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BACKGROUND The treatment of Ewing's sarcoma consists of chemotherapy for systemic and local disease. However, the role of radiation therapy, and/or surgical resection for definitive local treatment has yet to be determined. METHODS A retrospective review of 32 patients (24 males and 8 females) treated for femoral Ewing's sarcoma between 1970 and 1985 was performed. Patients were divided into 3 treatment groups: chemotherapy and radiotherapy (CR) (10); chemotherapy and surgery (CS) (9); and chemotherapy, surgery, and radiotherapy (CSR) (13). Patients in the CR group received a mean of 5320 centigray (cGy) of radiation and patients in the CSR group received a mean of 3590 cGy. Multiagent cyclophosphamide/doxorubicin based chemotherapy was used in all cases. Surgery consisted of wide resection or amputation. RESULTS Patients in the CR group had a higher risk of local recurrence than patients in the CS and CSR groups (P = 0.02, log rank). The combination of local recurrences and treatment complications necessitated surgery for 7 of 10 CR patients, whereas 1 of 9 and 4 of 13 in the CS and CSR groups required additional surgery. The median survival for the entire group was 39 months. Minimum follow-up for surviving patients was 45 months. Five-year survival consisted of 1 of 10 patients in the CR group, 2 of 9 in the CS group, and 7 of 13 in the CSR group. There were no statistically significant differences among the three survival curves. Tumor location within the femur was a significant prognostic variable. Distal femoral location had a survival advantage compared with proximal and mid-femur locations (P = 0.049, log rank). CONCLUSIONS Femoral Ewing's sarcoma remains a disease with a poor prognosis. Radiation alone for local treatment results in a high rate of local recurrence and complications. Our current local treatment strategy for femoral Ewing's sarcoma includes surgery in all and adjuvant radiotherapy in many of the patients. Cancer 1996;78:70-8.

We compared the outcome of patients with giant cell tumor of the distal radius treated by curettage/cryosurgery and en bloc resection, evaluating oncologic success, functional results, and complications. Thirty consecutive cases of giant cell tumor of the distal radius were treated at our institution between 1958 and 1988. Twenty-six patients were available for follow-up examination, with a minimum follow-up period of 3 years and median follow-up period of 9 years. Primary curettage/cryosurgery had a local recurrence in 3 of 12, and repeat curettage/cryosurgery achieved local control in in 16 of 18 primary and recurrent cases. The major complications in this group included skin necrosis, transient nerve palsies, and fragmentation with carpal collapse. An average of 60% of contralateral range of wrist motion was preserved. Ten patients underwent en bloc excision and arthrodesis for either primary or recurrent tumor; none developed local recurrence. The main complication in this group was failure of internal fixation and non-union at the graft-radius junction. Resultant strength and function were similar in both groups. Intralesional excision with adjunctive cryosurgery is an effective alternative to en bloc excision with the advantage of preserving the distal radius and wrist joint function, but with a notable complication rate. En bloc excision with arthrodesis is more suitable for extensive local disease with poor residual bone stock and as salvage for failed intralesional excision.

Background. Giant cell tumors (GCTs) of the sacrum are a difficult clinical problem. Wide excision (total sacrectomy) is associated with high morbidity and pelvic/spinal instability. Curettage with or without supplemental radiotherapy is associated with a high recurrence rate. In view of the proven effectiveness of cryosurgery as an adjunct to curettage for extremity GCT, cryosurgery was used for treatment of GCTs of the sacrum. Methods. Seven patients with GCTs of the sacrum were treated at our institution by conservative surgery from 1973 to 1992. Four patients presented with recurrent tumors after failing previous radiation treatment (dose, 5040 cGy). Four patients were treated with curettage with cryosurgery and three with limited excision with cryosurgery. In the latter procedure after limited excision of the caudal (below S2) part of the tumor, the upper sacral segments were treated with curettage and cryosurgery. This spared the important upper sacral roots and maintained the skeletal integrity. Results. At a median follow-up of 12.25 years (range, 2-14.2 years), all patients were disease free. Local recurrence developed in two patients. Both of these underwent repeat curettage and cryosurgery and have since remained disease free. Two patients had positive second look biopsy with microscopic tumor. Both of these were treated with repeat cryosurgery and have remained disease free. Two patient who developed solitary pulmonary metastases, underwent wedge resection and are alive without disease. No patient suffered neurologic deterioration. Conclusion. Conservative surgery (curettage or partial excision) with adjunct of cryosurgery is our preferred technique for the treatment of GCT of the sacrum. Satisfactory local control could be obtained by close observation, second look biopsy and repeat cryosurgery. The chief advantages of this method include preservation of pelvic and spinal continuity, speed and ease of surgical procedure and less potential blood loss. We recommend it over more radical sacrectomy due to low morbidity and less resultant neurologic deficits.

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.

