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Corkum KS, Craig BT, Piche N, Pio L, Fernandez-Pineda I, Malek MM, Lautz TB. Current Surgical Approach to Pulmonary Metastasectomy. Pediatr Blood Cancer 2025; 72 Suppl 2:e31468. [PMID: 39654090 DOI: 10.1002/pbc.31468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 11/14/2024] [Accepted: 11/15/2024] [Indexed: 04/08/2025]
Abstract
The lung is a common site of metastases for children and adolescents with a wide variety of solid tumors. The role for pulmonary metastasectomy is dictated by tumor histology and can serve either therapeutic or diagnostic purposes. Careful surgical planning is required to determine the optimal surgical approach and to ensure successful nodule localization. While high level data are limited, in appropriate situations pulmonary metastasectomy can confirm staging, guide therapy, improve survival, and reduce the need for other therapy escalations.
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Affiliation(s)
- Kristine S Corkum
- Division of Pediatric Surgery, Children's Hospital of Colorado, Aurora, Colorado, USA
| | - Brian T Craig
- Division of Pediatric Surgery, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA
| | - Nelson Piche
- Division of Pediatric Surgery, Université de Montréal, Montreal, Québec, Canada
| | - Luca Pio
- Department of Surgery, Bicêtre Hospital, Paris-Saclay University, GHU Paris Saclay Assistance Publique Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France
| | | | - Marcus M Malek
- Division of Pediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Timothy B Lautz
- Division of Pediatric Surgery, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
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2
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Christensen D, Belair JA, BasuMallick A, Brown SA, Klein M, Jiang W. Synchronous Low-Grade Central Osteosarcoma and Ewing Sarcoma: A Rare Case Report. Int J Surg Pathol 2025; 33:131-137. [PMID: 38504661 DOI: 10.1177/10668969241239675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2024]
Abstract
A 23-year-old female patient presented with radicular back pain, perineal numbness, and urinary retention. The patient was diagnosed with cauda equina syndrome and magnetic resonance imaging (MRI) of the spine revealed an enhancing osseous lumbar lesion causing severe central stenosis. A core needle biopsy of the lumbar spine showed microscopic features compatible with a small round blue cell tumor. CD99 and FLI1 were positive in the tumor cells. Next-generation sequencing demonstrated a EWSR1::FLI1 fusion. Given these findings, the spine lesion was diagnosed as Ewing sarcoma. The patient underwent surgical decompression of L2. On further workup, an MRI revealed an ill-defined enhancing mass of the right distal femur. This area was biopsied, demonstrating a fibro-osseous lesion with osteoblast proliferation containing nuclear atypia, low mitotic activity, and SATB2 positivity, diagnosed as low-grade central osteosarcoma (LGCOS). The patient underwent resection, which showed a classic LGCOS by histomorphology. Although fluorescence in-situ hybridization study for MDM2 gene amplification was negative, the overall findings are most consistent with LGCOS. These neoplasms are considered to be synchronous due to the presentation of each entity within 6 months. Considering the aggregate yearly incidence of Ewing sarcoma (approximately 1 case per 750 000 per year) and LGCOS (approximately 1 case per 10 million per year), the aggregate yearly probability of developing both of these genetically unrelated tumors in a single individual is 1 per 7.5 trillion per year, and it is likely such an event has never happened in the past.
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MESH Headings
- Humans
- Sarcoma, Ewing/pathology
- Sarcoma, Ewing/diagnosis
- Sarcoma, Ewing/genetics
- Sarcoma, Ewing/surgery
- Female
- Osteosarcoma/pathology
- Osteosarcoma/diagnosis
- Osteosarcoma/genetics
- Osteosarcoma/surgery
- Young Adult
- Neoplasms, Multiple Primary/pathology
- Neoplasms, Multiple Primary/diagnosis
- Neoplasms, Multiple Primary/surgery
- Neoplasms, Multiple Primary/genetics
- Bone Neoplasms/pathology
- Bone Neoplasms/diagnosis
- Bone Neoplasms/surgery
- Magnetic Resonance Imaging
- Lumbar Vertebrae/pathology
- Lumbar Vertebrae/surgery
- Lumbar Vertebrae/diagnostic imaging
- Oncogene Proteins, Fusion/genetics
- RNA-Binding Protein EWS/genetics
- Spinal Neoplasms/pathology
- Spinal Neoplasms/diagnosis
- Spinal Neoplasms/surgery
- Spinal Neoplasms/genetics
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/genetics
- Proto-Oncogene Protein c-fli-1/genetics
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Affiliation(s)
- Daniel Christensen
- Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Jeffrey A Belair
- Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Atrayee BasuMallick
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Scot A Brown
- Department of Orthopaedic Oncology, Rothman Orthopaedics, Philadelphia, PA, USA
| | - Michael Klein
- Department of Pathology, Hospital for Special Surgery, New York, NY, USA
- Department of Pathology and Laboratory Medicine, Weill Cornell College of Medicine, New York, NY, USA
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Wei Jiang
- Department of Pathology and Genomic Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
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Nagpal C, Ganguly S, Sasi A, Kumar V, Biswas B, Pushpam D, Kumar A, Agarwala S, Jain V, Dhua A, Yadav DK, Khan SA, Barwad A, Mirdha AR, Biswas A, Thulkar S, Bakhshi S. Ewing sarcoma among children 5 years of age or younger: Is it a different disease? Pediatr Blood Cancer 2024; 71:e31268. [PMID: 39138616 DOI: 10.1002/pbc.31268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 07/19/2024] [Accepted: 07/30/2024] [Indexed: 08/15/2024]
Abstract
INTRODUCTION Children ≤5 years of age with Ewing's sarcoma (ES) possibly have a distinct disease biology, data on which are scarce. We evaluated clinical features, outcomes, and prognostic factors of ES among children with age ≤5 years. METHODS Children with ES registered between 2003 and 2019 were included. Baseline clinical and treatment details were retrieved from medical records. Prognostic factors were identified using multivariable Cox regression. Clinical features and outcomes of children ≤5 years were compared with those greater than 5 years by chi-square and log-rank tests. Propensity score-matched (PSM) analysis was done to evaluate the impact of age on survival in the metastatic and localized subgroups. RESULTS Out of the 859 patients, 86 (10%) were ≤5 years of age (median age 4 years, 60 males [69.8%]). The most common location was the extremities (37.2%), followed by thorax (27.9%) and head and neck (H&N) (22.1%); baseline metastases were seen in 25 patients (29.8%). The median event-free-survival (EFS) and overall survival (OS) were 25.6 and 68.7 months, respectively. Metastatic disease predicted inferior OS (hazard ratio [HR] = 2.54, p = .018) and EFS (HR = 2.47, p = .007], symptom duration ≤3 months predicted an inferior OS (HR = 2.17, p = .048). Compared to age greater than 5 years, younger children had more H&N and less pelvic primaries (p < .001) and lesser baseline metastases (p = .037). PSM analysis did not reveal any significant impact of age on OS in the metastatic (HR = 1.59, p = .29) or localized cohort (HR = 1.77, p = .09). CONCLUSIONS Children with ES ≤5 years of age have a distinct favorable clinical presentation. However, age is not an independent prognostic factor for survival outcomes when adjusted for confounders.
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Affiliation(s)
- Chitrakshi Nagpal
- Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Shuvadeep Ganguly
- Department of Medical Oncology, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, India
| | - Archana Sasi
- Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Vivek Kumar
- Division of Neonatology, Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Bivas Biswas
- Department of Medical Oncology, Apollo Multispecialty Hospital, Kolkata, India
| | - Deepam Pushpam
- Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Akash Kumar
- Department of Medical Oncology, National Cancer Institute, All India Institute of Medical Sciences, Jhajjar, India
| | - Sandeep Agarwala
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Vishesh Jain
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Anjan Dhua
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Devender Kumar Yadav
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Shah Alam Khan
- Department of Orthopedics, All India Institute of Medical Sciences, New Delhi, India
| | - Adarsh Barwad
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Asit Ranjan Mirdha
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Ahitagni Biswas
- Department of Radiation Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay Thulkar
- Department of Radiodiagnosis, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Sameer Bakhshi
- Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
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Fritz CD, Basta AV, Gill J, Lewis VO, Bird JE, Austin MT. Pediatric Ewing Sarcoma Presentation, Treatment, and Outcomes Across Sociodemographic Groups. J Surg Res 2024; 303:322-331. [PMID: 39396459 DOI: 10.1016/j.jss.2024.09.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 08/27/2024] [Accepted: 09/16/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION In this study, we evaluate the association between sociodemographics and disease presentation, treatment, and survival for children, adolescents, and young adults with Ewing sarcoma. METHODS Case-level data were downloaded from The Surveillance, Epidemiology, and End Results database. Cases included patients ages 0-24 who were diagnosed with Ewing sarcoma between 2004 and 2020. RESULTS One thousand two hundred forty four patients were included in the analysis. When compared to non-Hispanic White (NHW) patients, Hispanic patients were more likely to present with tumors ≥8 cm (odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.24-2.36) and metastases (OR = 1.65, 95% CI = 1.23-2.20). Black patients were less likely to receive chemotherapy (OR = 0.25, 95% CI = 0.07-0.97). The 5-year disease-specific survival rate was 73% for NHW patients, 65% for Black patients, 67% for Asian patients and 66% for Hispanic patients. When accounting for confounding factors, Hispanic and Asian patients had higher probabilities of death due to cancer compared to NHW patients (HR = 1.41, 95% CI = 1.10-1.81; HR = 1.64, 95% CI = 1.09-2.48, respectively). Young adults and adolescents were significantly more likely to present with metastases, experience ≥1 month between diagnosis and treatment, and had lower survival. CONCLUSIONS Significant differences in Ewing sarcoma presentation, treatment, and survival were observed across age groups and race/ethnicity. Future work should focus on expanding access to care in underserved groups. Further qualitative studies could assist in determining the exact factors that prevent patients from accessing care or examine how genetic factors that contribute to Ewing sarcoma severity differ across demographic groups.
