2281 - Spatially Fractionated Radiotherapy Followed by Pre-Operative Radiotherapy for Resectable Soft Tissue Sarcoma: Interim Safety Results of a Prospective Trial
Presenter(s)
T. K. Yanagihara1,2, L. J. Rankine2, S. X. Chang2, D. L. Casey1,2, L. Du Pisanie3, L. G. Dodd4, R. J. Esther5, C. Kowalczyk1, Y. Z. Lee1,3, P. Mody3, K. A. Rodby6, P. M. Spanheimer7, J. N. Stein1,8, X. Tan9, M. Woodcock1,8, G. P. Gupta1,2, and J. E. Tepper1,2; 1Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 2Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, 3Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, 4Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, NC, 5Department of Orthopedics, University of North Carolina School of Medicine, Chapel Hill, NC, 6Division of Plastic Surgery, UNC Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, 7Division of Surgical Oncology, UNC Department of Surgery, Chapel Hill, NC, 8Division of Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, 9Gillings School of Global public health, University of North Carolina, Chapel Hill, NC
Purpose/Objective(s): Spatially fractionated radiotherapy (GRID) has traditionally been used when conventional radiotherapy (XRT) is not feasible and aims to deliver high doses of radiation while sparing intervening areas of normal tissue. However, limited data exist on GRID combined with full-dose conventional radiotherapy. The LCCC2250 trial (NCT06073067) evaluates treatment-naïve patients with soft tissue sarcoma (STS) receiving GRID followed by pre-operative XRT and surgical resection. This trial tests the safety, efficacy, and mechanism of action of GRID using a 3+3 safety lead-in with early stopping rules. Here, we present a pre-specified safety analysis of the initial cohort.
Materials/Methods: Eligible adult (=18 years) patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 and a primary or recurrent resectable STS (=5 cm) are eligible. Exclusion criteria include prior chemotherapy (for sarcoma), previous radiotherapy to the affected limb, wound healing impairments (e.g., uncontrolled diabetes), or significant ipsilateral lymphedema. Patients receive a single 18 Gy GRID dose using multileaf collimator-based 3D treatment planning. After 72–96 hours, ultrasound-guided core needle biopsies are obtained from peak and valley regions for correlative studies. Following biopsy, conventionally fractionated XRT (50 Gy in 25 fractions) is initiated. Patients then proceed to surgical resection, with no planned adjuvant local or systemic therapy.
Toxicities are graded using CTCAE v5.0, with a pause and expanded safety cohort triggered by:- Delay of =7 days in initiating XRT
- Treatment break of =6 consecutive days during XRT
- Treatment break of =14 non-consecutive days during XRT
- Delay of =30 days to scheduled surgical resection
- Any Grade =4 toxicity
Results: The first three patients were enrolled sequentially, and no safety events triggered a trial pause. All had high-grade sarcomas in the thigh, with maximum tumor dimensions of 10.9 cm, 25.3 cm, and 10.7 cm. Peak pain scores during radiotherapy were 4, 5, and 6 (on a 10-point scale). Adverse events (AEs) during XRT were dermatitis, fatigue, edema, neuropathy, and pain, and all were grade 1. All patients underwent margin-negative resection, with residual viable tumor percentages of 30%, 60%, and 50%. Postoperative maximum AE grade was 2 for wound healing. At analysis, all patients remained alive, with a median follow-up of 9 months from enrollment.
Conclusion: This is the first prospective trial evaluating GRID followed by preoperative XRT and surgical resection for curative treatment in STS. The pre-defined safety criteria have been met, allowing continued enrollment without an expanded safety cohort. Further interim analyses will monitor adverse events. Additional future analyses will assess pathologic responses and disease outcomes, and investigate the tumor-immune microenvironment through correlative studies.