The predictive potential of molecular detection in the nonmetastatic Ewing family of tumors

• Published in: Cancer 2004-03, Vol.100 (5), p.1053-1058
• Main Authors: Avigad, Smadar, Cohen, Ian J., Zilberstein, Julia, Liberzon, Ella, Goshen, Yacov, Ash, Shifra, Meller, Isaac, Kollender, Yehuda, Issakov, Josephine, Zaizov, Rina, Yaniv, Isaac
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Distribution; Biological and medical sciences; Bone Marrow - pathology; Bone Neoplasms - epidemiology; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Chi-Square Distribution; Child; Child, Preschool; chimeric transcript; Disease-Free Survival; DNA Primers; Ewing sarcoma; Female; Genetic Predisposition to Disease; Humans; Incidence; Male; Medical sciences; Molecular Biology; Neoplastic Cells, Circulating; prediction; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Recombinant Fusion Proteins - genetics; recurrence; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Sampling Studies; Sarcoma, Ewing - epidemiology; Sarcoma, Ewing - genetics; Sarcoma, Ewing - pathology; Sex Distribution; Survival Analysis; Transcription, Genetic; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20059

BACKGROUND Tumors in the Ewing family (EFTs) are the second most common bone tumors in children and adolescents. Despite aggressive chemotherapy, one‐third of patients with localized tumor still may develop recurrences. This implies that not all tumor cells are eradicated and that the patients may have a level of residual disease. EFTs are characterized by specific chromosomal translocations that result in chimeric transcripts that can be detected with reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis. METHODS The authors report the prognostic potential of the positive chimeric transcript (EWS/FLI1) in bone marrow (BM) and/or peripheral blood (PBL) in 26 patients with EFT during a long follow‐up period (median, 61 months). RESULTS At diagnosis, 43% of patients had positive RT‐PCR BM results, with no correlation to tumor progression (P = 0.3). During follow‐up, 58% of patients had positive RT‐PCR results in their last sample analyzed (BM and/or PBL). A highly significant correlation between the presence of the chimeric transcript and disease progression was detected (P = 0.0028). In a multivariate analysis, the percentage of tumor necrosis (P = 0.007) and RT‐PCR results during follow‐up (P = 0.02) remained significant prognostic markers. In 10 of 11 patients who developed disease progression, BM and/or PBL samples were positive for the chimeric transcript before evidence of overt clinical recurrence. CONCLUSIONS Occult tumor cells in BM and/or PBL samples during long follow‐up are strong predictors of recurrent disease in patients with nonmetastatic EFTs. Cancer 2004;100:1053–8. © 2004 American Cancer Society. Occult tumor cells in the bone marrow and/or peripheral blood were evaluated as a potential prognostic parameter in 26 patients with localized Ewing sarcoma during a long follow‐up period. The authors demonstrated that the presence of occult tumor cells is a strong predictor of recurrence.