients cured of malignant neoplasms in childhood
Yu.A. Оbukhov, Е.V. Zhukovskaya, A.V. Tushevskaya, L.V. Sidorenko
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: stomatology, leukemia, children
Introduction. Cancer treatment in childhood affects the tooth development by direct toxic effects on odontogenic cells, or on irregulations pathways of signalling interactions between ectoderm and mesenchyme. Proliferating preodontoblasts and their precursors generally have a higher sensitivity to unfavourable factors in comparison to the functioning mature cells (I. Thesleff, 2003). Mechanisms of the influence of antitumor therapy resulting in stomatological complications remain considerably unexplored (P. Kanchan et al., 2014). In addition, according to the data from a Childhood Cancer Survivor Study in a long-term period only 60.4 % of 9434 patients cured of cancer in childhood visit a dentist's room annually (M.W. Yeazel, 2004.).
Aim. Assessment of/to assess the condition of dental health in patients with acute lymphoblastic leukaemia (ALL) in prolonged remission.
Materials and methods. In 2014-2015 a preventive examination in 122 patients cured of ALL who were in remission for 2 years and for 2 and more years was performed at the Rehabilitation Centre "Russian Field". A comparison group comprised of 204 children with general somatic pathology who also received a course of rehabilitation at the centre during this period. Median age of the patients from the primary/initial/treatment group was 7.9 (4-16) years at the moment of examination. Median age of the children from a control group was 8.5 (4-17) years.
Results. Approximately a half of the patients from the control group (41.3 %) visited a dentist's room annually. Only 32 % of the patients from the primary/initial/treatment group visited a dentist every year and usually in order to perform sanitation. During the preventive examination by a dentist from the Rehabilitation Centre "Russkoe Pole" children with leukaemia show significant changes in hard tooth tissues of carious and noncarious origin both during temporary/transient mixed and during permanent occlusion. The connection between the severity of pathology and age is detected: the younger a child at the moment of treatment is, the more apparent changes of stomatological status it has. Symptoms of enamel dysmorphology in the form of demineralization foci, incisor sulci and pits, local hypoplasia, tooth erosion, rapid/acute carious injuries, pulpitis, pulpal polyps, periodontitis, sometimes increased tooth abrasion are detected in the patients from the primary/initial/treatment group (76 %) considerably more often than in the control group patients. There are either carious cavities or a plumbic ball in most molar teeth. Simplified OHI-S index was > 1.6 that corresponds to the unsatisfactory and poor oral hygiene in 2/3 of the primary/initial/treatment group patients.
Conclusion. Difficulty in the management of children with hemablastosis occurs when children are not only afraid of stomatological intervention but also tolerate hygienic manipulations in oral cavity with effort. In addition, up to 30 % of parents and patients refer to doctors' recommendations about limited hygienic procedures although there are vast opportunities of using sensitive toothbrushes, medical toothpastes, elixirs. The patients of this group require special facilities/remedies/tools and methods of treatment regarding the primary disease not only in an oncohematological hospital/in-patient facility but also at a dentist's room.
E.V. Zhukovskaya
Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia Key words: tumours, metabolic syndrome, children
Introduction. Metabolic syndrome (MetS) development in children who had received treatment for malignant neoplasms is a fact repeatedly reported in literature (C. Bizzarri et al., 2015; N.M. Abu-Ouf et al., 2015). Genetic determinants of metabolism, character of nutrition, cultural peculiarities can form a certain specificity of the occurence and clinical manifestations of this anticancer treatment complication. Aim. To investigate the spread of metabolic syndrome in reconvalescents of malignant neoplasms.
Materials and methods. The enrolment of 105 patients admitted to the Rehabilitation Centre "Russian Field" was carried out according to the following criteria: a child is to be in the first remission for 2 or more years; antitumor therapy compulsorily/definitely involved polychemotherapy ± irradiation ± surgical treatment. 38 patients had the diagnosis «lymphoma» (C82,83); 16 patients - «acute lymphoblastic leukaemia» (C91.0); 15 - «nephroblastoma» (C64); 14 - «soft tissue tumors» (C48,49), 14 - «neuroblastoma» (C47); 8 - «bone sarcomas» (C40,41). In order to detect carbohydrate-lipid metabolism disorders an obligatory investigation of patients was performed: family anamnesis, body mass index (BMI) assessment, common blood count, biochemical testing, glucose tolerance test (GTT), HOMA (The Homeostatic Model Assessment) index calculation, ultrasound investigation on indications, consultation with an endocrinologist.
No child was diagnosed with diabetes mellitus. Since it was impossible to confirm the presence of episodes of carbohydrate metabolism disorder and/or development of steroidogenic diabetes based on the presented medical documents in all patients, this parameter was not taken into account in the course of the treatment.
