A pilot study evaluating the use of sirolimus in children and young adults with desmoid-type fibromatosis
Corresponding Author
Aaron R. Weiss
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Correspondence
Aaron Weiss, Department of Pediatrics, Division of Pediatric Hematology-Oncology, Maine Medical Center, 22 Bramhall St, Portland, ME 04102, USA.
Email: [email protected]
Search for more papers by this authorSarah Dry
Department of Pathology Bone, Soft Tissue and GI Pathology, University of California Los Angeles, Los Angeles, California, USA
Search for more papers by this authorClara Maygar
Department of Pathology Bone, Soft Tissue and GI Pathology, University of California Los Angeles, Los Angeles, California, USA
Search for more papers by this authorAnya Cutler
MaineHealth Institute for Research, Portland, Maine, USA
Search for more papers by this authorChristine W. Lary
Roux Institute and the Bouve College of Health Sciences at Northeastern University, Portland, Maine, USA
Search for more papers by this authorCarmen Khoo
MaineHealth Institute for Research, Portland, Maine, USA
Deceased.
Search for more papers by this authorJillian E. Fergione
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorMelanie M. Hounchell
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorKathleen Glick
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorMeghen Browning
Division of Hematology/Oncology, Department of Pediatrics, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA
Search for more papers by this authorSun Ha Choo
Division of Hematology/Oncology, Department of Pediatrics, Rady Children's Hospital, San Diego, California, USA
Search for more papers by this authorDouglas S. Hawkins
Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, Washington, USA
Search for more papers by this authorJoanne Lagmay
Division of Hematology/Oncology, Department of Pediatrics, University of Florida Health Science Center, Gainesville, Florida, USA
Search for more papers by this authorMichelle Manalang
Department of Pediatrics, Marshfield Marshfield Medical Center, Marshfield, Wisconsin, USA
Search for more papers by this authorStephen X. Skapek
Division of Hematology/Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorBrenda Weigel
Division of Hematology/Oncology, Department of Pediatrics, University of Minnesota/Masonic Cancer Center, Minneapolis, Minnesota, USA
Search for more papers by this authorStephanie Verwys
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorNoah Federman
Departments of Pediatrics and Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA
Search for more papers by this authorCorresponding Author
Aaron R. Weiss
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Correspondence
Aaron Weiss, Department of Pediatrics, Division of Pediatric Hematology-Oncology, Maine Medical Center, 22 Bramhall St, Portland, ME 04102, USA.
Email: [email protected]
Search for more papers by this authorSarah Dry
Department of Pathology Bone, Soft Tissue and GI Pathology, University of California Los Angeles, Los Angeles, California, USA
Search for more papers by this authorClara Maygar
Department of Pathology Bone, Soft Tissue and GI Pathology, University of California Los Angeles, Los Angeles, California, USA
Search for more papers by this authorAnya Cutler
MaineHealth Institute for Research, Portland, Maine, USA
Search for more papers by this authorChristine W. Lary
Roux Institute and the Bouve College of Health Sciences at Northeastern University, Portland, Maine, USA
Search for more papers by this authorCarmen Khoo
MaineHealth Institute for Research, Portland, Maine, USA
Deceased.
Search for more papers by this authorJillian E. Fergione
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorMelanie M. Hounchell
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorKathleen Glick
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorMeghen Browning
Division of Hematology/Oncology, Department of Pediatrics, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA
Search for more papers by this authorSun Ha Choo
Division of Hematology/Oncology, Department of Pediatrics, Rady Children's Hospital, San Diego, California, USA
Search for more papers by this authorDouglas S. Hawkins
Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, Washington, USA
Search for more papers by this authorJoanne Lagmay
Division of Hematology/Oncology, Department of Pediatrics, University of Florida Health Science Center, Gainesville, Florida, USA
Search for more papers by this authorMichelle Manalang
Department of Pediatrics, Marshfield Marshfield Medical Center, Marshfield, Wisconsin, USA
Search for more papers by this authorStephen X. Skapek
Division of Hematology/Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Search for more papers by this authorBrenda Weigel
Division of Hematology/Oncology, Department of Pediatrics, University of Minnesota/Masonic Cancer Center, Minneapolis, Minnesota, USA
Search for more papers by this authorStephanie Verwys
Division of Hematology/Oncology, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA
Search for more papers by this authorNoah Federman
Departments of Pediatrics and Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA
Search for more papers by this authorThe findings within this study were presented as an oral abstract at the annual Desmoid Tumor Research Foundation Meeting in September 2018, Philadelphia, PA, USA.
Abstract
Deregulation of the mTOR pathway may play an important role in tumor biology when the APC/β-catenin pathway is disrupted in desmoid-type fibromatosis (DT). A pilot study was conducted to determine whether sirolimus can block the mTOR pathway (primary aim) as well as determine whether it can safely be given in the preoperative setting, decrease tumor size/recurrence, and decrease tumor-associated pain in children and young adults (secondary aims) with DT. Nine subjects ages 5–28 years were enrolled from 2014 to 2017 across four centers. Sirolimus was feasible and was associated with a nonstatistically significant decrease in pS706K activation.
CONFLICT OF INTEREST STATEMENT
Aaron R. Weiss is chair of the Desmoid Tumor Research Foundation Medical Advisory Board, is on the medical advisory board for SpringWorks Therapeutics (no honoraria), and is a paid consultant for BioAtla. Noah Federman has received speaking and advisory honoraria from Bayer AG. Noah Federman receives grant support from NCI/NCATS CTSA and CIRM.
Supporting Information
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