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Affiliation(s)
- Connor D Fritz
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
| | - Anthony V Basta
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Jonathan Gill
- Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Valerae O Lewis
- Department of Orthopaedic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Justin E Bird
- Department of Orthopaedic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Mary T Austin
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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Wells ME, Eckhoff MD, Davis W, Singh V, Rajani R, Polfer EM. Ewing Sarcoma in the Pediatric Population: Predictors of Survival Within the United States. J Am Acad Orthop Surg Glob Res Rev 2024; 8:01979360-202410000-00017. [PMID: 39436736 PMCID: PMC11498927 DOI: 10.5435/jaaosglobal-d-24-00281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 08/25/2024] [Indexed: 10/25/2024]
Abstract
INTRODUCTION Bone and joint tumors are the third most common cause of pediatric cancer-related deaths in the United States. Although there have been improvements in survival rates among pediatric cancer patients over the past few decades, bone and joint cancers remain the exception. Considering current clinical trials involving novel targeted therapies, the establishment of updated mortality rates and predictors of survival for this cancer would be prudent. This investigation sought to determine updated 5-year survival rates and predictors of survival among pediatric Ewing sarcoma (ES) of bone treated within the United States. METHODS The National Cancer Database was retrospectively inquired for all pediatric ES cases within the most updated bone and joint public use file available in September 2022. The reported data were truncated to only include patients with reported 5-year vital (ie, survival) status. Cox proportional hazard regression was conducted on both the truncated data and the entire cohort to validate the findings. The patients were then separated into alive versus deceased cohorts, and univariate regression analysis was done followed by multivariable regression of notable variables of interest. RESULTS Overall, an aggregated 5-year survival rate of 74.5% was found in the included patient cohort. Patients with localized cancer had a comparatively improved 5-year survival rate of 84.70% as opposed to those with macrometastatic disease on presentation with a survival rate of 50.4%. Patient demographic-, tumor-, and treatment-specific variables all demonstrated an effect on survival. The multivariable predictors of worse mortality were found to include older age, larger tumor size (>8 cm), macrometastatic disease on presentation, and positive surgical margins. CONCLUSION This analysis serves to establish updated survival rates of pediatric ES treated within the United States to set standards for comparison among future studies. Continued multi-institutional and international collaboration is needed to optimize current treatment results and develop novel targeted therapies.
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Affiliation(s)
- Matthew E. Wells
- From the Department of Orthopedic Surgery, William Beaumont Army Medical Center (Dr. Wells, Dr. Eckhoff, and Dr. Polfer); the Department of Orthopedic Surgery, Texas Tech University Health Sciences Center El Paso (Dr. Wells, Dr. Eckhoff, Dr. Davis, Dr. Rajani, and Dr. Polfer); and Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX (Dr. Singh)
| | - Michael D. Eckhoff
- From the Department of Orthopedic Surgery, William Beaumont Army Medical Center (Dr. Wells, Dr. Eckhoff, and Dr. Polfer); the Department of Orthopedic Surgery, Texas Tech University Health Sciences Center El Paso (Dr. Wells, Dr. Eckhoff, Dr. Davis, Dr. Rajani, and Dr. Polfer); and Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX (Dr. Singh)
| | - William Davis
- From the Department of Orthopedic Surgery, William Beaumont Army Medical Center (Dr. Wells, Dr. Eckhoff, and Dr. Polfer); the Department of Orthopedic Surgery, Texas Tech University Health Sciences Center El Paso (Dr. Wells, Dr. Eckhoff, Dr. Davis, Dr. Rajani, and Dr. Polfer); and Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX (Dr. Singh)
| | - Vishwajeet Singh
- From the Department of Orthopedic Surgery, William Beaumont Army Medical Center (Dr. Wells, Dr. Eckhoff, and Dr. Polfer); the Department of Orthopedic Surgery, Texas Tech University Health Sciences Center El Paso (Dr. Wells, Dr. Eckhoff, Dr. Davis, Dr. Rajani, and Dr. Polfer); and Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX (Dr. Singh)
| | - Rajiv Rajani
- From the Department of Orthopedic Surgery, William Beaumont Army Medical Center (Dr. Wells, Dr. Eckhoff, and Dr. Polfer); the Department of Orthopedic Surgery, Texas Tech University Health Sciences Center El Paso (Dr. Wells, Dr. Eckhoff, Dr. Davis, Dr. Rajani, and Dr. Polfer); and Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX (Dr. Singh)
| | - Elizabeth M. Polfer
- From the Department of Orthopedic Surgery, William Beaumont Army Medical Center (Dr. Wells, Dr. Eckhoff, and Dr. Polfer); the Department of Orthopedic Surgery, Texas Tech University Health Sciences Center El Paso (Dr. Wells, Dr. Eckhoff, Dr. Davis, Dr. Rajani, and Dr. Polfer); and Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center El Paso, El Paso, TX (Dr. Singh)
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Choderlos de Laclos X, Risbourg S, Brennan B, Bertucci F, Gaspar N, Gelderblom H, Hawkins DS, Janeway K, Juergens H, Kasper B, Krailo MD, Cécile Le Deley M, Marec-Bérard P, McCabe MG, Metzler M, Ranft A, Strauss S, Tabone MD, Windsor R, Dirksen U, Gandemer V. Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials. Eur J Cancer 2024; 208:114229. [PMID: 39032218 PMCID: PMC11331277 DOI: 10.1016/j.ejca.2024.114229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/10/2024] [Accepted: 07/12/2024] [Indexed: 07/23/2024]
Abstract
INTRODUCTION Ewing sarcoma (ES), is a rare cancer affecting children, adolescents and adults. After VIDE (vincristine-ifosfamide-doxorobucin-etoposide) induction chemotherapy, Busulfan-Melphalan (BuMel) high-dose chemotherapy followed by autologous hematopoietic stem cells transplantation improved outcomes in unfavourable localized ES, but with more toxicities than conventional chemotherapy (VAI: Vincristine-dactinomycin-Ifosfamide). We evaluated whether the risk of acute toxicity associated with BuMel compared to VAI varied according to age in patients recruited in the R2Loc and R2Pulm randomised trials of the Euro-E.W.I.N.G.99 and Ewing-2008 trials. METHODS We included patients with a localized high-risk disease, or pulmonary or pleural metastasis. We analysed the risk of severe toxicity according to randomised treatment group (VAI versus BuMel) and age group (<12 years, 12-17 years, 18-24 years, ≥25 years). We evaluated the heterogeneity of treatment effects by age group using interaction terms in logistic multivariable models. RESULTS The analysis included 243 patients treated with VAI and 205 with BuMel. Overall, BuMel was associated with a higher risk of severe acute toxicity than VAI particularly haematological, gastrointestinal, liver, sinusoidal occlusive syndrome, and infections. Severe haematological toxicity and lower general condition were significantly more frequent in younger patients, whatever treatment. We did not observe any significant heterogeneity in terms of the excess risk of severe toxicities associated with BuMel compared to VAI according to age group. CONCLUSION The excess of acute toxicity associated with BuMel compared to VAI does not vary significantly with age, suggesting the feasibility of BuMel across all age groups.
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Affiliation(s)
| | - Séverine Risbourg
- Methodology and Biostatistics Unit, Oscar Lambret Centre, 3 Rue Frédéric Combemale, Lille, France.
| | - Bernadette Brennan
- Department of paediatric oncology, Royal Manchester Children's Hospital, Manchester, UK.
| | - François Bertucci
- Department of Medical Oncology, Paoli-Calmettes Institute, Aix-Marseille Université, 232 Boulevard de Sainte-Marguerite, Marseille, France.
| | - Nathalie Gaspar
- Department of Oncology for Child and adolescent, Gustave Roussy, 114 rue Edouard Vaillant, Villejuif, France.
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, The Netherlands.
| | - Douglas S Hawkins
- Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
| | - Katherine Janeway
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center, USA.
| | - Heribert Juergens
- Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Germany, West German Cancer Centre (WTZ) Network, Muenster, Germany.
| | - Bernd Kasper
- University of Heidelberg, Mannheim University Medical Center, Mannheim Cancer Center (MCC), Sarcoma Unit, Mannheim, Germany.
| | - Mark D Krailo
- University of Southern California, Los Angeles, CA, USA.
| | - Marie Cécile Le Deley
- Methodology and Biostatistics Unit, Oscar Lambret Centre, 3 Rue Frédéric Combemale, Lille, France.
| | - Perrine Marec-Bérard
- Department of Pediatric Oncology, Institut d'Hématologie et d'Oncologie Pédiatrique, 28 Prom. Léa et Napoléon Bullukian, Lyon, France.
| | - Martin G McCabe
- Division of Cancer Sciences, University of Manchester & The Christie NHS Foundation Trust, Manchester, UK.
| | - Markus Metzler
- Department of Pediatrics, University Hospital Erlangen, and NCT WERA, Erlangen, Germany.
| | - Andreas Ranft
- Pediatrics III, University Hospital Essen, Essen, Germany, West German Cancer Centre (WTZ), German Consortium for Translational Cancer Research (DKTK), and National Center for Tumordiseases site Essen, Essen, Germany.
| | - Sandra Strauss
- London Sarcoma Service, UCL Hospitals NHS Foundation Trust, London, UK.
| | - Marie-Dominique Tabone
- Pediatric Hematology and Oncology Department, Armand Trousseau Hospital, AP-HP, Sorbonne University, 26 avenue du Docteur Arnold-Netter, Paris, France.
| | - Rachael Windsor
- London Sarcoma Service, UCL Hospitals NHS Foundation Trust, London, UK.
| | - Uta Dirksen
- Pediatrics III, University Hospital Essen, Essen, Germany, West German Cancer Centre (WTZ), German Consortium for Translational Cancer Research (DKTK), and National Center for Tumordiseases site Essen, Essen, Germany.
| | - Virginie Gandemer
- Department of Pediatric Onco-hematology, University Hospital, 16 Bd de Bulgarie, Rennes, France.
