Radosław Chaber

Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory Ewing sarcoma

Patients with metastatic, progressive or recurrent Ewing sarcoma (ES) have a dismal outcome. The combination of irinotecan and temozolomide has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination with vincristine for patients with relapsed and refractory ES.

Validation of a multi‐modal treatment protocol for Ewing sarcoma—A report from the polish pediatric oncology group

Ewing sarcoma (ES) is the second most common paediatric malignant bone tumor. Advances in multi‐disciplinary care have resulted in significant improvement in cure rates over the last decades. However, the generalization of those results in countries traditionally excluded from large cooperative trials has yet to be demonstrated. We report the results of modern multi‐disciplinary care for patients with ES in Poland.

Ovarian function in female survivors after multimodal Ewing sarcoma therapy

With advances in cancer care, more young women with Ewing sarcoma (ES) survive after treatment. Thus, we sought to analyze the ovarian function in prepubertal, pubertal and postpubertal females and young women receiving multimodal therapy for ES, and to identify patients at risk of infertility on whom fertility preservation would be indicated.

Internal hemipelvectomy in the management of pelvic Ewing sarcoma - are outcomes better than with radiation therapy?

BACKGROUND Pelvic Ewing sarcoma (ES) is commonly associated with a worse prognosis. Large size and location limit local control options to radiation therapy, and local recurrences are common. We evaluated the impact of hemipelvectomy and radiation on outcomes, including function. MATERIALS AND METHODS Thirty-nine patients (median age 13.5years) with ES of the pelvis and sacral bones were treated during the period 2000-2012. Fifteen were treated with definitive radiotherapy (RT), 9 patients underwent hemipelvectomy alone, and 15 were treated with combined hemipelvectomy and RT. RESULTS Twenty patients (51.2%) are alive with a median follow-up 3.2years from diagnosis. Median time from diagnosis to relapse was 1.3years. Three-year estimates of EFS and OS were 47% and 61%, respectively. Patients treated with surgery or surgery with RT had better outcome than patients treated with RT only (3-year OS 78% or 81% vs. 36%, respectively, p=0.00083). The outcome of patients with pelvic ES treated with hemipelvectomy was not significantly different from the outcome of all patients with Ewing sarcoma treated on the national Polish protocol. CONCLUSIONS Internal hemipelvectomy offers good chances of cure for patients with pelvic ES, with a reasonable rate of complications and good function.

Clinical features and treatment outcomes of peripheral T-cell lymphoma in children. A current data report from Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)

PURPOSE Peripheral T-cell lymphomas (PTCL) are lymphoproliferative disorders derived from post-thymic cells, that occur extremely rarely in children. The optimal treatment of pediatric PTCL remains still unclear. PATIENTS AND METHODS Ten children with PTCL from 3 up to 18 years of age registered by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) were retrospectively analyzed. All patients were treated with different regimens including protocols: for lymphoblastic lymphoma in 7 cases, for anaplastic large cell lymphoma in 1, CHOP in 1. Five of the 10 patients with PTCL were classified as stage II; 4 as stage III and 1 as stage IV due to extralymphatic organs (bone marrow) involvement. Four histological subtypes of PTCL were recognized: extranodal NK/T-cell lymphoma, nasal type (ENTNT), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), subcutaneous panniculitis-like T-cell lymphoma (SPL), Sezary syndrome (SS). After first-line therapy 9 patients initially achieved complete remission, 4 relapsed, 5 died. One patient achieved remission spontaneously. Three children (1 with stage IV and 2 in relapse) underwent high-dose chemotherapy with allogeneic bone marrow stem cell transplantation and all of them are alive and in CR. RESULTS The cumulative probability of 5-year overall survival (OS) for our whole group was 63.9% (95%CI: 35.2-88.2%) with a median follow-up time of 48.4 months (range 24-90+ months). The 5-year event free survival (EFS) was 81%. PTCLs are a heterogeneous and rare group of childhood NHLs. CONCLUSIONS According to our experience the standard chemotherapy for precursor lymphomas seems to be a beneficial treatment option for children with PTCL. Allogeneic stem cell transplantation may improve the outcome in selected patients.

Immunohistochemical Expression of Procaspase-3 and Its Clinical Significance in Childhood Non-Hodgkin Lymphomas

Previous studies have shown differences in expression levels of apoptosis regulatory proteins in non-Hodgkin lymphomas (NHLs) and indicated the correlation of procaspase-3 (proC-3) and caspase-3 activation to the response of chemotherapy. We investigated whether proC-3 expression in tumor biopsies of childhood NHLs is related to clinical outcome. Formalin-fixed paraffin-embedded tissues from 58 children with NHL were evaluated for proC-3 expression by immunochemistry analysis. The study included 20 cases of Burkitt lymphoma, 7 cases of diffuse large B-cell lymphoma, 18 cases of anaplastic large cell lymphoma (ALCL), and 13 cases of precursor lymphoblastic lymphoma. The highest expression level of proC-3 was observed in ALCL. In the multivariate analysis the higher clinical stage of disease and higher expression level of proC-3 were independent and appear to be significant prognostic factors of treatment failure. Our results suggest that the high expression level of proC-3 may be a powerful independent predictor of response to chemotherapy and progression-free survival in childhood NHLs.

