Clinical value of [18-F]] fluorodeoxyglucose positron emission tomography imaging in soft tissue sarcomas.
(33/1415)
OBJECTIVE: To evaluate positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) for clinical application in soft tissue sarcomas. SUMMARY AND BACKGROUND DATA: FDG PET is a promising noninvasive method for the preoperative assessment of soft tissue sarcomas and may complement radiologic tomography. METHODS: Data from 50 consecutive patients with 59 masses, either suspicious for primary or locally recurrent soft tissue sarcoma, were prospectively gathered. The semiquantitative FDG uptake (standardized uptake values [SUVs]) was calculated in tumor and normal tissue (muscle). Histopathology of surgical specimens and follow-up data were used as control criteria. RESULTS: In primary soft tissue sarcomas, PET displayed a sensitivity of 91% and a specificity of 88%. Local recurrence was detected with a sensitivity of 88% and a specificity of 92%. All intermediate-grade and high-grade soft tissue sarcomas (primary and locally recurrent) were visualized with a precise differentiation from muscle. Fifty percent of the low-grade sarcomas showed an FDG uptake equivalent to muscle (false-negative results in one primary and three recurrent soft tissue sarcomas). Benign soft tissue tumors (e.g., lipoma, leiomyoma, ganglion) did not accumulate FDG. Inflammation resulted in an increased FDG uptake. The semiquantitative FDG uptake (SUVs) correlated with tumor grade but not with size and histologic type. CONCLUSION: High-grade and intermediate-grade soft tissue sarcomas are amenable to PET imaging, whereas low-grade lesions may not be depicted. SUVs for FDG correlate with tumor grade in soft tissue sarcomas. Benign soft tissue tumors are differentiated from higher-grade soft tissue sarcomas. These data show that FDG-PET can complement preoperative radiologic assessment for soft tissue sarcomas and that FDG-PET is a powerful diagnostic tool for detecting high-grade and intermediate-grade local recurrence. (+info)
Localized pigmented villonodular synovitis of the knee joint: neoplasm or reactive granuloma? A review of 18 cases.
(34/1415)
OBJECTIVE: The localized form of pigmented villonodular synovitis of the knee joint is a rare disease with limited alteration of the synovial membrane, the pathogenesis of which is the subject of controversial discussion. METHODS: Eighteen cases have been documented in our hospital since 1976. All of the patients had additional cartilage or meniscus damage. Treatment consisted of excision of the lesion and the adjacent synovial membrane, as well as therapy of the additional damage. RESULTS: The patients who had received such therapy were followed for 3-9 yr, without any clinical, sonographic or magnetic resonance tomographic signs of recurrence. In addition to the lack of a tendency towards recurrence, none of the cases displayed any further characteristics of the diffuse form of villonodular synovitis, such as invasiveness or malignant transformation. CONCLUSIONS: We therefore suggest that pigmented villonodular synovitis of the knee joint should be classified more strictly than before into a potentially neoplastic (diffuse) form and a reactive granulomatous (local) form. From the cases observed, we conclude that degenerative joint lesions may be the cause of the reactive granulomatous form. (+info)
Phenotypic alterations in Kaposi's sarcoma cells by antisense reduction of perlecan.
(35/1415)
Metastasis is a sequence of events including proliferation, migration, adhesion, invasion and subsequent metastatic growth of tumour cells in distant organs. We previously showed that highly metastatic variants of murine melanoma cells express higher levels of the basement membrane proteoglycan perlecan than low or non metastatic variants and expression of an antisense perlecan can reduce metastatic potential. In contrast, antisense expression of perlecan in fibrosarcoma cells was reported to enhance tumorigenesis. To better understand the role of perlecan in angiogenesis we have transfected KS-IMM, an immortalized cell line derived from a human Kaposi s sarcoma, with an antisense perlecan construct and investigated the positive/negative role of perlecan in KS. KS-IMM cells were transfected with either empty vector (neo) or the antisense perlecan construct and clones were isolated. Immuno-blot analysis showed a reduction of perlecan levels in two (AP3 and AP4) isolated clones, in Northern blot analysis endogenous perlecan was undetectable in the AP3 and AP4 clones, while it was present in the neo control clones. AP clones had a reduced migration to HGF in Boyden chambers as compared to neo clones. Proliferation in low serum or serum-free conditions was strongly reduced in the AP clones as compared to the neo control cells. The neotransfected cells showed rapid proliferation in low serum supplemented with HGF and VEGF, while antisense transfected clones showed little response. Finally, AP-trasfected KS-IMM cells had significantly reduced migration to VEGF and HGF with respect to controls. In contrast, when the AP transfected cells were injected in nude mice they paradoxically showed enhanced tumor growth as compared to controls. Our preliminary data indicate that perlecan reduction plays a crucial role on Kaposi s sarcoma cell migration and proliferation in vitro. However, in vivo KS-IMM depleted of perlecan had a growth advantage. A possible hypothesis is that perlecan is necessary for growth of KS-IMM cells in vitro, however its down-regulation might promote angiogenesis through increased angiogenic growth factor diffusion, resulting in enhanced tumor growth in vivo. (+info)
Effect of reresection in extremity soft tissue sarcoma.
