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

Nina A. Mayr, James W. Snider, William F. Regine, Majid Mohiuddin, Daniel S. Hippe, José Peñagarícano, Mohammed Mohiuddin, Mahesh R. Kudrimoti, Hualin Zhang, Charles L. Limoli, Quynh Thu Le, Charles B. Simone

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Purpose: Spatially fractionated radiation therapy (SFRT), which delivers highly nonuniform dose distributions instead of conventionally practiced homogeneous tumor dose, has shown high rates of clinical response with minimal toxicities in large-volume primary or metastatic malignancies. However, prospective multi-institutional clinical trials in SFRT are lacking, and SFRT techniques and dose parameters remain variable. Agreement on dose prescription, technical administration, and clinical and translational design parameters for SFRT trials is essential to enable broad participation and successful accrual to rigorously test the SFRT approach. We aimed to develop a consensus for the design of multi-institutional clinical trials in SFRT, tailored to specific primary tumor sites, to help facilitate development and enhance the feasibility of such trials. Methods and Materials: Primary tumor sites with sufficient pilot experience in SFRT were identified, and fundamental trial design questions were determined. For each tumor site, a comprehensive consensus effort was established through disease-specific expert panels. Clinical trial design criteria included eligibility, SFRT technology and technique, dose and fractionation, target- and normal-tissue dose parameters, systemic therapies, clinical trial endpoints, and translational science considerations. Iterative appropriateness rank voting, expert panel consensus reviews and discussions, and public comment posting were used for consensus development. Results: Clinical trial criteria were developed for head and neck cancer and soft-tissue sarcoma. Final consensus among the 22 trial design categories each (a total of 163 criteria) was high to moderate overall. Uniform patient cohorts of advanced bulky disease, standardization of SFRT technologies and dosimetry and physics parameters, and collection of translational correlates were considered essential to trial design. Final guideline recommendations and the degree of agreement are presented and discussed. Conclusions: This consensus provides design guidelines for the development of prospective multi-institutional clinical trials testing SFRT in advanced head and neck cancer and soft-tissue sarcoma through in-advance harmonization of the fundamental clinical trial design among SFRT experts, potential investigators, and the SFRT community.

Original languageEnglish
Article number100866
JournalAdvances in Radiation Oncology
Issue number2
StatePublished - Mar 1 2022

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging


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