High Dose Chemotherapy with MIBG I131 in Treatment of Patients with Neuroblastoma of High-Risk: a Cohort Study

Background. Poor-risk neuroblastoma treatment is still a challenge because of high relapse rate. Combination of high dose chemotherapy (HDCT) with MIBG I131 radiotherapy is a relatively new strategy for consolidation regimens in some patients with neuroblastoma. Objective. The aim of the study was to assess the safety and efficacy of a complex consolidation in a treatment of high-risk neuroblastoma patients in a pilot clinical trial. Methods. In our cohort study we analyzed toxicity along with 2- and 4- years OS and EFS in a cohort of 12 patients who got a consolidation based on Treo/ Mel HDCT in combination with MIBG I131 as a part of high-risk neuroblastoma treatment protocol since 2014 till 2018. The study was conducted in the Pediatric Oncology and Hematology Scientific Research Institute of Blokhin’s National Medical Cancer Research Center (Moscow). The treatment with MIBG I131 was done in settings of isolated ward of Russian Scientific Center of Roentgenology and Radiology. Results. Maximum cumulative organ toxicity of grade 2 or less was seen in 92% of patients. There was no treatment-related mortality. OS for 2 and 4 years was 87,5% ± 11,7% (for both time points). EFS for 2 and 4 years – 61,4 ± 15,3% and 49,1 ± 16,4%, respectively. Conclusion. Consolidation regimen based on Treo/Mel with MIBG I131 is safe. As a part of treatment program, it provides 4-years EFS for about a half of patients with poor-risk neuroblastoma with active residual tumor at the moment of consolidation.

Approaches to the Treatment of Children with Esthesioneuroblastoma: Literature Review

The incidence of esthesioneuroblastoma in children under 15 years of age is 0.1 per 100.000 children. Distinctive histological features of this tumor are diffuse accumulation of neuron-specific enolase, synaptophysin, chromogranin, and variable expression of cytokeratins. Diagnosis of the tumor includes endoscopic examination of the nasal cavity and nasopharynx, magnetic resonance imaging (MRI) and computed tomography (CT) of the skull base, paranasal sinuses with intravenous contrast. PET-CT is advisable to use for the detection of regional and distant metastases, as well as for suspected relapse. In patients of adult age, a negative effect on the outcome of the disease was detected, the detection of metastases in the lymph nodes of the neck, the presence of tumor cells at the edges of tumor resection and a high degree of malignancy of the tumor according to the Hyams system. Therapeutic approaches depend on the stage of esthesioneuroblastoma by Kadish. In the A-stage, surgical treatment is advisable. In the presence of tumor cells at the edges of the resection or residual tumor, radiation therapy is performed. In case of B-stage, surgical treatment is combined with the mandatory irradiation of the primary tumor area. In patients with the C-stage, neoadjuvant chemotherapy or radiation is performed, followed by a surgical treatment, adjuvant chemotherapy and/or radiation therapy. Patients with D-stage chemoradiation therapy is indicated. There is no consensus on an effective drug regimen. Overall 5-year survival varies significantly depending on the design of the study — 55% to 98%. Further study of the features of the clinical picture, morphological and molecular features and the course of the disease will help to improve our understanding of the nature of the tumor.

«Graft-Versus-Host» Disease after Haploidentical Hematopoietic Stem Cell Transplantation from Relative Donors in Children with Cancer, Prophylaxis Regimens and Correlation with «Graft-Versus-Tumor» Effect: a Retrospective Cohort Study

