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. 2017 Dec;64(12):10.1002/pbc.26645.
doi: 10.1002/pbc.26645. Epub 2017 May 18.

Histology, fusion status, and outcome in metastatic rhabdomyosarcoma: A report from the Children's Oncology Group

Erin R Rudzinski  1 , James R Anderson  2 , Yueh-Yun Chi  3 , Julie M Gastier-Foster  4   5 , Caroline Astbury  4   5 , Frederic G Barr  6 , Stephen X Skapek  7 , Douglas S Hawkins  8   9 , Brenda J Weigel  10 , Alberto Pappo  11 , William H Meyer  12 , Michael A Arnold  4   5 , Lisa A Teot  13 , David M Parham  14
Affiliations

Histology, fusion status, and outcome in metastatic rhabdomyosarcoma: A report from the Children's Oncology Group

Erin R Rudzinski et al. Pediatr Blood Cancer. 2017 Dec.

Abstract

Background: Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) has historically been of prognostic and therapeutic importance. However, classification has been complicated by shifting histologic criteria required for an ARMS diagnosis. Children's Oncology Group (COG) studies after IRS-IV, which included the height of this diagnostic shift, showed both an increased number of ARMS and an increase in the proportion of fusion-negative ARMS. Following diagnostic standardization and histologic re-review of ARMS cases enrolled during this era, analysis of low-risk (D9602) and intermediate-risk (D9803) rhabdomyosarcoma (RMS) studies showed that fusion status rather than histology best predicts prognosis for patients with RMS. This analysis remains to be completed for patients with high-risk RMS.

Procedure: We re-reviewed cases on high-risk COG studies D9802 and ARST0431 with an enrollment diagnosis of ARMS. We compared the event-free survival (EFS) and overall survival by histology, PAX-FOXO1 fusion, and clinical risk factors (Oberlin score) for patients with metastatic RMS using the log-rank test.

Results: Histology re-review resulted in reclassification as ERMS for 12% of D9802 cases and 5% of ARST0431 cases. Fusion-negative RMS had a superior EFS to fusion-positive RMS; however, poorer outcome for metastatic RMS was most related to clinical risk factors including age, primary site, and number of metastatic sites.

Conclusions: In contrast to low- or intermediate-risk RMS, in metastatic RMS, clinical risk factors have the most impact on patient outcome. PAX-FOXO1 fusion is more common in patients with a high Oberlin score, but fusion status is not an independent biomarker of prognosis.

Keywords: ARST0431; D9802; fusion status; high risk; histology; rhabdomyosarcoma.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Event-free survival for D9802 (solid lines) and ARST0431 (dashed lines) including (a) all patients, (b) ERMS only, and (c) ARMS only
FIGURE 2
FIGURE 2
Event-free survival (EFS) by histology and fusion status for D9802 and ARST0431 cases combined including (a) all histologic subtypes and (b) fusion status alone
FIGURE 3
FIGURE 3
Product-limit survival estimates with number of subjects at risk. Event-free survival by Oberlin risk score
See this image and copyright information in PMC

References

    1. Newton WA, Gehan EA, Webber BL, et al. Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification–an Intergroup Rhabdomyosarcoma Study. Cancer. 1995;76:1073–1085. - PubMed
    1. Barr FG, Smith LM, Lynch JC, et al. Examination of gene fusion status in archival samples of alveolar rhabdomyosarcoma entered on the Inter-group Rhabdomyosarcoma Study-III trial: A report from the Children’s Oncology Group. J Mol Diagn. 2006;8:202–208. - PMC - PubMed
    1. Sorensen PH, Lynch JC, Qualman SJ, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhab-domyosarcoma: A report from the children’s oncology group. J Clin Oncol. 2002;20:2672–2679. - PubMed
    1. Rudzinski ER, Teot LA, Anderson JR, et al. Dense pattern of embryonal rhabdomyosarcoma, a lesion easily confused with alveolar rhabdomyosarcoma: A report from the soft tissue sarcoma committee of the Children’s Oncology Group. Am J Clin Pathol. 2013;140:82–90. - PMC - PubMed
    1. Arnold MA, Anderson JR, Gastier-Foster JM, et al. Histology, fusion status, and outcome in alveolar rhabdomyosarcoma with low-risk clinical features: A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2016;63:634–639. - PMC - PubMed