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7
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Rechl V, Ranft A, Bhadri V, Brichard B, Collaud S, Cyprova S, Eich H, Ek T, Gelderblom H, Hardes J, Haveman LM, Hartmann W, Hauser P, Heesen P, Jürgens H, Kanerva J, Kühne T, Raciborska A, Rascon J, Streitbürger A, Uhlenbruch Y, Timmermann B, Kersting J, Pham MT, Dirksen U. Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum. Sarcoma 2024; 2024:4751914. [PMID: 38524902 PMCID: PMC10960648 DOI: 10.1155/2024/4751914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 02/29/2024] [Accepted: 03/04/2024] [Indexed: 03/26/2024] Open
Abstract
Background Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.
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Affiliation(s)
- Victor Rechl
- Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Andreas Ranft
- Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- German Cancer Consortium, Partnersite, Essen, Germany
| | - Vivek Bhadri
- Chris O'Brien Lifehouse, Camperdown, Australia
- Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
| | - Benedicte Brichard
- Cliniques Universitaires Saint Luc, Department of Pediatric Hematology and Oncology, Université Catholique de Louvain, Brussels, Belgium
| | - Stephane Collaud
- Lung Clinic, Department of Thoracic Surgery, Cologne Merheim Hospital, University of Witten/Herdecke, Witten, Germany
| | - Sona Cyprova
- Charles University, Motol Child Ren's Hospital, Prague, Czech Republic
| | - Hans Eich
- Radiotherapy and Radiooncology, University Hospital Muenster, West German Cancer Center Network, Muenster, Germany
| | - Torben Ek
- Childhood Cancer Center Queen Silvia Children's Hospital, Gothenburg, Sweden
| | - Hans Gelderblom
- Leiden University Medical Center, Department of Medical Oncology, Leiden, NL, USA
| | - Jendrik Hardes
- German Cancer Consortium, Partnersite, Essen, Germany
- Clinic of Tumororthopedics, University Hospital Essen, West German Cancer Centre, Essen, Germany
| | - Lianne M. Haveman
- Princess Máxima Center for Pediatric Oncology, Department of Solid Tumors, Utrecht, Netherlands
| | - Wolfgang Hartmann
- Gerhard Domagk Institute for Pathology, University Hospital Muenster, West German Cancer Center Network, Muenster, Germany
| | - Peter Hauser
- Velkey László Child's, Health Center, Borsod-Abaúj-Zemplén County University Teaching Hospital, Miskolc, Hungary
| | - Philip Heesen
- Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Heribert Jürgens
- Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, West German Cancer Center Network, Münster, Germany
| | - Jukka Kanerva
- HUS Helsinki University Hospital, New Children's Hospital, Div. Hematology and Stem Cell Transplantation, Helsinki, Finland
| | - Thomas Kühne
- Department of Oncology/Hematology, University Children's Hospital Basel, Basel, Switzerland
| | - Anna Raciborska
- Mother and Child Institute, Department of Oncology and Surgical Oncology for Children and Youth, Warsaw, Poland
| | - Jelena Rascon
- Center for Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania
- Clinics of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Arne Streitbürger
- German Cancer Consortium, Partnersite, Essen, Germany
- Clinic of Tumororthopedics, University Hospital Essen, West German Cancer Centre, Essen, Germany
| | - Yasmin Uhlenbruch
- Patient Representative, St. Josef's Hospital Bochum, University Hospital, Bochum, Germany
| | - Beate Timmermann
- German Cancer Consortium, Partnersite, Essen, Germany
- Clinic for Particle Therapy, West German Proton Beam Centre, University Hospital Essen, West German Cancer Centre, German Cancer Research Centre (DKTK), Essen, Germany
| | - Josephine Kersting
- Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- German Cancer Consortium, Partnersite, Essen, Germany
| | - Minh Thanh Pham
- Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Uta Dirksen
- Pediatrics III, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- German Cancer Consortium, Partnersite, Essen, Germany
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8
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Hu X, Fujiwara T, Sun Y, Huang W, Yan W. Does primary tumor resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis ? EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2023; 32:4362-4376. [PMID: 37870700 DOI: 10.1007/s00586-023-07985-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 09/14/2023] [Accepted: 10/02/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Recent studies demonstrated that primary tumor resection (PTR) improves survival of patients with metastatic bone sarcomas. However, it remains quite unclear regarding the role of PTR in the treatment of sarcomas of pelvic bones with synchronous metastasis at diagnosis. METHODS Using the Surveillance, Epidemiology, and End Results Program, we enrolled a total of 385 patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at initial diagnosis, including 139 patients with osteosarcoma, 176 with Ewing sarcoma, and 70 with chondrosarcoma. Association between PTR and disease-specific survival (DSS) were investigated using the univariable and multivariable Cox regression models. Hazard ratio (HR) and 95% confidence interval (CI) were reported. Representative institutional PTR strategies and clinical outcomes for patients with metastatic pelvic sarcomas from our cancer center were displayed. RESULTS The usage rate of PTR was 28.1% (39/139) in osteosarcoma, 13.6% (24/176) in Ewing sarcoma, and 41.4% (29/70) in chondrosarcoma with synchronous metastatic lesions. PTR was not associated with an improved DSS for metastatic pelvic osteosarcoma (HR = 0.686, 95% CI = 0.430 ~ 1.094, P = 0.113) and Ewing sarcoma (HR = 0.580, 95% CI = 0.291 ~ 1.154, P = 0.121). The use of PTR was associated with an improved DSS for metastatic pelvic chondrosarcoma (HR = 0.464, 95% CI = 0.225 ~ 0.954, P = 0.037). CONCLUSION Primary lesion resection may provide a survival benefit for metastatic chondrosarcoma, but not for osteosarcoma and Ewing sarcoma of pelvic bones, sacrum, and coccyx. This population-based study recommends an active surgical intervention for metastatic chondrosarcoma while non-surgical treatment for metastatic osteosarcoma and Ewing sarcoma of the pelvis in terms of survival improvement.
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Affiliation(s)
- Xianglin Hu
- Department of Musculoskeletal Oncology, Spinal Tumor Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Tomohiro Fujiwara
- Department of Orthopaedic Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Yangbai Sun
- Department of Musculoskeletal Oncology, Spinal Tumor Center, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Wending Huang
- Department of Musculoskeletal Oncology, Spinal Tumor Center, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Wangjun Yan
- Department of Musculoskeletal Oncology, Spinal Tumor Center, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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9
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Jawad MU, Theriault RV, Thorpe SW, Randall RL. Socioeconomic disparities in musculoskeletal oncology. J Surg Oncol 2023; 128:425-429. [PMID: 37537984 DOI: 10.1002/jso.27361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 05/13/2023] [Indexed: 08/05/2023]
Abstract
Musculoskeletal oncology is a clinical specialty dealing with a diverse population of patients with metastatic bone disease, hematological malignancies with musculoskeletal manifestations, primary bone malignancies and soft tissue sarcomas. There are wide-spread disparities including socioeconomic (SES) and insurance-related disparities reported in the literature. In this review, we'll summarize the disparities surrounding the musculoskeletal oncology.
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Affiliation(s)
- Muhammad U Jawad
- Department of Orthopedic Surgery, Samaritan Health System, Corvallis, Oregon, USA
| | - Raminta V Theriault
- Department of Orthopedic Surgery, UC Davis School of Medicine, Corvallis, Oregon, USA
| | - Steven W Thorpe
- Department of Orthopedic Surgery, UC Davis School of Medicine, Corvallis, Oregon, USA
| | - R Lor Randall
- Department of Orthopedic Surgery, UC Davis School of Medicine, Corvallis, Oregon, USA
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10
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Sirikul W, Buawangpong N, Pruksakorn D, Charoentum C, Teeyakasem P, Koonrungsesomboon N. The Survival Outcomes, Prognostic Factors and Adverse Events following Systemic Chemotherapy Treatment in Bone Sarcomas: A Retrospective Observational Study from the Experience of the Cancer Referral Center in Northern Thailand. Cancers (Basel) 2023; 15:cancers15071979. [PMID: 37046640 PMCID: PMC10092999 DOI: 10.3390/cancers15071979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/15/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
This study aimed to assess survival outcomes, prognostic factors, and adverse events following chemotherapy treatment for osteosarcoma and Ewing’s sarcoma. This retrospective observational study was conducted to collect the data of the patients with osteosarcoma or Ewing’s sarcoma who received chemotherapy treatment between 2008 and 2019. The flexible parametric survival model was performed to explore the adjusted survival probability and the prognostic factors. A total of 102 patients (79 with osteosarcoma and 23 with Ewing’s sarcoma) were included. The estimated 5-year disease-free survival (DFS) and 5-year overall survival (OS) probabilities in patients with resectable disease were 60.9% and 63.3% for osteosarcoma, and 54.4% and 88.3% for Ewing’s sarcoma, respectively, whereas the 5-year DFS and 5-year OS for those with unresectable/metastatic disease remained below 25%. Two prognostic factors for osteosarcoma included a response to neoadjuvant chemotherapy and female gender. Ewing’s sarcoma patients aged 25 years and older were significantly associated with poorer survival outcomes. Of 181 chemotherapy treatment cycles, common self-reported adverse symptoms included tumor pain (n = 32, 17.7%), fever (n = 21, 11.6%), and fatigue (n = 16, 8.8%), while common grade III adverse events included febrile neutropenia (n = 13, 7.3%) and neutropenia (n = 9, 5.1%). There was no chemotherapy-related mortality (grade V) or anaphylaxis events.
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Affiliation(s)
- Wachiranun Sirikul
- Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nida Buawangpong
- Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Dumnoensun Pruksakorn
- Department of Orthopedic, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Chaiyut Charoentum
- Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Pimpisa Teeyakasem
- Department of Orthopedic, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nut Koonrungsesomboon
- Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Correspondence: ; Tel.: +66-5393-5353
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11
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Disch AC, Boriani S, Luzzati A, Rhines LD, Fisher CG, Lazary A, Gokaslan ZL, Chou D, Clarke MJ, Fehlings MG, Schaser KD, Germscheid NM, Reynolds JJ. Extradural Primary Malignant Spinal Tumors in a Population Younger than 25 Years: An Ambispective International Multicenter Study on Onco-Surgical Outcomes. Cancers (Basel) 2023; 15:cancers15030845. [PMID: 36765803 PMCID: PMC9913243 DOI: 10.3390/cancers15030845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Extradural malignant primary spinal tumors are rare and outcome data, especially for younger patients, is limited. In a worldwide (11 centers) study (Predictors of Mortality and Morbidity in the Surgical Management of Primary Tumors of the Spine study; ClinicalTrials.gov Identifier NCT01643174) by the AO Spine Knowledge Forum Tumor, patients surgically treated for primary tumors of the spine between 1992 and 2012, were retrospectively analyzed from a prospective database of their medical history. Medical history, tumor characteristics, diagnostics, treatments, cross-sectional survival, and local recurrences were analyzed. Sixty-eight cases (32 f; 36 m), at an average age of 18.6 ± 4.7 years at the time of diagnosis, were identified (median follow-up 2.9 years). The most common entities were Ewing's sarcoma (42.6%). Of the patients, 28% had undergone previous spine tumor surgery in another center (84% with intralesional margins). Resection was considered "Enneking appropriate" (EA) in 47.8% of the cases. Of the patients, 77.9% underwent chemotherapy and 50% radiotherapy. A local recurrence occurred in 36.4%. Over a third of patients died within a 10-year follow-up period. Kaplan-Meier-analysis demonstrated statistically significant overall survival (p = 0.007) and local recurrence rates (p = 0.042) for tumors treated with EA surgery versus Enneking inappropriate surgery. Aggressive resection of extradural primary malignant spinal tumors combined with adjuvant therapy reveals low local recurrence rates and better outcomes overall in younger patients.
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Affiliation(s)
- Alexander C. Disch
- University Center for Orthopedics, Trauma & Plastic Surgery, University Comprehensive Spine Center (UCSC), University Hospital Carl Gustav Carus Dresden at the TU Dresden, 01307 Dresden, Germany
- Correspondence:
| | | | | | - Laurence D. Rhines
- Department of Neurosurgery, MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Charles G. Fisher
- Department of Orthopaedics, Faculty of Medicine, The University of British Columbia, Vancouver, BC V5Z 1M9, Canada
| | - Aron Lazary
- National Center for Spinal Disorders, 1126 Budapest, Hungary
| | - Ziya L. Gokaslan
- Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Rhode Island Hospital and The Miriam Hospital, Providence, RI 02903, USA
| | - Dean Chou
- Department of Neurosurgery, The UCSF Spine Center, University of California, San Francisco, CA 94143, USA
| | | | - Michael G. Fehlings
- Department of Surgery Halbert Chair, Spinal Program University of Toronto, Toronto Western Hospital University Health Network, Toronto, ON M5T 2S8, Canada
| | - Klaus-Dieter Schaser
- University Center for Orthopedics, Trauma & Plastic Surgery, University Comprehensive Spine Center (UCSC), University Hospital Carl Gustav Carus Dresden at the TU Dresden, 01307 Dresden, Germany
| | | | - Jeremy J. Reynolds
- Oxford Spinal Surgery Unit, Oxford University Hospitals, Oxford OX3 7LE, UK
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12
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Al-Marshad AY, AlMazrua IS, AlMulla F, Alaboud M, Alrifaie O, Shaheen M, Rajeev P. Unusual presentation of Ewing sarcoma; a case report and literature review. Int J Surg Case Rep 2022; 99:107479. [PMID: 36152369 PMCID: PMC9568706 DOI: 10.1016/j.ijscr.2022.107479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/03/2022] [Accepted: 08/07/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction and importance Ewing's sarcoma is an aggressive malignancy primarily affecting skeletal system in children and young adults. Case presentation We report an unusual case of Ewing sarcoma in a 14-year-old boy with clinical and radiological features of rapid onset metachronous skeletal metastasis (within 4 weeks of diagnosis). Clinical discussion Although the deterioration of symptoms was very rapid, it is unusual to note that in the presence of such widespread metastatic disease the lungs per se remained uninvolved. Conclusion We describe a unique case of metastatic Ewing's sarcoma who showed rapid systemic disease progression with widespread skeletal metastases (and CNS involvement) but without any evidence of pulmonary involvement.
Ewing sarcoma is considered aggressive malignancy primarily affecting skeletal system. It is usually very slowly progressive in nature (years). This case presentation showed aggressiveness behavior with very unpredictable outcomes short period from diagnosis to metastasis. Up to our knowledge, this atypical and rapid disease progression (within a month of diagnosis) was not previously reported in literature.
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13
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Huang R, Huang D, Wang S, Xian S, Liu Y, Jin M, Zhang X, Chen S, Yue X, Zhang W, Lu J, Liu H, Huang Z, Zhang H, Yin H. Repression of enhancer RNA PHLDA1 promotes tumorigenesis and progression of Ewing sarcoma via decreasing infiltrating T‐lymphocytes: A bioinformatic analysis. Front Genet 2022; 13:952162. [PMID: 36092920 PMCID: PMC9453160 DOI: 10.3389/fgene.2022.952162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Background: The molecular mechanisms of EWS-FLI-mediating target genes and downstream pathways may provide a new way in the targeted therapy of Ewing sarcoma. Meanwhile, enhancers transcript non-coding RNAs, known as enhancer RNAs (eRNAs), which may serve as potential diagnosis markers and therapeutic targets in Ewing sarcoma. Materials and methods: Differentially expressed genes (DEGs) were identified between 85 Ewing sarcoma samples downloaded from the Treehouse database and 3 normal bone samples downloaded from the Sequence Read Archive database. Included in DEGs, differentially expressed eRNAs (DEeRNAs) and target genes corresponding to DEeRNAs (DETGs), as well as the differentially expressed TFs, were annotated. Then, cell type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) was used to infer portions of infiltrating immune cells in Ewing sarcoma and normal bone samples. To evaluate the prognostic value of DEeRNAs and immune function, cross validation, independent prognosis analysis, and Kaplan–Meier survival analysis were implemented using sarcoma samples from the Cancer Genome Atlas database. Next, hallmarks of cancer by gene set variation analysis (GSVA) and immune gene sets by single-sample gene set enrichment analysis (ssGSEA) were identified to be significantly associated with Ewing sarcoma. After screening by co-expression analysis, most significant DEeRNAs, DETGs and DETFs, immune cells, immune gene sets, and hallmarks of cancer were merged to construct a co-expression regulatory network to eventually identify the key DEeRNAs in tumorigenesis of Ewing sarcoma. Moreover, Connectivity Map Analysis was utilized to identify small molecules targeting Ewing sarcoma. External validation based on multidimensional online databases and scRNA-seq analysis were used to verify our key findings. Results: A six-different-dimension regulatory network was constructed based on 17 DEeRNAs, 29 DETFs, 9 DETGs, 5 immune cells, 24 immune gene sets, and 8 hallmarks of cancer. Four key DEeRNAs (CCR1, CD3D, PHLDA1, and RASD1) showed significant co-expression relationships in the network. Connectivity Map Analysis screened two candidate compounds, MS-275 and pyrvinium, that might target Ewing sarcoma. PHLDA1 (key DEeRNA) was extensively expressed in cancer stem cells of Ewing sarcoma, which might play a critical role in the tumorigenesis of Ewing sarcoma. Conclusion: PHLDA1 is a key regulator in the tumorigenesis and progression of Ewing sarcoma. PHLDA1 is directly repressed by EWS/FLI1 protein and low expression of FOSL2, resulting in the deregulation of FOX proteins and CC chemokine receptors. The decrease of infiltrating T‐lymphocytes and TNFA signaling may promote tumorigenesis and progression of Ewing sarcoma.
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Affiliation(s)
- Runzhi Huang
- Department of Orthopedics, School of Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Tongji University School of Medicine, Shanghai, China
| | - Dan Huang
- Tongji University School of Medicine, Shanghai, China
| | - Siqiao Wang
- Tongji University School of Medicine, Shanghai, China
| | - Shuyuan Xian
- Tongji University School of Medicine, Shanghai, China
| | - Yifan Liu
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Minghao Jin
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinkun Zhang
- Tongji University School of Medicine, Shanghai, China
| | - Shaofeng Chen
- Department of Orthopedics, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Xi Yue
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Zhang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Jianyu Lu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Huizhen Liu
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zongqiang Huang
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Tongji University School of Medicine, Shanghai, China
- *Correspondence: Zongqiang Huang, ; Hao Zhang, ; Huabin Yin,
| | - Hao Zhang
- Department of Orthopedics, Naval Medical Center of PLA, Second Military Medical University, Shanghai, China
- *Correspondence: Zongqiang Huang, ; Hao Zhang, ; Huabin Yin,
| | - Huabin Yin
- Department of Orthopedics, School of Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China
- *Correspondence: Zongqiang Huang, ; Hao Zhang, ; Huabin Yin,
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14
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Li W, Dong S, Lin Y, Wu H, Chen M, Qin C, Li K, Zhang J, Tang ZR, Wang H, Huo K, Xie X, Hu Z, Kuang S, Yin C. A tool for predicting overall survival in patients with Ewing sarcoma: a multicenter retrospective study. BMC Cancer 2022; 22:914. [PMID: 35999524 PMCID: PMC9400324 DOI: 10.1186/s12885-022-09796-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 06/10/2022] [Indexed: 11/06/2023] Open
Abstract
OBJECTIVE The aim of this study was to establish and validate a clinical prediction model for assessing the risk of metastasis and patient survival in Ewing's sarcoma (ES). METHODS Patients diagnosed with ES from the Surveillance, Epidemiology and End Results (SEER) database for the period 2010-2016 were extracted, and the data after exclusion of vacant terms was used as the training set (n=767). Prediction models predicting patients' overall survival (OS) at 1 and 3 years were created by cox regression analysis and visualized using Nomogram and web calculator. Multicenter data from four medical institutions were used as the validation set (n=51), and the model consistency was verified using calibration plots, and receiver operating characteristic (ROC) verified the predictive ability of the model. Finally, a clinical decision curve was used to demonstrate the clinical utility of the model. RESULTS The results of multivariate cox regression showed that age, , bone metastasis, tumor size, and chemotherapy were independent prognostic factors of ES patients. Internal and external validation results: calibration plots showed that the model had a good agreement for patient survival at 1 and 3 years; ROC showed that it possessed a good predictive ability and clinical decision curve proved that it possessed good clinical utility. CONCLUSIONS The tool built in this paper to predict 1- and 3-year survival in ES patients ( https://drwenleli0910.shinyapps.io/EwingApp/ ) has a good identification and predictive power.