We report 3 patients with a second bone involved with osteosarcoma. They were found among approximately 200 cases of limb-sparing surgery with chemotherapy. 1 patient had the unusual finding of a positive MRI scan with all other routine tests negative. The first and then the second bone tumor were successfully removed with limb-sparing surgery. All 3 patients are doing well, with no evidence of disease.

(1994). Limb-Sparing Surgery for Extremity Sarcoma. Cancer Investigation: Vol. 12, No. 5, pp. 497-504.

The parosteal lipoma is a rare but recognizable lesion. The combination of (a) a well-defined, radiolucent, soft-tissue mass that on CT is confirmed to be entirely composed of homogenous mature adipose tissue and (b) an osseous excresence and/or saucerization at the attachment of the soft-tissue mass to the subjacent cortex should be diagnostic. We were unable to find any other case report of a parosteal lipoma coexisting with another lipoma in the same individual.

The proper management of soft tissue sarcomas, that offering the highest cure rate while attempting limb sparing should the extremities be involved, requires a standard approach best achieved with the TNM classification. Such staging of the sarcomatous lesion is based primarily on the histologic grade, followed by size and finally histologic classification. The definitive approach is surgical, with muscle group dissection employed at all sites, including the extremities, trunk, and head and neck region. Radiation therapy alone or in combination with chemotherapy improves survival in all high-grade lesions at risk for recurrence. Evaluation of the primary and recurrent lesion by computed tomography, magnetic resonance when necessary, and angiography offers the best approach for evaluation of the lesion in treatment planning. © 1992 Wiley-Liss, Inc.

PURPOSE Adjuvant chemotherapy improves disease-free survival (DFS) for patients with osteogenic sarcoma (OS). We reviewed our experience with OS to determine prognostic factors, the role of preoperative chemotherapy and subsequent histologic response, and the role of salvage chemotherapy after poor initial response. METHODS From 1975 to 1984, we saw 279 patients with previously untreated OS without metastasis. All patients received intensive chemotherapy and underwent surgical resection of primary tumor. Chemotherapy included high-dose methotrexate; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH); and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. RESULTS DFS was not affected by use of preoperative chemotherapy versus immediate surgery, by use of limb-sparing surgery versus amputation, age, sex, or dose intensity of chemotherapy. DFS did correlate with serum lactate dehydrogenase (LDH), alkaline phosphatase, primary tumor site, race, and histologic response to preoperative chemotherapy. There was no difference in DFS for patients with a poor histologic response who did or did not receive cisplatin, although patients who did receive cisplatin had a longer time to relapse. The 5-year DFS was 76% for patients aged less than or equal to 21 years who had extremity primary tumor and were treated with the T10 protocol. CONCLUSIONS 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.

The authors discuss rare primary skeletal non-Hodgkin's lymphoma in 16 patients treated from 1973 to 1989. The symptoms of these patients related to bone lesions in 95% of the cases. These bone lesions were monostotic or polyostotic, with or without regional and distant metastases. The locations of these lesions were long bones in 13 patients, pelvic bones in seven patients, and skull and vertebral bodies in two patients. The anatomical locations of these lesions in the bones were diaphysis alone in one patient, epiphysis in two patients, metaphysis in three patients, and a combination of diaphyseal, epiphyseal, and metaphyseal lesions in seven patients. Extraskeletal involvement was present in nine patients; extraskeletal sites included regional or distant lymph node involvement in seven cases, the mediastinum in two, lung nodules in two patients, the skin and subcutaneous regions in four patients; bone marrow in three patients, and peripheral nervous system (PNS) in one patient. Two patients had stage I disease, three had stage II disease, eight had stage III disease, and three had stage IV disease. The majority of patients had large noncleaved cell diffuse lymphomas or DHL by Rappaport classification. All patients were treated with the LSA2-L2 protocol; six patients received radiation therapy to the affected bone, and ten patients received no radiation therapy. Three patients failed on treatment within the first 4 months of therapy. Two patients developed a second tumor, one in the radiation therapy field and the other in a patient who received no radiation therapy. Eleven patients are alive without evidence of disease, with a median observation time of 6.5 years. The event-free survival for the 16 patients receiving LSA2-L2 was 73%, and the lymphoma-free survival was 81%. Extension of disease to multiple sites or location of the primary site was not of prognostic significance, but the finding of central nervous system (CNS), PNS, or bone marrow disease at diagnosis was. Whether the skeletal lesions were uni- or multifocal, with regional or distant metastases, the prognosis for lymphoma-free survival was good. The role of radiation therapy for all patients and intensive treatment for earlystage disease is discussed. The authors conclude that chemotherapy is the most important modality of treatment for any stage, histology, or location of the tumor. This chemotherapy shou ld include drugs that have been shown to be effective in the treatment of pediatric lymphoma, such as cyclophosphamide, cytosine arabinoside, vincristine, methotrexate, and daunomycin, in dosages sufficient to produce marrow suppression and early recovery, allowing for continuous or intermittent therapy. Radiation therapy should be used if there is no response or progression of disease (demonstrated either clinically or by scans, confirmed by a biopsy) within the first few months of treatment. © 1992 Wiley-Liss, Inc.