(36/1415)
OBJECTIVE: To determine whether reresection affects survival in patients with inadequately resected, primary extremity soft tissue sarcoma. This study correlates reresection with local recurrence-free survival, metastasis-free survival, and disease-free survival. SUMMARY BACKGROUND DATA: Soft tissue sarcomas are rare neoplasms, with an incidence of approximately 6,000 per year in the United States. Because these tumors are rare and benign soft tissue tumors are common, many are initially thought to be benign and are excised without wide margins. METHODS: Patients who underwent treatment for primary tumors from July 1982 to June 1999 at a single institution were the subject of study. Two groups of patients were analyzed: those who underwent one definitive resection (one operation) and those whose tumors were previously resected and who were then referred for subsequent reresection (two operations). Patients were given adjuvant radiation or chemotherapy according to the standard of care. RESULTS: Of 1,092 patients with primary extremity soft tissue sarcoma underwent resection, 685 underwent definitive radical resection and 407 underwent reresection after undergoing excisional resection elsewhere. Median follow-up was 4.8 years. The 5-year disease-free survival rate of the definitive resection (one operation) group was 70%; that of the reresection (two operations) group was 88%. On multivariate analysis, reresection was adjusted and controlled for age, grade, depth, size, histology, and margins. Reresection remained a significant predictor of improved disease-free survival, even after these adjustments. To determine whether this difference was stage- or referral-biased, the patient population was divided by AJCC stage. In all stages there was a trend toward improved outcome; this was most marked for those with stage III disease (>5 cm, high-grade, and deep). CONCLUSIONS: Patients with extremity soft tissue sarcoma who undergo reresection with two "primary" operations have an improved survival compared with those who undergo one operation. The most plausible explanation, referral and selection bias, is questionable given the significance of reresection as a variable after adjusting for stage and other risk factors. This suggests that where indicated and possible, reresection should be liberally applied in patients with primary extremity soft tissue sarcoma. (+info)
Follicular thyroid cancer presenting initially with soft tissue metastasis.
(37/1415)
Follicular thyroid cancer rarely manifests itself as a distant metastatic lesion. We report a case of an otherwise asymptomatic 58-year-old woman with follicular thyroid cancer who initially presented with a soft tissue mass on the right scapular region. An incisional biopsy specimen of soft tissue metastasis showed thyroid follicular neoplasm. Upon this diagnosis, the thyroid gland was re-evaluated by ultrasound, which demonstrated a solitary, hypoechoic nodule in the right lobe. Ultrasonography guided fine-needle aspiration biopsy of the thyroid nodule confirmed follicular neoplasm and the diagnosis of metastatic follicular thyroid cancer was established. The patient refused any type of treatment and left hospital against medical advice. 2.5 years later the patient was admitted to the hospital with giant, sarcoma-like multiple soft tissue masses. On this admission, the serum thyroglobulin level was extremely elevated (3500 ng/ml) and she only accepted to receive chemotherapy. Epirubicin and cyclophosphamide were administered. She received three courses of chemotherapy and is alive with a stable disease after 3 months of follow-up. This case of follicular thyroid cancer is reported because of its uncommon initial presentation with soft tissue metastasis which spread to multiple areas as giant soft tissue masses during follow-up. (+info)
The effect of an individual's cytochrome CYP3A4 activity on docetaxel clearance.
