SARC018: A SARC PILOT MULTICENTER STUDY OF PREOPERATIVE RADIATION AND SURGERY IN PATIENTS WITH HIGH- RISK DESMOID TUMORS Robert S. Benjamin, M.D.

Objectives  The trial ’ s primary objectives are to determine feasibility of performing a multicenter study of radiation therapy through SARC and to determine overall progression-free survival from start of treatment in these patients.

Background  Patients with desmoid fibromatosis and 45F beta catenin mutation (28% in our series) who underwent surgical resection as initial therapy at our institution have a 45% 3- or 5-year recurrence-free survival compared with about 80% for those with 41A mutation or no detectable mutation.

Background (continued)  Radiation therapy has been effective in the treatment of desmoid patients with a similar degree of local control as surgery.  Of the 7 patients received radiotherapy in combination with surgery, 2 (28%) experienced tumor recurrence within the follow up period, in contrast with 21/27 patients (77%) who have not been treated with radiation.

Screening  Slides for diagnosis and unstained slides or blocks for DNA extraction should be sent to Dr. Dina Lev at M.D. Anderson.  Patients with 45F beta catenin mutation would be considered for the protocol.

Eligibility  Desmoid tumor with 45 F beta catenin mutation and no FAP mutation.  Tumor must be  Resectable  <25 cm in largest dimension  Location such that radiation can be delivered with acceptable normal tissue toxicity  In an region that has not been previously irradiated

Pretreatment Evaluation  MRI with and without contrast should be obtained on each patient.  The post-contrast T1 image will be used for radiation planning.

Radiation Therapy  Either 3D conformal radiation therapy or intensity modulated radiation therapy or electron radiotherapy may be utilized as deemed appropriate.  A prescription dose of 50 Gy in 25 daily fractions will be prescribed.

Surgery  Wide resection of the tumor will be performed 4-8 weeks following completion of radiation therapy.

Follow-up  In addition to physical examination, CT, MRI, or Ultrasound will be performed on the following schedule:  Years 1-3: Every 4 months  Years 4-5: Every 6 months  Years 6-10: Every 12 months

Radiation Therapy Quality Assurance  Radiation treatment planning records will be sent to Dr. Ashleigh Guadagnolo at M.D. Anderson for review.  If any portion of the gross target volume (GTV) receives <50 Gy, that is a major protocol violation.  If any portion of the clinical target volume (CTV) receives <50 Gy, that is a minor protocol violation.

Statistical Considerations  This is a pilot study to determine if a larger study could be performed and is of clinical interest.  Major protocol violations should not exceed 3 patients (10%).  A median progression-free survival of >4.5 years would be of interest, while a median progression-free survival of 2.6 years would not warrant further study.