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Rhabdoid Tumors: The Medical University of Vienna Experience
456 Conclusion: The Hedgehog pathway plays a central role in MRTs and can be efficiently blocked by ATO resulting in inhibition of cell proliferation and induction of apoptosis in vitro. Liposomal application of ATO has the potential for a targeted therapy using antibody-conjugated immunoliposomes to improve the pharmacokinetic properties of ATO and reduce systemic toxicity.
Genomic Alterations in Atypical Teratoid/Rhabdoid Tumors: The Medical University of Vienna Experience €bel, Thomas Czech, Christine Haberler, Thomas Stro Monika Chocholous, Christian Dorfer, Irene Slavc Institute of Neurology, Medical University of Vienna, Austria
Background: To date, the only recurrent genomic aberration detected in atypical teratoid/rhabdoid tumors (AT/RTs) are alterations within the SMARCB1/INI1 gene. They comprise deletions including copy neutral LOH, mutations, and duplications. Patient outcome is in general very poor with rapid disease recurrence despite treatment, and death due to progression. However, improved patient outcome could be achieved with an intensive multimodal therapy developed at the Medical University of Vienna (MUV). Methods: Tumor tissues and constitutional DNA from 16 patients treated at the MUV for primary or recurrent tumors were analyzed using immunohistochemistry, MLPA and Sanger sequencing, as well as SNP arrays in 3 patients. Patient age at diagnosis ranged between 3 months and 22 years (median 32.5 months). 5 were females, 11 males. Tumor location was in 10 patients supratentorial and in 6 patients posterior fossa. Results: The tumor tissue of all patients showed immunohistochemically loss of SMARCB1/INI1 expression, diagnostic for AT/RT. In 8 patients (50%) homozygous deletions of the SMARCB1/INI1 gene were observed. In 3 patients (18.8%) the combination of a coding sequence mutation and a deletion was found. In 5 (31.2%) tumors only one hit was detectable within the tumor tissue (4 deletions, 1 mutation). In 3 patients a germline alteration was found, including 2 deletions and 1 coding sequence mutation. Patients with germline mutations were 3, 6 and 35 months at diagnosis. 13 patients, including 1 patient with germline mutation are alive, 3 patients died of disease. Discussion: To date no genotype/phenotype correlations exist, therefore documentation of genomic alterations and outcome of AT/RT patients is important to detect patients who might have an improved survival.
Extra-Cranial Malignant Rhabdoid Tumor in Children: A Single Institute Experience Che Ry Hong a, Hyoung Jin Kang a, Ji Won Lee a, Sung-Hye Park b, Kyung Duk Park a, Hee Young Shin a a Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; b Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
Background: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. It has a poor prognosis, with published 5-year overall survival between 15 to 36%. Due to its’ extreme rarity, most of the available data is based on retrospective case series. To add to the current
Abstracts knowledge of this disease, we reviewed the children treated for extra-cranial MRT in our institute. Methods: A retrospective medical record review was done on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children’s Hospital between January 2003 and July 2013. Results: Ten children (7 boys, 3 girls) were diagnosed with extracranial MRT at median age of 8 months old. Six patients (60%) had renal MRT and 4 (40%) had soft tissue MRT in submental, paraspinal, retrosternal or coccygeal area. Five patients (50%) had metastasis at diagnosis and 3 of these patients had metastases to the lungs. The entire cohort received chemotherapy and 3 patients (30%) received additional high dose chemotherapy with autologous stem cell rescue after conditioning with melphalan, etoposide and carboplatin. Seven patients (70%) had surgical resections; 3 had upfront surgery and 4 had delayed surgery. Five patients (50%) had therapeutic irradiations. Concerning the treatment results, 3 patients progressed and 2 relapsed. The overall survival of the cohort was 50.0% with median follow-up duration of 25 months (range, 3 to 112 months). Children with lung metastasis had significantly worse survival compared to those with metastasis to sites other than the lungs or those without metastasis; OS 0% versus 50.0% versus 80.0% (PZ0.003). Conclusion: Our study reaffirmed the highly aggressive nature of extra-cranial MRT, but showed a slight improvement in survival compared to previous reports. Children with lung metastasis were shown to have substantially worse outcome. Devising treatment strategies for lung metastasis is thus imperative.
Malignant Rhabdoid Tumors of Soft Tissue. Single Center Experience in Russia Denis Kachanov a, Margarita Teleshova a, Anastasia Usychkina a, Roman Moiseenko a, Guzel Muftakhova a, Anna Mitrofanova b, Tatyana Shamanskaya a, Svetlana Varfolomeeva a a Department of Clinical Oncology, Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow; b Department of Pathology, Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow
Background: Malignant rhabdoid tumor (MRT) of soft tissue represents the rare entity. The aim of the study was to analyze clinical data and preliminary therapy results in a cohort of patients with MRT of the soft tissue treated in federal cancer center in Russian Federation. Methods: 7 patients included in this analysis were treated in Federal Research Center of Pediatric Hematology, Oncology and Immunology during the period of 02.2012-09.2013. All diagnosis were established by histopathologic examination and confirmed by lack of nuclear expression of INI1. Patients were treated according to European Rhabdoid Tumor Registry recommendations. Results: Median age at diagnosis was 9 months (range 0.3-66 months). Diagnosis was verified on the 1st year of life in 5 (71.4%) cases. M:F ratio was 1.3:1. Topography of primary tumor included liver - 3 (42.8%) cases, deep soft tissues of a neck - 2 (28.6%), abdominal cavity - 1 (14.3%), orbit - 1 (14.3%). 3 (42.8%) patients had localized disease, 4 (57.2%) had distant metastases. Clinical group distribution according to Intergroup Rhabdomyosarcoma Study: III e 2 (28.6%), IV - 5 (71.4%, in 1 case due to tumor rupture). Median follow up time was 8.5 months.
