Intensive chemotherapy can achieve DFS for a high proportion of patients with OS. Although it is a powerful predictor of DFS, histologic response to preoperative chemotherapy cannot be assessed at diagnosis. We have not shown an ability to salvage patients with an unfavorable response. We need to increase the proportion of patients with a favorable response, identify the patients who will have an unfavorable response, and develop novel treatments to salvage poor responders.

Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. A l l patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, H D M T X with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin i n addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%)) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival i n responding patients and i n helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease free survival raw reported to date for osteogenic sarcoma.

Sixty‐six cases of aneurysmal bone cyst were reviewed clinically, pathologically and radiologically. Different therapies, including curettage, block excision, amputation and radiation therapy, and a new treatment, cryosurgery, were employed. Cryosurgery, which avoids the growth and neoplastic complications of radiation therapy and the loss of bone with block excision, had an extremely low rate of recurrence when compared to simple curettage. In manometric studies of 6 cysts, 3 had elevated vascular pressures as high as arteriolar levels. Thirty‐two percent of the aneurysmal bone cysts had an accompanying benign primary lesion of bone. Based on these findings, a new hypothesis for the etiology and pathogenesis of aneurysmal bone cysts was proposed: a primary lesion of bone initiates an osseous, arteriovenous fistula and thereby creates, via its hemodynamic forces, the secondary reactive lesion of bone, which we term aneurysmal bone cyst.

Almost a quarter of a century has passed since mesenchymal chondrosarcoma, a rare, insufficiently studied and still poorly understood cartilage neoplasm has been described. Based on 35 cases diagnosed and treated at this Cancer Center, this study found 20 males and 15 females with an average age of 26 years (range, 6–70 years). All but five of the tumors arose in the skeleton in the femur, humerus, and ilium in five cases each, while the os calcis (a rare site for any other osseous tumor) gave rise to this tumor in four instances. Pain was the cardinal symptom in 27 patients. The lesional size varied from 4 to 18 cm (average, 9.5 cm). Histologic examination revealed nine of the tumors to be of the small cell undifferentiated types while the others were of the “hemangiopericytomatoid” variant. According to this subclassification, patients with the small cell type of lesions responded to combination chemotherapy and irradiation, as usually do other small cell sarcomas. The addition of surgical resection may be of value especially in the patients with the hemangiopericytomatoid variant. Preliminary results in the treatment of five such patients with evaluable disease suggest that this combined treatment approach is encouraging. Follow‐up analysis of all patients revealed a 37.9 months median survival, and 28% to be alive at ten years.

From 1973From -1975 patients with biopsied primary osteogenic sarcoma were treated with preoperative chemotherapy followed by surgical ablation of the primary tumor. Surgery was delayed in order to obtain a custom-fitted prosthetic bone implant in an attempt to avoid amputation. Preoperative chemotherapy included high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (T-5 protocol) and was administered for 3 months preoperatively and continued with the inclusion of cyclophosphamide for approximately 5 months postoperatively. At a follow-up period of 30-52 months, 23 of 31 patients (75%) are surviving (21 of 23 with no evidence of disease). Histologic examination of primary tumor removed at surgery revealed varying degrees of tumor destruction (from very little effect to no evidence of viable tumor) attributable to the effect of chemotherapy. The 2 1 patients that are disease-free survivors had a more complete effect of preoperative chemotherapy on the primary tumor. Some patients achieving favorable effects upon the primary tumor did so only after the dose of HDMTX was escalated to greater than the starting dose of 8 g/m2. Preoperative chemotherapy for all patients with osteogenic sarcoma would seem to offer the following advantages: 1) Evaluation of the effect of HDMTX with CFR on the primary tumor with escalation of the dose of HDMTX until a clinical response is observed, thus defining the dose of HDMTX effective in that patient, to be continued postoperatively as adjuvant therapy; 2) The early use of systemic therapy to eradicate distant microfoci of disease that will eventually kill the patient if not adequately treated by effective chemotherapy; 3) Allow more time for postoperative healing without the need to start adjuvant chemotherapy immediately; and 4) Provide the surgeon time to plan resection surgery. To date, 20 additional patients with biopsy proven osteogenic sarcoma have been treated with more aggressive preoperative chemotherapy (T-7) for approximately 2 $4 months prior to definitive surgery (resection or amputation).

During the period 1931 to 1970, 50 cases of radiation‐induced osteogenic sarcoma were seen at the Memorial and James Ewing Hospitals. Twenty‐two of these cases had previously been described; the present paper adds an additional 28 cases to the existing series and reviews those factors related to the development of neoplastic changes. In 35 patients, there was evidence of preexisting bone pathology in the form of benign osseous growths. Fifteen patients had soft‐part and visceral neoplasms, such as retinoblastoma, seminoma, and breast carcinoma, the involved bone lying in the pathway of the radiation beam. Symptoms ranged from a palpable tender mass in the involved bone to intestinal obstruction secondary to metastatic radiation‐induced osteogenic sarcoma. Essentially all bones in the skeletal system appear to have been vulnerable. The radiation dosages ranged from 1,200 rads given in a few weeks to 24,000 rads given in 2 years. Induction time covered a period of 4 through 30 years with a mean of 9 years. Thirty‐two of the patients developing this neoplasm have since died of their disease.

Two hundred seventy‐nine consecutive patients with Stage II osteogenic sarcoma of the appendicular skeleton treated between 1976 and 1986 were studied to identify predictors of long‐term survival. Survival was 77% and 73% at 5 and 10 years, respectively, with continuously disease‐free survival being 70% and 69%. On univariate analysis, the most significant predictors of survival were the location of the primary lesion, local control of the tumor, and the degree of necrosis in the primary tumor after intravenous neoadjuvant chemotherapy (histologic response). On initial multivariate analysis, similarly, only location and histologic response to chemotherapy predicted disease‐free outcome. After statistical control for local recurrence, only histologic response to chemotherapy was retained as an independent predictor, suggesting that in this data set, the location of primary lesion exerted its effect only secondarily through its association with the ability to provide local control. The risk of local recurrence was almost fivefold higher in tumors of the femur than in tumors of other locations (relative risk, 4.6) and, within the femur, was more than threefold higher in the proximal femur than in the distal femur (relative risk, 3.4). None of the other primary tumor or patient characteristics studied yielded independent predictive significance for survival. The rate of failure was almost fivefold as high in those with an incomplete response to chemotherapy compared with those with a complete response to chemotherapy (relative risk, 4.9; 95% confidence interval, 2.2 to 11). Even in those patients with minimal or no necrosis in the primary tumor, ultimately 62% and 54% were disease‐free at 5 and 10 years, respectively.

Cryosurgery combined with routine "second look" biopsy has been previously reported in our initial series of 25 cases and has been demonstrated to be a promising modality in the treatment of giant cell tumors of bone. Further refinement of this surgical technique by more careful preliminary curettage has now significantly improved the rate of local tumor control and has markedly reduced the incidence of associated complications. While the problems of infection, fracture, delayed bone healing and local tumor recurrence have not been completely eliminated, our experience with 27 additional cases shows that it has been possible to develop a highly reliable procedure for the eradication of tumor while usually preserving joint motion and avoiding arthrodesis or amputation. The 1.9% malignancy rate is much lower than the previously reported papers by Hutter and Jaffe.