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Affiliation(s)
- Wenle Li
- Department of Orthopedic Surgery II, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, 710004, China
- College of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China
- Molecular Imaging and Translational Medicine Research Center, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, 361005, China
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, 712099, China
| | - Shengtao Dong
- Department of Spine Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, China
| | - Yuewei Lin
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Huitao Wu
- Intelligent Healthcare Team, Baidu Inc, Beijing, 100089, China
| | - Mengfei Chen
- Emergency Department, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, 750000, China
| | - Chuan Qin
- Department of Spine Surgery, Liuzhou People's Hospital, Liuzhou, 545000, China
| | - Kelin Li
- Department of Spine Surgery, Liuzhou People's Hospital, Liuzhou, 545000, China
| | - JunYan Zhang
- Medical Big Data Research Center, PLA General Hospital, Beijing, 100853, China
- National Engineering Laboratory for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Zhi-Ri Tang
- School of Physics and Technology, Wuhan University, Wuhan, 430072, China
| | - Haosheng Wang
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, 130000, China
| | - Kang Huo
- Neurology department, Xi'an jiaotong university 1st affiliated hospital, Xian, 71000, China
| | - Xiangtao Xie
- Department of Spine Surgery, Liuzhou People's Hospital, Liuzhou, 545000, China
| | - Zhaohui Hu
- Department of Spine Surgery, Liuzhou People's Hospital, Liuzhou, 545000, China.
| | - Sirui Kuang
- Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, China.
| | - Chengliang Yin
- Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, China.
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15
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Guo AW, Liu YS, Li H, Yuan Y, Li SX. Ewing sarcoma of the ileum with wide multiorgan metastases: A case report and review of literature. World J Gastrointest Oncol 2022; 14:1585-1593. [PMID: 36160753 PMCID: PMC9412928 DOI: 10.4251/wjgo.v14.i8.1585] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 05/02/2022] [Accepted: 07/11/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Ewing sarcoma (ES) is an aggressive small round cell tumor that usually occurs in younger children and young adults but rarely in older patients. Its occurrence in elderly individuals is rare. ES of the ileum with wide multiorgan metastases is rarely reported and difficult to distinguish radiologically from other gastrointestinal tract tumors.
CASE SUMMARY A 53-year-old man presented with right lower quadrant pain for 2 wk. Computed tomography results showed a heterogeneous mass within the ileum and widespread multiorgan metastases. This mass was biopsied, and pathological examination of the resected specimen revealed features consistent with an extraskeletal ES.
CONCLUSION This case emphasizes the importance of recognizing this rare presentation in the small intestine to broaden the differential diagnosis of adult intraabdominal tumors.
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Affiliation(s)
- Ai-Wen Guo
- Department of Radiology, Affiliated Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, Chengdu 611731, Sichuan Province, China
| | - Yi-Sha Liu
- Department of Pathology, Affiliated Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China
| | - Hang Li
- Department of Radiology, Affiliated Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China
| | - Yi Yuan
- Department of Radiology, Affiliated Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China
| | - Si-Xun Li
- Department of Radiology, Affiliated Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China
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16
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Li W, Xu C, Hu Z, Dong S, Wang H, Liu Q, Tang ZR, Li W, Wang B, Lei Z, Yin C. A Visualized Dynamic Prediction Model for Lymphatic Metastasis in Ewing's Sarcoma for Smart Medical Services. Front Public Health 2022; 10:877736. [PMID: 35602163 PMCID: PMC9114797 DOI: 10.3389/fpubh.2022.877736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 03/28/2022] [Indexed: 11/30/2022] Open
Abstract
Background This study aims to predict the lymphatic metastasis in Ewing's sarcoma (ES) patients by nomogram. The risk of lymphatic metastasis in patients with ES was predicted by the built model, which provided guidance for the clinical diagnosis and treatment planning. Methods A total of 929 patients diagnosed with ES were enrolled from the year of 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The nomogram was established to determine predictive factors of lymphatic metastasis according to univariate and multivariate logistic regression analysis. The validation of the model performed using multicenter data (n = 51). Receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the prediction accuracy of the nomogram. Decision curve analysis (DCA) was implemented to illustrate the practicability of the nomogram clinical application. Based on the nomogram, we established a web calculator to visualize the risk of lymphatic metastases. We further plotted Kaplan-Meier overall survival (OS) curves to compare the survival time of patients with and without lymphatic metastasis. Results In this study, the nomogram was established based on six significant factors (survival time, race, T stage, M stage, surgery, and lung metastasis), which were identified for lymphatic metastasis in ES patients. The model showed significant diagnostic accuracy with the value of the area under the curve (AUC) was 0.743 (95%CI: 0.714–0.771) for SEER internal validation and 0.763 (95%CI: 0.623–0.871) for multicenter data external validation. The calibration plot and DCA indicated that the model had vital clinical application value. Conclusion In this study, we constructed and developed a nomogram with risk factors to predict lymphatic metastasis in ES patients and validated accuracy of itself. We found T stage (Tx OR = 2.540, 95%CI = 1.433–4.503, P < 0.01), M stage (M1, OR = 2.061, 95%CI = 1.189–3.573, P < 0.05) and survival time (OR = 0.982, 95%CI = 0.972–0.992, P < 0.001) were important independent factors for lymphatic metastasis in ES patients. Furthermore, survival time in patients with lymphatic metastasis or unclear situation (P < 0.0001) was significantly lower. It can help clinicians make better decisions to provide more accurate prognosis and treatment for ES patients.
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Affiliation(s)
- Wenle Li
- Department of Orthopedics, Xianyang Central Hospital, Xianyang, China.,Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Chan Xu
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Zhaohui Hu
- Department of Spinal Surgery, Liuzhou People's Hospital, Liuzhou, China
| | - Shengtao Dong
- Department of Spine Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Haosheng Wang
- Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, China
| | - Qiang Liu
- Department of Orthopedics, Xianyang Central Hospital, Xianyang, China
| | - Zhi-Ri Tang
- School of Physics and Technology, Wuhan University, Wuhan, China
| | - Wanying Li
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Bing Wang
- Clinical Medical Research Center, Xianyang Central Hospital, Xianyang, China
| | - Zhi Lei
- Chronic Disease Division, Luzhou Center for Disease Control and Prevention, Luzhou, China.,Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
| | - Chengliang Yin
- Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
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CyberKnife Stereotactic Radiosurgery for an unusual case of large brain metastases from Ewing's sarcoma in a paediatric patient. Adv Radiat Oncol 2022; 7:100979. [PMID: 35814851 PMCID: PMC9260128 DOI: 10.1016/j.adro.2022.100979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 04/16/2022] [Indexed: 11/20/2022] Open
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Bosma SE, van der Heijden L, Sierrasesúmaga L, Merks HJHM, Haveman LM, van de Sande MAJ, San-Julián M. What Do We Know about Survival in Skeletally Premature Children Aged 0 to 10 Years with Ewing Sarcoma? A Multicenter 10-Year Follow-Up Study in 60 Patients. Cancers (Basel) 2022; 14:cancers14061456. [PMID: 35326609 PMCID: PMC8946787 DOI: 10.3390/cancers14061456] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/08/2022] [Accepted: 03/10/2022] [Indexed: 02/06/2023] Open
Abstract
(1) Background: Younger age has been associated with better overall survival (OS) in Ewing sarcoma (ES), especially under the age of 10. The favorable survival in younger patients underlines the need for minimizing treatment burden and late sequelae. Our study aimed at describing clinical characteristics, treatment and outcome of a cohort of ES patients aged 0−10. (2) Methods: In this retrospective multicenter study, all consecutive ES patients aged 0−10, treated in four sarcoma centers in the Netherlands (n = 33) and one in Spain (n = 27) between 1982 and 2008, with a minimum follow-up of 10 years, were included. OS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were calculated. Potential factors of influence on OS (risk and protective factors) were analyzed. (3) Results: 60 patients with median follow-up 13.03 years were included. All patients were treated with chemotherapy in combination with local treatment, being surgery alone in 30 (50%) patients, radiotherapy (RT) alone in 12 (20%) patients or surgery plus RT in 18 (30%) patients (12 pre- and 6 postoperative). Limb salvage was achieved in 93% of patients. The 10-OS, -LRFS and -DMFS are 81% (95% CI: 71−91%), 89% (95% CI: 85−93%) and 81% (95% CI: 71−91%), respectively. Six patients developed LR, of which two developed subsequent DM; all had axial ES (pelvis, spine or chest wall), and these patients all died. Ten patients developed DM; eight died due to progressive disease, and two are currently in remission, both with pulmonary metastasis only. Negative or wide resection margin was significantly associated with better OS. Age < 6 years, tumor volume < 200 mL, absence of metastatic disease and treatment after 2000 showed trends towards better OS. Two patients developed secondary malignancy; both had chemotherapy combined with definitive RT for local treatment. (4) Conclusions: Overall survival of these youngest patients with ES was very good. Limb salvage surgery was achieved in >90% of patients. Wide resection margin was the only factor significantly associated with better survival.
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Affiliation(s)
- Sarah E. Bosma
- Department of Orthopedic Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.E.B.); (L.v.d.H.)
| | - Lizz van der Heijden
- Department of Orthopedic Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.E.B.); (L.v.d.H.)
| | - Luis Sierrasesúmaga
- Department of Pediatrics, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Hans J. H. M. Merks
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.M.M.); (L.M.H.)
| | - Lianne M. Haveman
- Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands; (H.J.H.M.M.); (L.M.H.)
| | - Michiel A. J. van de Sande
- Department of Orthopedic Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.E.B.); (L.v.d.H.)
