Prognostic significance and tumor biology of regional lymph node disease in patients with rhabdomyosarcoma: a report from the Children's Oncology Group

Abstract

Purpose: Regional lymph node disease (RLND) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of RLND to prognosis for patients with RMS.

Patients and methods: Patient characteristics and survival outcomes for patients enrolled onto Intergroup Rhabdomyosarcoma Study IV (N = 898, 1991 to 1997) were evaluated among the following three patient groups: nonmetastatic patients with clinical or pathologic negative nodes (N0, 696 patients); patients with clinical or pathologic positive nodes (N1, 125 patients); and patients with a single site of metastatic disease (77 patients).

Results: Outcomes for patients with nonmetastatic alveolar N0 RMS were significantly better than for patients with N1 RMS (5-year failure-free survival [FFS], 73% v 43%, respectively; 5-year overall survival [OS], 80% v 46%, respectively; P < .001). Patients with a single site of alveolar metastasis had even worse FFS and OS (23% FFS and OS, P = .01) when compared with patients with N1 RMS; however, the differences was not as large as the differences between patients with N0 RMS and N1 RMS. For embryonal RMS, there was no statistically significant difference in FFS or OS (P = .41 and P = .77, respectively) for patients with N1 versus N0 RMS. Gene array analysis of primary tumor specimens identified that genes associated with the immune system and antigen presentation were significantly increased in N1 versus N0 alveolar RMS.

Conclusion: RLND alters prognosis for alveolar but not embryonal RMS. For patients with N1 disease and alveolar histology, outcomes were more similar to distant metastatic disease rather than local disease. Current data suggest that more aggressive therapy for patients with alveolar N1 RMS may be warranted.

Fig 1.

Failure-free survival curves for patients who are regional lymph node disease (RLND) negative, patients who are RLND positive, and patients with one site of metastatic disease in (A) both embryonal and alveolar rhabdomyosarcoma (RMS), (B) alveolar RMS only, and (C) embryonal RMS only.

Fig 2.

Representative photomicrograph of rhabdomyosarcoma tissue after dual immunofluorescence staining for myogenin (MGN, red) and immunoglobulin (Ig, green). (A, C) Low magnification (×100) shows densely cellular tumor (4,6-diamidino-2-phenylindole) in which regions containing MGN- and Ig-expressing cells generally overlap (*). (B, D) Higher magnification (×630) shows that some MGN-expressing nuclei are in cells expressing Ig on the cell surface (arrow), whereas others are not (arrowhead). Staining here is representative of four separate samples.

Fig A1.

Failure-free survival curve for patients with rhabdomyosarcoma with clinically positive or pathologically confirmed regional lymph node disease. No statistical difference between patients with clinically positive or pathologically confirmed disease (P = .35).

Fig A2.

Overall survival curves for patients who are regional lymph node disease (RLND) negative, patients who are RLND positive, and patients with one site of metastatic disease in (A) both embryonal and alveolar rhabdomyosarcoma (RMS), (B) alveolar RMS only, and (C) embryonal RMS only.

Fig A3.

Expression matrix derived from hierarchical clustering of 198 probe sets representing genes differentially expressed between regional lymph node disease (RLND) –negative and RLND-positive alveolar rhabdomyosarcoma. Colored heat map depicts expression above (red) and below (blue) the median (black) expression level for each probe set (rows) across the samples (columns).