Malignant Progression in Two Children with Multiple Osteochondromas

Multiple Osteochondromas (MO) is a disease of benign bony growths with a low incidence of malignant transformation. Secondary chondrosarcoma in children is rare even in children with MO. Making a diagnosis of malignancy in low-grade cartilage tumors is challenging and requires consideration of clinical, radiographic, and histopathological factors. We report two cases of skeletally immature patients with MO who presented with rapidly enlarging and radiographically aggressive lesions consistent with malignant transformation. Both underwent allograft reconstruction of the involved site with no signs of recurrence or metastatic disease at a minimum of four-year follow-up

NYESO-1/LAGE-1s and PRAME Are Targets for Antigen Specific T Cells in Chondrosarcoma following Treatment with 5-Aza-2-Deoxycitabine

Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.A minority (36%) of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic chondrosarcoma patients where no proven systemic therapies exist

Assessment of Objective Ambulation in Lower Extremity Sarcoma Patients with a Continuous Activity Monitor: Rationale and Validation

In addition to patient reported outcome measures, accelerometers may provide useful information on the outcome of sarcoma patients treated with limb salvage. The StepWatch (SW) Activity Monitor (SAM) is a two-dimensional accelerometer worn on the ankle that records an objective measure of walking performance. The purpose of this study was to validate the SW in a cross-sectional population of adult patients with lower extremity sarcoma treated with limb salvage. The main outcome was correlation of total steps with the Toronto Extremity Salvage Score (TESS). In a sample of 29 patients, a mean of 12 days of SW data was collected per patient (range 6–16), with 2767 average total steps (S.D. 1867; range 406–7437). There was a moderate positive correlation between total steps and TESS (r=0.56,  P=0.002). Patients with osseous tumors walked significantly less than those with soft tissue sarcoma (1882 versus 3715, P<0.01). This study supports the validity of the SAM as an activity monitor for the objective assessment of real world physical function in sarcoma patients

[F-18]-fluorodeoxy-D-glucose–positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults

BACKGROUND: Response to neoadjuvant chemotherapy is 1 of the most powerful prognostic factors for extremity osteosarcoma. [F-18]-fluorodeoxy-D-glucose–positron emission tomography (FDG-PET) is a noninvasive imaging modality that is used to predict histopathologic response. To determine the prognostic value of FDG-PET response for progression-free survival (PFS) in osteosarcoma, the authors of this report reviewed the University of Washington Medical Center experience. METHODS: Forty patients with extremity osteosarcoma were evaluated by FDG-PET. All patients received neoadjuvant and adjuvant chemotherapy. FDG-PET standard uptake values (SUVs) before neoadjuvant chemotherapy (SUV1) and after neoadjuvant chemotherapy (SUV2) were analyzed and correlated with histopathologic response. RESULTS: The median SUV1 was 6.8 (range, 3.0-24.1), the median SUV2 was 2.3 (range, 1.2-12.8), and the median SUV2 to SUV1 ratio (SUV2:1), was 0.36 (range, 0.12-1.10). A good FDG-PET response was defined as anSUV2 <2.5 or an SUV2:1 ≤0.5. FDG-PET responses according to SUV2 and SUV2:1 were concordant with histologic response in 58% and 68% of patients, respectively. SUV2 was associated with outcome (4-year PFS, 73% for SUV2 <2.5 vs 39% for SUV2 ≥2.5; P = .021). Both the initial disease stage and the histologic response were associated with outcome. CONCLUSIONS: FDG-PET imaging of extremity osteosarcoma was correlated only partially with a histologic response to neoadjuvant chemotherapy. An SUV2 <2.5 was associated with improved PFS. Future prospective studies are warranted to determine whether FDG-PET imaging may be used as a predictor of outcome independent of initial disease stage. Cancer 2009. © 2009 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63561/1/24421_ftp.pd

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