Jeffrey J. Eckardt

Limb salvage for skeletal and soft tissue sarcomas multidisciplinary preoperative therapy

One hundred eighty‐three patients with malignant skeletal (83) or soft tissue sarcoma (100) were entered into the multimodality preoperative limb salvage protocol. Local recurrences were observed in 5 of 183 (2.7%). Six patients required amputation because of complications, and 13 patients died within 1 year from metastatic disease. There was no statistical difference in survival rates between a series of patients who had amputation and adjuvant therapy and patients treated by limb salvage and adjuvant therapy. Overall survival rates for patients with soft tissue sarcoma were 76%. Although the exact reason for the improved local control is not known, it is our belief that it is the result of the multidisciplinary therapy that destroys microscopic disease at the periphery of the primary tumor.

Etiology and results of tumor endoprosthesis revision surgery in 64 patients.

From December 1980 to December 1995, 278 patients underwent primary custom endoprosthesis replacements for neoplastic disease at the University of California, Los Angeles and have been followed up for a minimum of 2 years or to death. The endoprosthesis reconstruction failed in 64 patients, including 10 additional patients referred for revision of their replacements. Failure was defined as the complete removal of a prosthesis for any reason. The cause of failure were aseptic loosening (44%), fatigue fracture (16%), local recurrence (14%), infection (13%), and failure of the expansion mechanism (6%). Forty-eight of 64 failed endoprostheses were managed by endoprosthesis reconstruction with most being revised using the same type of prosthesis. Nine of these patients with failed replacements experienced a second failure and four went on to require an amputation. Aseptic loosening and mechanical failure accounted for most of the failures and they were revised successfully. Sixty percent of the infected cases were salvaged satisfactorily by endoprosthetic revision, whereas, 89% of the local recurrences resulted in amputation. Based on endoprosthesis survival the 7-year failure rates were 31% and 34% for primary and revision reconstructions, respectively. The functional results for the patients with endoprosthesis revisions either were better, unchanged, or on average only slightly lower than results of patients with a surviving endoprosthesis.

Pulmonary metastases of stage IIB extremity osteosarcoma and subsequent pulmonary metastases.

PURPOSE This study investigated prognostic factors in nonmetastatic high-grade extremity osteosarcoma and the prognosis following resection of subsequent pulmonary metastases, with emphasis on the effect of chemotherapy-induced tumor necrosis. PATIENTS AND METHODS We reviewed 111 consecutive patients with high-grade nonmetastatic extremity osteosarcoma treated with preoperative chemotherapy and surgical resection, with additional review of 36 patients who had subsequent pulmonary metastases resected. RESULTS The overall 5-year survival rate was 53%. In resected primary tumors, tumor-free resection margin (P < .001) and increasing chemotherapy-induced tumor necrosis (> 90% threshold, P < .003) correlated with increased metastasis-free survival. Relative risk factors for metastases were as follows: tumor-containing resection margin (most likely to metastasize); poor response to preoperative chemotherapy and/or lack of postoperative chemotherapy (next worse prognosis); and excellent response to preoperative chemotherapy (> or = 90% necrosis) combined with postoperative chemotherapy (best prognosis). The 5-year survival rate following pulmonary metastasis resection was 23%, whereas a 0% 4-year survival rate followed development of bony metastases (P < .001). The extent of tumor necrosis in resected pulmonary metastases did not affect prognosis. Survival was best in patients with three or fewer pulmonary nodules (P < .048), four or fewer recurrent pulmonary nodules (P < .047), unilateral pulmonary metastases (P < .037), or longer intervals between primary tumor resection and metastases (P < .082). CONCLUSION Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after the Initial Cycle of Neoadjuvant Chemotherapy in High-Grade Soft-Tissue Sarcomas

Purpose: In patients with soft-tissue sarcoma (STS), the early assessment of treatment responses is important. Using positron emission tomography/computed tomography (PET/CT) with [18F]fluorodeoxyglucose (FDG), we determined whether changes in tumor FDG uptake predict histopathologic treatment responses in high-grade STS after the initial cycle of neoadjuvant chemotherapy. Experimental Design: From February 2006 to March 2008, 50 patients with resectable high-grade STS scheduled for neoadjuvant therapy and subsequent tumor resection were enrolled prospectively. FDG-PET/CT before (baseline), after the first cycle (early follow-up), and after completion of neoadjuvant therapy (late follow-up) was done. Tumor FDG uptake and changes were measured by standardized uptake values. Histopathologic examination of the resected specimen provided an assessment of treatment response. Patients with ≥95% pathologic necrosis were classified as treatment responders. FDG-PET/CT results were compared with histopathologic findings. Results: At early follow-up, FDG uptake decreased significantly more in 8 (16%) responders than in the 42 (84%) nonresponders (−55% versus −23%; P = 0.002). All responders and 14 of 42 nonresponders had a ≥35% reduction in standardized uptake value between baseline and early follow-up. Using a ≥35% reduction in FDG uptake as early metabolic response threshold resulted in a sensitivity and specificity of FDG-PET for histopathologic response of 100% and 67%, respectively. Applying a higher threshold at late follow-up improved specificity but not sensitivity. CT had no value at response prediction. Conclusion: A 35% reduction in tumor FDG uptake at early follow-up is a sensitive predictor of histopathologic tumor response. Early treatment decisions such as discontinuation of chemotherapy in nonresponding patients could be based on FDG-PET criteria.

