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Purpose: SFRT (Spatially fractionated radiation therapy (SFRT) is important in its concept of covering whole or partial tumors with inhomogeneous radiation doses and gives the field more creativity and complimentary applications to supplement the standard school of radiation therapy. SFRT, such as GRID therapy, has been shown to offer benefits in bulky tumor settings. However, the optimal dose and fractionation of SFRT are yet to be explored. Therefore, a prospective, multicenter, dose-escalation trial was initiated. We are proposing a new treatment methodology,  (called Stereotactic Centralized Ablative Radiation Therapy, (SCART), for bulky or metastatic tumors, which is based on the principles of SFRT, by using SBRT methods to deliver an ablative radiation dose to the central portion of the target while keeping the dose to surrounding normal tissue to a relatively low level. We performed a prospective dose escalation study of SCART  for bulky metastatic or recurrent cancer. The purpose of the study was to determine dose-limiting toxicities (DLTs)  and the Maximum Tolerated Dose (MTD) of SCART.

Methods and Materials:  This study was registered at ClinicalTrials.gov Identifier: NCT0488198, and approved at Foshan Chancheng Hospital. Patients with unresectable solid "bulky" nonhematological malignancies with limited treatment options were enrolled and received SCART with a prescription to the central spot in the tumor with a peripheral dose to the tumor edge at around 20% isodose line of the prescription dose. Five dose levels were proposed. The primary endpoint was the maximum tolerated dose (MTD), defined as the highest dose where zero of three or one of six patients experienced grade 3 dose-limiting toxicity (DLT), scored according to the Common Toxicity Criteria for Adverse Events v. 4.03, up to 6 months after SCART.

Results: A total of 21 patients received SCART and have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 toxicity was observed in any of the enrolled patients.  The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.29 months (range: 0.99 - 25.58). Three patients out of the 15 patients with available data for local recurrence (LR) were found to have an LR and the median time to LR was 16.01 months (range: 0.99 - 25.58). There appears to be a trend of tumors decreasing from the patient's first visit date, or pre-SCART, to their final volume post-SCART.  The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.49% (SD: 40.89, p-value:0.009).

Conclusion: SCART dose was safely dose escalated to 24 X 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART.  This regimen will be used in future phase II trials.