Lipomatous Soft-tissue Tumors.

Lipomatous soft-tissue tumors are the most common neoplasms encountered by physicians. They range from benign lipomas to high-grade liposarcomas. Unplanned excisions of sarcomas are commonly due to the presumptive diagnosis of lipoma and can be avoided by understanding their diagnostic magnetic resonance imaging appearance. Magnetic resonance images should be obtained for all soft-tissue masses that are deep to fascia or those >5 cm in subcutaneous tissue. Atypical lipomatous tumors present as large deep fatty masses and have a propensity for local recurrence and a small risk of malignant transformation. Well-differentiated liposarcomas are histologically identical to atypical lipomatous tumors but have a markedly worse prognosis secondary to their anatomic location. Masses that lack isointense signal to subcutaneous fat on MRI may represent a sarcoma and require a biopsy before definitive treatment. Large deep lipomatous masses and liposarcomas should be sent to a sarcoma referral center for definitive treatment.

Soft Tissue Sarcoma Response to Two Cycles of Neoadjuvant Chemotherapy: A Multireader Analysis of MRI Findings and Agreement with RECIST Criteria and Change in SUVmax.

RATIONALE AND OBJECTIVES: When soft tissue sarcomas are treated with neoadjuvant chemotherapy, the number of cycles of chemotherapy is usually dependent on the tumor's initial response. Popular methods to assess tumor response include Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which rely solely on tumor size, and maximum standardized uptake value (SUVmax) reduction in positron emission tomography (PET), which requires an expensive and high radiation test. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI) may offer a good alternative by providing additional information beyond tumor size. MATERIALS AND METHODS: Following IRB approval, a retrospective review identified patients with soft tissue sarcomas who underwent both PET and MRI before and after two cycles of neoadjuvant chemotherapy. Five readers independently examined the MRI exams for: changes in size, T2 or T1 signal, necrosis and degree of enhancement. Readers then made a subjective binary assessment of tumor response to therapy. Each reader repeated the anonymized randomized reading at least 2 weeks apart. 18 F-FDG PET exams were interpreted by a nuclear medicine specialist. The maximum standardized uptake values (SUVmax) for pre and post-chemotherapy exams were compared. Intra- and inter-reader agreement was assessed using Cohen's kappa and Light's kappa, respectively. . RESULTS: Twenty cases were selected for this multireader study, of which 9 (45%) were responders and 11 were nonresponders by SUVmax. Using all MRI criteria, 43% were classified as responders based on MRI and 1.5% were classified as responders by RECIST criteria. Using PET as the reference, the sensitivity and the specificity of the MRI diagnosis for response using all findings were 50% and 63%, respectively. There was fair to moderate intrareader (kappa = 0.37) and inter-reader (kappa = 0.48) agreement for the MRI diagnosis of response. None of the individual MRI signal characteristics were significantly different between the PET responders and nonresponders. Additionally, no MRI findings were significantly different between those with and without good clinical responses. CONCLUSION: By our assessment, there is a poor correlation between tumor response by RECIST criteria and PET SUVmax. In addition, varying MR features did not help in diagnosing tumor response. Imaging of tumor response remains a challenging area that requires further research.

Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

Gadolinium Contrast Enhancement Improves Confidence in Diagnosing Recurrent Soft Tissue Sarcoma by MRI.

RATIONALE AND OBJECTIVES: To determine how utilization of postgadolinium magnetic resonance imaging (MRI) influenced reader accuracy and confidence at identifying postoperative soft tissue sarcoma (STS) recurrence among readers with various levels of expertise. MATERIALS AND METHODS: This retrospective study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. Postoperative MRI from 26 patients with prior STS resection (13 patients with confirmed recurrence, 13 without recurrence) was reviewed. Four blinded readers of varying expertise (radiology resident, fellow, attending, and orthopedic oncologist) initially evaluated only the precontrast images and rated each MRI for recurrence on a 5-point confidence scale. Assessment was repeated with the addition of contrast-enhanced sequences. Diagnostic accuracy based on confidence ratings was evaluated using the area under the receiver operating characteristic curve (AUC). Changes in confidence ratings were calculated using Wilcoxon signed-rank test. RESULTS: All readers demonstrated good diagnostic accuracy both with and without contrast-enhanced images (AUC >0.98 for each reader). When contrast-enhanced images were made available, the resident recorded improved confidence with both assigning (P = 0.031) and excluding recurrence (P = 0.006); the fellow showed improved confidence only with assigning recurrence (P = 0.015); and the surgeon showed improved confidence in excluding recurrence (P = 0.003). The addition of contrast-enhanced images did not significantly influence the diagnostic confidence of the attending radiologist. CONCLUSIONS: Diagnostic accuracy of MRI was excellent in evaluating postoperative STS recurrence, and reader confidence improved depending on expertise when postgadolinium imaging was included in the assessment.

