Faculty Bibliography

OBJECTIVE: To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. SUMMARY BACKGROUND DATA: Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. METHODS: From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. RESULTS: Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. CONCLUSIONS: Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival

AIM OF THE STUDY: To assess the impact of repeated F-18 FDG studies on the management of patients with bone and soft tissue (B&S) sarcomas. MATERIAL AND METHODS: Twenty patients with B&S tissue tumors (11 M and 9 F age 17-72 years) had 52 F-18 FDG Dual Head Coincidence Imaging (DHCI) studies. 7 patients were followed for 6 months to 2 years clinically after removal of the primary tumor. Thirteen patients were evaluated for suspected recurrences. Patient's preparation, F-18 FDG injection and imaging procedure were done according to department protocol. Attenuation corrected images were interpreted visually by 3 trained physicians. Tumor to background ratios were calculated for all lesions. RESULTS: In 13 patients having both studies, baseline FDG and CT/MRI were concordant in 8 patients, FDG detected more lesions in 3 patients but it did not detect 4 metastatic pulmonary nodules in 2 patients. Follow up studies showed stable disease in 10 patients while 6 patients who showed worsening disease needed to change their chemotherapy. Surgery was avoided in 2 patients and 2 patients showed improved response. CONCLUSION: Repeated F-18 FDG DHCI examinations proved to have an impact on the clinical management of patients with malignant bone and soft tissue sarcoma. It helps to differentiate postoperative changes from local recurrence

Purpose: The clinical use of PET FDG in the work-up of patients with bone and soft tissue malignant tumors is rapidly increasing. The recognition of any source of artifact, therefore, is important to avoid interpretation pitfalls.Procedures: Two patients with complete knee joint replacement by metallic prosthesis in the course of their treatment for malignant bone and soft tissue sarcoma were evaluated by PET F-18 FDG imaging using a dual head coincidence gamma camera.Results: Both studies demonstrated in the attenuation-corrected images intense increase activity at the joint space between the metallic prosthetic surfaces at the level of the knee joint. No uptake, however, was noted in the same location on the non-attenuation-corrected images. Subsequent bone and thallium-201 scans confirmed the absence of tumor recurrence in the first patient. The second patient had multiple follow up F-18 FDG scans over a period of 16 months that show no changes from the baseline study.Conclusion: In the F-18 FDG PET images of patients with total knee metallic prosthesis, an intense activity tends to be seen in the joint space, only in the attenuation-corrected images. Such pattern of uptake is considered artifactual and should always be verified in the non-attenuated images

Gastrointestinal stromal sarcomas, formerly categorized as leiomyosarcomas of gastrointestinal origin, have a common pattern of intraperitoneal dissemination. Despite surgical resection with or without adjuvant systemic chemotherapy the vast majority of these patients succumb to intraperitoneal sarcomatosis and/or hepatic metastases. In an attempt to improve upon the morbidity and mortality associated with this disease we and several other centers have begun treating these patients with intraperitoneal chemotherapy. We have found that aggressive surgical resection with postoperative intraperitoneal chemotherapy has significantly lowered the peritoneal recurrence rate in patients with recurrent gastrointestinal stromal sarcomas as compared to those who have undergone surgical resection alone. However, this treatment approach has proven to be ineffective in preventing hepatic metastases, and thus has had little effect upon overall survival. With the treatment of primary rather than recurrent disease we hope to interrupt the disease process at an earlier stage further decreasing peritoneal recurrences and potentially improving survival

Limb salvage is now possible for the majority of patients with extremity sarcomas. Although overall prognosis is primarily based on tumor size and histologic grade, complete surgical excision and local control is essential for cure. There are, however, certain anatomic locations such as the flexor fossae in which a complete surgical margin is difficult to attain, and surgery without adjuvant therapy has a high local failure and amputation rate. We have found that preoperative adjuvant therapy consisting of chemotherapy and radiation followed by surgical excision with tumor-free margins has been successful in treating flexor fossa sarcomas with high limb salvage (96%), local control (89%) and overall survival rates (70%). These results are comparable to patients with similar large, high-grade extremity tumors in other compartmental locations

BACKGROUND: Recurrent abdominal sarcomas have an extremely high rate of recurrence and poor overall survival. A prospective study was initiated to assess the feasibility, toxicity, and benefit of surgical resection and intraperitoneal chemotherapy for improving local control of disease and overall survival. METHODS: Fifty-four patients underwent surgical excision of all gross disease and postoperative intraperitoneal chemotherapy with mitoxantrone. Thirty-five patients had peritoneal disease only (stage II), and 19 patients had peritoneal disease with hepatic metastases (stage III). RESULTS: Nine (17%) patients remain free of disease with a mean follow-up of 37 months. The remaining 45 patients (83%) have had recurrence, with a mean interval to recurrence of 11 months. Stage (P = .001) and grade (P = .005) were the only two variables found to significantly affect recurrence. There was an overall peritoneal recurrence rate of 48% and an overall hepatic failure rate of 69%. Nineteen (35%) of the patients are alive, with a mean follow-up of 46 months. The overall 5-year survival was 31%. The 5-year survival for stage II patients was 46%; for stage III patients, it was only 5%. Stage (P = .001) and grade (P = .056) were the only two variables found to significantly affect survival. There were no treatment-related deaths, and only 5 patients (9%) developed local complications. CONCLUSIONS: Aggressive surgical resection and intraperitoneal chemotherapy for recurrent abdominal sarcomas is a feasible treatment approach with minimal toxicity. Although this treatment had little effect on the hepatic spread of this disease and thus overall survival, it appears to have significantly lowered the rate of peritoneal recurrence and may provide a survival benefit for patients with disease limited to the peritoneum