Stereotactic Body Radiotherapy in the Treatment of Advanced Adenocarcinoma of the Pancreas

Objectives: The aim of the study was to assess the feasibility and safety of stereotactic body radiotherapy (SBRT) in patients with advanced pancreatic adenocarcinoma. Methods: We reviewed outcomes of 71 patients treated with SBRT for pancreatic cancer between July 2004 and January 2009. Forty patients (56%) had locally unresectable disease, 11 patients (16%) had local recurrence following surgical resection, 8 patients (11%) had metastatic disease, and 12 patients (17%) received adjuvant SBRT for positive margins. The median dose was 24 Gy (18–25 Gy), given in a single-fraction SBRT (n = 67) or fractionated SBRT (n = 4). Kaplan-Meyer survival analyses were used to estimate freedom from local progression (FFLP) and overall survival (OS) rates. Results: The median follow-up among surviving patients was 12.7 months (4–26 months). The median tumor volume was 17 mL (5.1–249 mL). The overall FFLP rates at 6 months/1 year were 71.7%/48.5%, respectively. Among those with macroscopic disease, FFLP was achieved in 77.3% of patients with tumor size <15 mL (n = 22), and 59.5% for ≥15 mL (n = 37) (P = 0.02). FFLP was achieved in 73% following 24 to 25 Gy, and 45% with 18 to 22 Gy (P = 0.004). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%, respectively. Grade 1–2 acute and late GI toxicity were seen in 39.5% of patients. Three patients experienced acute grade 3 toxicities. Conclusions: SBRT is feasible, with minimal grade ≥3 toxicity. The overall FFLP rate for all patients was 64.8%, comparable to rates with external beam radiotherapy. This shorter treatment course can be delivered without delay in adjuvant systemic therapy.

[1]  Albert C Koong,et al.  Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. , 2004, International journal of radiation oncology, biology, physics.

[2]  Helen Hickey,et al.  A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. , 2004, The New England journal of medicine.

[3]  R H Hruban,et al.  Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. , 1997, Annals of surgery.

[4]  R. Timmerman,et al.  Stereotactic Body Radiation Therapy: A Comprehensive Review , 2007, American journal of clinical oncology.

[5]  K. Campbell,et al.  Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  Peter Neuhaus,et al.  Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. , 2007, JAMA.

[7]  S. Ellenberg,et al.  Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. , 1985, Archives of surgery.

[8]  J. Cameron,et al.  Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas. , 2010, International journal of radiation oncology, biology, physics.

[9]  M. Kalser,et al.  Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer , 1987, Cancer.

[10]  D. DavidS.ShimmM. Perez and Brady's Principles and Practice of Radiation Oncology , 2008 .

[11]  C. Wille,et al.  Current concepts in stereotactic radiosurgery - a neurosurgical and radiooncological point of view , 2009, European journal of medical research.

[12]  R. Abrams,et al.  Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. , 2008, JAMA.

[13]  Quynh-Thu Le,et al.  Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. , 2005, International journal of radiation oncology, biology, physics.

[14]  J. Mountz,et al.  Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. , 2009, International journal of radiation oncology, biology, physics.

[15]  P. Engstrom,et al.  Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil--an Eastern Cooperative Oncology Group study. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. , 1988, Journal of the National Cancer Institute.

[17]  F. Mícek [Cancer of the pancreas]. , 1965, Bratislavske lekarske listy.

[18]  Daniel T Chang,et al.  Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas , 2009, Cancer.

[19]  Comparative therapeutic trial of radiation with or without chemotherapy in pancreatic carcinoma. Gastrointestinal Tumor Study Group. , 1979, International journal of radiation oncology, biology, physics.

[20]  J. Barkin,et al.  Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5‐fluorouracil), and high dose radiation + 5‐fluorouracil. The gastrointestinal tumor study group , 1981, Cancer.

[21]  H. Oettle,et al.  CONKO-001: Final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC) , 2008 .

[22]  D. Heron,et al.  Frameless Stereotactic Radiosurgery for Recurrent Head and Neck Carcinoma , 2006, Technology in cancer research & treatment.

[23]  J. Jeekel,et al.  Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. , 1999, Annals of surgery.

[24]  J. Kench,et al.  Margin clearance and outcome in resected pancreatic cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.