scholarly journals Rhabdomyosarcoma in the first year of life. Experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

2021 ◽  
Vol 20 (1) ◽  
pp. 76-90
Author(s):  
T. V. Stradomskaya ◽  
D. Yu. Kachanov ◽  
N. S. Grachev ◽  
A. V. Akhaladze ◽  
M. V. Teleshova ◽  
...  
Keyword(s):  
High Risk ◽  
Confidence Interval ◽  
Local Control ◽  
Stage Iv ◽  
First Year ◽  
Event Free Survival ◽  
Free Survival ◽  
Pediatric Hematology ◽  
National Medical ◽  
First Year Of Life

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood, but is very rare in infants. RMS diagnosed during the first year of life is reported to have poor outcome. The aim of the study was to analyze the results of therapy of RMS in the first year of life treated in federal center in Russian Federation. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All prospectively registered patients with RMS in infants treated during the period 02.2012–05.2018 (75 month) were included. Diagnosis was confirmed by histology. All patients were examined and stratified according to the GPOH Cooperative Weichteilsarkom Study (CWS) Group guidance 2009. 13 prospectively registered patients with RMS in infants treated during the period were included. Median age at initial diagnosis was 6.7 (range 0.23–11.9) months. The tumor was detected prenatally at 32 and 33 weeks of gestation in 2 (15%) patients. The age of these patients was ≤ 1 month in 2 of 13 patients. Tumor size was ≤ 5 cm in 8 (61,5%) of 13 patients. Median volume tumor was 24 (range 0.001–150) ml. The primary site was head and neck (n = 4; 31.5%), pelvis (n = 3; 23%), extremities (n = 3; 23%), genitourinary system (n = 2; 15%), other (n = 1; 7.5%). IRS stage distribution was stage III in 12 (92.5%) patients, stage IV – 1 (7.5%). Regional nodal metastasis (N1) occurred in 1 (7.5%) patient with tumor of the head and neck nonparameningeal. Distant metastasis occurred in 1 (7.5%) patient and the site of spread was subcutaneous fat (blueberry muffin syndrome), pleura, roots of both lungs, pancreas, bone marrow. Histology of these infants was RMA (n = 6; 46%), RME (n = 6; 46%) and spindle-cell RMS (n = 1; 7.5%). The FOXO1-fusion positive status was found in 4/6 patients RMA by fluorescence in situ hybridization (FISH). 11/13 (85%) patients were categorized as high risk, 1/13 (7.5%) as very high risk, 1/13 (7.5%) – treatment for stage IV patients with metastatic disease. All patients (n = 13; 100%) received chemotherapy according to CWS guidance 2009 protocol. All patients were administered at a reduced dose according to body weight. The distribution of treatment regimens was as follows: 11/13 (85%) – IVA, 1/13 (7.5%) – IVADO, 1/13 (7.5%) – CEVAIE. 3/13 patients aged less than 1 month was administered chemotherapy according to VAC. Initial surgery included biopsy in 8/13, surgery – 5/13 (R2 – resection). Local control was provided in 11/13 (85%) patients: only surgery in 7/13 (54%) patients, only radiotherapy in 1/13 (7.5%), radiotherapy and surgery 1/13 (7.5%), only brachytherapy 1/13 (7.5%), brachytherapy and surgery in 1/13 (7.5%). 2/13 patients were not local control: one patient with favorable site (vagina) and one patient with stage IV that showed complete response after chemotherapy in both cases. Radiotherapy including brachytherapy was administered of the all patients at the over 1 year. Radiotherapy was used in 2 of 13 patients (dose range 50.4 Gy and 51.2 Gy), brachytherapy – 36 Gy. At the start of the radiotherapy the age was 21.1 and 13.37 months, brachytherapy – 12,4 and 14,5 months. Second-look surgery was performed in 9/13 (69%) patients: R0 (n = 7), R1 (n = 1), R2 (n = 1). 2/9 patients were performed mutilating surgery: orbital exenteration and cystectomy. Induction therapy was completed in 12 (92.5%) of 13 patients. Median follow-up time was 42.7 (range 3.7–90) months. 8 patients were alive, 5 died. 8/13 patients whom alive were observation: 6/8 patients no relapse/progressive, 2/8 patients – remission after local relapse and progression. 3-year overall survival was 68,4% (95% confidence interval 42,6–94,1. 3-year event-free survival was 46,2% (95% confidence interval 19,1–73,3). Patients aged less than 1 year are particularly problematic. The relatively low event-free survival rate in this age group is associated with the impossibility of carrying out the entire volume of multimodal therapy and required a tailored therapeutic approach. 

Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy

2012 ◽  
Vol 30 (28) ◽  
pp. 3533-3539 ◽  
Author(s):  
Arnauld Verschuur ◽  
Harm Van Tinteren ◽  
Norbert Graf ◽  
Christophe Bergeron ◽  
Bengt Sandstedt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
High Risk ◽  
Pulmonary Metastases ◽  
Stage Iv ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

scholarly journals BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group

Blood ◽  
2011 ◽  
Vol 117 (9) ◽  
pp. 2596-2603 ◽  
Author(s):  
Kara M. Kelly ◽  
Richard Sposto ◽  
Raymond Hutchinson ◽  
Vickie Massey ◽  
Kathleen McCarten ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Treatment Strategies ◽  
Stage Iv ◽  
Disease Stage ◽  
Oncology Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Field Radiation

AbstractDose-intensified treatment strategies for Hodgkin lymphoma (HL) have demonstrated improvements in cure but may increase risk for acute and long-term toxicities, particularly in children. The Children's Oncology Group assessed the feasibility of a dose-intensive regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in children with high-risk HL (stage IIB or IIIB with bulk disease, stage IV). Rapidity of response was assessed after 4 cycles of BEACOPP. Rapid responders received consolidation therapy with guidelines to reduce the risk of sex-specific long-term toxicities of therapy. Females received 4 cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) without involved field radiation therapy (IFRT). Males received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with IFRT. Slow responders received 4 cycles of BEACOPP and IFRT. Ninety-nine patients were enrolled. Myelosuppression was frequent. Rapid response was achieved by 74% of patients. Five-year event-free-survival is 94%, IFRT with median follow-up of 6.3 years. There were no disease progressions on study therapy. Secondary leukemias occurred in 2 patients. Overall survival is 97%. Early intensification followed by less intense response-based therapy for rapidly responding patients is an effective strategy for achieving high event-free survival in children with high-risk HL. This trial is registered at http://www.clinicaltrials.gov as #NCT00004010.

scholarly journals Results of the use of cladribine in children with acute myeloid leukemia in the treatment according to the AML-MM-2006 protocol

2021 ◽  
Vol 20 (1) ◽  
pp. 40-45
Author(s):  
D. A. Venyov ◽  
I. I. Kalinina ◽  
T. Yu. Salimova ◽  
D. A. Evseev ◽  
V. E. Matveev ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Risk Group ◽  
Research Center ◽  
Control Group ◽  
Consolidation Therapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Pediatric Hematology ◽  
National Medical ◽  
Significant Therapeutic Effect

The aim of this work was to evaluate the results of the use of cladribine in the treatment according to the AML-MM-2006 protocol as post-remission therapy in children. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The article presents the experience of treating children with AML at the Russian Children's Clinical Hospital, and later at the Dmitry Rogachev National Research Center within the framework of the AML-MM-2006 protocol. For the period from 2006 to 2018, 25 children were included in the study. As a comparison, to assess the effectiveness of therapy, the remaining cohort of patients from the intermediate risk group, which consisted of 83 children, was selected. Ultimately, the addition of cladribine in consolidation therapy did not show a significant therapeutic effect (event-free survival 0.47 ± 0.1 for the cladribine group, 0.52 ± 0.06 for the control group), including the development of relapse (56% patients in the cladribine group had a relapse, in the control group – in 34.5%). Thus, the study proved that further inclusion of cladribine in consolidation therapy for primary AML is inappropriate. 

