Image-Guided Stereotactic Radiosurgery for Locally Advanced Pancreatic Adenocarcinoma Results of First 85 Patients
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
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.
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: T3–4 85; N+ 16, Nx 57, N0 12; M0 64, M1 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 cm3. 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%.
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.
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%).
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.
- American Cancer Society. Cancer Facts & Figures 2009 Atlanta: American Cancer Society; 2009.
- Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (eds). SEER Survival Monograph; Cancer Survival Among Adults: US SEER Program, 1988–2001, Patient and tumor characteristics. NCI, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.
- Bilimoria KY, Bentrem DJ, Ko CY, et al. Validation of the 6th Edition AJCC Pancreatic Cancer Staging System Report from National Cancer Database. Cancer 2007;110:738–744. CrossRef
- Moertel CG. Frytak S. Hahn RG. O'Connell MJ. Reitemeier RJ. Rubin J. Schutt AJ. Weiland LH. Childs DS. Holbrook MA. Lavin PT. Livstone E. Spiro H. Knowlton A. Kalser M. Barkin J. Lessner H. Mann-Kaplan R. Ramming K. Douglas HO Jr. Thomas P. Nave H. Bateman J. Lokich J. Brooks J. Chaffey J. Corson JM. Zamcheck N. Novak JW. 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. Cancer 1981;48(8):1705–1710. CrossRef
- Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. Journal of the National Cancer Institute 1988;80(10):751–755. CrossRef
- Gastrointestinal Tumor Study Group. Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer 1985;56(11):2563–2568. CrossRef
- Huguet F. Andre T. Hammel P. Artru P. Balosso J. Selle F. Deniaud-Alexandre E. Ruszniewski P. Touboul E. Labianca R. de Gramont A. Louvet C. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. Journal of Clinical Oncology 2007;25(3):326–331. CrossRef
- Chauffert B. Mornex F. Bonnetain F. Rougier P. Mariette C. Bouche O. Bosset JF. Aparicio T. Mineur L. Azzedine A. Hammel P. Butel J. Stremsdoerfer N. Maingon P. Bedenne L. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Annals of Oncology 2008;19(9):1592–1599. CrossRef
- Wilkowski R. Boeck S. Ostermaier S. et al. Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer-a multi-center randomized phase II study. Brit J of Cancer 2009;101:1853–1859. CrossRef
- Haddock MG. Swaminathan R. Foster NR. Hauge MD. Martenson JA. Camoriano JK. Stella PJ. Tenglin RC. Schaefer PL. Moore DF Jr. Alberts SR. Gemcitabine, cisplatin, and radiotherapy for patients with locally advanced pancreatic adenocarcinoma: results of the North Central Cancer Treatment Group Phase II Study N9942. Journal of Clinical Oncology 2007;25(18):2567–2572. CrossRef
- Small W Jr. Berlin J. Freedman GM. Lawrence T. Talamonti MS. Mulcahy MF. Chakravarthy AB. Konski AA. Zalupski MM. Philip PA. Kinsella TJ. Merchant NB. Hoffman JP. Benson AB. Nicol S. Xu RM. Gill JF. McGinn CJ. Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. Journal of Clinical Oncology 2008;26(6):942–947. CrossRef
- Burris HA. Moore MJ. Andersen J. Green MR. Rothenberg ML. Modiano MR. Cripps MC. Portenoy RK. Storniolo AM. Tarassoff P. Nelson R. Dorr FA. Stephens CD. Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Journal of Clinical Oncology 1997;15(6):2403–2413.
- Moore MJ. Goldtein D. Hamm J. et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of National Cancer Institute of Canada Clinical Trial Group. J. Clin Oncol 2007;25:1960–1966. CrossRef
- Klaassen DJ. MacIntyre JM. Catton GE. Engstrom PF. Moertel CG. 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. Journal of Clinical Oncology 1985;3(3):373–378.