Health-related quality of life following treatment for extremity soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: The primary objective of this study was to estimate the change in health-related quality of life (HRQL) 1 year following treatment for extremity soft tissue sarcoma (STS), measured by the EQ-5D. Secondary objectives included determining clinical variables associated with HRQL at 1 year, estimating the proportion with a clinically important difference (CID) in HRQL, and evaluating variability within EQ-5D domains. METHODS: Patients over the age of 16 years, treated for a localized extremity STS, were included. The EQ-5D change score from pre-treatment to 1-year follow-up was determined. The association of clinical variables with EQ-5D scores was estimated using a linear regression model. The proportion of patients with a CID in HRQL score was determined. A vector analysis of the EQ-5D domains was undertaken. RESULTS: The mean EQ-5D change score was 0.02. Age, sex, disease status, and initial EQ-5D score were associated with EQ-5D score at 1 year. There was a CID improvement in 32% and a deterioration in 24%. The anxiety and depression domain demonstrated the most change between baseline and 1 year after treatment. CONCLUSION: Most patients maintain a high level of HRQL following treatment for extremity STS. J. Surg. Oncol. 2016;114:821-827. © 2016 2016 Wiley Periodicals, Inc.

Massive exophytic malignant peripheral nerve sheath tumor.

We present a case of a solitary neurofibroma involving the right posterior shoulder of a 69-year-old man with degeneration into a massive, malignant peripheral nerve sheath tumor measuring more than 3 times the average reported size. The radiographic, magnetic resonance imaging, and computed tomographic features are compared with the gross appearance and pathology.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas.

PURPOSE: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. METHODS AND MATERIALS: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. RESULTS: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. CONCLUSIONS: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

The Imaging and Pathological Features of Metastatic Leiomyosarcoma in the Gallbladder.

Uterine leiomyosarcoma is a rare and aggressive malignancy with poor overall prognosis. There have been few reports of metastatic leiomyosarcoma in the gallbladder. We report a case of a 41-year-old female who underwent total abdominal hysterectomy due to presumed uterine fibroids. The postoperative pathology revealed high-grade pleomorphic leiomyosarcoma, with involvement of the uterine serosal surface. She subsequently underwent exploratory laparotomy, followed by pelvic radiation and chemotherapy. Since initial management she has developed metastatic disease and has been under treatment and surveillance for 11 years. She has undergone multiple surgical procedures and numerous lines of systemic therapy for metastatic leiomyosarcoma, including cholecystectomy for a metastatic lesion in the gallbladder. There have been no previous reports of metastatic leiomyosarcoma in the gallbladder. Despite extensive metastatic disease this patient has had prolonged survival with multi-modality management.

Quality of life measures in soft tissue sarcoma.

The assessment of health-related quality of life (HRQL) via patient-reported outcomes has the potential to answer critical questions and improve the care of soft tissue sarcoma (STS). This review outlines the rationale for quality of life measures in sarcoma, and details various instrument types: disease- and anatomic-specific, provider-generated, generic HRQL and health state utilities. Prior usage in STS populations, relative advantages of specific patient-reported outcome measures and a framework for selecting appropriate measures are discussed. Uniform incorporation of validated HRQL measures in STS clinical research would further the understanding of patient wellbeing beyond traditional clinical measures, and more widespread use of health state utilities measures in particular has the potential to facilitate comparative effectiveness research.

Validation of the SF-6D Health State Utilities Measure in Lower Extremity Sarcoma.

Aim. Health state utilities measures are preference-weighted patient-reported outcome (PRO) instruments that facilitate comparative effectiveness research. One such measure, the SF-6D, is generated from the Short Form 36 (SF-36). This report describes a psychometric evaluation of the SF-6D in a cross-sectional population of lower extremity sarcoma patients. Methods. Patients with lower extremity sarcoma from a prospective database who had completed the SF-36 and Toronto Extremity Salvage Score (TESS) were eligible for inclusion. Computed SF-6D health states were given preference weights based on a prior valuation. The primary outcome was correlation between the SF-6D and TESS. Results. In 63 pairs of surveys in a lower extremity sarcoma population, the mean preference-weighted SF-6D score was 0.59 (95% CI 0.4-0.81). The distribution of SF-6D scores approximated a normal curve (skewness = 0.11). There was a positive correlation between the SF-6D and TESS (r = 0.75, P < 0.01). Respondents who reported walking aid use had lower SF-6D scores (0.53 versus 0.61, P = 0.03). Five respondents underwent amputation, with lower SF-6D scores that approached significance (0.48 versus 0.6, P = 0.06). Conclusions. The SF-6D health state utilities measure demonstrated convergent validity without evidence of ceiling or floor effects. The SF-6D is a health state utilities measure suitable for further research in sarcoma patients.

The multidisciplinary management of giant cell tumor of bone.

Giant cell tumor of bone is a locally aggressive lesion with a predilection for local recurrence, and in a small proportion of patients, metastatic disease can develop. Surgery is the mainstay of management for extremity-based lesions. For tumors located in challenging anatomical locations such as the sacrum and spine however, surgery may be associated with unacceptable functional morbidity. There are limited data regarding other treatment modalities such as radiation therapy, cytotoxic chemotherapy, interferon and bisphosphonates. Serial arterial embolization can be effective in some cases. Recent evidence has demonstrated denosumab to be a promising agent in the treatment of unresectable or metastatic disease.