Background. «Graft-versus-host» disease (GVHD) is a major complication of allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the main cause of non-relapse mortality. The actual problems of alternative donors HSCTs are GVHD prophylaxis and its distinction from «graft-versus-tumor» (GVT) effect. Objective. Assessment of incidence and severity of GVHD in children with very high-risk cancer after non-T-depleted haplo-HSCT; searching some correlation between controlled chronic GVHD (chGVHD) and GVT effect after HSCT, compare cyclosporine (CSA) and tacrolimus based GVHD prophylaxis. Methods. We provided the GVHD assessment in 74 recipients of haplo-HSCs from relatives since 2001 till 2018 in retrospective cohort study. Effect of chGVHD on the HSCT results was assessed in 23 patients with acute myeloid leukemia (AML) and 15 patients with solid tumors. We analyzed the incidence of severe acute and chronic GVHD in patients who received CSA or tacrolimus-based prophylaxis. Results. The incidence of severe aGHVD in our study was 15%, chGVHD — 12%. Switch CSA to tacrolimus resulted in reduction of severe aGVHD from 21% to 9% and full elimination of severe extensive chGVHD. Controlled chGVHD after haplo-HSCT was associated with relapse reduction from 48.7% to 30% and improvement of overall survival (OS) from 46.5% to 80.8% in patients with AML. We haven’t seen any clinically significant antitumor effect of graft in patients with solid tumors. Conclusion. In our study the incidence of severe GVHD corresponds to world data after HSCTs from alternative donors, it went down after switch from CSA to tacrolimus. We found some correlation between controlled chGVHD development and HSCT results improvement in patients with AML. The GVT effect of haplo-graft in solid tumors is almost absent.

Relevance of Bone Scintigraphy in the Diagnostic Algorithm for Examining Treatment-Naive Pediatric Patients with Langerhans Cell Histiocytosis: a Retrospective Cohort Study

Background. Histiocytosis is a heterogeneous group of rare diseases of unknown etiology. Langerhans cell histiocytosis (LCH) is characterized by an abnormal proliferation of histiocytes (activated dendric cells and macrophages). LCH is the most common form of histiocytosis, it is a potentially fatal diseases. Early detection of LCH plays an important role in its prognosis and outcome. However, the role of advanced methods of nuclear medicine in diagnosis of LCH is still to be researched. We have long-term experience in observing pediatric patients with LCH. Taking into the account the difficulty of diagnostic task for bone scintigraphy in identifying lytic bone destruction, we stated the following objective of the study. Objective. Our aim was to perform retrospective analysis of bone scintigraphy examinations of treatment-naive pediatric patients with LCH and calculate the diagnostic efficacy of bone scintigraphy. Methods. We retrospectively analyzed 55 examinations of treatment-naive pediatric patients (the median age was 5.9 years) with proven case of LCH (2014–2018). Results. During examination we visualized 82 lesions with pathological level of accumulation of radiopharmaceutical in 55 patients. 78 with high level of accumulation (>120%); 3 with slightly increased level of accumulation (100–120%) and 1 with lower than normal level of accumulation (<100%). The median level of accumulation of radiopharmaceutical was 276%: max. level of accumulation was 1422% (patient with subtotal involvement of femoral bone), min. — 60% (patient with lytic destruction in orbital bone). During X-Ray we found out 91 pathological focuses of bone lytic destruction. In 3 patients with polyostotic form we found extra focuses on scintigraphy, which were confirmed with following examination and X-Ray. 8 lesions were not found on scintigraphy in 8 patients. Сonclusion. Bone scintigraphy with 99mTc-MDP in treatment-naïve pediatric patients with proven case of LCH showed sensitivity — 91.0%, specificity — 50.0%, NPV — 11.1%, and PPV — 98.8%.

Oncological Morbidity of Children in the Arkhangelsk Region and the Nenets Autonomous District: An Ecological Study

