Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group.
ABSTRACT To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy.
Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc).
Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy.
Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.
- SourceAvailable from: Johannes H M Merks[Show abstract] [Hide abstract]
ABSTRACT: Background In pediatric rhabdomyosarcoma (RMS), evaluation of lymph node involvement (N1) is an important staging aspect, but difficult to assess. The aim of our study was to evaluate the assessment of lymph node infiltration and impact on outcome in N1 RMS patients. Methods We identified 277 non-metastatic RMS patients diagnosed and treated between 1990 and 2008. Patients with recorded N1 disease were evaluated for their diagnostic procedures and outcome. Results In 13.7% N1 status was reported. In 19 of 34 N1 patients, lymph node biopsies were performed for histologically confirmation. Different treatment modalities were used to treat lymph node metastases. In total 23 of 31 patients received local treatment of the node (11/23 RT, 4/23 surgery, and 8/23 both). All patients received chemotherapy. Lymph node relapse occurred in 7 of 31 patients who were treated with one or two modalities. Only 1 (14%) of 8 patients treated with three modalities relapsed. In N0 patients 10 (4.2%) of 239 had a regional lymph node relapse, and 9 of 10 died. Conclusion Lymph node metastases are an essential part of staging. Node positivity contributes to relapse of disease. Nodal relapse is also associated with a high mortality rate. These data imply that nodal assessment needs to be optimal and standardized for improved staging.Journal of Pediatric Surgery 03/2014; 49(3):416–419. · 1.31 Impact Factor
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ABSTRACT: A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma.PLoS ONE 01/2013; 8(1):e55072. · 3.53 Impact Factor
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ABSTRACT: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, affecting very young patients. These tumors often cause significant functional damage because of their aggressive growth pattern. In addition, their metastatic potential can present as a complex and challenging situation. RMS can present in various anatomical sites and often pose significant obstacle in choosing local control modalities. When feasible, surgery plays an important role for initial diagnosis and complete tumor removal; delayed primary re-excision and second-look surgery after initial chemotherapy are gaining more acceptance. Because of high-metastatic risk, systemic chemotherapy is also necessary. Novel agents are emerging which may alter the disease course in high-risk disease where the cure rate is still low. Radiation therapy is an important tool in the management of RMS and has gone through significant evolution during past four decades. This review will outline treatment strategies adopted in children RMS. The primary focus will be the North American approach with attention to advancements in radiation therapy, surgical techniques, and systemic therapies.Journal of Radiation Oncology. 06/2012; 2(2).