Commentary & Perspective

Commentary & Perspective on
"Dedifferentiated Chondrosarcoma: The Role of Chemotherapy with Updated Outcomes"
by Ian D. Dickey, MD, et al.

Commentary & Perspective by
Dempsey Springfield, MD*,
Leni and Peter W. May Department of Orthopaedic Surgery, Mount Sinai Medical Center, New York, New York

David Dahlin, MD, a pathologist who recently passed away, drew our attention to this separate and lethal primary sarcoma of bone in an article that he coauthored with John Beabout, a radiologist, published in Cancer in 1971¹. They, like the authors of this article, were practicing at the Mayo Clinic in Rochester, Minnesota.

Dedifferentiated chondrosarcoma has been recognized as a tumor with an unusually high rate of early metastasis. Historically, surgery has been the mainstay of treatment, often combined with adjuvant irradiation and/or chemotherapy, but the prognosis of this neoplasm has been such that most patients have died of the disease and many of the survivors have had local recurrence. The patients in this series did not do any better than those treated in the past. Considering the advances that have been made in the treatment of sarcomas in general, this is a little surprising.

For almost all high-grade sarcomas of bone, adjuvant chemotherapy has dramatically decreased metastatic disease. For example, patients with high-grade classic osteosarcoma who were treated with surgery alone had less than a 20% chance of survival at five years, while those treated with surgery and adjuvant chemotherapy had at least a 65% chance of survival. Patients with Ewing sarcoma had less than a 15% chance of five-year survival in the time before the use of adjuvant chemotherapy, and their expected survival is now also at least 65%. As these diseases are seen primarily in young patients who tolerate chemotherapy better than adults, it is possible that the poor rate of survival in patients with dedifferentiated chondrosarcoma could be due to their age; however, when adjuvant chemotherapy was given to adults with osteosarcoma or with malignant histiocytoma of bone, there was a dramatic improvement in survival².

Improvements in survival with the use of adjuvant chemotherapy for other high-grade sarcomas of bone were easy to demonstrate because the survival without chemotherapy was so infrequent that even a small improvement was statistically significant. Early in the history of the use of even a single chemotherapeutic agent (now considered almost a homeopathic treatment) there was such dramatic improvement in outcomes that the use of adjuvant chemotherapy for high-grade sarcomas of bone became routine very quickly. With the extremely poor rates of survival for patients with dedifferentiated chondrosarcoma, improvement with use of adjuvant chemotherapy should be just as easy to demonstrate.

Dedifferentiated chondrosarcoma should not be an exception, but this and prior reports of the results with adjuvant chemotherapy have not suggested much benefit. The diagnosis is so rare that, to my knowledge, no prospective controlled studies have been performed. To my knowledge, the only published report of improved survival is a retrospective study of twenty-two patients³. Six patients who had surgery alone all died within one year, while four of eleven patients who had surgery and adjuvant chemotherapy survived for more than two years. The authors used doxorubicin and cisplatin in all but one patient, who was given doxorubicin and vincristine. These results were encouraging, and it was expected that the addition of methotrexate and especially ifosfamide, as was done by Dickey and his associates in their study, would lead to an even better rate of survival. It did not, and the rate of survival of the patients in that study was still very poor. It is unfortunate that the addition of ifosfamide did not improve the rate of survival as there are no current drugs with known cytotoxicity against sarcomas that have not been tried.

What should we do with this information? First, it confirms other conclusions that dedifferentiated chondrosarcoma is a lethal disease and that surgery alone is inadequate treatment. Second, it seems clear that dedifferentiated chondrosarcoma is different from other primary bone sarcomas, at least with respect to its response to adjuvant chemotherapy. Third, it does not mean that we should discontinue the use of adjuvant chemotherapy in the treatment of patients with dedifferentiated chondrosarcoma; it does mean that we need a better protocol and probably different drugs. Fourth, it supports the recommendation that rare malignant tumors such as dedifferentiated chondrosarcomas need to be treated at centers that are participants in multi-institutional protocols so that sufficient numbers of patients can be obtained to improve our understanding of the disease and our treatment methods.

*The author did not receive grants or outside funding in support of his research or preparation of this manuscript. He did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the author is affiliated or associated.

References

1. Dahlin DC, Beabout JW. Dedifferentiation of low-grade chondrosarcomas. Cancer. 1971;28:461-6.
2. Capanna R, Bertoni F, Bacchini P, Bacci G, Guerra A, Campanacci M. Malignant fibrous histiocytoma of bone. The experience at the Rizzoli Institute: report of 90 cases. Cancer. 1984;54:177-87.
3. Mitchell AD, Ayoub K, Mangham DC, Grimer RJ, Carter SR, Tillman RM. Experience in the treatment of dedifferentiated chondrosarcoma. J Bone Joint Surg Br. 2000;82:55-61.

Copyright © 2004 by the The Journal of Bone and Joint Surgery, Inc.