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The most significant impact on outcome in chest wall RMS patients is metastatic disease at diagnosis. The locoregional failure rate is high but does not appear to impact survival. Alternative treatment strategies are needed for chest wall RMS, but aggressive surgical excision may not be necessary.
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Objective To assess the potential utility of a novel non-invasive muscle oxygen measurement to determine the presence of muscle hypoxia in patients with anemia. Background Recent assessment of the risk/benefit ratio of blood transfusion has led to clinical strategies optimizing transfusion decisions. These decisions are primarily based upon hematocrit (Hct), but not oxygen delivery, the primary function of red blood cells (RBCs). We hypothesized that muscle oxygenation (MOx) would correlate with Hct in patients with anemia and may be a physiologically relevant determinant of transfusion threshold. Methods/Materials MOx was noninvasively determined in children in the Cancer and Blood Disorders Center ambulatory clinic at Seattle Children’s Hospital using a custom-designed optical probe and spectrometer. MOx was compared with contemporaneous Hct. In subjects receiving RBCs, MOx and Hct were also determined following transfusion. Results MOx ranged from 36.7 to 100%, and Hct ranged from 17.0 to 38.6% in 27 measurements from 16 patients. High MOx values were associated with high Hct. Mean MOx for patients with normal Hct for age (n=5) was 95.9 ± 2.9%. RBC transfusion increased mean Hct from 19.1 ± 1.5% to 29.3 ± 2.0, and mean MOx from 67.9 ± 21.1% to 89.9 ± 9.8%. Among six transfusion episodes (in five patients) with initial Hct < 22, only three had a pre-transfusion MOx of < 70%. Patients with lowest pre-transfusion MOx had the largest increase in MOx after transfusion. Conclusions These preliminary data suggest that MOx may aid in making transfusion decisions when used in combination with hematocrit.
The IGF-1R pathway is activated in many cancer types which has led to clinical development of many IGF1R targeted therapeutics. Multiple clinical trials targeting IGF1R are currently underway, however after initial optimism in NSCLC and Ewing's sarcoma, several trials have failed to show efficacy or had severe toxicity. Pretreatment quantitation of tumor IGF1R protein expression remains a challenge due to high homology between IGF1R and the insulin receptor. Thus, there is a need for a specific and quantitative clinical assay for IGF1R protein expression. The ability to quantify IGF1R expression and determine signaling pathway activation status directly in formalin-fixed paraffin-embedded (FFPE) patient tissue biopsies should help identify patients most likely to benefit from anti-IGF1R therapies. We have developed a quantitative IGF1R assay which can be performed directly in FFPE patient tissue. This approach is based on the Liquid Tissue®-SRM technology platform which enables relative and absolute quantification of proteins and their phosphorylation status directly in formalin fixed tissue. The IGF1R-specific SRM assay was preclinically validated on cell lines expressing a range of IGF1R protein. The expression levels of IGF1R in seven formalin fixed rhabdomyosarcoma (RMS) cell lines were measured by SRM mass spectrometry. We detected a range of IGF1R expression from 68 to 333 amol/ug for these cell lines, values that showed extremely high correlation with antibody based techniques. Analysis of FFPE human rhabdomyosarcoma xenograft explants demonstrates that variable levels of IGF1R expression can be measured accurately. In xenografts where treatment with a therapeutic IGF1R antibody caused tumor regression there was a concomitant loss of IGF1R expression. We have extended these studies by characterizing the expression of IGF1R in a clinical cohort of 25 RMS tumors. IGF1R was detected in 13/14 embryonal RMS tumors and all 11 syncytial RMS tumors. The range of expression in these tissues was 50–250 amol/ug of protein tissue. However, there was one tumor which expressed ∼4500 amol/ug of IGF1R and may represent a stable amplification, or mutation resulting in this extremely high level of IGF1R expression. Additional studies are underway to continue characterization of this tumor. These novel techniques for quantifying IGF1R protein expression in FFPE RMS tumor tissue may enhance our ability to select patients for IGF1R targeted therapy. We are extending this work in two ways. First we are initiating retrospective analysis of IGF1R levels in a sarcoma trial of an IGFR targeted therapy, and second, we are also preparing to use this assay for prospective analysis of FFPE sarcoma tissue in a future IGF1R targeted therapy trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C153.
Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Over the past four decades, the outcome for pediatric ALL has rapidly improved secondary to the participation of children on clinical trials, resulting in standardization of the treatment. Some have argued that the best outcome results from participation in a pediatric clinical trial. To address the potential benefits and barriers to participation in a clinical trial, we analyzed clinical trial participation in pediatric ALL at a large single institution. Methods: We evaluated 322 ALL patients < 22 years old at diagnosis who receive their initial therapy at Seattle Children’s Hospital Regional Medical Center (S-CHRMC) between January 1997 and December 2005. Using a retrospective chart review, we analyzed the following variables: study participation (SP) or non-participation (NP) in an ALL therapeutic study, gender, race, patient immunophenotype, risk group (standard risk (SR), high risk (HR) or infant), home state, and distance of primary residence from S-CHRMC. S-CHRMC is the largest pediatric cancer center in the Pacific Northwest, with referrals from Washington, Alaska, Montana, Idaho and Wyoming. Events were defined as relapse or death from any cause. Results: The overall 5 year event free survival (EFS) was 78% (+/− 2.5%). 157 patients participated in a treatment research study (49%). Only risk group was associated with EFS. SP and NP had similar EFS. Gender, race, immunophenotype, home state, or distance from primary residence were not associated with outcome. There was no difference in study participation by gender, race, home state, or distance of primary residence. There were trends to increased participation in SR vs HR (54% vs 35%, p value 0.15) and B lineage vs T lineage (50% vs 35%, p value 0.11). Variable n 5 year EFS p value Study participation No 165 76 (+/− 3.9) 0.47 Yes 157 81 (+/− 3.3) Risk group SR 175 85 (+/− 3.0) HR 132 73 (+/− 4.2) (0.038 to SR) Infant 15 59 (+/−12.9) (0.011 to SR) Discussion: Participation in a research study for treatment of pediatric ALL was not associated with improved outcome in our large single institution series. Study participation was not different by clinical features, including distance to the primary residence. Strict standardization of treatment for all patients may contribute to the similar outcome for SP and NP.
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