Spatially Fractionated GRID Radiation Therapy for the Treatment of Soft Tissue Sarcoma in Patients Undergoing Standard Radiation Therapy and Surgery

Inclusion Criteria

• Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. Subjects is willing and able to comply with study procedures based on the judgement of the investigator.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 – 2 (Karnofsky Performance Status equivalent of 50 – 100).
• Histological or cytological evidence/confirmation of soft tissue sarcoma as determined by core-needle biopsy or excision biopsy (i.e., fine needle biopsy is not allowed). If the diagnostic tissue is not available or sufficient to perform correlative studies, must be willing to provide the mandatory pre-treatment core- needle biopsy. In some cases of soft tissue sarcoma (STS), patients undergo an attempted surgical resection for a presumed benign condition and the specimen reveals malignancy. Such patients are allowed so long as a complete, oncologic, resection was not performed/attempted and there is ≥ 5 cm of remaining primary tumor.
• Multidisciplinary determination (involving at least surgical and radiation oncology) that standard of care treatment consists of pre-operative conventionally fractionated XRT and complete surgical resection. Patients must be eligible for resection as determined by a board-certified surgical oncologist with experience in resection of STS.
• Primary tumor measuring ≥ 5 cm in greatest dimension clinically or by cross-sectional imaging. Sites permissible include the trunk, abdomen, and upper (including shoulder, arm, elbow, forearm, and hand) and lower (including hip, thigh, knee, leg, and foot) extremities.
• Patients with lymph node metastases are allowed if the primary tumor is ≥ 5 cm and there is sufficient anatomical separation between the primary tumor and involved lymph nodes to allow treatment of the primary tumor with GRID but not the lymph nodes.
• Patients with metastatic disease are allowed if the patient is planned to have a complete surgical resection of their primary disease and meet other eligibility criteria.
• The subject must be willing to provide a mandatory research biopsy 72-96 hours after receiving GRID therapy and prior to SOC XRT and tumor resection with one needle pass into a peak-dose region and one needle pass into a trough-dose region.
• Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Prior radiation and/or chemotherapy for a prior diagnosis of cancer are allowed if 1) the patient has no known measurable disease from the prior cancer and 2) at least 5 years has passed from the last cancer-directed treatment (including endocrine therapy for breast and prostate cancer).
• Subjects must have a life expectancy of at least 12 months.
• Females of childbearing potential must have a negative serum or urine pregnancy test that is obtained after the standard pre-radiation fertility discussion with their provider and before study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
• Must be willing to follow SOC conception guidelines for patients receiving radiotherapy and who may father (male) or bear (female) children.
• XRT must follow SOC as per National Comprehensive Cancer Network (NCCN) guidelines.
• If any protocol visits are planned to be performed virtually, the patient must have the technical ability to utilize a video-enabled form of telemedicine or have the ability to submit digital images, to assess skin reaction.

Exclusion Criteria

• Subjects who have received prior radiotherapy to the tumor site.
• Subjects who have undergone tumor resection of the primary tumor or who have developed tumor recurrence after resection with residual grade ≥ 2 toxicities in the area to be treated with GRID.
• History of serious or non-healing wound, ulcer, or bone fracture in the treatment limb within the last 5 years.
• History of clinically significant lymphedema in the treatment limb.
• History of lupus, scleroderma, Sjogren’s syndrome, Ehlers-Danlos syndrome (any type), or other collagen vascular disease that may pose a relative contraindication, due to increased risk of skin or soft tissue toxicity, with radiation.
• History or evidence of active autoimmune disease (e.g., hepatitis, colitis) within 6 months of enrollment; or any history of chronic autoimmune disease that has required systemic treating (i.e., use of corticosteroids, immunosuppressive drugs) within 5 years of enrollment, including inflammatory bowel disease even if bowel is not within the field of irradiation.
• Sarcoma is thought to be arising in a lymph node without a primary site ≥ 5 cm (i.e., GRID treatment is intended for primary disease, not irradiation of lymph nodes).
• Active infection requiring systemic antibiotics or antivirals.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Treatment with any investigational drug or prior cancer treatment (prior radiation and/or chemotherapy) within 5 years prior to study treatment.
• Subject is receiving prohibited medications or treatments.