4 research outputs found

    Systemic chemotherapies retain antitumor activity in desmoid tumors independent of specific mutations in CTNNB1 or APC: A multi-institutional retrospective study

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    PURPOSE: Determine whether specific CTNNB1 or APC mutations in patients with desmoid tumor were associated with differences in clinical responses to systemic treatments. EXPERIMENTAL DESIGN: We established a multi-institutional dataset of previously treated patients with desmoid tumor across four U.S. sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, desmoid tumor location, and treatment regimen. RESULTS: A total of 259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First- and second-line cPFS, rPFS, and TTNT were not significantly affected by mutation subtype; however, APC-mutant desmoid tumors demonstrated nonstatistically significant inferior outcomes. Extremity/trunk desmoid tumor location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared with surgery or other therapies, including estrogen-receptor blockade and imatinib. OS was significantly worse with APC or CTNNB1 negative/other mutations. CONCLUSIONS: Mutation subtype did not affect responses to specific systemic therapies. APC mutations and nonextremity desmoid tumor locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk desmoid tumors should be prospectively evaluated. See related commentary by Greene and Van Tine, p. 3911

    Parameterization of solar radiation from model and observations

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    The influence of the external and internal structure of clouds on the incoming solar radiation cannot yet be included in parameterizations used in numerical models. Based on numerical simulations, SCHEWSKI and MACKE (2003) (Schewski-parameterization) have shown that a robust link exists between the domain averaged cloud and the domain averaged solar broadband radiation fluxes, despite the 3d nature of the cloud fields involved. The present work revisits this approach with observed cloud (cloud cover and liquid water path) and radiation (downwelling shortwave radiative flux) properties obtained from the Richard Assmann Observatory (RAO) of the German Weather Service in Lindenberg. Applying the original (model based) cloud-radiation parameterization by SCHEWSKI and MACKE (2001) to observed domain averaged cloud fields yields an overall good correlation between observed and parameterized downwelling solar radiation fluxes. However, the parameterized fluxes strongly underestimate the observations. The Schewski parameterization has been modified by removing the bias and re-adjusting the parameterization coefficients to match the observed cloud and radiation correlation. Furthermore, the empirical parameterization by ZILLMAN (1972) has been implemented for describing the clear conditions. Applying the new parameterization to an independent data set provides significant improvements. However, the accuracy remains in the order of previously used one-or two-parameter empirical cloud-radiation parameterizations. We conclude that cloud cover and liquid water path, i.e. those data that are available from large scale climate models, cannot be regarded as sufficient to describe the cloud radiative effect at the surface

    Systemic chemotherapies retain anti-tumor activity in desmoid tumors independent of specific mutations in CTNNB1 or APC: A multi-institutional retrospective study

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    Determine if specific CTNNB1 or APC mutations in desmoid tumor (DT) patients were associated with differences in clinical responses to systemic treatments. We established a multi-institutional dataset of previously-treated DT patients across four US sarcoma centers, including demographic and clinicopathologic characteristics, treatment regimens, and clinical and radiographic responses. CTNNB1 or APC mutation status was determined from prior pathology records, or archival tissue was requested and analyzed by Sanger sequencing and/or next-generation sequencing. Evaluable patients with mutation results were analyzed to determine clinical progression-free survival (cPFS), RECIST 1.1 PFS (rPFS), time to next treatment (TTNT), and overall survival (OS). Kaplan-Meier analysis and Cox proportional hazard regression were performed to identify differences in cPFS, rPFS, TTNT, and OS by mutation subtype, DT location and treatment regimen. 259 evaluable patients were analyzed for at least one of the survival outcomes, with 177 patients having mutation data. First and second line cPFS, rPFS and TTNT were not significantly affected by mutation subtype, however APC mutant DTs demonstrated non-statistically significant inferior outcomes. Extremity/trunk DT location and treatment with doxorubicin-based, methotrexate/vinca alkaloids and sorafenib regimens were associated with better clinical outcomes compared to surgery, or "other" therapies including estrogen-receptor blockade and imatinib. Overall survival was significantly worse with APC or CTNNB1 negative/other mutations. Mutation subtype did not affect responses to specific systemic therapies. APC mutations and non-extremity DT locations remain prognostic for worse outcomes, and earlier initiation of systemic therapy for these higher-risk DTs should be prospectively evaluated
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