CODOX-M/IVAC (NCI 89-C-41) for Children and Adolescents with Small Non-Cleaved and Large B-Cell Lymphomas. A 14 Years Monocentric Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3308-3308
Author(s):  
Maria Luisa Moleti ◽  
Anna Maria Testi ◽  
Luigi Malandruccolo ◽  
Elisabetta Todisco ◽  
Edoardo Pescarmona ◽  
...  
Keyword(s):  
High Risk ◽  
Children And Adolescents ◽  
Stage Iv ◽  
Low Risk ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Large B Cell

Abstract Over the last 14 years, at our Institute, we have used the NCI 89-C-41 protocol designed by I. Magrath in children and adolescents with small non-cleaved cell (SNCL) and large B-cell (LBCL) lymphomas. In the 1996 paper (J Clin Oncol 1996, 14: 925–34), Magrath et al reported an event-free survival of 92% at 2 years, in adults and children with SNCL. In this protocol, patients with a single extra-abdominal mass or completely resected abdominal disease and LDH <350 IU/L are classified as low-risk; all other patients are defined as high-risk. Low-risk patients receive 3 cycles of the CODOX-M regimen, a combination of cyclophosphamide, doxorubicin, prednisone, vincristine, high-dose methotrexate and intrathecal therapy. High-risk patients receive 4 alternating CODOX-M and IVAC regimens. The IVAC protocol includes ifosfamide, etoposide, high-dose cytarabine and intrathecal methotrexate. We describe hereby the results obtained in 35 patients younger than 21 years with SNCL and LCBL, seronegative for the HIV, treated with the NCI 89-C-41 protocol between September 1989 and March 2003 at our Institute. Median age at presentation was 12.1 years, ranging form 2.6 to 21 years. Thirty patients had SNCL and 5 LBCL. According to Murphy’s staging system, 17 were classified as stage II, 9 as stage III and 9 as stage IV (all with bone marrow involvement that was >25% in 3; 1 with associated CNS disease). Two patients were defined as low risk, while 33 were high-risk. The CNS+ patient received additional IT therapy. G-CSF was given in case of neutropenia associated to severe infections. Thirty-two of the 35 patients (91%) achieved a CR. The remaining 3 patients (SNCL, stages II, III and IV) obtained a PR after the first 2 cycles, but the disease rapidly progressed and led to death in all 3. One patient with stage IV SNCL died in CR of fungal meningitis, during the fourth cycle neutropenia. Three complete responders (SNCL, stage III) relapsed after 2, 2 and 33 months from the end of therapy. Only 1 of them is alive and well in second CR after a stem cell transplant. A life-threatening tumor lysis syndrome was observed in 2 patients; metabolic alterations caused seizures in 1 of them that resolved without sequelae. The hematological toxicity was acceptable; in low-risk patients no thrombocytopenias were observed and neutropenia lasted from 0 to 3 days. For high-risk patients, the median time to PMN >0.5 x 109/L after each cycle was 7, 6, 6 and 6 days (range 0–19), respectively, and to PLTS >50 x 109/L was 6 days (range 0–36). Infections were observed only in high-risk patients with 13 bacterial sepsis, 1 disseminated fungal infection and 12 localized infections. Mucositis (WHO >2) was the main extra-hematological side-effect occurring usually after the CODOX-M regimen; transient peripheral neuropathy occurred in 4 patients after the CODOX-M cycle. No acute and late liver, pulmonary and cardiac toxicities were registered. The 7-years overall survival and event free-survival are 83 and 80%. The results of our study indicate that the NCI 89-C-41 protocol, originally designed for SNCL patients, has confirmed its feasibility and documented its long-term efficacy in a series of children and adolescents with both SNCL and LBCL managed at a single center and with a median follow-up extended to 10 years.