A recurrent lumbo-sacral chordoma with high-grade cartilaginous and spindle cell components is described. The tumor was excised from a 71-year-old man who previously had a conventional chordoma resected from his sacrum 26 years earlier. The original conventional chordoma was treated postoperatively with external beam radiation therapy, and the patient was free of disease until he presented at the age of 71 with leg weakness. Computerized tomography revealed a lumbo-sacral soft tissue mass. This was excised and found to have three distinct histologic aspects. The largest component was that of a conventional chordoma. The second component consisted of islands of malignant cartilage intimately admixed with the cells of the conventional chordoma. The third component consisted of high-grade malignant, poorly differentiated spindle cells. This case suggests that chondroid chordomas do exist and that they may also occur outside of the spheno-occipital region.

A 20-year follow-up of children who had complete resection of pulmonary metastases from osteogenic sarcoma of the extremities was undertaken. Four of six 10-year survivors survived more than 19 years even with multiple metastases and as many as nine thoracotomies. Fifty percent of the 10-year survivors developed second primary cancers during the second decade of follow-up.

The preoperative insertion of a needle under computed tomographic scan, performed under local anesthesia, is a convenient and important new way to localize the nidus in osteoid osteoma. It necessitates less bone removal, which should reduce the postoperative fracture rate. It should also help to locate the lesion during surgery. Some clinical points and previously unstressed pathologic findings are also discussed.

Local recurrence of rectal cancer develops in the posterior bony pelvis as an isolated event in about half of the patients with recurrence. Although radiation can palliate sacral root pain, the disease is usually progressive and is rarely amenable to conventional resection. We have adapted a surgical technique usually used for primary sacral tumors, which permits a complete en bloc excision of recurrent rectal cancer in most instances. This approach consists of a laparotomy with pelvic dissection and mobilization of structures to be resected. The patient is repositioned prone and the posterior pelvis (sacrum and side walls) is then resected with preservation of appropriate nerve roots of the posterior pelvis and the sciatic nerve. Reconstruction is done with muscle and skin flaps. We have done 21 such procedures, of which, 11 were for pelvic recurrence of rectal adenocarcinoma. Seven patients had resections for cure and four had palliative resections of fungating or infected tumors. All but one patient was postabdominal perineal resection and nine patients had been irradiated (3000-9000 rads). Two patients had received up to 9000 rads in separate courses (external beam in one and interstitial radiation in the other). The posterior extent of resection was S1-2 to 5 in six patients; S3 to 5 in three patients, and S4-5 in two patients. Anterior exenteration was performed in three patients and three patients had additional resection of other organs. In the curative resection group, three patients are living free of disease at six, ten, and 52 months, and one patient was NED at 60 months, but has again had tumor recurrance and is living with disease at 65 months. One patient died of disease at 13 months and one patient died of a pulmonary embolus following resection for ureteral obstruction at five months. One postoperative death occurred from a cerebrovascular accident at 52 days. In the palliative resection group, three patients survived with relief of local tumor symptoms four, eight, and 12 months. One patient who had received a total of 9000 rads developed flap necrosis, small bowel fistula and died 60 days after resection. Although this is a small series, it suggests that abdominal sacral resection of locally advanced pelvic cancer is feasible and may provide good palliation in most and possible cure in some patients who develop recurrence after primary resection of adenocarcinoma of the rectum.

Twenty previously untreated children with primary Ewing's sarcoma and 8 children with primary tumor and metastatic disease were treated with surgery or radiation therapy (6,000-7,000 rads) for their primary tumor and T-2 chemotherapy. Of the 20 children with primary Ewing's sarcoma treated with T-2 "adjuvant" chemotherapy, 15 had no evidence of recurrent disease for from 31+-82+ months (median 46+ months) from the start of treatment. The actuarial 5-year disease-free survival rate for this group of patients was 75%. Eight patients presenting with metastatic disease had complete responses to T-2 chemotherapy, but 7/8 with metastatic disease eventually had tumor recurrence. Examination of the treatment failures, both those patients relapsing after adjuvant chemotherapy for primary Ewing's sarcoma (5), and those relapsing after having a complete response of metastatic disease (7) to T-2 chemotherapy, revealed that all relapses occurred at the end of the second year of T-2 chemotherapy or after chemotherapy was stopped. In addition, of 23 patients receiving "curative" radiation therapy to their primary tumor, 5 had local recurrence (22%) and 6 (26%) had severe functional debility secondary to combined radiation therapy and T-2 chemotherapy. The conclusions drawn from this experience have led us to consider a new approach to the treatment of Ewing's sarcoma, namely: 1) more aggressive initial or "induction" chemotherapy with subsequent T-2 "maintenance" chemotherapy to eradicate more completely all metastatic microfoci of disease presumed to be present in patients with primary tumor at the time of diagnosis, and ostensively present in patients with metastatic disease; 2) the use of surgery alone or in combination with moderate doses of radiation therapy in those patients in whom we can predict a high frequency of local recurrence (pelvic lesions) or a high percentage of "functional failures" (young children with lower extremity lesions). Preliminary results with this latter approach are encouraging with 11/13 patients with primary Ewing's sarcoma free of disease at 12+-26+ months. A longer follow-up of this more aggressive treatment is needed to determine the superiority of this approach for both increased survival and improved late physical rehabilitation.