- Chang DT. Schlenberg D. Shen J. et al. Stereotactic Radiotherapy for unresectable Adenocarcinoma of the pancreas. Cancer 2009;115:665–672. CrossRef
- Koong AC. Christofferson E. Le QT. Goodman KA. Ho A. Kuo T. Ford JM. Fisher GA. Greco R. Norton J. Yang GP. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. International Journal of Radiation Oncology, Biology, Physics. 2005;63(2):320–323.
- Koong AC. Le QT. Ho A. Fong B. Fisher G. Cho C. Ford J. Poen J. Gibbs IC. Mehta VK. Kee S. Trueblood W. Yang G. Bastidas JA. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. International Journal of Radiation Oncology, Biology, Physics 2004;58(4):1017–1021.
- Hoffelt C. & Didolkar M. Stereotactic radiosurgery for unresectable adenocarcinoma of pancreas. Initial experience at Sinai Hospital of Baltimore. In: Urschel HC (ed) Robotic radiosurgery: treating tumors that move with respiration. Springer, Berlin 2007. pp. 177–192.
- National Cancer Institute common toxicity criteria version 2.0. Available at: http://ctep.cancer.gov/forms/CTCv20_4-30-992.pdf. Accessed 18 Jan 2010.
- Therasse P. Arbuck SG. Eisenhauer EA. Wanders J. Kaplan RS. Rubinstein L. Verweij J. Van Glabbeke M. Van Oosterom AT. Christian MC. Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. Journal of the National Cancer Institute 2000;92(3):205–216. CrossRef
- Fu D. Kahn R. Wang B. et al. Xsight Lung tracking system: a fiducial-less method for respiratory motion tracking. In: Urschel HC (ed) Treating tumors that move with respiration. Springer, Berlin 2007. pp. 265–282. CrossRef
- Sayeh S. Wang J. Main WR. Kilby W. Maurer CR: Respiratory motion tracking for robotic radiology. In: Urschel HC (ed) Treating tumors that move with respiration. Springer, Berlin 2007. pp. 15–29. CrossRef
- Kaplan E. Meier P. NON-parametric estimation of incomplete observations. Journal of the American Statistical Association 1958;53:457–481. CrossRef
- Sener SF. Fremgen A. Menck HR. Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985-1995, using the National Cancer Database. J Am Coll Surg 1999;189:1–7. CrossRef
- Kalser MH. Ellenberg SS. Pancreatic cancer: Adjuvant combined radiation and chemotherapy following curative resection. Archives of Surgery 1985;120(8):899–903.
- Klinkenbijl JH. Jeekel J. Sahmoud T. van Pel R. Couvreur ML. Veenhof CH. Arnaud JP. Gonzalez DG. de Wit LT. Hennipman A. Wils J. 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. Annals of Surgery 1999;230(6):776–784. CrossRef
- Neoptolemos JP. Stocken DD. Friess H. Bassi C. Dunn JA. Hickey H. Beger H. Fernandez-Cruz L. Dervenis C. Lacaine F. Falconi M. Pederzoli P. Pap A. Spooner D. Kerr DJ. Buchler MW. European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. New England Journal of Medicine 2004;350(12):1200–1210. CrossRef
- Oettle H. Post S. Neuhaus P. Gellert K. Langrehr J. Ridwelski K. Schramm H. Fahlke J. Zuelke C. Burkart C. Gutberlet K. Kettner E. Schmalenberg H. Weigang-Koehler K. Bechstein WO. Niedergethmann M. Schmidt-Wolf I. Roll L. Doerken B. Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297(3):267–77. CrossRef
- Regine WF. Winter KA. Abrams RA. et al. Fluorouracil vs gemcitabine chemotheraphy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 2008;299:1019–1026. CrossRef
- Riall TS. Nealon WH. Goodwin JS. Zhang D. Kuo YF. Townsend CM Jr. Freeman JL. Pancreatic cancer in the general population: Improvements in survival over the last decade. Journal of Gastrointestinal Surgery 2006;10(9):1212–1224. CrossRef
- White R. Lee C. Anscher M. Gottfried M. Wolff R. Keogan M. Pappas T. Hurwitz H. Tyler D. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Annals of Surgical Oncology 1999;6(1):38–45. CrossRef