Monitoring the adequacy of surgical margins after resection of bone and soft-tissue sarcoma.

PURPOSE: Local recurrence of a bone or soft-tissue sarcoma is a devastating complication. Minimizing the proportion of positive surgical margins, or tumor contamination, during resection is of paramount importance. METHODS: Resections of sarcomas were prospectively evaluated and considered inadequate if unplanned microscopic or macroscopic positive surgical margins were identified or if inadvertent tumor contamination of the wound occurred. Monitoring of performance was continuously performed with a statistical process control method, the cumulative sum test, and regular meetings were held to discuss the reasons for failures. A target performance of 5 % inadequate procedures was chosen. RESULTS: A total of 146 sarcomas-106 soft tissue and 40 bone-were resected during the monitoring period. Six (4 %) procedures were considered inadequate: three patients had inadvertent tumor contamination of the wound, two patients had unplanned microscopic positive margins, and one patient had both. Performance was considered to be adequate during the whole monitoring period. CONCLUSIONS: With adequate preoperative planning and surgical technique, the risk of an inadequate resection can be limited. Implementation of a statistical process control method allows for ongoing performance monitoring and ensures that quality remains adequate over time.

Using the CUSUM test to control the proportion of inadequate open biopsies of musculoskeletal tumors.

BACKGROUND: Biopsies of musculoskeletal tumors lead to alterations in treatment in almost 20% of cases. Control charts are useful to ensure that a process is operating at a predetermined level of performance, although their use has not been demonstrated in assessing the adequacy of musculoskeletal biopsies. QUESTIONS/PURPOSES: We therefore (1) assessed the incidence of and the reasons for inadequate musculoskeletal biopsies when following guidelines for performing the procedure; and (2) implemented a process control chart, the CUSUM test, to monitor the proportion of inadequate biopsies. METHODS: We prospectively studied 116 incisional biopsies. The biopsy was performed according to 10 rules to (1) minimize contamination in the tissues surrounding the tumor; and (2) improve accuracy. A frozen section was systematically performed to confirm that a representative specimen was obtained. Procedures were considered inadequate if: (1) another biopsy was necessary; (2) the biopsy tract was not appropriately placed; and (3) the treatment provided based on the diagnosis from the biopsy was not appropriate. RESULTS: Five (4.3%) of the 116 incisional biopsy procedures were considered failures. Three patients required a second repeat open biopsy and two were considered to receive inappropriate treatment. No alarm was raised by the control chart and the performance was deemed adequate over the monitoring period. CONCLUSIONS: The proportion of inadequate musculoskeletal open biopsies performed at a referral center was low. Using a statistical process control method to monitor the failures provided a continuous measure of the performance.

Responsiveness of the SF-36 and WOMAC following periacetabular osteotomy for acetabular dysplasia.

BACKGROUND: Periacetabular osteotomy is a relatively common reconstructive procedure for the adolescent or young adult with acetabular dysplasia. Although several measures have been used to characterize the outcome, the responsiveness of these measures in this population has not been determined. The purpose of this study was to estimate the responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Short Form-36 (SF-36) in patients with acetabular dysplasia treated with periacetabular osteotomy. METHODS: Eighty-three patients with acetabular dysplasia treated with periacetabular osteotomy between 2000 and 2005 completed the WOMAC and SF-36 both preoperatively and postoperatively. The scores on each domain of these outcome measures were calculated and analyzed to determine the parameters of responsiveness, including the minimal detectable change at the 90% confidence level. RESULTS: The mean duration of follow-up was 1.9 years. Comparison of the effect size, standardized response mean, and minimal detectable change for the SF-36 and WOMAC demonstrated that the WOMAC was more sensitive to change than the SF-36 was, particularly in the physical function domain (minimal detectable change, 9.1) and the pain domain (minimal detectable change, 5.5). Only one of the eight domains of the SF-36, bodily pain, demonstrated a change in outcome that exceeded the minimal detectable change, which was 2.38. CONCLUSIONS: Both the WOMAC and the SF-36 demonstrated adequate responsiveness to change over time in patients with acetabular dysplasia treated with periacetabular osteotomy, although the WOMAC was more sensitive to change. These results indicate that the WOMAC is sufficiently responsive to be used as a joint-specific measure for assessing changes following periacetabular osteotomy for the treatment of acetabular dysplasia.

Skeptical thinking series: an introduction to skeptical thinking in the evaluation of claims.

The aim of this study is to introduce the concept of skeptical thinking to evaluate a claim using the six component (Falsifiability, Logic, Comprehensiveness, Honesty, Replicability, and Sufficiency) FiLCHeRS method. These six rules were used to assess whether claims should be accepted or rejected. As this is an introductory study, there are no concrete results to report, although the conclusion is that the method of skeptical thinking using the FiLCHeRS method is a suitable and logical approach to evaluate a claim.