The value of adjuvant chemotherapy in primary osteogenic sarcoma (OSA) is still considered controversial by some. One reason may be that various reported series include patients with widely varying prognostic variables. To address this, the effect of chemotherapy on the continuous disease-free (CNED) survival was analyzed in 100 patients aged 21 yr or less with OSA of the femur. This classically poor prognostic group of patients represented 51% of all primary OSA seen at the Memorial Sloan-Kettering Cancer Center during the study interval. This study includes all patients aged 21 yr or less with fully malignant (Grade III-IV/IV) OSA of the femur and no metastases treated from November 1973 through November 1981. The first (T-4) protocol (31 patients) consisted of high dose methotrexate (HDMTX) with leucovorin rescue, cyclophosphamide (Cyc), and adriamycin. In the second (T-7) protocol (23 patients) the dose of HDMTX was increased to 12 g/m2 for prepubescent patients, and bleomycin, Cyc, and dactinomycin replaced Cyc. The current (T-10) protocol (46 patients) uses the same CT as T-7, but patients not having a complete response of the primary tumor to preoperative CT receive additional cisplatinum (120 mg/m2) with adriamycin (30 mg/m2/day for two consecutive days). In 31 patients treated with T-4 the CNED survival was 32% with a minimum follow up of over 7 yr. On T-7, 15/23 patients with femur primaries had a CNED survival of 65% with all of the surviving patients followed for more than 5 yr. The addition of cisplatinum in T-10 has resulted in CNED survival rate of 77% in 34/44 patients (excluding two patients that died CNED during and after treatment); the median follow-up patients who are alive CNED is 33 months, with a minimum of 2 yr follow up on the last patient entered.

Five of twenty-seven chondrosarcomas seen at the Hospital for Special Surgery from 1952 to 1972 showed fibrosarcomatous dedifferentiation. One was primary and four were secondary, three in patients with enchondromas and one in a patient with Ollier's disease. The development of purely fibrosarcomatous metastases in less than one year in four of the five patients emphasizes the malignant nature of this change.

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. All 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, HDMTX 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 in 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 in responding patients and in 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 rate reported to date for osteogenic sarcoma.

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.

Chondrosarcoma of the foot is a very unusual entity. A case arising from a solitary osteocartilagenous exostosis is presented and the literature is reviewed and discussed.

A prospective comparison of the accuracy of MR and CT in determining the anatomic extent of disease was carried out in 40 patients who had histologically proved soft-tissue sarcomas of the extremities. Tumor resection, performed by using either en bloc excision or amputation in all patients, allowed detailed pathologic verification of imaging findings. Image analysis included measurement of maximum tumor dimensions, notation of tumor position in relation to deep fascia, recording of anatomic compartment and individual muscle involvement, and documentation of the spatial relationships between tumor, neurovascular structures, underlying bones, and joints. MR and CT were equally accurate in measurement of maximal tumor diameter, detection of tumor depth, and delineation of tumor, neurovascular, osseous, and articular relationships. Evaluation of anatomic compartment and individual muscle involvement was more accurately accomplished with MR imaging; nine (23%) of 40 MR studies showed tumor involvement of one or more individual muscles that appeared normal in CT scans. These results suggest that MR imaging may be the staging procedure of choice in patients with soft-tissue sarcomas of the extremities.

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.

Twenty-three patients with rhabdomyosarcoma and 15 patients with Ewing's sarcoma, treated with radiation therapy to the local site and systemic multiagent chemotherapy are described. Acute reactions from combination chemotherapy and radiation therapy were noted in both groups of patients. These reactions often appeared after low doses of irradiation, required unplanned interruptions of treatments, and in some patients, led to discontinuation of radiation therapy. The chronic effects on normal tissues in both groups of patients have been severe in several cases.

The survival times in a control series of 145 cases of osteogenic sarcoma without pulmonary resections including records of pulmonary nodules and surgical wedge excisions, suggest that pulmonary resection is a noteworthy adjunct treatment. The 5-year survival of patients subjected to repeated pulmonary surgery is known for 22 patients who were under the age of 21. Where aggressive pulmonary resections were performed, i.e., repeated thoracotomies, and multiple wedge resections of nodules, a 5-year survival rate of 31 per cent (after date of primary amputation) is noted and compared to a previous study of 145 cases, 121 of which had untreated pulmonary metastases, and at 5 years, only 2 per cent of these patients with metastases were still alive. Lung wedge resection survivals are highly significant statistically although survival with residual disease must be considered in part at least, due to aggressive chemotherapy (i.e., high dose methotrexate with citrovorum rescue in combination with other drugs).