- Correspondence: ; Tel.: +31-71-526-3606
| | - Mikel San-Julián
- Department of Orthopedic Surgery and Traumatology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
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Worawongsakul R, Steinmeier T, Lin YL, Bauer S, Hardes J, Hecker-Nolting S, Dirksen U, Timmermann B. Proton Therapy for Primary Bone Malignancy of the Pelvic and Lumbar Region - Data From the Prospective Registries ProReg and KiProReg. Front Oncol 2022; 12:805051. [PMID: 35251976 PMCID: PMC8888414 DOI: 10.3389/fonc.2022.805051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/11/2022] [Indexed: 11/17/2022] Open
Abstract
PURPOSE/OBJECTIVES Multimodality treatments together with local proton therapy (PT) are commonly used in unresectable primary bone malignancies in order to provide better tumor control rate while maintaining good feasibility. The aim of this study is to provide data on outcome of PT for the challenging cohort of pelvic and lumbar bone tumors. METHODS AND MATERIALS This retrospective study includes all patients with primary bone malignancy of the pelvis and lumbar spine receiving PT in our institution between May 2013 and December 2019 enrolled in the prospective registries KiProReg and ProReg collecting information on demographics, treatment, tumor characteristics, toxicities, and outcome. RESULTS Eighty-one patients were enrolled with a median age of 19.7 years (1.3-85.8). The median follow-up time was 27.5 months (1.2-83.2). The majority of patients was male (64.2%), ECOG status of 0-1 (75.2%), underwent only biopsy (50.6%), received chemotherapy (69.1%) and was assigned for definite PT (70.4%). The predominant tumor characteristics were as follows: Ewing's sarcoma histology (58%), negative nodal involvement (97.5%) and no metastasis at diagnosis (81.5%). Median maximal diameter of tumor was 8 cm (1.4-20). LC, EFS and OS rate were 76.5, 60, and 88.1% at two years and 72.9, 45.7, and 68.9% at three years, respectively. Age over 20 years was a significant negative factor for LC, EFS, and OS. Metastatic disease at initial diagnosis affected OS and ECOG status of 2-4 affected EFS only. Regarding 17 relapsed cases (21%), isolated distant relapse was the most common failure (46.9%) followed by local failure (40.6%). Eleven out of 14 evaluable patients relapsed within high-dose region of radiotherapy. Acute grade 3-4 toxicity was found in 41 patients (50.6%) and all toxicities were manageable. Late grade 3 toxicity was reported in 7 patients (10.4%) without any of grade 4. Most common higher grade acute and late side effects concerned hematologic and musculoskeletal toxicity. CONCLUSION Proton therapy resulted in good oncological outcomes when being part of the multimodality treatment for pelvic and lumbar primary bone malignancies. However, distant metastases and local failures within the high-dose region of radiotherapy are still a common issue. Acute and late toxicities of combined therapy were acceptable.
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Affiliation(s)
- Rasin Worawongsakul
- Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, Essen, Germany
- Radiation Oncology Unit, Department of Diagnostic and Therapeutic Radiology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- West German Cancer Centre Network, Essen, Germany
| | - Theresa Steinmeier
- Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, Essen, Germany
- West German Cancer Centre Network, Essen, Germany
| | - Yi-Lan Lin
- Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, Essen, Germany
- West German Cancer Centre Network, Essen, Germany
| | - Sebastian Bauer
- West German Cancer Centre Network, Essen, Germany
- Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University of Duisburg-Essen, Essen, Germany
- German Cancer Consortium (DKTK), Essen, Germany
| | - Jendrik Hardes
- West German Cancer Centre Network, Essen, Germany
- German Cancer Consortium (DKTK), Essen, Germany
- Department of Orthopedic Oncology, University Hospital Essen, Essen, Germany
| | - Stefanie Hecker-Nolting
- Pediatrics 5 (Oncology, Hematology, Immunology), Klinikum Stuttgart Olgahospital, Stuttgart, Germany
| | - Uta Dirksen
- West German Cancer Centre Network, Essen, Germany
- German Cancer Consortium (DKTK), Essen, Germany
- Pediatrics III (Hematology, Oncology, Immunology, Cardiology, Pulmonology), University Hospital Essen, Essen, Germany
| | - Beate Timmermann
- Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, Essen, Germany
- West German Cancer Centre Network, Essen, Germany
- German Cancer Consortium (DKTK), Essen, Germany
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20
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Indelicato DJ, Mailhot Vega RB, Viviers E, Morris CG, Bradfield SM, Gibbs CP, Bradley JA. Modern Therapy for Chest Wall Ewing Sarcoma: An Update of the XXX Experience. Int J Radiat Oncol Biol Phys 2022; 113:345-354. [DOI: 10.1016/j.ijrobp.2022.02.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 02/03/2022] [Accepted: 02/06/2022] [Indexed: 12/25/2022]
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Trends in bacterial bloodstream infections and resistance in immuno-compromised patients with febrile neutropenia: a retrospective analysis. Eur J Pediatr 2021; 180:2921-2930. [PMID: 33835249 DOI: 10.1007/s00431-021-04056-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 03/13/2021] [Accepted: 03/29/2021] [Indexed: 10/21/2022]
Abstract
Bacterial infections remain a major cause of morbidity and mortality in immunocompromised children. From the onset of fever, an early administration of broad-spectrum antibiotics is begun; this strategy could induce emergence of multi-drug resistant bacteria (MDR). We describe the incidence and microbiological spectrum, including MDR bacteria of bacterial documented blood-stream infections (BSI) in immunocompromised children. A retrospective, descriptive study was conducted in a tertiary referral centre in France from January 2014 to December 2017. Our cohort included a large scale of patients with febrile neutropenia: haematological and oncological malignancies, haematopoietic stem cell transplantations, severe combined immunodeficiency syndromes. BSI were defined by positive blood culture samples associated with fever. Among 760 febrile neutropenia episodes in 7301 admitted patients, we identified 310 documented BSI with a mean of 7.4 BSI/1000 patient bed days. Only 2.9% BSIs were caused by MDR bacteria, none vancomycin resistant. Coagulase-negative staphylococci were identified in 49.7% BSI and Staphylococcus aureus caused 6.5% infections. Gram-negative bacilli accounted for 21.6% of isolated bacteria, Pseudomonas for 4.8%. The incidence of BSI annually decreased by 0.75% (p = 0.002).Conclusion: With a step-down strategy at 48 h of initial broad-spectrum antibiotic therapy, we reported a low number of MDR bacteria, no deaths related to BSI. What is Known: • Bacterial bloodstream infections are a leading cause of morbidity and mortality in immunocompromised children • Multi-drug resistant bacteria are emerging worldwide. What is New: • Initial broad-spectrum antibiotic therapy with a step-down strategy at 48 h: no deaths related to bloodstream infections with a low number of resistant bacteria. • Parental and nurse stewardship to decrease bloodstream infections incidence with a drop of staphylococcal infections.
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22
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Jagodzińska-Mucha P, Raciborska A, Koseła-Paterczyk H, Kozak K, Bilska K, Świtaj T, Falkowski S, Dawidowska A, Rutkowski P, Ługowska I. Age as a Prognostic Factor in Patients with Ewing Sarcoma-The Polish Sarcoma Group Experience. J Clin Med 2021; 10:jcm10163627. [PMID: 34441922 PMCID: PMC8397138 DOI: 10.3390/jcm10163627] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 08/14/2021] [Accepted: 08/15/2021] [Indexed: 12/03/2022] Open
Abstract
Ewing sarcoma (ES) is a rare and aggressive disease that requires multidisciplinary treatment with the use of chemotherapy, radiotherapy, and surgery. Our retrospective study aimed to analyze the prognostic factors and treatment results in different age groups of patients. Between 1998 and 2018, 569 patients with ES were treated in two referral centers. The patients were divided into four age groups (≤10 years; 11–18 years; 19–25, and >25). The treatment results and prognostic factors were assessed for each group. For statistical analyses, we used the Chi2 test, the Kaplan–Meier estimator with a log-rank test, and the multivariate Cox model. Five-year overall survival (OS) rate was 56%. In the age subgroups: ≤10 years, 11–18 years, 19–25 years, and >25 years, the 5-year OS rates were 75%, 58%, 41%, and 52%, respectively. Favorable prognostic factors: female gender (p = 0.024), non-axial localization (p = 0.005), VIDE regimen (p < 0.001), and surgery as a local treatment (p < 0.001) dominated in the group ≤10 years. In multivariate analysis, male (HR = 1.53), axial localization (HR = 1.46), M1 status at presentation (HR = 2.64), and age > 10 years (HR = 2.29) were associated with shorter OS. The treatment results in ES are significantly better in children aged ≤10 years; the challenge is to provide therapy for adolescents and young adults. The diagnostics and treatment of ES patients must be provided in referral centers.
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Affiliation(s)
- Paulina Jagodzińska-Mucha
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
- Correspondence: ; Tel.: +48-225-462-031
| | - Anna Raciborska
- Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, 01-211 Warsaw, Poland; (A.R.); (K.B.)
| | - Hanna Koseła-Paterczyk
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Katarzyna Kozak
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Katarzyna Bilska
- Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, 01-211 Warsaw, Poland; (A.R.); (K.B.)
| | - Tomasz Świtaj
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Sławomir Falkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Anna Dawidowska
- Early Phase Clinical Trials Unit, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland;
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
| | - Iwona Ługowska
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (H.K.-P.); (K.K.); (T.Ś.); (S.F.); (P.R.); (I.Ł.)
- Department of Oncology and Surgical Oncology for Children and Youth, Mother and Child Institute, 01-211 Warsaw, Poland; (A.R.); (K.B.)
