title: Image-guided stereotactic radiosurgery for locally advanced pancreatic adenocarcinoma results of first 85 patients.
abstract: BACKGROUND
  Locally advanced unresectable pancreatic adenocarcinoma is characterized by poor survival despite chemotherapy and conventional radiation therapy (RT). Recent advances in real-time image-guided stereotactic radiosurgery (SRS) have made it possible to treat these cancers in two to four fractions followed by systemic chemotherapy.
  
  
  OBJECTIVE
  The aims of this study includes the following: (1) obtain local control of the disease; (2) improve the survival of these unresectable patients; (3) evaluate the toxicity of SRS; and (4) report results of the largest series from a single center.
  
  
  METHODS
  Pancreatic SRS involves delivery of high doses of accurately targeted radiation given non-invasively in two to four fractions. We treated 85 consecutive patients with locally advanced and recurrent pancreatic adenocarcinoma from February 2004 to November 2009. Age range: 36-88 years, median 66 years; sex: 50 males, 35 females; race: 79 Caucasian, five African American, one Asian; histology: 80 adenocarcinoma, three islet cell, two other. Pre-SRS staging: T(3-4) 85; N(+) 16, N(x) 57, N(0) 12; M(0) 64, M(1) 21. All patients were unresectable at the time of SRS. Seventy-one had no prior surgical resection, and 14 had local recurrence after prior surgical resection. Twenty-nine patients had progression of disease after prior conventional RT. Location of the tumor: head, 57; body and tail, 28. Pre-SRS chemotherapy was given in 48 patients. All patients received gemcitabine-based chemotherapy regimen after SRS. Median tumor volume was 60 cm(3). PET/CT scans done in 55 patients were positive in 52 and negative in three patients. Average maximum standard uptake value was 6.9. Pain score on a scale of 1-10 was: 0-3 in 54, 4-7 in 18, and 8-10 in 13 patients. SRS doses ranged from 15 to 30 Gy with a mean dose of 25.5 Gy delivered in 3 days divided in equal fractions. Mean conformality index was 1.6, and mean isodose line was 80%.
  
  
  RESULTS
  Tumor control: complete, partial, and stable disease were observed in 78 patients for the duration of 3-36 months with median of 8 months. Pain relief was noted in majority of patients lasting for 18-24 weeks. Most of the patients died of distant disease progression while their primary tumor was controlled. Overall median survival from diagnosis was 18.6 months and from SRS it was 8.65 months. For the group of 35 patients with adenocarcinoma without prior surgical resection or RT and no distant metastases, the average and 1-year survival from diagnosis was 15 months and 50%, respectively, and from SRS it was 11.15 months and 30.5%, respectively.
  
  
  RESULTS
  A total of 19 (22.37%) patients developed grades III/IV GI toxicity including duodenitis, 12 (14.1%); gastritis, 11 (12.9%); diarrhea, three (3.5%); and renal failure was noted in one (1.2%). Three patient had both gastritis and duodenitis. Toxicity was significantly more prevalent in the first 40 patients compared with the last 45 patients (32.5 vs 13.9%).
  
  
  CONCLUSIONS
  SRS for unresectable pancreatic carcinoma can be delivered in three fractions with minimal morbidity and a local tumor control rate of 91.7%. The survival is comparable or better than the reported results for advanced pancreatic cancer, specifically for the group of previously untreated patients with unresectable tumors. Development of distant metastases remains a significant factor.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Sinai Hospital of Baltimore, 2401 W. Belvedere Avenue, Baltimore, MD 21225, USA. mdidolka@lifebridgehealth.org
authors.forename: Mukund S
authors.initials: MS
authors.lastname: Didolkar
authors.forename: Cardella W
authors.initials: CW
authors.lastname: Coleman
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Brenner
authors.forename: Kyo U
authors.initials: KU
authors.lastname: Chu
authors.forename: Nicole
authors.initials: N
authors.lastname: Olexa
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stanwyck
authors.forename: Airong
authors.initials: A
authors.lastname: Yu
authors.forename: Nagaraj
authors.initials: N
authors.lastname: Neerchal
authors.forename: Stuart
authors.initials: S
authors.lastname: Rabinowitz
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D016634:Radiosurgery; D025321:Surgery, Computer-Assisted; D016019:Survival Analysis