Spatially Fractionated Radiotherapy (GRID) Prior to Standard Neoadjuvant Conventionally Fractionated Radiotherapy for Bulky, High-Risk Soft Tissue and Osteosarcomas: Feasibility, Safety, and Promising Pathologic Response Rates

Abstract

Spatially fractionated radiotherapy (GRID) has been utilized primarily in the palliative and definitive treatment of bulky tumors. Delivered in the modern era primarily with megavoltage photon therapy, this technique offers the promise of safe dose escalation with potential immunogenic, bystander and microvasculature effects that can augment a conventionally fractionated course of radiotherapy. At the University of Maryland, an institutional standard has arisen to incorporate a single fraction of GRID radiation in large (.8 cm), high-risk soft tissue and osteosarcomas prior to a standard fractionated course. Herein, we report on the excellent pathologic responses and apparent safety of this regimen in 26 consecutive patients.

An International Consensus on the Design of Prospective Clinical–Translational Trials in Spatially Fractionated Radiation Therapy

“…Disease-specific series of definitively treated STS patients have been presented in abstract form 9 10 , and one outcome study 12 was recently published. These studies show high response rates, local control rates of 85-100% 9 12 and limb-sparing rate of 93% 9 in bulky (>8-10 cm) sarcomas, which overall exceed the outcomes of standard therapy [39][40][41] .…”

“…Spatially fractionated radiation therapy (SFRT) is a complex concept of increasing clinical, experimental and translational interest. Pilot studies have shown unexpectedly high tumor responses to SFRT and low toxicity in bulky metastatic and primary tumors [1][2][3][4][5][6][7][8][9][10][11][12][13] . The observed enhanced tumoricidal effects of SFRT are thought to be related to the vastly inhomogeneous dose distributions 4 14 15 .…”

“…Based on these hypothesis-generating studies [5][6][7][8][9][10][11][12][13] , well-designed prospective clinical trials, preferably multi-institutional studies, are now needed to rigorously study SFRT as a modality.…”

“…Pilot studies have shown low rates of toxicities and unexpectedly high tumor responses to SFRT in bulky metastatic and primary tumors. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 The observed enhanced tumoricidal effects of SFRT are thought to be related to the vastly inhomogeneous dose distributions. 4 , 14 , 15 The inherent advantages of ablative stereotactic radiosurgery or stereotactic radiation therapy like dose “peaks,” dispersed throughout the tumor, combined with interlaced low dose in the “valleys,” suited to preserve the tumor microenvironment and vasculature, are postulated to promote bystander and abscopal effects as potential underlying mechanisms for higher tumor response.…”

“… 1 , 2 , 3 , 4 These studies established the initial dose-response relationships and the need for combining SFRT with fractionated conventional radiation therapy. 2 , 3 More recently, smaller, disease-specific pilot studies in head and neck (H&N), 5 , 6 , 13 lung, 7 and cervical 8 cancer, sarcoma, 9 , 10 , 12 and melanoma 11 have advanced the SFRT concept from palliative treatment to curative-intent therapy of bulky primary tumors and showed similarly promising local control. They have also broadened the SFRT experience from reporting on palliative responses to providing early data on favorable survival outcomes in patients with nonmetastatic cancer 5 , 6 , 7 , 8 while affording longer follow-up for adverse effect assessment, which corroborates SFRT's overall favorable toxicity profile.…”