1113 - Endoscopic Ultrasound Fine Needle Injection of NBTXR3 Activated by Radiotherapy with Concurrent Chemotherapy for Adenocarcinoma of the Esophagus: Feasibility and Safety of the Phase I Dose Escalation Part for the Photon-Based Cohort
Presenter(s)
S. H. Lin1, E. Coronel2, S. Gandhi1, J. K. Bronk1, D. C. Qian1, J. Y. Chang1, M. S. O'Reilly1, M. S. Ning1, A. B. Chen1, Q. N. Nguyen3, D. N. Amaya1, C. Hoang1, L. Gentempo1, W. Hofstetter4, M. Blum Murphy5, A. C. Koong6, and Z. Liao1; 1Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
Neoadjuvant chemoradiation (CRT) had been a standard treatment for esophageal adenocarcinoma (EADC) but pathologic complete response (pathCR) is seen in only 25% of patients, necessitating the need to improve treatment response, particularly if organ preserving approach is being considered. We designed a phase I trial for direct tumor injection of NBTXR3 (R3), a hafnium oxide nanoparticle that enhances the local radiation effect when activated by ionizing radiation. We report the planned analysis of the safety of the first 9 patients in the photon cohort.Materials/Methods:
Stage 2-3 EADC planned for CRT to 50.4 Gy were enrolled. Two dose escalations at 3 dose levels will occur in 9 photon and 9 proton patients separately, with expansion of either cohort after safety is established for up to 30 patients. All photon patients are treated with volumetric arc therapy. The primary objective is to determine the safety and recommended phase 2 dose (RP2D) in either radiation cohorts. Bayesian optimal interval (BOIN) design with accelerated titration is used for R3 dose escalation based on the drug volume % of the GTV: 15%, 22% and 33%. Patients were premedicated within 12 hours of the procedure with methylprednisolone. 22 gauge fine needle injection (FNI) was performed under endoscopic ultrasound (EUS) guidance (EUS-FNI), at a rate of 1 cc/min, to distribute R3 throughout the tumor mass through multiple sites of injections. Verification CT scan is taken within 3 days of the injection to visualize the distribution of the radiopaque R3 prior to starting CRT. Toxicity assessments use CTCAE v5.0. Dose limiting toxicity begins on day of injection and ends upon completion of the 4-week post CRT recovery window.Results:
Only one patient each was treated at 15% and 22%, with 7 treated at 33% administered prior to CRT. There were no complications during EUS-FNI. In the first patient, significant tumor swelling was seen 3 days after injection which required adaptive replanning, but this issue was ameliorated after the introduction of steroid premedication. All patients completed CRT without toxicity that could be attributable to R3, with the expected CRT related toxicities of fatigue, esophagitis, and lymphopenia. Two of the 6 patients with surgery had pathCR, and 4 of 6 had major pathologic response. 4 developed distant recurrence after CRT with or without surgery. R3 were visualized on the verification scan for all patients, and those who didn’t get surgery, the particles remain within the esophageal wall for all patients seen in follow up. No long-term stricture or delayed adverse effects were noted at a minimal follow up of 6 months post CRT.Conclusion:
In this first cohort of 9 photon treated patients with EADC, the RP2D is 33%, without safety concerns, and no periprocedural or delayed adverse events were noted. Initial clinical response and outcomes are promising. The study continues accrual for the proton cohort. Amendment is ongoing for inclusion of both squamous and adenocarcinomas.