Forty-five children with osteogenic sarcoma metastatic to the lung were treated with sequential chemotherapy, consisting of high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), adriamycin, and cyclophosphamide, and the surgical removal of all pulmonary metastases when possible. Fourteen of the 45 patients had complete removal of all metastases at initial thoracotomy, followed by adjuvant chemotherapy. Ten of these 14 patients are surviving (all with no evidence of disease) for from 24–56 months (median 33+months) from the start of treatment. Thirty-one of the 45 patients had diffuse pulmonary metastases and were treated with chemotherapy followed by multiple thoracotomies and further chemotherapy. Twelve of these 31 patients have no evidence of disease for from 6–41+ months (median 19+ months). The correlation of clinical response, with the surgical and histologic findings at the time of thoracotomy, following chemotherapy in this latter group of patients, has helped us to define the proper dose and scheduling of chemotherapy when used in an adjuvant situation. It also has provided a model for the efficacy of adjuvant chemotherapy in osteogenic sarcoma. In addition, this experience has led us to propose the following guidelines for the management of osteogenic sarcoma patients with pulmonary metastases: 1) pulmonary metastases large enough to be seen on roentgenogram should eventually be removed if possible, 2) patients with late occurring solitary pulmonary metastases should undergo initial surgical removal of pulmonary metastases, followed by “adjuvant” chemotherapy, and 3) patients with rapidly occurring or apparent multiple pulmonary metastases should undergo chemotherapy initially; if pulmonary metastases shrink in size or do not change in size over a period of 2–6 months of chemotherapy, an attempt should be made surgically to excise all “residual” disease prior to the continuation of chemotherapy. This approach to the treatment of osteogenic sarcoma in patients with pulmonary metastases has yielded an unexpectedly high disease-free and prolonged survival rate, and demonstrates the value of aggressive treatment in this group of patients who classically had an extremely poor prognosis.

From 1949 to 1977, 39 patients with localized malignant retrorectal tumors were treated at Memorial Sloan-Kettering Cancer Center. Chordomas were the most frequent histologic type (38 per cent of patients) followed by neurogenic tumors (15 per cent) chondrosarcomas, hemangiopericytomas, and embryonal adenocarcinomas (8 per cent each). Treatment consisted of surgical excision in 28 patients (18 of whom received adjuvant radiotherapy and/or chemotherapy). Ten patients were treated nonsurgically, receiving radiation and/or chemotherapy alone. Large tumors were most successfully managed by a combined surgical approach consisting of exploratory celiotomy, rectal mobilization, and bilateral hypogastric artery (with middle sacral artery and vein) ligation, followed by transsacral tumor excision with incontinuity sacrectomy. For all treated patients, survival at 5, 10, 15 and 20 years was 69 per cent, 50 per cent, 37 per cent and 20 per cent, respectively. Long-term disease-free survival (17 to 25 years post treatment) was noted in six patients. [Key words: Tumor(s), retrorectal, malignant; Tumor(s), treatment].

This paper presents a preliminary report of 66 patients who underwent en bloc resection for osteogenic sarcoma of the femur (34 patients), tibia (12 patients), shoulder girdle (19 patients), and fibula (1 patient). Presentation of a limb, without sacrificing the principles of cancer surgery, is a desirable goal in people with osteogenic sarcoma. Up to the present time, amputation has been regarded by most authorities as the only well-established typical curative treatment for this malignancy. Usually when a tumor is close to a joint, amputation includes excision of a part of the adjacent joint as well as a wide removal of the involved bone to encompass both area of potential capsular-joint local skip and possible intraosseous skip areas of tumor. The former has been observed more than the latter. In an effort to improve survival rates, the distal femur lesion (having the lowest extremity cure rate in our opinion) requires removal of the whole bone. The following study was undertaken to determine whether en bloc resection in association with intensive chemotherapy is a realistic alternative to radical amputation and chemotherapy. We believe our definition of osteogenic sarcoma, unlike some, excludes the good prognostic medullary invading juxtacortical osteogenics, chondrosarcomas (making bone), and includes telangiectatic osteogenic sarcomas. Therefore, our cure rate, with amputation under the age of 21 was 17% with no evidence of disease. Any paper not analyzing the age of the patient (under 21 years old) cannot in itself be comparable. Cure rates of older patients can be as high as 35% according to Dr. Andrew Huvos at our hospital.

Sixty patients with sacrococcygeal chordoma, who were seen at this center between 1946 and 1985, were studied with particular attention to the radiographic findings. This study was undertaken because of the large number of these cases and comparison was made between the plain films available in 39 patients and the computed tomography CT studies in 22. Bone destruction was found in 78% on plain films but in 90% on CT. A soft tissue mass was identified in plain films in 60% but in 90% on CT. Calcific debris was found in plain films in 44% but in 87% on CT. Mostly the debris consisted of coarse irregular fragments and probably represented sequestrated necrotic bone. Myelography was performed in only 15 patients. Angiography was studied in 10 cases. Of the 60 patients 88% underwent surgical resection. The tumor recurred in 80% and in only 20% was there no evidence of recurrence. Distant metastases occurred in 24% of patients. Fifty percent survived 5 years; 28% survived 10 years; mean survival 7.5 years.

