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Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study

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....

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Autores principales: Nathenson, Michael J., Hu, Junxiao, Ratan, Ravin, Somaiah, Neeta, Hsu, Robert, DeMaria, Peter J., Catoe, Heath W., Pang, Angela, Subhawong, Ty K., Amini, Behrang, Sweet, Kevin, Feister, Katharina, Malik, Karan, Jagannathan, Jyothi, Braschi-Amirfarzan, Marta, Sheren, Jamie, Caldas, Yupanqui, Moreno Tellez, Cristiam, Rosenberg, Andrew E., Lazar, Alexander J., Maki, Robert G., Benedetto, Pasquale, Cohen, Jonathan, Trent, Jonathan C., Ravi, Vinod, Patel, Shreyaskumar, Wilky, Breelyn A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475245/
https://www.ncbi.nlm.nih.gov/pubmed/35180772
http://dx.doi.org/10.1158/1078-0432.CCR-21-4504
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author Nathenson, Michael J.
Hu, Junxiao
Ratan, Ravin
Somaiah, Neeta
Hsu, Robert
DeMaria, Peter J.
Catoe, Heath W.
Pang, Angela
Subhawong, Ty K.
Amini, Behrang
Sweet, Kevin
Feister, Katharina
Malik, Karan
Jagannathan, Jyothi
Braschi-Amirfarzan, Marta
Sheren, Jamie
Caldas, Yupanqui
Moreno Tellez, Cristiam
Rosenberg, Andrew E.
Lazar, Alexander J.
Maki, Robert G.
Benedetto, Pasquale
Cohen, Jonathan
Trent, Jonathan C.
Ravi, Vinod
Patel, Shreyaskumar
Wilky, Breelyn A.
author_facet Nathenson, Michael J.
Hu, Junxiao
Ratan, Ravin
Somaiah, Neeta
Hsu, Robert
DeMaria, Peter J.
Catoe, Heath W.
Pang, Angela
Subhawong, Ty K.
Amini, Behrang
Sweet, Kevin
Feister, Katharina
Malik, Karan
Jagannathan, Jyothi
Braschi-Amirfarzan, Marta
Sheren, Jamie
Caldas, Yupanqui
Moreno Tellez, Cristiam
Rosenberg, Andrew E.
Lazar, Alexander J.
Maki, Robert G.
Benedetto, Pasquale
Cohen, Jonathan
Trent, Jonathan C.
Ravi, Vinod
Patel, Shreyaskumar
Wilky, Breelyn A.
author_sort Nathenson, Michael J.
collection PubMed
description 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
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spelling pubmed-94752452023-01-05 Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study Nathenson, Michael J. Hu, Junxiao Ratan, Ravin Somaiah, Neeta Hsu, Robert DeMaria, Peter J. Catoe, Heath W. Pang, Angela Subhawong, Ty K. Amini, Behrang Sweet, Kevin Feister, Katharina Malik, Karan Jagannathan, Jyothi Braschi-Amirfarzan, Marta Sheren, Jamie Caldas, Yupanqui Moreno Tellez, Cristiam Rosenberg, Andrew E. Lazar, Alexander J. Maki, Robert G. Benedetto, Pasquale Cohen, Jonathan Trent, Jonathan C. Ravi, Vinod Patel, Shreyaskumar Wilky, Breelyn A. Clin Cancer Res Translational Cancer Mechanisms and Therapy 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 American Association for Cancer Research 2022-09-15 2022-02-18 /pmc/articles/PMC9475245/ /pubmed/35180772 http://dx.doi.org/10.1158/1078-0432.CCR-21-4504 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Translational Cancer Mechanisms and Therapy
Nathenson, Michael J.
Hu, Junxiao
Ratan, Ravin
Somaiah, Neeta
Hsu, Robert
DeMaria, Peter J.
Catoe, Heath W.
Pang, Angela
Subhawong, Ty K.
Amini, Behrang
Sweet, Kevin
Feister, Katharina
Malik, Karan
Jagannathan, Jyothi
Braschi-Amirfarzan, Marta
Sheren, Jamie
Caldas, Yupanqui
Moreno Tellez, Cristiam
Rosenberg, Andrew E.
Lazar, Alexander J.
Maki, Robert G.
Benedetto, Pasquale
Cohen, Jonathan
Trent, Jonathan C.
Ravi, Vinod
Patel, Shreyaskumar
Wilky, Breelyn A.
Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study
title Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study
title_full Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study
title_fullStr Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study
title_full_unstemmed Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study
title_short Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study
title_sort systemic chemotherapies retain antitumor activity in desmoid tumors independent of specific mutations in ctnnb1 or apc: a multi-institutional retrospective study
topic Translational Cancer Mechanisms and Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475245/
https://www.ncbi.nlm.nih.gov/pubmed/35180772
http://dx.doi.org/10.1158/1078-0432.CCR-21-4504
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