THE ROLE OF ADJUVANT RADIOTHERAPY IN THE TREATMENT OF RESECTABLE DESMOID TUMORS

PURPOSE Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. METHODS AND MATERIALS A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. RESULTS Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p < or = 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p = 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (+/-12%) with surgery alone, and 78% (+/-14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p < or = 0.01). Patients with positive margins and primary disease had a trend towards improved local control with adjuvant radiotherapy, but this was not statistically significant. None of the patients treated with radiotherapy developed serious complications or a secondary malignancy. CONCLUSIONS Margin status is the most important predictor of local recurrence for patients with resectable, unifocal desmoid tumor. Adjuvant radiotherapy is indicated in the treatment of patients with positive margins following wide excision of recurrent disease. The role of adjuvant radiotherapy in patients with positive margins following resection of primary disease is controversial, and should be based on a balanced discussion of the potential morbidity from radiotherapy compared to the potential morbidity of another local recurrence. Adjuvant radiotherapy is less likely to benefit those with clear margins due to the excellent results for these patients treated with surgery alone. The local control of desmoid tumor in the adjuvant setting is excellent with total doses ranging from 50-60 Gy, with acceptable morbidity. Field sizes should be generous to prevent marginal recurrences, and large volume MRIs of patients with extremity lesions should be used to identify those patients with multifocal disease.

Giant cell tumor of bone.

Giant cell tumor GCT of bone remains a difficult and challenging management problem because there are no absolute clinical, radiographic, or histologic parameters that accurately predict the tendency of any single lesion to recur or metastasize. Ennekings and Campanaccis radiographic classifications and surgical staging are helpful in planning the initial surgical treatment, because they have observed that a number of the active (Stage 2) lesions and most of the aggressive (Stage 3) lesions have a higher incidence of local recurrence when treated by curettage alone. The bad reputation of curettage and bone grafting is undeserved and arose because of the indiscriminate application of this technique to lesions irrespective of their surgical stage. The ideal aim in the management of GCT is to eradicate the tumor and still save the joint. Curettage, possibly with adjuvant chemical or thermal cauterization, and with bone grafting or polymethyl methacrylate instillation, maintains the structural integrity of the bone and allows for early function. Good results with these techniques when applied to Stage 1 and many Stage 2 lesions may be expected in 70%--80% of the cases. Repetitive freezes with liquid nitrogen, though resulting in a lower recurrence rate, carry with them a not insignificant risk of local complications, require prolonged bracing, and incur the risk of late fracture. When GCTs occur in expendable bones, en bloc resection is the treatment of choice. En bloc resection of major joints requires a facility with reconstruction techniques including the use of allografts, large autogenous grafts and fusion, or custom arthroplasty. These are technically difficult procedures with many early and late complications. Patients have restricted function, and may require prolonged bracing even when uncomplicated. These techniques are therefore reserved for the Stage 3 and selected Stage 2 lesions. Hand lesions have been ineffectively treated by curettage and grafting, and are best treated by early en bloc or ray resection. Multicentric lesions should be handled as individual primary tumors would be in those locations. Radiation therapy has its major role in the treatment of giant cell tumors of the spine and sacrum that are not amenable to complete surgical resection, though long-term sarcomatous change must be looked for. Because of the complex management problem this rare tumor presents, it is recommended that management of giant cell tumor of bone, including the biopsy, the definitive surgery, and the follow-up examination, be carried out by individuals and institutions familiar with this entity.

Expandable endoprosthesis reconstruction in skeletally immature patients with tumors.