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Khan S, Abid Z, Haider G, Bukhari N, Zehra D, Hashmi M, Abid M, Ibrahim U. Incidence of Ewing's Sarcoma in Different Age Groups, Their Associated Features, and Its Correlation With Primary Care Interval. Cureus 2021; 13:e13986. [PMID: 33884237 PMCID: PMC8054948 DOI: 10.7759/cureus.13986] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Introduction Primary care interval is the time duration from a patient’s first presentation to the final diagnosis. Ewing’s sarcoma is a rare small round blue cell bone tumor originating from neuroectoderm and undifferentiated neuroepithelial cells, having an annual incidence of approximately one case per million in the United States. In this study, we analyzed the age pattern among patients diagnosed with Ewing’s sarcoma undergoing management, along with associated features including involved site, regional lymphadenopathy, and distant metastasis at the time of presentation and their correlation with the primary care interval. Methods This is a cross-sectional study carried out at the Oncology department of a Tertiary Care Government Hospital in Karachi, Pakistan. The duration of our study was from January 2020 to December 2020. During this period, all patients with proven diagnosis of Ewing’s sarcoma between ages 10 years and 65 years were included in the study. All the participants of the study were divided into groups, based on the age and site of the tumor. Results A total of 895 cases of bone cancer were reported. Among these, 147 cases (16.4%) had Ewing’s sarcoma. Of these patients, 88 were male (60%) while 59 (40%) were female. The mean age of patients was 18.9 ± 3.2 years. Ewing’s sarcoma most commonly occurred during 15 to 20 years of age. The most common region involved was lower limb (n=76, 52%) followed by upper limb (n=63, 43%) followed by pelvis (n=8, 5.4%). Conclusion The peak time for the occurrence of Ewing’s sarcoma is from 15 years to 20 years of age. Regional painful swelling is the most common presenting feature in our study population. Factors causing a prolonged primary care interval include early age of onset, non-specific clinical presentation, and insufficient knowledge of the primary care physician, which results in poor prognosis. Hence, it is important to consider Ewing’s sarcoma as a differential on the first presentation especially in the high-risk age group.
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Affiliation(s)
| | - Zain Abid
- Oncology, Jinnah Postgraduate Medical Center, Karachi, PAK
| | - Ghulam Haider
- Oncology, Jinnah Postgraduate Medical Center, Karachi, PAK
| | - Neelma Bukhari
- Oncology, Jinnah Postgraduate Medical Center, Karachi, PAK
| | - Desaar Zehra
- Oncology, Jinnah Postgraduate Medical Center, Karachi, PAK
| | - Madiha Hashmi
- Oncology, Jinnah Postgraduate Medical Center, Karachi, PAK
| | - Masooma Abid
- Oncology, Jinnah Postgraduate Medical Center, Karachi, PAK
| | - Umer Ibrahim
- Emergency Department, National Medical Center, Karachi, PAK
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Alder KD, Morris MT, Hao Z, Li L, Yu KE, Lee FY. Avoiding Limb-Length Discrepancy with Reconstruction of a Massive Tibial Defect Using a Bone Allograft and a Minimally Invasive Lengthening System in a Pediatric Patient: A Case Report. JBJS Case Connect 2021; 10:e0456. [PMID: 32649132 DOI: 10.2106/jbjs.cc.19.00456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
CASE A 7-year-old boy was found to have Ewing sarcoma of the left tibia. The sarcoma was resected, and the defect was reconstructed using a humeral head allograft and intramedullary limb-lengthening nail. CONCLUSIONS Limb-salvage reconstruction in children can be complicated by the sacrifice of epiphyseal plates and limb-length discrepancies and thus requires techniques tailored to each case.
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Affiliation(s)
- Kareme D Alder
- 1Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut
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25
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Xu G, Wu H, Xu Y, Zhang Y, Lin F, Baklaushev VP, Chekhonin VP, Peltzer K, Wang X, Mao M, Wang G, Cui P, Zhang C. Homogenous and Heterogenous Prognostic Factors for Patients with Bone Sarcoma. Orthop Surg 2021; 13:134-144. [PMID: 33305494 PMCID: PMC7862145 DOI: 10.1111/os.12851] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 10/01/2020] [Accepted: 10/01/2020] [Indexed: 11/29/2022] Open
Abstract
OBJECTIVE The aim of this study was to examine the survival rate of patients with different bone sarcomas and to investigate homogenous and heterogenous prognostic factors for different types of bone sarcomas. METHODS This is a retrospective analysis of records from the Surveillance, Epidemiology, and End Result (SEER) database. Clear information on the distant metastasis of cancer is provided in the SEER database for patients diagnosed between January 2010 and December 2016. Data for the four types of malignant bone sarcomas were extracted, including osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Patients with bone sarcomas originated from other sites, diagnosed at autopsy, or indicated in death certification were excluded. The overall survival was calculated for the entire cohort and across different bone sarcomas using the Kaplan-Meier method. A subgroup analysis of the different survival rates of four types of bone sarcomas in various levels of each variable was conducted and the differences were tested with the log-rank test. Cox proportional hazard regression analysis was performed to determine the prognostic factors. Variables with P < 0.05 in the univariate Cox regression analysis were further analyzed using a multivariate Cox regression analysis. The prognostic factors in four groups of bone sarcomas were compared to determine the homogenous and heterogenous factors. RESULTS A total of 4732 patients were included with a follow up of 25 (0-83) months. The mean age of patients was 39.7 ± 24.1 years. The 1-year, 3-year, and 5-year overall survival rate for the entire cohort was 86.2% (95% confidence interval [CI]: 85.2%-87.2%), 70.5% (95% CI: 68.9%-72.1%), and 63.0% (95% CI: 61.2%-64.8%), respectively. Factors including age older than 40 years, higher grade, regional and distant stage, tumor in the extremities, T2 stage, bone and lung metastases, and non-surgery were significantly associated with the poor survival of the entire cohort. The mean overall survival duration of patients with chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma was 66.86 (95% CI: 64.06-69.66), 63.53 (95% CI: 61.81-65.25), 58.06 (95% CI: 55.49-60.62) and 54.91 (95% CI: 53.14-56.69) months, respectively. Compared with chordoma, the hazard ratio (HR) and 95% CI for patients with chondrosarcoma, Ewing sarcoma, and osteosarcoma were 1.30 (95% CI: 1.04-1.62; P = 0.023), 1.69 (95% CI: 1.33-2.14; P < 0.001), and 2.00 (95% CI: 1.61-2.48; P <0.001), respectively. Different bone sarcomas showed homogenous and heterogenous prognostic factors. CONCLUSION Different clinicopathological characteristics and prognoses were revealed in patients with osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. The risk factors can potentially guide prognostic prediction and sarcoma-specific treatment.
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Affiliation(s)
- Guijun Xu
- Department of OrthopaedicsTianjin HospitalTianjinChina
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Haixiao Wu
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Yao Xu
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Yanting Zhang
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Feng Lin
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Vladimir P Baklaushev
- Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFederal Biomedical Agency of the Russian FederationMoscowRussian Federation
| | - Vladimir P Chekhonin
- Department of Basic and Applied NeurobiologyFederal Medical Research Center for Psychiatry and NarcologyMoscowRussian Federation
| | - Karl Peltzer
- Department of Research and InnovationUniversity of LimpopoTurfloopSouth Africa
| | - Xin Wang
- Department of Epidemiology and BiostatisticsFirst Affiliated Hospital, Army Medical UniversityChongqingChina
| | - Min Mao
- Department of PathologyFirst Affiliated Hospital, Army Medical UniversityChongqingChina
| | - Guowen Wang
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
| | - Ping Cui
- Department of Public HealthJining Medical UniversityJiningChina
| | - Chao Zhang
- Department of Bone and Soft Tissue TumorsTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for CancerTianjinChina
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Campbell KM, Shulman DS, Grier HE, DuBois SG. Role of bone marrow biopsy for staging new patients with Ewing sarcoma: A systematic review. Pediatr Blood Cancer 2021; 68:e28807. [PMID: 33219750 DOI: 10.1002/pbc.28807] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/19/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022]
Abstract
The incidence of bone marrow metastasis (BMM) in newly diagnosed Ewing sarcoma (ES) is variable across studies. An optimal staging strategy for detecting BMM is not defined. While bone marrow (BM) biopsy and/or aspirate (BMBA) have been the gold standard, [F-18]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect BMM may decrease reliance on BMBA. We conducted a systematic review to assess incidence of BMM and the role of FDG-PET. We observed a pooled incidence of BMM by BMBA of 4.8% in all newly diagnosed ES patients and 17.5% among patients with metastatic disease. Only 1.2% of patients had BMM as their sole metastatic site. FDG-PET detection of BMM compared to BMBA demonstrated pooled 100% sensitivity and 96% specificity, positive predictive value of 75%, and negative predictive value of 100%. In the era of FDG-PET imaging, omission of BMBA may be considered in patients with otherwise localized disease after initial staging studies.
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Affiliation(s)
- Kevin M Campbell
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts
| | - David S Shulman
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts
| | - Holcombe E Grier
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts
| | - Steven G DuBois
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts
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27
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Affiliation(s)
- Nicolò Riggi
- From the Institute of Pathology, Faculty of Biology and Medicine, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (N.R., I.S.); and the Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, and the Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge - both in Massachusetts (M.L.S.)
| | - Mario L Suvà
- From the Institute of Pathology, Faculty of Biology and Medicine, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (N.R., I.S.); and the Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, and the Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge - both in Massachusetts (M.L.S.)
| | - Ivan Stamenkovic
- From the Institute of Pathology, Faculty of Biology and Medicine, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (N.R., I.S.); and the Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, and the Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge - both in Massachusetts (M.L.S.)