Twenty-two cases of epithelioid sarcoma seen and/or treated at Memorial Hospital are presented. With the exception of one tumor which occurred in the neck, all the sarcomas arose in the upper (15 cases) or lower extremities (6 cases). Ten originated in the hand. At the time of initial treatment, 14/22 patients were between 20 and 40 years of age. The tumor most commonly presented as a nodular lesion and involved dermis, subcutaneous tissue, fascia and tendons, and when it recurred (13 cases) it tended to grow proximally along tendons and fascial planes. Of special interest was the finding of vascular invasion in surgical specimens removed from 5 patients. Four of these represented recurrent tumor, and in two cases the vascular invasion was massive. Two of these patients also demonstrated tumor emboli in pulmonary vessels and cardiac involvement at autopsy. Metastasis to regional lymph nodes occurred in eight cases (42%). Follow-up ranging from 2 to 34 years (average of 8 years) was obtained for 19 cases (86%). Eleven patients are alive with disease or died as a result of their sarcoma (58% of the follow-up group). Adverse prognostic factors included recurrence after initial local excision, vascular invasion and lymph node metastasis. All of the patients with intravenous extension of tumor and 6 of 8 patients with lymph node involvement died with pulmonary metastases. Our data suggest that cure may best be achieved by amputation or by an exceptionally wide en bloc excision as early as possible, depending upon the location and extent of the original tumor.

Cryosurgery combined with a routine "second look" biopsy is a promising modality of treating giant-cell tumors of bone. Clearly malignant tumors are not considered suitable for this treatment. While complications such as infection, fracture, and delayed union occurred, it was possible to eradicate tumors while preserving joint motion and avoiding amputations in a far greater percentage of cases than has been possible with former methods.

In a study of eighteen patients with pelvic Ewing's sarcoma who were treated with a multidisciplinary approach, chemotherapy was effective in controlling systemic spread of the tumor. Surgery coupled with improved methods of chemotherapy provided results that were statistically superior to those obtained with radiation and chemotherapy alone in control of the local pelvic lesion. A twofold increase in the survival rate was seen at a median follow-up of thirty-six months in the patients who had the resection. Our results suggest that pelvic Ewing's sarcoma is best treated by initial chemotherapy, followed by local wide marginal resection of the pelvic lesion coupled with perimeter radiation therapy and concluded with additional chemotherapy. Survival rates of patients with pelvic Ewing's sarcoma may then approach the excellent survival rates of patients with lesions in more favorable anatomical locations.

Four patients, two of them former caisson workers, had malignant tumors of bone associated with bone infarcts in the femur. One of the tumors was osteogenic sarcoma and the other three were malignant fibrous histiocytomas. Despite amputation and other treatment, only one patient survived.

This is a review of the experience at Memorial Hospital using chemotherapy combined with surgical excision for control of pulmonary metastases in osteogenic sarcoma. Effective multiple drug chemotherapy was able to control small deposits of osteogenic sarcoma in the lung, making surgical resection of residual visible nodules worthwhile. Surgical resection was most successful for solitary nodules or where multiple nodules were shrunk or at least prevented from growing by chemotherapy. Eight percent of these patients with pulmonary metastases initially or subsequently showed bilateral lung disease. When two or more nodules were found at th oracotomy, they were never confined to one lobe. For these reasons, wedge resections or segmental resections were the most commonly indicated procedures. Results justify an aggressive surgical approach to these lesions including multiple wedge resections of all lesions found at thoracotomy, chest wall resection and multiple bilateral thoracotomies. Chemotherapy alone cannot be expected to cure metastatic osteogenic sarcoma of the lung, but combined with surgical resection of residual disease the results are encouraging.

Eight cases of primary malignant giant cell tumor of bone were reviewed. There was a wide range in age from 17 to 76 years, with the sixth decade of life being the most common. The tumor was more frequent among females (male to female ratio--3:5). The most common sites of occurrence were in the region of the knee, with the distal end of femur and the proximal end of tibia affected in three and two cases, respectively. Pain and swelling of the involved regions were the most common complaints. The roentgenographic and pathologic features and the treatment were analyzed in detail. Although these cases were considered malignant, the follow-up periods varying from 4 to 15 years were available in six of the eight cases; only one patient died of tumor, 8 months after the surgical procedure. One patient died of unrelated cause, but the others were all alive with no evidence of disease. The pertinent literature was analyzed and examples of secondary malignant giant cell tumors of bone were compared to those of this present series to delineate differences in natural history and clinicopathologic features. It was clearly established that primary malignant giant cell tumor of bone is a separate entity with a more favorable clinical behavior, particularly if the disease process is eradicated early on either by cryosurgery, en bloc radical resection, or amputation.