scholarly journals Choroid plexus carcinoma in children

2021 ◽  
Vol 20 (1) ◽  
pp. 66-74
Author(s):  
A. F. Valiakhmetova ◽  
L. I. Papusha ◽  
A. V. Sanakoeva ◽  
L. V. Shishkina ◽  
O. I. Budanov ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Ethics Committee ◽  
Partial Resection ◽  
Event Free Survival ◽  
Total Resection ◽  
Free Survival ◽  
Pediatric Hematology ◽  
National Medical ◽  
Choroid Plexus Carcinomas ◽  
Optimal Treatment Strategy

Choroid plexus carcinomas (CPCs) are rare pediatric tumors with a generally poor prognosis. Currently there is no definite optimal treatment strategy for this neoplasm. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. This study included patients with a verified diagnosis of CPC at the age 0 to 18 years in the period from 01.01.2009 to 31.12.2019. A total of 32 patients were registered. The median age was 2.65 years; 93.5% of CPCs were localized in the lateral ventricles. Initial metastases were found in 21.8% of cases; 5-year event-free survival (EFS) in children with metastases was lower than in those who did not have metastases 29 ± 17% and 49 ± 12%. In our cohort, gross total resection (GTR) was performed in 65.6% of patients. The five-year EFS in patients with complete CPC removal was higher than in patients who underwent subtotal and partial resection (63 ± 13%, 12 ± 11%, and 0%, respectively). In addition, overall survival (OS) was slightly higher in those who underwent GTR compared with subtotal and partial resection (74 ± 12%, 67 ± 16%, and 0%, respectively). Of the 32 children with CPCs, 15 children received programm chemotherapy, 17 non-programm chemotherapy, 5-year EFS in patients who received programm and non-programm chemotherapy was 79 ± 11% and 0%, respectively (p = 0.0006), 5-year OS in patients who received programm and non-programm chemotherapy was 93 ± 7% and 36 ± 14% (p = 0.0054). 

scholarly journals Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3494
Author(s):  
Xiaofei Sun ◽  
Zijun Zhen ◽  
Ying Guo ◽  
Yuanhong Gao ◽  
Juan Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Conventional Treatment ◽  
Maintenance Treatment ◽  
Antibody Therapy ◽  
Aggressive Treatment ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Stage 4 ◽  
Risk Patients

Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB were included. Patients with complete/very good partial remission (CR/VGPR/PR) to conventional treatment received, or not, oral metronomic MT for 1 year. Two hundred and seventeen high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a CR/VGPR/PR to conventional treatment, of the patients with stage 4, 106 receiving and 61 not receiving oral metronomic MT, and the 3-year event-free survival (EFS) rate was 42.5 ± 5.1% and 29.6 ± 6%, respectively (p = 0.017), and overall survival (OS) rate was 71.1 ± 4.7% and 59.4 ± 6.4%, respectively (p = 0.022). A total of 117 high-risk patients with oral metronomic MT had EFS rate of 42.7 ± 4.8%. The toxicity of MT was mild. For high-risk NB patients without ASCT or anti-GD2 antibody therapy, stage 4, MYCN amplication and patients with stage 4 not receiving oral metronomic MT after CR/VGPR/PR were independent adverse prognostic factors. Oral metronomic MT can improve survival in high-risk NB patients in CR/VGPR/PR without ASCT or anti-GD2 antibodies therapy.

scholarly journals Pharmacokinetics of 13-cis-Retinoic acid in high-risk neuroblastoma patients

2020 ◽  
Vol 19 (4) ◽  
pp. 20-31
Author(s):  
E. A. Litvin ◽  
D. T. Utalieva ◽  
D. Yu. Kachanov ◽  
A. V. Pshonkin ◽  
M. Ya. Yadgarov ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Medical Research ◽  
High Performance ◽  
Plasma Concentrations ◽  
Neuroblastoma Cells ◽  
Research Center ◽  
Therapeutic Drug ◽  
Pediatric Hematology ◽  
National Medical