Genomic Alterations in Atypical Teratoid/Rhabdoid Tumors: The Medical University of Vienna Experience €bel, Thomas Czech, Christine Haberler, Thomas Stro Monika Chocholous, Christian Dorfer, Irene Slavc Institute of Neurology, Medical University of Vienna, Austria
Background: To date, the only recurrent genomic aberration detected in atypical teratoid/rhabdoid tumors (AT/RTs) are alterations within the SMARCB1/INI1 gene. They comprise deletions including copy neutral LOH, mutations, and duplications. Patient outcome is in general very poor with rapid disease recurrence despite treatment, and death due to progression. However, improved patient outcome could be achieved with an intensive multimodal therapy developed at the Medical University of Vienna (MUV). Methods: Tumor tissues and constitutional DNA from 16 patients treated at the MUV for primary or recurrent tumors were analyzed using immunohistochemistry, MLPA and Sanger sequencing, as well as SNP arrays in 3 patients. Patient age at diagnosis ranged between 3 months and 22 years (median 32.5 months). 5 were females, 11 males. Tumor location was in 10 patients supratentorial and in 6 patients posterior fossa. Results: The tumor tissue of all patients showed immunohistochemically loss of SMARCB1/INI1 expression, diagnostic for AT/RT. In 8 patients (50%) homozygous deletions of the SMARCB1/INI1 gene were observed. In 3 patients (18.8%) the combination of a coding sequence mutation and a deletion was found. In 5 (31.2%) tumors only one hit was detectable within the tumor tissue (4 deletions, 1 mutation). In 3 patients a germline alteration was found, including 2 deletions and 1 coding sequence mutation. Patients with germline mutations were 3, 6 and 35 months at diagnosis. 13 patients, including 1 patient with germline mutation are alive, 3 patients died of disease. Discussion: To date no genotype/phenotype correlations exist, therefore documentation of genomic alterations and outcome of AT/RT patients is important to detect patients who might have an improved survival.
Extra-Cranial Malignant Rhabdoid Tumor in Children: A Single Institute Experience Che Ry Hong a, Hyoung Jin Kang a, Ji Won Lee a, Sung-Hye Park b, Kyung Duk Park a, Hee Young Shin a a Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; b Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
Background: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. It has a poor prognosis, with published 5-year overall survival between 15 to 36%. Due to its’ extreme rarity, most of the available data is based on retrospective case series. To add to the current
Abstracts knowledge of this disease, we reviewed the children treated for extra-cranial MRT in our institute. Methods: A retrospective medical record review was done on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children’s Hospital between January 2003 and July 2013. Results: Ten children (7 boys, 3 girls) were diagnosed with extracranial MRT at median age of 8 months old. Six patients (60%) had renal MRT and 4 (40%) had soft tissue MRT in submental, paraspinal, retrosternal or coccygeal area. Five patients (50%) had metastasis at diagnosis and 3 of these patients had metastases to the lungs. The entire cohort received chemotherapy and 3 patients (30%) received additional high dose chemotherapy with autologous stem cell rescue after conditioning with melphalan, etoposide and carboplatin. Seven patients (70%) had surgical resections; 3 had upfront surgery and 4 had delayed surgery. Five patients (50%) had therapeutic irradiations. Concerning the treatment results, 3 patients progressed and 2 relapsed. The overall survival of the cohort was 50.0% with median follow-up duration of 25 months (range, 3 to 112 months). Children with lung metastasis had significantly worse survival compared to those with metastasis to sites other than the lungs or those without metastasis; OS 0% versus 50.0% versus 80.0% (PZ0.003). Conclusion: Our study reaffirmed the highly aggressive nature of extra-cranial MRT, but showed a slight improvement in survival compared to previous reports. Children with lung metastasis were shown to have substantially worse outcome. Devising treatment strategies for lung metastasis is thus imperative.
Malignant Rhabdoid Tumors of Soft Tissue. Single Center Experience in Russia Denis Kachanov a, Margarita Teleshova a, Anastasia Usychkina a, Roman Moiseenko a, Guzel Muftakhova a, Anna Mitrofanova b, Tatyana Shamanskaya a, Svetlana Varfolomeeva a a Department of Clinical Oncology, Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow; b Department of Pathology, Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow
Background: Malignant rhabdoid tumor (MRT) of soft tissue represents the rare entity. The aim of the study was to analyze clinical data and preliminary therapy results in a cohort of patients with MRT of the soft tissue treated in federal cancer center in Russian Federation. Methods: 7 patients included in this analysis were treated in Federal Research Center of Pediatric Hematology, Oncology and Immunology during the period of 02.2012-09.2013. All diagnosis were established by histopathologic examination and confirmed by lack of nuclear expression of INI1. Patients were treated according to European Rhabdoid Tumor Registry recommendations. Results: Median age at diagnosis was 9 months (range 0.3-66 months). Diagnosis was verified on the 1st year of life in 5 (71.4%) cases. M:F ratio was 1.3:1. Topography of primary tumor included liver - 3 (42.8%) cases, deep soft tissues of a neck - 2 (28.6%), abdominal cavity - 1 (14.3%), orbit - 1 (14.3%). 3 (42.8%) patients had localized disease, 4 (57.2%) had distant metastases. Clinical group distribution according to Intergroup Rhabdomyosarcoma Study: III e 2 (28.6%), IV - 5 (71.4%, in 1 case due to tumor rupture). Median follow up time was 8.5 months.