From 1973--1975, 31 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 21 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 1/2 months prior to definitive surgery (resection or amputation). Doses of HDMTX were escalated where necessary and good clinical responses were obtained in 19 of 20 patients. In the majority of patients, no evidence of viable tumor was found on histologic examination of the surgically removed primary tumor. All 20 patients are surviving free of active disease at this brief follow-up period of 4--20 months.

A previously identified tumor-associated antigen of human sarcomas, S1, has been studied to characterize further its association with neoplasia. We used an immunofluorescence test on 166 serum specimens from normal persons and 295 from patients with neoplasia to determine the distribution of S1 antibody. The prevalence of antibody to S1 in the normal population varies considerably with age. Thirty-nine (91 per cent) of 43 persons between five and 20 years of age had serum antiS1 activity, whereas of 39 above the age of 41 only 13 (33 per cent) were similarly reactive. Neoplasia may induce the reappearance of S1 antibody. Significant antibody levels were found in more than 80 per cent of patients with carcinoma of the breast, lung and melanoma 41 years of age or older. An inverse relation of antibody prevalence to extent of disease was noted in persons with Hodgkin's disease. Available data suggest that S1 is a "heterophil" type of antigen. Although not tumor-specific, S1 may prove useful both for...

In twenty-four cases of juxtacortical osteogenic sarcoma, three histological grades of malignancy were identified and correlated with the prognosis. The eighteen patients with Grade-I or II tumors had a significantly better prognosis than the six with Grade-III lesions. The three grades could not be distinguished roentgenographically. Grade I and II tumors, which showed a high cure rate after amputation, may be amenable to en block resection, provided the entire tumor can be removed with a good margin of uninvolved soft tissue and underlying bone. Grade-III tumors, on the other hand, had a poor prognosis despite early radical surgery.

Since May 1970, 67 consecutive patients with primary (nonmetastatic) Ewing's sarcoma were treated with adjuvant chemotherapy (CT) in addition to radiation therapy (RT) or surgery for the primary tumor. The first 19 patients were treated with four-drug sequential CT (T-2). The second protocol was a seven-drug induction combination CT (T-6) followed by T-2 maintenance CT; in both protocols CT was continued for 18 months. The current protocol (T-9) consists of combination CT given continuously for a period of 9 months. Of the entire group of 67 patients, 47 (70%) had axial and proximal lesions (pelvis, spine, rib, humerus, and femur) and 20 (30%) had distal lesions (forearm, leg, and foot); 53/67 (79%) are surviving free of disease 12--118 months (median 41 months) from the start of treatment. Fifteen of 23 (65%) patients with axial lesions, 19/24 (79%) patients with proximal lesions, and 19/20 (95%) patients with distal lesions are free of disease. Disease-free survivors include 28/39 (72%) male patients and 25/28 (89%) female patients. Thirty-four patients had RT, and 33 had surgery or surgery and RT, in addition to chemotherapy, for local treatment. The disease-free survival rate was 76% in the RT group and 82% in the surgery group; failure in the RT group was attributable to local recurrence in 7/34 (21%) patients. Recent experience with T-9 CT has demonstrated that CT given prior to RT or surgery can cause a great reduction in the size of the primary tumor while allowing the pathologically-eroded bone to heal prior to the initiation of RT; this also allows the high-risk patient with an axial primary (pelvis or spine) to tolerate the aggressive CT needed to prevent distant metastases. In addition to dramatically increasing survival in patients with Ewing's sarcoma, combination CT has helped achieve permanent local control. The superior survival rates for all sites of primary tumor are attributable to the early use of aggressive combination CT.

Since October 1973, 185 patients 21 years of age or younger with primary osteogenic sarcoma of an extremity were treated with adjuvant chemotherapy. Twenty-five of the first fifty-two patients (48%) have remained free of disease for a median of 7 years. In the next chemotherapy protocol most patients had chemotherapy prior to amputation or resection, during which time the dose of high-dose methotrexate was escalated in many patients to that needed to shrink the primary tumor. For a median of 4 years 43 of 54 patients (80%) have remained free of disease. In the current protocol, the response of the primary tumor to chemotherapy with high-dose methotrexate was used to select postoperative adjuvant chemotherapy for the patient. With the latter approach 73 of 79 patients (92%) have remained continuously free of disease for a median of 2 years. This experience demonstrates the value of chemotherapy in increasing the cure rate in osteogenic sarcoma and that the response to preoperative chemotherapy can help select postoperative chemotherapy to produce an even higher potential cure rate for osteogenic sarcoma.

