Late effects of chemotherapy and radiotherapy in osteosarcoma and Ewing sarcoma patients

Abstract

BACKGROUND:Patients with osteosarcoma and Ewing sarcoma have achieved longer survival over the past decades, but late side effects of chemotherapy and radiotherapy have become important concerns. METHODS: The authors reviewed all patients with localized osteosarcoma or Ewing sarcoma who had been enrolled in the Italian Sarcoma Group neoadjuvant protocols from 1983 through 2006. Data were updated in December 2010 to determine 3 endpoints: the incidence of a secondary primary cancer (designated as ''second malignant neoplasm'' [SMN]), infertility, and cardiotoxicity. RESULTS: Data were available on 883 patients with osteosarcoma and 543 patients with Ewing sarcoma. In the osteosarcoma group, there were 39 SMNs (4.4%) in 36 patients; in the Ewing sarcoma group, 15 patients (2.8%) experienced a single SMN each. The cumulative 10-year and 20-year incidence of an SMN (AEstandard error) was 4.9% AE 0.9% and 6.1% AE 1.2%, respectively, in the osteosarcoma group and 3.4% AE 0.9% and 4.7% AE 1.6%, respectively, in the Ewing sarcoma group. The most common SMN in the osteosarcoma group was breast cancer (n ¼ 11), and the most common SMN in the Ewing sarcoma group was radiotherapy-induced osteosarcoma (n ¼ 6). After 20 years, the risk of developing an SMN increased, whereas the risk of a recurrence of the primary tumor decreased. Permanent sterility was more common in males than in females. Doxorubicin cardiotoxicity occurred in 18 patients with osteosarcoma (2%) and in 7 patients with Ewing sarcoma (1.3%). CONCLUSIONS: The awareness of late side effects in long-term survivors of primary bone cancers should encourage longer followup. Cancer 2012;118:5050-9.

CD99 Triggering in Ewing Sarcoma Delivers a Lethal Signal through p53 Pathway Reactivation and Cooperates with Doxorubicin

“…Roughly 70% of patients with localized disease at diagnosis can now be cured with conventional agents (1) at risk of suffering low quality of life due to limb-salvage procedures, prolonged dose-dense chemotherapy, development of chronic severe pathologies and risk of secondary malignancies (2). For patients with metastasis prognosis remains grim (3) and few treatments can be offered to those who relapse after first-line therapies.…”

Pre-chemotherapy preservation of fertility in male patients with high-grade malignant bone and soft tissue tumors

“…Of these, ifosfamide is currently considered a key drug for the treatment of high-grade bone and soft tissue tumors. Longhi et al (4) reported that 20/26 male patients had developed oligospermia or azoospermia following chemotherapy with high-dose ifosfamide (median dose, 42 g/m 2 ) for osteosarcoma. Williams et al (21) reported that gonadal dysfunction occurs at a total ifosfamide dose of >60 g/m 2 .…”

“…Certain types of high-grade bone and soft tissue tumors, such as osteosarcoma, Ewing's sarcoma and synovial sarcoma, are most commonly encountered among adolescents and young adults. With the increase in the number of long-term survivors, latent treatment-related adverse effects have generated new concerns (4).…”

Salivary gland second cancer after bone sarcoma treatment

“…These cancers are referred as second malignant neoplasms (SMN) or second cancers and may occur in 2-5 % (mean 3.5 %) of childhood cancer survivors within 5-25 years (mean 10 years) after diagnosis and treatment for a bone sarcoma [5][6][7]. The etiology of SMN is unclear; treatment-related factors, genetic syndromes, and environmental exposures have been implicated [8].…”