Does Ifosfamide Therapy Improve Survival of Patients With Dedifferentiated Chondrosarcoma?

Abstract

Background Dedifferentiated chondrosarcoma remains a significant therapeutic challenge. Studies performed to date have not identified efficacious chemotherapy regimens for this disease. Questions/purposes We sought to (1) evaluate the disease-specific survival at 2 and 5 years of patients with dedifferentiated chondrosarcoma; (2) assess the prognostic variables (both patient-and treatment-related), including the use of chemotherapy with ifosfamide, that relate to survivorship; and (3) assess specific toxicities associated with ifosfamide use. Methods Data from 41 patients with dedifferentiated chondrosarcoma diagnosed and treated at the University of Texas MD Anderson Cancer Center from 1986 to 2010 were analyzed for demographics, treatments, oncologic outcomes, and prognostic variables. There were 14 women and 27 men. The mean age at diagnosis was 58 years (range, 26-86 years). Seven patients presented with metastasis. Surgical resection alone was performed in 11 patients; resection and chemotherapy in 26 patients; resection and radiotherapy in two patients; and resection, chemotherapy, and radiotherapy in two patients. Ifosfamide-based regimens were used for 16 patients. In general, ifosfamide was used when the tumor was located in the trunk or if cisplatin was discontinued as a result of toxicity. Minimum followup was 8 months (median, 68 months; range, 8-281 months). Survival was estimated using Kaplan-Meier plots and analyzed by using the Cox proportional hazards model. Results Disease-specific survival rates at 2 and 5 years were 33% and 15%, respectively. Multivariate analysis revealed that treatment without ifosfamide-based chemotherapy was the only independent negative prognostic factor for disease-specific survival (hazard ratio, 0.4; 95% confidence interval, 0.17-0.92; p = 0.03). Ifosfamide was discontinued in a patient as a result of renal dysfunction and was decreased in dose in another patient who developed encephalopathy. Conclusions In this small retrospective study, it appeared that ifosfamide-based adjuvant chemotherapy combined with surgical resection offered a treatment advantage compared with patients who did not receive the drug in Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This work was performed at

Chondrosarcoma of the Osseous Spine

“…These are recognized in the literature as particularly aggressive tumors and frequently necessitate chemotherapy in addition to primary surgery for treatment in the long bones. 18,19 In congruence with prior literature, we also found tumor grade and extent of disease to be independent prognostic indicators of both OS and DSS. Given that the majority of the cases were poorly differentiated or anaplastic on histology and presented with at least local invasion at the time of diagnosis, this association stands to reason when considering that a 5% to 20% chondrosarcomas are high-grade (16.4% in this study), aggressive malignancies with significant soft tissue extension, particularly in the spine.…”

“…34 In context, this finding is consistent with children tolerating higher doses of chemotherapy, which is used in instances of advanced disease in mesenchymal and dedifferentiated chondrosarcoma, that may be otherwise intolerable in older patients for therapeutic effect. 18,19,35 Although there was an observed trend, the decade of diagnosis was not found to be associated with a statistically significant improvement in survival in either univariate or multivariate analysis, or for chondrosarcoma variants. Contextually, this may suggest that advances in radiation therapy and chemotherapy regimens have not been as successful for chondrosarcoma as for other bone tumors.…”

“…Here, chemotherapy and sometimes radiation therapy are used a last resort where surgical resection alone is ineffective for such aggressive tumors. 18,19 For these reasons, the optimal treatment for chondrosarcoma of the spine remains controversial.…”

Prognostic Factors in Dedifferentiated Chondrosarcoma: A Retrospective Analysis of a Large Series Treated at a Single Institution

“…DDCS is slightly more frequent in males. Patients with DDCS are older than those with conventional lesions, with a mean age of around 60 years (range: 15-90 years) [1,3,[6][7][8][9]. e most common sites were the femur and pelvis, followed by humerus and scapula [1,3,6].…”

Dedifferentiated Chondrosarcoma Demonstrating Osteosarcomatous Differentiation

“…[6] 78 42 10 10.5 Capanna et al [7] 46 18 30 10 Mercuri et al [8] 74 23 9 12 Mitchell et al [9] 22 6 9 9 Dickey et al [10] 42 N/A 22 7.5 Bruns et al [11] 13 3 5 9.7 Staals et al [12] 123 92 25 13 Staals et al [13] 18 9 7 14 Grimer et al [14] 337 104 81 16 Yokota et al [15] 9 N/A 4 10 Italiano et al [16] 42 N/A N/A N/A Kawaguchi et al [17] 41 N/A 25 18 pts = Patients, DDC = dedifferentiated chondrosarcoma, N/A = not applicable. patients declined chemotherapy.…”