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28
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Scheer M, Blank B, Bauer S, Vokuhl C, Stegmaier S, Feuchtgruber S, Henssen A, Sparber-Sauer M, Eggert A, Handgretinger R, Pekrun A, Rossig C, Rutkowski S, Schlegel PG, Schrappe M, Simon T, Kazanowska B, Niggli F, Ladenstein R, Ljungman G, Jahnukainen K, Fuchs J, Bielack SS, Koscielniak E, Klingebiel T. Synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups: a report of the Cooperative Weichteilsarkom Studiengruppe (CWS). J Cancer Res Clin Oncol 2020; 146:953-960. [PMID: 31932909 DOI: 10.1007/s00432-019-03121-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 12/24/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Older age is associated with worse outcome in synovial sarcoma (SS) patients. Differences in disease presentation among distinct age groups, however, are currently unknown. METHODS SS patients < 21 years registered in consecutive CWS trials over the period of 1981-2018 were evaluated. Characteristics were analyzed according to age groups using the Fisher's exact test. RESULTS The study population included 432 SS patients. Disease characteristics differed according to age groups of children (0-12 years, n = 176), adolescents (13-16 years, n = 178), and young adults (17-21 years, n = 78). The proportion of invasive tumors (T2) was significantly higher in older patients: children 33%, adolescents 39% and young adults 54%, p = 0.009805. Similarly, the proportion of tumors > 10 cm was higher (13%, 21%, 31%; p = 0.005657) whereas conversely, the proportion of small tumors < 3 cm was lower in older patients (29%, 24%, 6%; p = 0.000104). The presence of metastases at first diagnosis was also highest in older patients (6%, 10%, 21%, p = 0.000963). Notably, the proportion of thigh tumors was higher in older patients (p = 0.04173), whereas the proportion of head-neck tumors was lower in older patients (p = 0.08896). CONCLUSIONS The rates of large, invasive tumors and the presence of metastases are significantly associated with older patient age. Localization to the thigh is more frequent in older patients. DISCUSSION The causes for these variations require further exploration.
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Affiliation(s)
- Monika Scheer
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany.
| | - Bernd Blank
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany
| | - Sebastian Bauer
- Sarcoma Center, West German Cancer Center, University of Duisburg-Essen, Essen, Germany
| | - Christian Vokuhl
- Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Sabine Stegmaier
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany
| | - Simone Feuchtgruber
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany
| | - Anton Henssen
- Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Monika Sparber-Sauer
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany
| | - Angelika Eggert
- Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ruppert Handgretinger
- Department of Pediatric Hematology and Oncology, University Children's Hospital, University Hospital Tuebingen, Tuebingen, Germany
| | - Arnulf Pekrun
- Department of Pediatric Hematology and Oncology, Hospital Bremen-Mitte, Bremen, Germany
| | - Claudia Rossig
- Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany
| | - Stefan Rutkowski
- Pediatric Hematology and Oncology, University Hamburg-Eppendorf, Hamburg, Germany
| | - Paul-Gerhardt Schlegel
- University Children's Hospital, Pediatric Oncology, Hematology, Stem Cell Transplantation, University of Wuerzburg, Wuerzburg, Germany
| | - Martin Schrappe
- Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Thorsten Simon
- Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty, Cologne, Germany
| | | | - Felix Niggli
- Department of Pediatric Oncology, University of Zuerich, Zuerich, Switzerland
| | - Ruth Ladenstein
- St. Anna Kinderspital and St. Anna Kinderkrebsforschung e.V., Vienna, Austria
| | - Gustaf Ljungman
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Kirsi Jahnukainen
- New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Jörg Fuchs
- Department of Pediatric Surgery and Urology, University Children's Hospital, Tuebingen, Germany
| | - Stefan S Bielack
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany
- Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany
| | - Ewa Koscielniak
- Klinikum Stuttgart, Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Kriegsbergstrasse 62, 70174, Stuttgart, Germany
- Department of Pediatric Hematology and Oncology, University Children's Hospital, University Hospital Tuebingen, Tuebingen, Germany
| | - Thomas Klingebiel
- Hospital for Children and Adolescents, Goethe-University, Frankfurt (Main), Germany
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29
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Ceci C, Atzori MG, Lacal PM, Graziani G. Role of VEGFs/VEGFR-1 Signaling and its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models. Int J Mol Sci 2020; 21:E1388. [PMID: 32085654 PMCID: PMC7073125 DOI: 10.3390/ijms21041388] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 02/13/2020] [Accepted: 02/14/2020] [Indexed: 12/14/2022] Open
Abstract
The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.
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Affiliation(s)
- Claudia Ceci
- Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (C.C.); (M.G.A.)
| | - Maria Grazia Atzori
- Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (C.C.); (M.G.A.)
| | - Pedro Miguel Lacal
- Laboratory of Molecular Oncology, “Istituto Dermopatico dell’Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico”, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy;
| | - Grazia Graziani
- Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; (C.C.); (M.G.A.)
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30
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Ju HY. Ewing Sarcoma. CLINICAL PEDIATRIC HEMATOLOGY-ONCOLOGY 2019. [DOI: 10.15264/cpho.2019.26.1.27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Hee Young Ju
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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31
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Jiang S, Wang G, Chen J, Dong Y. Comparison of clinical features and outcomes in patients with extraskeletal vs skeletal Ewing sarcoma: an SEER database analysis of 3,178 cases. Cancer Manag Res 2018; 10:6227-6236. [PMID: 30538569 PMCID: PMC6260126 DOI: 10.2147/cmar.s178979] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background The clinicopathological characteristics, outcomes and prognostic factors of primary extraskeletal Ewing sarcoma (EES) remained insufficiently explored. We aimed to examine these aspects and compared the same with skeletal Ewing sarcoma (SES). Patients and methods We identified Ewing sarcoma, peripheral primitive neuroectodermal tumors or Askin tumor patients who were registered in the Surveillance, Epidemiology, and End Results database from 1973 to 2014. Clinicopathological features were assessed by using Fisher’s exact tests. Cancer-specific survival (CSS) and overall survival (OS) were estimated by using the Kaplan–Meier method and the Cox proportional hazards model. Prognostic factors were identified by multivariate Cox regression analysis. Results The age of patients with EES was diagnosed to be higher and they were more likely to be female (46.1% vs 36.2%; P<0.001), have tumor <10 cm (49.8% vs 35.4%; P<0.001), have regional node involvement (5.4% vs 1.0%; P<0.001) and receive surgery (69.1% vs 53.8%; P<0.001) compared to patients with skeletal tumors. Metastatic status did not differ by origin. Kaplan–Meier analysis showed that the origin had significant difference in CSS and OS among patients aged 0–19 years and with metastatic stage at presentation, but not in patients aged 20–39, ≥40 years and with no-metastatic stage. A Cox multivariable model controlling for differences between groups confirmed inferior survival for patients with EES. Age, tumor size, tumor stage and surgery were the most important factors significantly influencing both CSS and OS in the EES and SES patients. Race, year of diagnosis and tumor site were associated with CSS and OS among patients with SES, but failed in EES. Conclusion The clinicopathological characteristics, outcomes and prognostic factors differed among patients with EES compared to patients with SES. Extraskeletal origin was an unfavorable prognostic factor.
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Affiliation(s)
- Sujing Jiang
- Department of Medical Oncology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China,
| | - Guannan Wang
- Department of Medical Oncology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China,
| | - Jieyu Chen
- Department of Medical Radiology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Ying Dong
- Department of Medical Oncology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China,
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32
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Grünewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E, Kovar H, Sorensen PH, Delattre O, Dirksen U. Ewing sarcoma. Nat Rev Dis Primers 2018; 4:5. [PMID: 29977059 DOI: 10.1038/s41572-018-0003-x] [Citation(s) in RCA: 500] [Impact Index Per Article: 71.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Ewing sarcoma is the second most frequent bone tumour of childhood and adolescence that can also arise in soft tissue. Ewing sarcoma is a highly aggressive cancer, with a survival of 70-80% for patients with standard-risk and localized disease and ~30% for those with metastatic disease. Treatment comprises local surgery, radiotherapy and polychemotherapy, which are associated with acute and chronic adverse effects that may compromise quality of life in survivors. Histologically, Ewing sarcomas are composed of small round cells expressing high levels of CD99. Genetically, they are characterized by balanced chromosomal translocations in which a member of the FET gene family is fused with an ETS transcription factor, with the most common fusion being EWSR1-FLI1 (85% of cases). Ewing sarcoma breakpoint region 1 protein (EWSR1)-Friend leukaemia integration 1 transcription factor (FLI1) is a tumour-specific chimeric transcription factor (EWSR1-FLI1) with neomorphic effects that massively rewires the transcriptome. Additionally, EWSR1-FLI1 reprogrammes the epigenome by inducing de novo enhancers at GGAA microsatellites and by altering the state of gene regulatory elements, creating a unique epigenetic signature. Additional mutations at diagnosis are rare and mainly involve STAG2, TP53 and CDKN2A deletions. Emerging studies on the molecular mechanisms of Ewing sarcoma hold promise for improvements in early detection, disease monitoring, lower treatment-related toxicity, overall survival and quality of life.
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Affiliation(s)
- Thomas G P Grünewald
- Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. .,Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. .,German Cancer Consortium, partner site Munich, Munich, Germany. .,German Cancer Research Center, Heidelberg, Germany.
| | - Florencia Cidre-Aranaz
- Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. .,Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. .,German Cancer Consortium, partner site Munich, Munich, Germany. .,German Cancer Research Center, Heidelberg, Germany.
| | - Didier Surdez
- INSERM U830, Équipe Labellisé LNCC, PSL Université, SIREDO Oncology Centre, Institut Curie, Paris, France
| | - Eleni M Tomazou
- Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria
| | - Enrique de Álava
- Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville/CIBERONC, Seville, Spain
| | - Heinrich Kovar
- Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.,Department of Pediatrics, Medical University Vienna, Vienna, Austria
| | - Poul H Sorensen
- British Columbia Cancer Research Centre and University of British Columbia, Vancouver, Canada
| | - Olivier Delattre
- INSERM U830, Équipe Labellisé LNCC, PSL Université, SIREDO Oncology Centre, Institut Curie, Paris, France
| | - Uta Dirksen
- German Cancer Research Center, Heidelberg, Germany.,Cooperative Ewing Sarcoma Study group, Essen University Hospital, Essen, Germany.,German Cancer Consortium, partner site Essen, Essen, Germany
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