- Wolff RA. Chemotherapy for pancreatic cancer: From metastatic disease to adjuvant therapy. Cancer J 2007;13:175–184. CrossRef
- Bendel J & Goldberg RM. Targeted agents in the treatment of pancreatic cancer; history and lessons learned. Current opinion in Oncology 2007;19:390–395. CrossRef
- Rocha-Lima CM. New directions in management of advanced cancers a review. Anti-cancer drugs 2008;19:435–446. CrossRef
- Minn AY. Schellenberg D. Maxim P. et al. Pancreatic tumor motion on a single planning 4D-CT does not correlate with intrafraction tumor motion during treatment. AM J Clin Oncol 2009;32:364–368. CrossRef
- Fowler JF. The linear–quadratic model and progression radiotherapy. Br J Radiol 1989;62: 679–694. CrossRef
- Whelden TE. Deehan C. Wheldon GE. et al. The linear quadratic transformation of dose-volume histogram in fractioned radiotherapy. Radiother Oncol 1998;46: 285–295. CrossRef
- Sindelar WF. Kinsella TJ. Studies of intraoperative radiotherapy in carcinoma of the pancreas. Annals of Oncology 1999;10 (Suppl 4):226–230. CrossRef
- Tepper JE. Noyes D. Krall J. Sause MD. et al. Intraoperative radiation therapy of pancreatic carcinoma: A report of RTOG-8505. Int. J. Radiation Oncology Biol Phys 1991;21:1145–1149.
- Ko AH. Quivey JM. Venook AP. Bergsland EK. Dito E. Schillinger B. Tempero MA. A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. International Journal of Radiation Oncology, Biology, Physics 2007;68(3):809–816.
- Murphy JD. Adusumilli S. Griffith KA. Ray ME. Zalupski MM. Lawrence TS. Ben-Josef E. Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. International Journal of Radiation Oncology, Biology, Physics 2007;68(3):801–808.
- Krishnan S. Rana V. Janjan NA. Varadhachary GR. Abbruzzese JL. Das P. Delclos ME. Gould MS. Evans DB. Wolff RA. Crane CH. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer 2007;110(1):47–55. CrossRef
- Mahadevan A. Jain S. Goldstein M. et al. Stereotactic body radiotherapy and gemcitabine for locally advanced pancreatic cancer. International Journal of Radiation Oncology, Biology, Physics 2010 (in press). doi:10.1016/j.ijrobp.2009.08.046.
- Polistina F. Costantin G. Casamassima F. et al. Unresectable locally advanced pancreatic cancer: A multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration. Annals of Surgical Oncology. 2010;17(8):2092–2101. CrossRef
- Kalser MH. Barkin J. MacIntyre JM. Pancreatic cancer: Assessment of prognosis by clinical presentation. Cancer 1985;56(2):397–402. CrossRef
- Lillemoe KD. Cameron JL. Kaufman HS. Yeo CJ. Pitt HA. Sauter PK. Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial. Annals of Surgery 1993;217(5):447–457. CrossRef
- Wong GY. Schroeder DR. Carns PE. Wilson JL. Martin DP. Kinney MO. Mantilla CB. Warner DO. Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. JAMA 2004;291(9):1092–1099. CrossRef
- Image-Guided Stereotactic Radiosurgery for Locally Advanced Pancreatic Adenocarcinoma Results of First 85 Patients
Journal of Gastrointestinal Surgery
Volume 14, Issue 10 , pp 1547-1559
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Locally advanced pancreatic carcinoma
- Stereotactic radiosurgery
- Industry Sectors
- Author Affiliations
- 1. Division of Surgical Oncology, Department of Surgery, Sinai Hospital of Baltimore, 2401 W. Belvedere Avenue, Baltimore, MD, 21225, USA
- 2. Department of Radiation Oncology, Sinai Hospital of Baltimore, Baltimore, USA
- 3. Department of Mathematics and Statistics, University of Maryland at Baltimore County Campus, Baltimore, MD, USA
- 4. Department of Radiology, Sinai Hospital of Baltimore, Baltimore, USA