TY - JOUR
T1 - Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC
T2 - A Multi-institutional Retrospective Study
AU - Nathenson, Michael J.
AU - Hu, Junxiao
AU - Ratan, Ravin
AU - Somaiah, Neeta
AU - Hsu, Robert
AU - DeMaria, Peter J.
AU - Catoe, Heath W.
AU - Pang, Angela
AU - Subhawong, Ty K.
AU - Amini, Behrang
AU - Sweet, Kevin
AU - Feister, Katharina
AU - Malik, Karan
AU - Jagannathan, Jyothi
AU - Braschi-Amirfarzan, Marta
AU - Sheren, Jamie
AU - Caldas, Yupanqui
AU - Tellez, Cristiam Moreno
AU - Rosenberg, Andrew E.
AU - Lazar, Alexander J.
AU - Maki, Robert G.
AU - Benedetto, Pasquale
AU - Cohen, Jonathan
AU - Trent, Jonathan C.
AU - Ravi, Vinod
AU - Patel, Shreyaskumar
AU - Wilky, Breelyn A.
N1 - Publisher Copyright:
© 2022 TheAuthors.
PY - 2022/9/15
Y1 - 2022/9/15
N2 - 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 nextgeneration 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 bymutation 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, APCmutant 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.
AB - 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 nextgeneration 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 bymutation 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, APCmutant 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.
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U2 - 10.1158/1078-0432.CCR-21-4504
DO - 10.1158/1078-0432.CCR-21-4504
M3 - Article
C2 - 35180772
AN - SCOPUS:85136163670
SN - 1078-0432
VL - 28
SP - 4092
EP - 4104
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -