The Safety and Efficacy of SCART for Bulky Metastatic or Recurrent Cancer, a Phase I Study

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.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.A total of 21 patients received SCART and have eligible data for study follow-up. The dose was escalated for two patients to 24 GyX3. No grade 3 toxicity was observed in any of the enrolled patients. The median SCART dose was 18 Gy (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). Of 15 patients with available data for progression free survival, 9 had a local recurrence or were deceased. Estimated median survival (i.e., when survival is 50%) was equal to16.80 months (95% CI = 13.90, NA). The survival rate at 12 months and 24 months were72.22% and 24.07%, respectively. Of 15 patients with available data for time to local recurrence, 3 people had a local recurrence. The percent of patients that were free from local recurrence at one and two years after the beginning of SCART treatment was 85.56% for both.Despite the high dose delivered and the excellent local control achieved; the incidence of Any toxicity was unexpectedly low. Multiple courses of SCART are possible. The optimal dose, volume and timing of SCART still need more study.