Safety of dose escalation for pancreatic cancer using a uni-directional, Pd-103 implantable radiation device: Results of a phase I trial
PURPOSE/OBJECTIVE(S): Pancreatic cancer is a challenging disease to treat with approximately 30% local recurrence following surgery. A uni-directional palladium (Pd-103) device implanted at the time of surgery during tumor resection may decrease the local recurrence rate. We performed a dose escalation study to determine the maximum tolerable dose (MTD) for the implantable device. MATERIALS/METHODS: A Phase I/II Clinical Trial to implant the Pd-103 device in pancreatic cancer patients with borderline resectable/locally advanced disease is ongoing. All patients received at least 8 weeks of combination chemotherapy prior to enrollment. Patients were prescribed neoadjuvant radiation with a median dose of 50.4 Gy (range 30-55). Phase I investigated 25 Gy and 35 Gy EQD2 (37.8 Gy and 50.4 Gy physical dose) dose levels, prescribed to 5 mm depth. 11 patients were treated with a device consisting of a matrix of Pd-103 radiation sources on a bio-absorbable membrane with a gold shield embedded in each source to attenuate radiation in one direction from the device. Primary endpoint was vascular toxicity at 2 months. Secondary endpoints included additional operating room time, source migration, and disease recurrence at 3 months follow up. RESULTS: Median age was 64.1 (range 47-79) and 7 of 11 patients were male. Sources were implanted successfully in 11 patients during surgery with radiation sources directed toward the retroperitoneal margin. For the first 5 patients, implants were prescribed to deliver 25 Gy EQD2. 1 of 5 patients suffered a pneumothorax immediately following surgery judged to be unrelated to the device. For the next 6 patients, prescription dose was increased to 35 Gy EQD2. 1 of 6 had an SMV thrombosis possibly related to the device. Device placement added 23 min (range 8-37 min). No sources migrated during the 3-month follow up period. Two of 11 patients developed metastasis: one hepatic metastasis, and another pulmonary metastasis. There was no local disease recurrence within the follow up period. CONCLUSION: Patients tolerated the device well with only one adverse event possibly related to study treatment. A MTD of 35 Gy EQD2 was determined to be safe for this patient population and is being prescribed in the phase II portion of the study. The permanently implantable, uni-directional, Pd-103 device delivers a targeted dose boost to the surgical margin in this difficult to treat patient population. The ongoing phase II protocol is currently enrolling additional subjects to evaluate local control at 1 year.