The BCL-2 protein in precursor B acute lymphoblastic leukemia in children.

The BCL-2 protein plays an important role in controlling apoptosis. Disorders of this process can lead to the emergence and development of acute lymphoblastic leukemia (ALL) and can determine the resistance of leukemic cells to chemotherapy. The levels of BCL-2 mRNA were determined in 20 children with pre-B ALL using RT-polymerase chain reaction and the percentage of BCL-2+ cells in 51 patients using flow cytofluorometry. Similar levels of BCL-2 mRNA (P=0.18) with a higher percentage of cells BCL-2+ (P=0.04) were shown in the bone marrow of patients with pre-B ALL compared to normal peripheral blood mononuclear cells. We could not find any connection between the level of BCL-2 mRNA or the percentage of BCL-2+ cells and selected clinical features. A high percentage of BCL-2+ cells and high levels of BCL-2 mRNA did not affect the 5-year overall survival probability nor the 5-year relapse-free survival probability. These results may indicate a high activity of mechanisms promoting the development of the final form of the BCL-2 protein from mRNA in leukemic cells. A high BCL-2 level does not affect the clinical course or worsen the prognosis in children with ALL.

Distinguishing Ewing sarcoma and osteomyelitis using FTIR spectroscopy

The differential diagnosis of Ewing sarcoma and osteomyelitis can be challenging and can lead to delays in treatment with possibly devastating results. In this retrospective, small-cohort study we demonstrate, that the Fourier Transformed Infrared (FTIR) spectra of osteomyelitis bone tissue can be differentiated from Ewing sarcoma and normal bone tissue sampled outside tumour area. Significant differences in osteomyelitis samples can be seen in lipid and protein composition. Supervised learning using a quadratic discriminant analysis classifier was able to differentiate the osteomyelitis samples with high accuracy. FTIR spectroscopy, alongside routine radiological and histopathological methods, may offer an additional tool for the differential diagnosis of osteomyelitis and ES.

Prediction of Ewing Sarcoma treatment outcome using attenuated tissue reflection FTIR tissue spectroscopy

Ewing sarcoma is the second most common type of primary bone cancer and predominantly affects children and young people. Improved outcome prediction is key to delivering risk-adjusted, appropriate and effective care to cancer patients. Advances in the Fourier Transform Infrared (FTIR) spectroscopy of tissues enable it to be a non-invasive method to obtain information about the biochemical content of any biological sample. In this retrospective study, attenuated tissue reflection FTIR spectroscopy of biopsy samples from paediatric patients reveals spectral features that are diagnostic for Ewing Sarcoma. Furthermore, our results suggest that spectral features such as these may be of value for the prediction of treatment outcome independent to well-known, routinely used risk factors.

Immune Consequences of in vitro Infection of Human Peripheral Blood Leukocytes with Vesicular Stomatitis Virus

Background: Oncolytic vesicular stomatitis virus (VSV) can be delivered intravenously to target primary and metastatic lesions, but the interaction between human peripheral blood leukocytes (PBLs) and VSV remains poorly understood. Our study aimed to assess the overall immunological consequences of ex vivo infection of PBLs with VSV. Methods: Phenotypic analysis of lymphocyte subsets and apoptosis were evaluated with flow cytometry. Caspase 3/7 activity was detected by luminescence assay. Virus release was evaluated in a murine cell line (L929). Gene expression and cytokine/chemokine secretion were assessed by real-time PCR and multiplex assay, respectively. Results: Ex vivo infection of PBLs with VSV elicited upregulated expression of RIG-I, MDA-5, tetherin, IFITM3, and MxA. VSV infection triggered rapid differentiation of blood monocytes into immature dendritic cells as well as their apoptosis, which depended on caspase 3/7 activation. Monocyte differentiation required infectious VSV, but loss of CD14+ cells was also associated with the presence of a cytokine/chemokine milieu produced in response to VSV infection. Conclusions: Systemic delivery is a major goal in the field of oncolytic viruses. Our results shed further light on immune mechanisms in response to VSV infection and the underlying VSV-PBL interactions bringing hope for improved cancer immunotherapies, particularly those based on intravenous delivery of oncolytic VSV.