Survival Data for 648 Patients with Osteosarcoma Treated at One Institution Henry J. Mankin, MD*; Francis J. Hornicek, MD, PhD*; Andrew E. Rosenberg, MD†; David C. Harmon, MD‡; and Mark C. Gebhardt, MD* During the past 30 years, the orthopaedic oncology group at the Massachusetts General Hospital has treated 648 patients with osteosarcoma centrally located in the bone. Using re- cords maintained in a specifically designed computer system, a study was done to assess the factors that seemed to influ- ence the survival outcome. The overall survival for the entire series was 68% at an average followup of 6 ± 4 years. Death occurred at a mean of 3 ± 3 years. Patient gender had no effect, but age of the patient was correlated with survival data, with the poorest survival for the older patients. Surgi- cal treatment had no effect on outcome, but the Musculo- skeletal Tumor Society stage of the lesion, the presence of metastases or local recurrence, and the chemotherapeutic treatment (very dependent on the drugs available and adju- vant versus neoadjuvant administration at various decades) all had a profound effect. In addition, anatomic location, size of the tumor, and percentage of tumor cells killed after neo- adjuvant chemotherapy all had an effect on outcome. Although relatively rare by standards of other malignant tumors, osteosarcoma is the most common primary malig- nancy of bone. 9,10,15,19,23,75,78 The tumor most often af- fects young people between the ages of 10 and 25 years, and approximately 1500 new cases are seen annually in the United States. 9,23,48,78 The tumor most frequently occurs in the distal femur or proximal tibia and is thought to be more frequent in males than females. 9,23,48,77 Although no clear genetic error is associated with the entity, the disease is known to have a relationship with retinoblastoma in the Li-Fraumeni syndrome, 9,23,24,47,60,72 and with the dermatologic disorder, Rothmund-Thompson syn- drome. 1,9,17,21,23,61 Some of the more aggressive lesions show a greater degree of aneuploidy on flow cytometry 23,54,70 or germ cell alterations in p53, c-fos, 23,33,43,45,59,70,81 or other gene and enzyme factors including MDM2 45,81 and HER2/erb-2, 35,51,82 cyclooxy- genase-2, 22 PCNA, 43 p-glycoprotein, 1,39,58,68 and bone morphogenetic proteins. 73 Some of the rarer special forms of osteosarcoma include telangiectatic, fibrohistiocyt- ic, chondroblastic, and metachronous osteosarco- mas, 7,9,23,38,48,55,61 but only the last two seem to have a better prognosis than the rest. In addition, in adults, lesions that closely resemble osteosarcoma may occur in patients with Paget’s disease, radiation damage, or occasionally in sites of osteonecrosis. 9,11,23,31,37,78 The prognosis for patients with osteosarcoma has been the subject of numerous studies during the years. The ear- liest description of malignant bone neoplasms was by Dupuytren in 1805 25 who declared them to be very ag- gressive, but it was not until 1879 that Gross described osteosarcoma as a highly malignant bone-forming neo- plasm. 36 In 1950, Coley and Harrold reported an 11% survival for patients from Sloan Kettering Cancer Memo- rial Hospital, 12 and in the 1950s Jaffe, 41 Lichtenstein, 48 and Stein and Beller 71 proposed that only 10% of patients with osteosarcoma are likely to survive. In 1957, Coventry and Dahlin defined the 10-year survival rate for patients with osteosarcoma treated at the Mayo Clinic to be 15%. 15 In 1962,Weinfeld and Dudley reported a followup study on 94 patients treated at the Massachusetts General Hos- pital and stated that the 5-year and the 10-year survival rates were 14% and 9% respectively. 80 Even with ampu- tation the prognosis for this tumor was considered among the worst for connective tissue lesions. 18,19,32,56,75 Received: January 26, 2004 Revised: June 18, 2004 Accepted: August 9, 2004 From the Departments of *Orthopaedic Oncology, †Medical Oncology, and ‡Pathology, Massachusetts General Hospital, Harvard Medical School, Bos- ton, MA. Each author certifies this he or she has no commercial associations (eg consultancies, stock ownership, equity interest, patent licensing arrange- ments, etc) that might pose a conflict of interest with the submitted article. Each author certifies that his or her institution has approved the human protocol for this investigation and all investigations were conducted in con- formity with ethical principles of research. Correspondence to: Henry J. Mankin, MD, Gray 6 Orthopaedics, Massachu- setts General Hospital, Boston, MA 02114. Phone: 617-726-2735; Fax: 617- 726-6823; E-mail: hmankin@partners.org. DOI: 10.1097/01.blo.0000145991.65770.e6 CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Number 429, pp. 286–291 © 2004 Lippincott Williams & Wilkins 286