Based on our prior experience in treating children with metastatic osteogenic sarcoma, a multidrug regimen was developed. Nine children with evaluable osteogenic sarcoma were treated with vincristine 1.5 mg/m2 on day 1, highdose methotrexate 200-300 mg/kg i.v. on day 2, with p.o. citrovorum factor "rescue" 9 mg every 6 hours x 12, followed in 2 weeks by cyclophosphamide 40 mg/kg i.v., then 2 weeks later Adriamycin 1.5 mg/kg/day x 2; in 2 weeks cyclophosphamide was repeated. After a 2-week rest, the 56-day cycle was repeated for a total period of 1 year. Oropharyngeal mucositis was the most frequent severe manifestation of gastrointestinal toxicity. Hematologic depression was mild to severe. Nine patients with clinically evaluable osteogenic sarcoma and no previous chemotherapeutic treatment were treated with this regimen. One patient had only a transient shrinkage in tumor mass, and one patient had no progression of multiple pulmonary and bone metastases for 16 months while on therapy. Of the remaining seven patients, all had clinically significant responses with tumor regression demonstrated for from 5 to 20+ months. Four of these patients (three presenting with primary tumor and pulmonary metastases) demonstrated regression of their primary tumor. In an attempt to increase the cure rate in osteogenic sarcoma, chemotherapy that has proven to be effective against metastatic osteogenic sarcoma should now be employed as prophylactic therapy, after amputation, at cancer treatment centers where it can be safely and effectively administered.

In an attempt to shrink primary osteogenic sarcoma and allow complete surgical removal of the primary tumor, without amputating the involved limb, intensive preoperative chemotherapy with high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (ADR) was initiated in 20 patients with biopsy-proven primary osteogenic sarcoma of the distal femur (15 patients) and proximal tibia (five patients). Following intensive chemotherapy, en bloc resection of the primary tumor with prosthetic replacement of the involved bone was planned. After surgery, adjuvant chemotherapy, consisting of HDMTX with CFR, ADR, and high dose cyclophosphamide was given sequentially for 1 year. Of 20 patients with primary osteogenic sarcoma (two with evidence of pulmonary metastases), 18 had primary tumors that could be clinically measured. Of these 18, 17 demonstrated a decrease in the size of primary tumor prior to surgery, while on chemotherapy. To date, 12 of these patients with osteogenic sarcoma of the distal femur have had total femur and knee joint replacement, and three patients with osteogenic sarcoma of the proximal tibia have had total knee replacement. In all 15 patients, surgical margins were grossly and microscopically free of tumor. There has been no evidence of soft tissue recurrence in any of the 15 patients who have undergone surgery for from 2 to 15 months postoperatively. These preliminary results indicate that with the use of aggressive chemotherapy, it is possible to demonstrate objective tumor regression in primary osteogenic sarcoma, allowing the surgeon to perform en bloc resection of tumor and prosthetic replacement of the involved bone. Although the limb is preserved, it is important to stress that extensive surgery yielding tumor-free margins is performed. The ultimate evaluation of this approach to the treatment of primary osteogenic sarcoma awaits longer observation, to determine limb function and the continued disease-free status, once adjuvant chemotherapy is discontinued.

In June 1963, a lyophilized homogenous vaccine prepared from the primary tumor tissue was given to a child with osteogenic sarcoma and pulmonary metastasis. During the 15-day course of injections the child gained 7 pounds; following treatment the disease progressed and the patient died. However, the temporary improvement suggested that immunotherapy may have inhibited tumor growth. A more formal controlled trial of immunotherapy in less advanced disease, designed by the author, was begun in April 1966. At first, the vaccine was prepared in the laboratory of Dr. C. Sourham and later by the immunological team of Dr. R. A. Good, L. Old, H. Oettgen and Y. Hirsut. Patients under the age of 25 with osteogenic sarcoma of the long bones but no evidence of spread beyond the primary site and who had been treated by amputation were included in the study. The autogenous vaccine was given in the postoperative period following amputation. If multiple metastasis (usually pulmonary) appeared, the vaccine was judged a failure. If there was subsequent pulmonary resection for multiple metastases, any observed beneficial effect was credited to this surgical treatment [1]. A preliminary report is presented on the patients who received vaccine treatment through April 1973 (Fig. 1).

The author has briefly discussed radiation therapy, immunotherapy, and chemotherapy in the treatment of some of the more commonly encountered disease entities affecting the shoulder girdle. Specific operations and their indications are discussed. However, utilizing physical and x-ray examination, arteriography, lymphangiography, and bone scan information, the surgeon may decide that the routine operation is not indicated for a particular tumor problem. He should be able to be flexible and to modify the operation according to the specific presenting problem and not be bound by routine fixed rules. In this way the patient can be assured of the very best treatment.

An elevation of the eosinophils in the differential count of the bone marrow was found in the two patients presented in this paper (and in the three others mentioned). This was in sharp contrast to the peripheral-blood studies which revealed no remarkable deviation from the normal counts expected. Bone-marrow findings as described in this paper may be helpful in leading one toward the diagnosis of eosinophilic granuloma. A new method of counting eosinophils in the bone marrow is described and can be used to check counts done by smear or clotted and fixed marrow sections.

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.