Rhabdomyosarcoma in adolescent and young adult patients: current perspectives

Abstract

Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients, while the pleomorphic variant is rare in children and seen more often in adults. Advances in the research of the embryonal and alveolar variants have improved our understanding of certain genes and biologic pathways that are involved in RMS, but much less is known for the other variants. Multimodality therapy that includes surgery and chemotherapy with or without radiation therapy is the mainstay of treatment for RMS. Improvements in the risk stratification of the pediatric patients based on presurgical (primary tumor site, tumor size, regional lymph node involvement, presence of metastasis) and postsurgical parameters (completeness of resection or presence of residual disease or metastasis) has allowed for the treatment assignment of patients in different studies and therapeutic trials, leading to increases in 5-year survival from 25%–70% over the past 40 years. However, for adult patients, in great part due to rarity of the disease and the lack of consensus on optimal treatment, clinical outcome is still poor. Many factors have been implicated for the differing outcomes between pediatric RMS versus adult RMS, such as the lack of standardized treatment protocols for adult RMS patients and the increased prevalence of advanced presentations. Now that there are increased numbers of survivors, we can appreciate the sequelae from therapy in these patients, such as bone growth abnormalities, endocrinopathies, and infertility. Improvements in risk stratification have led to clinical trials using lower doses of chemotherapy or radiation therapy with the intention of decreasing the incidence of side effects without compromising survival outcome.

Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance

“…Regarding the latter, a three-drug combination is currently utilized: vincristine, actinomycin D and cyclophosphamide (VAC). This regimen has become the basis for RMS therapy with the incorporation of other agents such as etoposide, doxorubicin, ifosfamide, cisplatin and others for intermediate risk patients, with scarce clinical outcome improvement 36 .…”

Combined application of arsenic trioxide and lithium chloride augments viability reduction and apoptosis induction in human rhabdomyosarcoma cell lines

“…Estimated 350 new cases of RMS are diagnosed each year in patients under 20 years of age in the United States [1]. …”

Biologic and Clinical Aspects of Rhabdomyosarcoma

“…1,6 Although the origins of RMS are not clear, RMS occurs when there is a disruption within the genetic differentiation pathway in myogenic precursor cells, so that RMS cells display features of undifferentiated fetal myoblasts. 9 Consistent with this observation RMS cells have been shown to upregulated fetal genes such as FGFR4 (fibroblast growth factor receptor 4), NOTCH2 (neurogenic locus notch homolog protein 2), UBE2C (ubiquitin-conjugating enzyme E2 C), UHRF1 (ubiquitin- like, containing PHD and RING finger domains 1), and YWHAB genes.…”

“…For children under 20, 15% of cancer cases are sarcomas. 1 Rhabdomyosarcoma (RMS) is a type of sarcoma that is caused by a disruption in the pathway of primitive mesenchymal stem cells directed towards myogenesis. 2 Although RMS is a very rare form of cancer, it is the most common pediatric sarcoma primarily affecting children before the age of 5, yet is very rare in adults.…”