Table 1.
Studies describing clinical correlates of PAX3- and/or PAX7-FOXO1 translocations among patients with RMS
| Clinical Characteristics Assessed |
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|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | Total N, by histology |
Total N, by translocation status |
Age | Gender | Primary Site |
Tumor Size | Metastatic Disease |
IRS Group | Survival Status |
Worse Prognostic Marker |
Main Findings |
| Kelly (1997) Ref #15 |
27 ARMS 3 ERMS 4 Other |
18 PAX3 16 PAX7 0 F− |
√ | √ | √ | √ | √ | √ |
PAX3- FOXO1 |
Four-yr EFS for patients with PAX3-FOXO1 was 17% v. 43% for those with PAX7-FOXO1 (p=0.04). Patients with PAX3-FOXO1 translocation tended to be older (median 13 v. 6 yrs, p=0.01), have primary extremity lesions (82% v. 22%, p=0.001) or metastatic disease (44% v. 19%, p=0.03). |
|
| Anderson (2001) Ref #16 |
38 ARMS 43 ERMS 10 OTHER |
37 PAX3 8 PAX7 46 F− |
√ | √ | √ | √ | √ |
PAX3- FOXO1 |
Four-yr EFS for patients with PAX3-FOXO1 was inferior (20% v. 70%, p<0.0001).Patients with PAX3-FOXO1 translocation tended to be older (median age 9 v. 3 yrs, p=0.001), have higher stage disease (63% v. 38% stage 3-4, p=0.006). |
||
| Sorensen (2002) Ref # 7 |
78 ARMS 69 ERMS 24 Other |
43 PAX3 17 PAX7 111 F− |
√ | √ |
PAX3- FOXO1 (only if metastatic disease) |
PAX3-FOXO1 and PAX7-FOXO1 fusion transcripts were detected in 55% and 22% of alveolar RMS patients, respectively; 23% were fusion-negative. All other RMS patients lack transcripts. Fusion status was not associated with outcome differences in ARMS patients with localized disease; however, among those with metastatic disease, PAX3-FOXO1 was associated with inferior overall survival (8% v. 75%, p=0.0015). Fusion negative status suggested an intermediate risk: relative risk of relapse 11.5 (95% CI 5.1-25.6) for PAX3-FOXO1, 4.9 (1.4-17.3) for F− and 1.3 (0.2-10.2) for PAX7 patients, respectively. |
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| Barr (2006) Ref #17 |
59 ARMS | 35 PAX3 11 PAX7 13 F− |
√ | √ | √ | √ | √ | √ | √ | Neither | No differences in FFS between groups; however, patients who had available fusion data for analysis had superior 5-yr FFS (75% v. 45%, p=-.0015). Neither translocation was associated with FFS or OS in multivariate models. |
| Williamson (2010) Ref #8 |
133 ARMS 77 ERMS |
94 F+ 39F− |
√ | √ | √ | √ | √ | √ | Any F+ | ERMS patients were not assessed for fusion status. ARMS F+ patients had inferior 5-yr EFS compared to ARMS F− and ERMS patients (20% v. 60% v. 55%, respectively, p<0.001). The relative risk of death for F+ RMS patients was 2.5 after adjustment for stage and histology (95% CI 1.2-5.1). ARMS F+ patients were more likely to have unfavorable sites of disease (79% v. 53% v. 57%, respectively, p=0.002) and metastatic disease (43% v. 8% v. 12%, respectively, p<0.001). |
|
| Stegmaier (2011) Ref #18 |
121 ARMS | 72 PAX3 29 PAX7 20 F− |
√ | √ | √ | √ | √ | √ | √ | Neither | Patients with PAX3-FOXO1 translocation tended to be older than those with PAX7-FOXO1 (63% v. 17% older than 10 yrs, p=0.0001) and have higher rates of metastatic disease (50% v. 24%, p=0.017). There was no difference in EFS between patients in the two groups. 5-yr EFS for PAX3-FOXO1 3 was 38.9% v. 18.2% for PAX7-FOXO1 (p=0.235). Compared to non- analyzed, historical controls, localized patients who had fusion data for analysis had inferior EFS (29% v. 51%, p=0.009), regardless of fusion status. |
| Dumont (2011) Ref #9 |
31 ARMS 62 ERMS 12 Other |
14 PAX3 4 PAX7 34 F− |
√ | √ | Neither | Fifty-two percent of samples identified any fusion status (+ or −). Patients with ARMS and either translocation were more likely to have metastatic disease (39%) compared to fusion-negative ARMS or ERMS patients (both 22%, p=0.0081). No associations were detected between fusion transcripts and survival. |
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RMS: Rhabdomyosarcoma; IRS Group: Intergroup Rhabdomyosarcoma Study Group post-surgical stage; ARMS: Alveolar RMS; ERMS: Embryonal RMS; F−: Fusion-negative patients; EFS: Event-Free Survival; F+: Fusion-positive (either PAX3- or PAX7-FOXO1)