ABSTRACT NO.: OP-354
Carbohydrate-lipid metabolism disorder in patients with oncohematological pathology
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Results. A burdened familial history concerning adiposis/obesity and diabetes mellitus was diagnosed in 62 (59 %) patients; BMI > 25 was registered in 59 (55 %), 27 patients of them (26 %) had BMI > 30, variants of dyslipidaemia were found/noted/registered in 43 patients (41 %), HOMA index > 2,5 - in 32 (30 %). A stable increase in arterial pressure exceeding age standards was registered only in 6 adolescents older 14 years, the diagnosis "arterial hypertension" (AHT) was not established in them previously. Individual combination of symptoms of MetS under consideration was the following: insulin resistance in combination with dyslipidaemia was found in 32 (30 %) patients, only 24 % of them had an increased BMI, 22 % place of deviation in parameters of Ca metabolism, including high level of osteoporosis markers; all 6 adolescents with AHT were included in the group of children with MetS. Group of patients with MetS comprised 13 children with lymphomas, 9 - with leukemia, 2 - with nephroblastoma, 2 - with neuroblastoma, 2 - with soft tissue tumors, 4 - with bone sarcomas.
Conclusion. In patients with different oncohematological diseases increased body mass was registered in 59 (55 %) cases, of which insulin resistance (the main symptom of MetS) was found only in 25 (24 %) observations. No dependence on the diagnosis, the intensity of antitumor therapy performed was detected in this group. Taking into account a high frequency of MetS among late effects from the performed treatment, further data acquisition in order to define the intensity of a dose-dependent effect of the use of chemotherapeutic agents, the role of genetic predisposition in its development, gender and age specificity is necessary. It is probably useful to transfer MetS from the category of late effects from cytostatic treatment and consider its symptoms during nutrition regulation, moments relating to regime at most early at the stages of a child's treatment in order to carry out prophylaxis of further development of life-threatening complications (A.E. Kero et al., 2016).
ABSTRACT NO.: P-399
Second tumours in patients cured of malignant neoplasms in childhood
O. Gerasimova1, A.P. Shapochnik2, A.V. Klimushkin2, L.V. Sidorenko2
Orenburg Regional Clinical Oncology Dispensary, Russia; 2Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russia
Key words: second tumours, children
Introduction. Patients cured of malignant neoplasms in childhood are at high risk for developing second tumours. The risk of neoplasms in reconvalescents is approximately 10 times higher than in general population that seems important due to the increasing number of survivors in whom later second tumours are registered.
Second tumour is the leading cause of death in the long-term follow-up period regarding the patients cured of childhood cancer. Generally these are solid tumours, breast cancer, thyroid tumours, skin tumours and brain malignant tumours. There is a clear connection between the above mentioned tumours and radiation exposure defined by the latency period exceeding 10 years.
Other nosological entities of second tumours such as leukaemia (myeloid forms or myelodysplastic syndrome) are associated with the use of cytostatic therapy are distinguished by a shorter induction period. Alkylating agents and/or topoisomerase II derivatives are most commonly discussed among the anticancer drugs responsible for the development of second tumours.
Aim. To investigate medical frequency characteristics and structure of second tumours in patients cured of childhood cancer.
Materials and methods. A retrospective analysis of hospital database of 398 patients cured of malignant neoplasms in childhood from 1995 to 2010 at Orenburg Regional Clinical Oncology Dispensary was carried out. The duration of remission was 5-20 years.
Results. The diagnosis of second tumour was made in 5 (1.2 %) patients and this rate is lower than the rate reported by other authors (2-4 %). Explanation for this can be patients' migration outside the region, underestimation of data about the second tumour already in an adult patient. Thyroid cancer (TC) and cancer of the hairy part of the head were detected in 2 patients with acute lymphoblastic leukaemia (ALL) aged 18 and 22 with the remission period of 7 and 10 years. The patient with a retinoblastoma aged 12 (9 years after the end of radiation therapy (RT)) and the patient with a central nervous system (CNS) tumour aged 19 (5 years after the end of complex treatment) were also diagnosed with thyroid cancer (TC). 6 years after the end of treatment a meningioma developed as a second tumour in 1 patient with ALL aged 20. At the present moment all 5 patients are alive after operative removal of the second tumour.
Conclusion. All patients received total focal dose of 18-50 Gr at stages of primary tumor treatment. The development of thyroid cancer in 3 cases and solid neoplasms in the zone of primary tumour irradiation in 2 patients confirms the fact that radiation therapy (RT) is one of the factors of second tumour induction.
Early detection of pathological conditions associated with the effects of antitumor treatment, dynamic follow-up, use of preventive treatment strategies allow to reduce the disease incidence in adult patients cured of childhood cancer.
Recent studies allow to consider genetic predisposition as a risk modificator of the second tumour development. Although these conclusions require further verification, they provide opportunity to form new approaches that can help to develop effective strategies for the prophylaxis of late effects in patients cured in childhood.
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