PMID- 35180772 OWN - NLM STAT- MEDLINE DCOM- 20220916 LR - 20231109 IS - 1557-3265 (Electronic) IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 28 IP - 18 DP - 2022 Sep 15 TI - Systemic Chemotherapies Retain Antitumor Activity in Desmoid Tumors Independent of Specific Mutations in CTNNB1 or APC: A Multi-institutional Retrospective Study. PG - 4092-4104 LID - 10.1158/1078-0432.CCR-21-4504 [doi] 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 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. CI - (c)2022 The Authors; Published by the American Association for Cancer Research. FAU - Nathenson, Michael J AU - Nathenson MJ AD - Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. FAU - Hu, Junxiao AU - Hu J AD - Department of Biostatistics, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Ratan, Ravin AU - Ratan R AUID- ORCID: 0000-0002-4914-7922 AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Somaiah, Neeta AU - Somaiah N AUID- ORCID: 0000-0002-0146-7732 AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Hsu, Robert AU - Hsu R AUID- ORCID: 0000-0003-3957-6106 AD - Department of Medicine, University of Miami School of Medicine, Miami, Florida. FAU - DeMaria, Peter J AU - DeMaria PJ AUID- ORCID: 0000-0003-1313-6065 AD - Department of Medicine, University of Miami School of Medicine, Miami, Florida. FAU - Catoe, Heath W AU - Catoe HW AD - Department of Medicine, University of Miami School of Medicine, Miami, Florida. FAU - Pang, Angela AU - Pang A AD - Department of Medicine, Mount Sinai School of Medicine, New York, New York. FAU - Subhawong, Ty K AU - Subhawong TK AUID- ORCID: 0000-0003-0943-1168 AD - Department of Radiology, University of Miami School of Medicine, Miami, Florida. FAU - Amini, Behrang AU - Amini B AUID- ORCID: 0000-0002-4962-3466 AD - Department of Musculoskeletal Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Sweet, Kevin AU - Sweet K AD - Department of Radiology, University of Miami School of Medicine, Miami, Florida. FAU - Feister, Katharina AU - Feister K AUID- ORCID: 0000-0002-8479-341X AD - Department of Radiology, University of Miami School of Medicine, Miami, Florida. FAU - Malik, Karan AU - Malik K AD - Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. FAU - Jagannathan, Jyothi AU - Jagannathan J AD - Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Braschi-Amirfarzan, Marta AU - Braschi-Amirfarzan M AD - Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, and Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Sheren, Jamie AU - Sheren J AD - Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado. FAU - Caldas, Yupanqui AU - Caldas Y AUID- ORCID: 0000-0002-4666-3155 AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Moreno Tellez, Cristiam AU - Moreno Tellez C AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Rosenberg, Andrew E AU - Rosenberg AE AD - Department of Pathology, University of Miami School of Medicine, Miami, Florida. FAU - Lazar, Alexander J AU - Lazar AJ AUID- ORCID: 0000-0002-6395-4499 AD - Department of Pathology and Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Maki, Robert G AU - Maki RG AUID- ORCID: 0000-0002-9853-2528 AD - Department of Medicine, Mount Sinai School of Medicine, New York, New York. FAU - Benedetto, Pasquale AU - Benedetto P AD - Department of Medicine, University of Miami School of Medicine, Miami, Florida. FAU - Cohen, Jonathan AU - Cohen J AD - Department of Medicine, University of Miami School of Medicine, Miami, Florida. FAU - Trent, Jonathan C AU - Trent JC AUID- ORCID: 0000-0001-6169-5238 AD - Department of Medicine, University of Miami School of Medicine, Miami, Florida. FAU - Ravi, Vinod AU - Ravi V AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Patel, Shreyaskumar AU - Patel S AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Wilky, Breelyn A AU - Wilky BA AUID- ORCID: 0000-0001-5080-497X AD - Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. LA - eng GR - P30 CA046934/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (CTNNB1 protein, human) RN - 0 (beta Catenin) SB - IM CIN - Clin Cancer Res. 2022 Sep 15;28(18):3911-3913. PMID: 35819317 MH - *Fibromatosis, Aggressive/drug therapy/genetics/pathology MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Mutation MH - Prognosis MH - Retrospective Studies MH - beta Catenin/genetics PMC - PMC9475245 EDAT- 2022/02/19 06:00 MHDA- 2022/09/17 06:00 PMCR- 2022/09/15 CRDT- 2022/02/18 20:16 PHST- 2021/12/20 00:00 [received] PHST- 2022/01/23 00:00 [revised] PHST- 2022/02/16 00:00 [accepted] PHST- 2022/02/19 06:00 [pubmed] PHST- 2022/09/17 06:00 [medline] PHST- 2022/02/18 20:16 [entrez] PHST- 2022/09/15 00:00 [pmc-release] AID - 681621 [pii] AID - CCR-21-4504 [pii] AID - 10.1158/1078-0432.CCR-21-4504 [doi] PST - ppublish SO - Clin Cancer Res. 2022 Sep 15;28(18):4092-4104. doi: 10.1158/1078-0432.CCR-21-4504.