Background. The study of oncological morbidity in children, as well as the characteristics of its structure and the analysis of temporal trends within the subject of the Russian Federation is aimed at improving the organization of medical care: increasing early diagnosis, reliability of static data, and optimizing patient routing. Objective. Our aim was to analyze the incidence and its structure in children (0–17 years old) who lived in the Arkhangelsk Region and the Nenets Autonomous District in 2007–2016. Methods. The analysis of the incidence of malignant neoplasms of the child population in the Arkhangelsk region and the Nenets Autonomous District was carried out. Results. During the study period, the diagnosis of cancer was first established in 329 (including 6 patients from other subjects of the Russian Federation children (boys — 177, girls — 146) at the age of 0–17 years, of which 260 children at the age of 0–14 years and 63 — at the age of 15–17 years. The average annual incidence of children over 10 years was 14.3: for the age group 0–14 years old — 13.8, for the age group 15–17 years old — 16.6. During the analyzed period, there were significant fluctuations in annual incidence rates (minimum — 9.8 in 2010; maximum — 16.8 in 2009). The average annual incidence in the age group 15–17 years (16.6) was 18% higher than in the age group 0–14 years (14). The morbidity structure was characterized by some predominance of solid tumors (51.7%) over hemoblastosis (48.3%), and in the group of 0–14 years this ratio was 54.6/45.4%, in the group of 15–17 years — 50, 9/49.1%. Conclusion. In the analyzed subjects in recent years there has been practically no increase in the incidence in children. The incidence in the age group 15–17 years is slightly higher than in the age group 0–14 years. Changes in the morbidity structure are noted, mainly due to a decrease in the proportion of lymphomas.

Principles of Non-Pharmacological Correction of Skin Toxicity and Skin Manifestations of a Chronic «Graft Versus Host» Disease

This publication focuses on skin toxicity and skin manifestations of a chronic graft versus host disease (chGVHD). The article provides analysis of contemporary literature on these pathologies, presents new approach to preventing its development and also introduces pathogenetically determined patterns of non-drug correction of skin manifestations.

Life-Threatening Complications During Superselective Ophthalmic Arterial Chemotherapy for Retinoblastoma: Retrospective Cohort Study

Background. Retinoblastoma is the most common intraocular malignant tumor in children. Substantial advances have been made in field of local treatment, in particular, through the development of selective intraarterial chemotherapy (SIAC). Life-threatening cardio-respiratory disorders were reported during the course of SIAC at the moment of a.ophthalmica catheterization. Objective. Our aim was to improve the safety and effectiveness of anesthetic management in children with retinoblastoma. Methods. The retrospective study included patients (n=203) who underwent SIAC (517) under general anesthesia in 2013–2018. Results. Hemodynamic parameters in patients who underwent SIAC procedure for the first time (211) were analyzed, in 186 (88%) cases, smooth anesthesia was observed, the deviations of blood pressure and heart rate did not exceed 20% of the baseline values. In 25 (12%) cases, patients who underwent the first SIAC procedure developed bronchospasm with a decrease in respiratory volume of up to 30% from the initial values 10–20 seconds after catheterization of a.ophthalmica with microcatheter. When analyzing hemodynamic parameters in patients who underwent repeated SIAC procedures (2nd, 3rd sessions, etc.) (306), in 177 (58%) cases, a clinical picture of the trigemino-pulmonary reflex of varying severity manifested. Conclusion. Severe cardio-respiratory complications are often observed during SIAC in children with retinoblastoma. These reactions occur predominantly during the second or subsequent procedures and can be potentially life-threatening. All patients with retinoblastoma who undergo SIAC should be considered at high risk.

Evaluation of Treatment Outcomes in Children with Maxillofacial Vascular Tumors: Cohort Study

Background. The variety of the clinical features of vascular tumors in the maxillofacial area limits the choice of method and is able to make difficulties in the treatment. The combined method of treatment proposed by the authors (vascular sclerotherapy with concurrent propranolol intake) demonstrates high efficacy, lack of invasiveness, shortening the rehabilitation period and less side effects. Objective. The aim of the study was to increase the effectiveness of conservative treatment of vascular tumors of the maxillofacial area in young children by combining the method of sclerotherapy and taking propronolol. Methods. In a cohort study, the results of treatment of 80 children aged 2 months to 2 years with vascular tumors of the maxillofacial region (ICD-10: D18.0) were evaluated. A comparison was made of the results in 2 groups of children who were treated with different methods: combined (n =40; main group; sclerotherapy and taking propranolol) and propranolol monotherapy (n =40; comparison group). Analysis of the data obtained in the main group and the comparison group led to the development of the criteria for evaluating the treatment results: good (regression of vascular tumors and the absence of a cosmetic defect), satisfactory (reduction of vascular tumors by 2/3 or more with maintaining cosmetic defect) and unsatisfactory (gross cosmetic defect) in terms of changes in the volume of tumor, the diameter of the supply vessels and the values of the linear velocity of blood flow according to ultrasound data. Results. Subjects treated by the combined treatment had a significant regression of vascular tumors in the maxillofacial area compared with the comparison group: reduction of the tumor volume, diameter of the supply vessels and linear blood flow velocity according ultrasound data reached zero after 6 months from the start of combined treatment — 6 months earlier than in the comparison group (p <0.001). Conclusion. According to the results of the study, the advantage of the author’s method over the traditional method was demonstrated, which resulted in a reduction in the duration of treatment, a decrease in the risk as well as in a degree of complications.

