Endoscopic Ultrasound-Guided Interstitial Brachytherapy of Unresectable Pancreatic Cancer: Results of a Pilot Trial

Background and Study Aims: Intraoperative interstitial brachytherapy has been found to be effective when used during laparotomy to improve local control in patients with locally advanced pancreatic cancer. In this study, we report the results of using endoscopic ultrasound- (EUS-)guided interstitial brachytherapy in patients with advanced pancreatic cancer, with respect to tumor response, clinical response, safety, and complications.
Patients and Methods: Fifteen patients (eight men, seven women; median age 61 years) with unresectable pancreatic adenocarcinoma were enrolled into the study, eight patients with stage III disease and seven patients with stage IV disease. A mean number of 22 radioactive seeds per patient were implanted into the tumors by EUS-guided needle puncture. The mean total implanted activity was 20 mCi, the minimum peripheral dose was 14 000 cGy, and the mean volume of implants was 52 cm³. Patients were followed-up by examination and by imaging tests every 2 - 3 months: clinical end points included the Karnofsky performance status and pain responses, tumor response (assessed by computed tomography and/or EUS), and survival.
Results: During a median follow-up period of 10.6 months, the objective tumor response was classified as “partial” in 27 % of patients (with a median duration of partial response of 4.5 months), ”minimal” in 20 % patients, and indicative of “stable disease” in 33 % of patients. Clinical benefit was shown in 30 % of patients, mostly due to reduction in pain, but this lasted for a limited time. Local complications (pancreatitis and pseudocyst formation) occurred in three patients; grade III hematologic toxicity occurred in three patients without serious clinical sequelae.
Conclusions: EUS-guided intraoperative interstitial brachytherapy had a moderate local tumor effect and showed some clinical benefit in 30 % of the patients in this study. Combination of this form of treatment with external radiation and/or chemotherapy should be tested in future trials.

References

• 1 Takacsi-Nagy Z, Varga J, Poller I. et al . Successful treatment of a T1 cancer of the pancreatic head with high dose rate brachytherapy and external radiotherapy.  Hepatogastroenterology. 2002;  49 844-846
• 2 Bodner W R, Hilaris B S, Mastoras D A. Radiation therapy in pancreatic cancer: current practice and future trends.  J Clin Gastroenterol. 2000;  30 230-233
• 3 Soetikno R M, Chang K. Endoscopic ultrasound-guided diagnosis and therapy in pancreatic disease.  Gastrointest Endosc Clin N Am. 1998;  8 237-247
• 4 Chang K J, Nguyen P T, Thompson J A. Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma.  Cancer. 2000;  88 1325-1335
• 5 Hecht J R, Bedford R, Abbruzzese J L. et al . A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma.  Clin Cancer Res. 2003;  9 555-561
• 6 Chan H H, Nishioka N S, Mino M. et al . EUS-guided photodynamic therapy of the pancreas: a pilot study.  Gastrointest Endosc. 2004;  59 95-99
• 7 Goldberg S N, Mallery S, Gazelle G S, Brugge W R. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model.  Gastrointest Endosc. 1999;  50 392-401
• 8 Bhutani M S. Endoscopic ultrasonography: new developments and interesting trends.  Endoscopy. 2004;  36 950-956
• 9 Sun S, Qingjie L, Qiyong G. et al . EUS-guided interstitial brachytherapy of the pancreas: a feasibility study.  Gastrointest Endosc. 2005;  62 775-779
• 10 Yeo C J, Cameron J L, Lillemoe K D. et al . Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality.  Ann Surg. 2002;  236 355-368
• 11 Order S E, Siegel J A, Principato R. et al . Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: a phase I study.  Int J Radiat Oncol Biol Phys. 1996;  36 1117-1126