First-In-Human Phase 1 Study of a Nonwoven Fabric Bioabsorbable Spacer for Particle Therapy: Space-Making Particle Therapy (SMPT)

Abstract

PurposeSurgical spacer placement (SSP) is useful in particle therapy (PT) for patients with abdominal or pelvic tumors located adjacent to normal organs. We developed a nonwoven fabric bioabsorbable spacer made of polyglycolic acid (PGA) sutures that degrades via hydrolysis. We then conducted this first-in-human phase 1 study of the combination of SSP and PT using the PGA spacer, which we termed space-making PT (SMPT). This study aimed to evaluate the safety and efficacy of SMPT in patients with unresectable malignant tumor located adjacent to normal organs.Methods and MaterialsThe eligibility criteria included histologically proven malignant abdominal or pelvic tumor adjacent to the intestines, no metastasis, and no previous radiation therapy. Periodic computed tomography (CT) images were obtained before SSP and before, during, and after PT until the spacer disappeared. Treatment planning was performed for each CT image set until the end of PT, and doses for the planning target volume and organs at risk were analyzed. The thickness and volume of the PGA spacer were measured in each CT image set. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.ResultsFive patients were enrolled in this study. All patients received 70.4 Gy (relative biological effectiveness) of irradiation. V95% of the planning target volume before SSP, at the beginning of PT, and at the end of PT was 82.1% ± 11.3%, 98.1% ± 1.1%, and 97.1% ± 0.8%, respectively. The PGA spacers maintained enough thickness (≥1 cm) until the end of PT and disappeared within 8 months after SSP in all patients. No grade ≥3 acute adverse events were observed.ConclusionsThe SMPT is feasible and useful for abdominal or pelvic tumors adjacent to the intestines. This method may be applicable to unresectable tumors located adjacent to normal organs and may expand the indications of PT.

Space-Making Particle Therapy with Surgical Spacer Placement in Patients with Sacral Chordoma

“…This product might be the solution for increasing the efficacy and feasibility of SMPT. 27 With regard to the technical aspects of spacer operation, spacer placement for sacral chordoma is not difficult because the procedure is similar to low anterior resection of the rectum. Differences between the 2 procedures are the dissection layer and surgical view.…”

Impact on dose distribution and volume changes of a bioabsorbable polyglycolic acid spacer during chemo-proton therapy for a pediatric Ewing sarcoma

“…Changes in the volume of spacers in adults were plotted for reference from Ref. [ 16 ], and the volume reduction rates were similar between adults and our pediatric patient.…”

“…Right panel: changes in the relative volume of the PGA spacer implanted into adult patients (black circles, plotted from ref. [ 16 ]) and the pediatric patient (white circles). The broken lines indicate the volume reduction rate for adult patients.…”

“…It was folded into a two-layer sandwich and fixed together with an adhesion barrier Seprafilm® (Kaken Pharmaceutical Co. Ltd., Japan) in the retroperitoneal space between the tumor and the intestinal tract. It is encouraged that the spacer be used together with the adhesion barrier to avoid induction of the ileus [ 16 ]. There were no acute complications related to the procedure or the device itself.…”

“…The PGA spacer can maintain its thickness and volume for 3 months prior to degradation by hydrolysis in a living body. Long-term stability and safety of the spacer were confirmed in crab-eating monkeys [ 15 ], and its effectiveness has been demonstrated in clinical trials of particle therapy alone in adult patients [ 16 ]. However, the PGA spacer has not been shown to be effective in children so far.…”