Surgical Treatment of Lymphangiom in Children: Case Series

Background. Lymphangiomas are non-specific malformations that develop from the lymphatic vessels. Usually, the disease is asymptomatic, but there may be complications requiring emergency care. In the literature there is no consensus about the method of choice in the treatment of these formations. Description of A Case Series. The article is devoted to the evaluation of the efficacy of surgical treatment of lymphangiomas in children. There are also several clinical cases showing mediastinal lymphangioma with a clinical picture of respiratory failure, lymphangioma of the abdominal cavity, imitating the symptoms of an acute abdomen and lymphangioma of a rare anatomical localization. The results of treatment of 48 children for the period from 2008 to 2017 were analyzed at «Morozov Children Municipal Clinical Hospital» (Moscow). The basis of treatment was the removal of education within healthy tissues. When the radical intervention was impossible in 5 (10.4%) children we used resection of the tumor with sparing coagulation of the surface of the formation. Infectious complications arose in 3 (6.3%), lymphorrhea — in 13 (27.1%) patients. Recurrences of lymphangiomas developed in 2 (4.2%) patients. In the case of lymphorrhea, expectant management and parenteral nutrition were used. The repeated operations were performed with recurrences. The catamnesis ranges from 6 months to 10 years. Conclusion. Radical removal of lymphangiomas of internal organs can be recommended to children of any age as an effective way to treat this disease.

12-Years Experience of Implanted Venous Access Port Systems in Children with Cancer in a Multidisciplinary Hospital: Cross-Sectional Study

Background. Advances in oncology and hematology-oncology are associated with the development of advanced treatment programs. The main role among them one belongs to chemotherapy. Therapy requires adequate venous access and the most optimal is a fully-implantable venous system (venous port) that meets all the requirements for long-term and intermittent administration of drugs. Objective. The aim of our study was to analyze the experience of using IVAPS in the treatment of children with cancer in a multidisciplinary hospital. Methods. A retrospective study of the implantation of 192 IVAPS in children in the Morozovskaya State Children’s Clinical Hospital for 12 years from 2004 to 2015 was conducted. The average age of patients at the time of implantation is 53 months — 4 years and 4 months. The ratio by gender was equal. IVAPS were implanted under X-ray control in a surgery room by puncture technique in the subclavian and / or jugular veins mainly in patients with solid tumors (175/192; 91,2%), and with hemoblastomas (17/192; 8,8%). Results. The average lifetime of the IVAPS is 24 months. Intraoperative complications and complications in the short term (up to 30 days from the moment of implantation) were noted in 44/192 (23%) cases, in the long term (more than 30 days) — in 34/192 (17.7%). All intraoperative complications were resolved during surgery. In the long-term period, infection of the IVAPS was detected in 12 (6.25%) cases: gram-positive flora in 7/12 (58.3%) cases, gram-negative flora in 5/12 (41.7%); in 17/192 (8.9%) — thrombosis of the IVAPS, in 2/192 (1%) — violation of the integrity of the port-system. IVAPS were removed in 78/192 (40.6%) cases: due to the end of treatment — 66/78 (84.6%), due to infection — 12/78 (15.4%). 45/191 (23.6%) patients died from progression of the underlying disease, 89/191 (46.6%) achieved remission, 32/191 (16.8%) continue treatment, 25/191 (13.1%) dropped out from under observation. Conclusion. Considering the intensification of treatment protocols, it is reasonable to recommend the use of IVAPS in the treatment of children with cancer.