13-cis-Retinoic acid is a differentiation agent for neuroblastoma cells and is a part of post-consolidation therapy for high-risk patients. The effectiveness of this therapeutic approach is currently under study. 26 patients with high-risk neuroblastoma treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology were included in the study of 13-cis-Retinoic acid pharmacokinetics by high-performance liquid chromatography assay with ultraviolet detector depending on the method of administration of drug (swallowed capsules or opened capsules before administration). This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The current study showed that the therapeutic concentration of > 2 μM when taking 13-cis-Retinoic acid at a dose of 160 mg/m2/day was achieved in two groups, regardless of the method of drug administration. However, plasma concentrations of 13-cis-Retinoic acid at 4 hours after administration on the 14th day of therapy were higher in the group of patients who swallowed the capsules (4.1 ± 1.8 μM), compared to those who could not do it (1.9 ± 1.5 μM) (p = 0.022). The introduction into the clinical practice of therapeutic drug monitoring of 13-cis-retinoic acid in high-risk neuroblastoma patients with an assessment of peak concentration and dose adjustment of the following courses may be an important point in the attempt to optimize postconsolidation therapy and improve prognosis.

scholarly journals Primary and Metastatic Intracranial Ewing Sarcoma at Diagnosis: Retrospective International Study and Systematic Review

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1675
Author(s):  
Lianne M. Haveman ◽  
Andreas Ranft ◽  
Henk van den Berg ◽  
Stephanie Klco-Brosius ◽  
Ruth Ladenstein ◽  
...  
Keyword(s):  
Local Control ◽  
Ewing Sarcoma ◽  
Univariate Analysis ◽  
International Study ◽  
Cerebral Metastases ◽  
The Body ◽  
Event Free Survival ◽  
Free Survival ◽  
Metastatic Lesions ◽  
Chemotherapeutic Treatment

Intracranial Ewing sarcoma (EwS) is rare and publications on primary or metastatic intracranial EwS are minimal. The aim of this study was to describe incidence, clinical behavior, treatment, and factors associated with outcome in patients with primary intracranial EwS or patients with a primary extracranial EwS and cerebral metastases at diagnosis. We reviewed all patients with primary or with metastatic intracranial EwS at diagnosis registered in the International Clinical Trial Euro-E.W.I.N.G.99 (EE99). In total, 17 of 1435 patients (1.2%) presented with primary intracranial EwS; 3 of them had metastatic disease. Four patients (0.3%) with primary extracranial EwS presented with intracranial metastatic lesions. The 3-year event-free survival (EFS) was 64% and overall survival (OS) was 70% in patients with a primary intracranial EwS. Local control in patients with primary intracranial EwS consisted of surgery (6%), radiotherapy (RT) (18%), or both modalities (76%). Univariate analysis showed that patients < 15 years of age had significantly better outcome (EFS: 72%; OS: 76%) compared to those aged above 15 years (EFS: 13%; OS: 25%). In conclusion, primary intracranial EwS and extracranial EwS with cerebral metastases at diagnosis is rare, yet survival is comparable with local and metastatic EwS elsewhere in the body. Age and stage of disease are important prognostic factors. Besides chemotherapeutic treatment, local control with surgical resection combined with RT is recommended whenever feasible.

scholarly journals Dog ownership is associated with less wheezing among high-risk infants during the first year of life

2005 ◽  
Vol 115 (2) ◽  
pp. S136
Author(s):  
H.K. Kalra ◽  
P. Campo ◽  
D.I. Bernstein ◽  
L. Levin ◽  
R. Olds ◽  
...  
Keyword(s):  
High Risk ◽  
First Year ◽  
Dog Ownership ◽  
High Risk Infants ◽  
First Year Of Life
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