(38/1415)
Docetaxel is a chemotherapeutic agent effective in the treatment of various solid tumors. Patients given a standard dose of docetaxel exhibit wide interpatient variation in clearance (CL) and toxic effects. Docetaxel undergoes metabolism by cytochrome CYP3A4. Thus, interpatient variability in CYP3A4 activity may account in part for differences in toxicity and CL. Twenty-one heavily pretreated patients with metastatic sarcomas received docetaxel (100 mg/m2). Hepatic CYP3A4 activity in each patient was measured by the [14C-N-methyl]erythromycin breath test (ERMBT). Blood samples were taken at selected times over the next 24 h for pharmacokinetic analysis. Phenotypic expression of hepatic CYP3A4 activity measured by the ERMBT varied over 20-fold (administered 14C exhaled in 1 h: mean, 2.53%; range, 0.25-5.35%), which is similar to a normal control population. CL of docetaxel varied nearly 6-fold (mean, 21.0 liters/h/m2; range, 5.4-29.1 liters/h/m2). The ERMBT was the best predictor of CL when compared with serum alanine aminotransferase, albumin, alkaline phosphatase, or serum alpha-1-acidic glycoprotein. The natural log of ERMBT accounted for 67% of the interpatient variation in CL. Multivariate analysis showed that the natural log of ERMBT and albumin together accounted for 72% of the interpatient variation in CL. The greatest toxicity was seen in patients with the lowest ERMBT. Hepatic CYP3A4 activity is the strongest predictor of docetaxel CL and accounts for the majority of interpatient differences in CL. Patients with low CYP3A4 activity are at risk for having decreased CL and may thus experience increased toxicity from docetaxel. Those with high activity may be receiving a suboptimal dose. By measuring CYP3A4 activity, the ERMBT may be clinically useful in tailoring doses of CYP3A4 substrates, such as docetaxel, in certain individuals. (+info)
(F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma.
(39/1415)
Positron emission tomography (PET) can be used to measure tumor metabolism in sarcomas by measuring the standard uptake value (SUV) of (F-18) fluorodeoxyglucose (FDG). FDG-PET SUV has been shown to correlate with histological grade. We compared FDG-PET SUV in 89 bone and soft tissue sarcomas with histopathological features, including tumor grade, as well as with markers of cell proliferation and cell cycle regulatory gene expression that may be prognostically or therapeutically important. All patients had undergone PET before biopsy. Features evaluated included grade (National Cancer Institute for soft tissue or Mayo Clinic for bone), cellularity, and the number of mitoses per 10 400x fields. Deparaffinized, formalin-fixed sections were immunostained with antibodies to Ki-67 (MIB-1), p53 (DO7), p21WAF1 (EA10), and mdm-2 (1B10). For Ki-67, results were estimated as a percentage of positive cells. For p53 and mdm-2, only cases with >20% positive cells were considered to be overexpressing these proteins. For p21WAF1, only cases with <10% positive cells were considered to have lost normal p21WAF1 expression. Tumor S-phase percentage and ploidy were determined by flow cytometry. FDG-PET SUV was associated with histopathological grade, cellularity, mitotic activity, MIB labeling index, and p53 overexpression. No association was seen with p21WAF1, mdm-2, S-phase fraction, or ploidy. Tumor metabolism data acquired by FDG-PET may help ensure accurate grading and prognostication in sarcoma by guiding biopsy toward the most biologically significant regions of large masses. Further follow-up will be necessary to determine whether FDG-PET provides independent prognostic information. (+info)
Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft tissue sarcomas in adults: a study of the european organization for research and treatment of cancer soft tissue and bone sarcoma group.
(40/1415)
PURPOSE: To assess antitumor response and time to progression (TTP) with docetaxel compared with doxorubicin in first-line treatment of advanced and/or metastatic soft tissue sarcoma. PATIENTS AND METHODS: Patients with measurable soft tissue sarcoma lesions and adequate bone marrow, liver, and renal function were entered onto the study. They were randomized to either docetaxel 100 mg/m(2) given as a 1-hour intravenous infusion every 3 weeks or doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks. A maximum of seven cycles of treatment were scheduled. The study was designed as a randomized phase III study evaluating TTP by log-rank model. There was a clause for premature closure of the trial if fewer than five responses were observed among the first 25 assessable patients in the docetaxel treatment arm. RESULTS: Eighty-six patients were entered onto the study; 85 were assessable for toxicity and 83 for response. The rate of severe granulocytopenia was not significantly different between the two arms. Nausea (P =.001), vomiting (P <.001), and stomatitis (P =.005) were more common with doxorubicin therapy, whereas neurotoxicity was more frequent with docetaxel treatment. The response rate to doxorubicin therapy was 30% (95% confidence interval, 17% to 46%), whereas no responses to docetaxel therapy were seen (P <.001). In view of this, the trial was closed prematurely and the phase III study part was not conducted. CONCLUSION: Docetaxel is inactive in soft tissue sarcomas and cannot be recommended for further use in treatment of this disease. (+info)