Between September 1984 and January 1996, 32 expandable endoprostheses were used for limb reconstruction after resection of malignant bone tumors in patients who were skeletally immature. The 20 boys and 12 girls ranged in age from 3 to 15 years (mean, 9.7 years). One patient had a Stage IIA tumor, 22 patients had Stage IIB tumors, and seven patients had Stage III tumors according to the classification of the Musculoskeletal Tumor Society. There also were two patients with parosteal osteosarcomas. The histologic diagnosis was osteosarcoma in 23 patients and Ewings sarcoma in nine. All patients except the patients with parosteal osteosarcoma received standard neoadjuvant therapy. Twenty-two Lewis Expandable Adjustable Prostheses, four modular Wright Medical prostheses, four modular Howmedica prostheses, and two Techmedica expandable prostheses were used. Thirteen patients died, two have no evidence of disease, and 17 are continuously disease free. Sixteen of 32 patients (50%) have not had an expansion procedure because of early death in 10 and early amputation in three. Three patients are waiting to undergo an expansion procedure. Sixteen of the 32 patients (50%) have undergone 32 expansion procedures, to a maximum of 9 cm, without any infection. To maintain range of motion before the expansion procedure, a complete resection of the pseudocapsule was done routinely. Fourteen of the 32 patients did not have complications. Eighteen of the 32 patients had 27 complications. All Lewis Expandable Adjustable Prosthesis endoprostheses and the two nonmodular Techmedica prostheses were associated with a large amount of titanium debris. The childrens functional results were similar to the results reported for adults with an average Musculoskeletal Tumor Society rating of good to excellent at the knee, fair to good at the hip, and fair about the shoulder. Rehabilitation of the knee in very young patients (5-8 years) remains problematic and careful selection of patient and family is necessary. The Lewis Expandable Adjustable Prosthesis probably should be reserved for very young patients (5-8 years) and modular systems should be used for large preadolescent and adolescent children.

PULMONARY METASTASIS OF BENIGN GIANT CELL TUMOR OF BONE. SIX HISTOLOGICALLY CONFIRMED CASES, INCLUDING ONE OF SPONTANEOUS REGRESSION

Benign giant cell tumor of bone, despite being classified as benign, has the unusual ability to metastasize. Metastasis of such a tumor has been thought to be rare, with only approximately 50 such cases having been reported. However, as awareness of the metastatic potential of these tumors has increased, and methods of detection have improved, metastasis of benign giant cell tumor has been increasingly recognized. Six patients with pulmonary metastasis of giant cell tumor have been treated at a Los Angeles hospital since 1980. This represents 9.1% of all patients treated for benign giant cell tumor of bone over the same period at this institution, a higher rate than that encountered in previously published series. The early detection and treatment of this tumor is important, because those with complete resection of tumor have the best prognosis. The nature of these pulmonary metastases remains unpredictable, however, as evidenced by two of the cases in this series: one of spontaneous regression, and another of death caused by pulmonary failure.

Extramedullary porous coating to prevent diaphyseal osteolysis and radiolucent lines around proximal tibial replacements. A preliminary report.

Nineteen patients who had a primary malignant bone tumor of the proximal end of the tibia were managed with wide resection and implantation of a tibial endoprosthesis with cement, combined with a rotating-hinge knee replacement. In the first ten patients, a ring of porous coating was applied to the part of the tibial replacement that was just proximal to the intramedullary portion of the stem, to encourage ingrowth of bridging bone. No growth of bone into these porous rings occurred, and the rings were not applied to the next nine endoprostheses. During the subsequent follow-up period, progressive osteolysis (resorption of more than two millimeters of the proximal end of the remaining tibial cortex) developed in only one patient (who had a deep infection) in the group of ten patients who had a porous ring, compared with five of the nine patients who did not have a porous ring but in whom osteolysis developed. This difference was significant (p < 0.001). In addition, the tibial osteolysis was associated with the subsequent development of progressive periprosthetic radiolucent lines at the bone-cement interfaces (p = 0.001). We postulated that, in the patients who had an extramedullary porous ring, the periprosthetic fibrous capsule that formed around the extramedullary portion of all the implants became firmly adherent to the ring, thereby sealing off the part of the capsule that was distal to the ring. The particulate wear debris that was contained within the articular portion of the capsule could not reach the distal tibial bone surrounding the prosthetic stem, and debris-incited osteolysis, which leads to loosening, did not develop. If this mechanism is confirmed, it could have important implications for the design of implants that are used in joint replacement.

Endoprosthetic reconstruction for malignant upper extremity tumors

Between December 1980 and December 1992, 59 patients underwent 60 reconstructions with endoprostheses after resection of malignant tumors in the upper extremity. There were 32 male patients and 27 female patients, with a mean age of 33 years (range, 3-83 years). The type of reconstruction was based on the location of the primary tumor site. The histologic diagnoses included osteosarcoma, chondrosarcoma, Ewings sarcoma, malignant fibrous histiocytoma, soft tissue sarcoma, and fibrosarcoma of bone. Most of the patients had Stage IIB disease (N = 38), as established by the Musculoskeletal Tumor Society classification. An additional six patients had metastatic tumors to the upper extremity. Twenty-seven of 59 patients died of disease progression. Two patients died of other causes (chronic leukemia, human immunodeficiency virus infection). The 30 survivors had a mean followup of 90 months (range, 60-170 months). The Musculoskeletal Tumor Society functional analysis for the patients with a minimum 2-year followup (N = 41) averaged 74%. Sixteen of the 59 (27%) patients had local complications. Problems related to mechanical failure and infection were managed successfully with second operation. Amputation was rare, occurring in three of 60 (5%) patients and was related only to local recurrence. Endoprosthetic reconstructions of the upper extremity after tumor resections have proven to be successful.