Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Pancreatic cancer accounts for approximately 3% of cancer deaths in Europe. Locally advanced pancreatic cancer (LAPC) involves vascular structures, and resectability is low, with a median survival time of 6 to 11 months. We conducted a prospective, nonrandomized study of patients with LAPC to assess the effect of stereotactic body radiotherapy (SBRT) on local response, pain control, and quality of life (QOL).
Twenty-three patients with histologically confirmed LAPC underwent SBRT. Radiotherapy (30 Gy) was delivered in three fractions, and treatment toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE v. 3.0). All patients received also gemcitabine chemotherapy and were followed up until death. Local control was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, pain control was assessed with a visual analog scale, and QOL was assessed with the SF-36 instrument (Italian v. 1.6).
No grade 2 or higher acute or late toxicity was observed. The overall local response ratio was 82.6% (14 partial response, 2 complete response, 3 stable disease). SBRT showed a good short-term efficacy in controlling both pain and QOL. Median survival was 10.6 months, with a median follow-up of 9 months. The LAPC became resectable in 8% of the patients. Median time to progression of disease was 7.3 months. Six patients developed early metastatic disease.
The SBRT method is a promising treatment for LAPC. Local control rates, even compared to historical data from conventional radiotherapy, can be achieved with minimal toxicity. Resectability can also be achieved.
- Ferlay J, Bray F, Sankila R, Parkin DM. Cancer incidence, mortality and prevalence in the European Union, 1999. Lyon: IARC Press; 1998.
- Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 1.0. Lyon: IARC Press; 2001.
- Roazzi P, Capocaccia R, Santaquilani M, Carrani E, EUROCARE Working Group. Elecronic availability of EUROCARE-3 data: a tool for further analysis. Ann Oncol. 2003;14:v150–5. 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
- Alexakis N, Halloran C, Raraty M, et al. Current standards of surgery for pancreatic cancer. Br J Surg. 2004;91:1410–27. CrossRef
- Kayahara M, Nagakawa T, Ueno K, et al. An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging. Cancer. 1993;72:2118–23. CrossRef
- Hudson E, Hurt C, Mort D, et al. Induction chemotherapy followed by chemoradiation in locally advanced pancreatic cancer: an effective and well-tolerated treatment. Clin Oncol (R Coll Radiol). 2010;22:27–35.
- Turrini O, Viret F, Moureau-Zabotto L, et al. Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially advanced head pancreatic adenocarcinoma. Eur J Surg Oncol. 2009;35:1306–11.
- Koong AC, Le QT, Ho A, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58:1017–21.
- National Cancer Institute, Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0 (CTCAE). 2006. http://ctep.info.nih.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed 18 Jan 2010.
- Therasse P, Arbuck SG, Eisenhauer EA, et al. 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. J Natl Cancer Inst. 2000;92:205–16. CrossRef
- Moertel CG, Frytak S, Hahn RG, 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. Cancer. 1981;48:1705–10. CrossRef
- Brand R. Pancreatic cancer. Dis Mon. 2004;50:545–55. CrossRef
- Koong AC, Christofferson E, Le QT, 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. Int J Radiat Oncol Biol Phys. 2005;63:320–3.
- Wilkowski R, Thoma M, Weingandt H, Dühmke E, Heinemann V. Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose. JOP. 2005;6:216–30.
- Chang DT, Shellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72. CrossRef
- Hoyer M, Roed H, Sengelov L, et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76:48–53. CrossRef
- Shellenberg D, Goodman KA, Lee F, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72:678–86.
- Rezai P, Mulcahy MF, Tochetto SM, Berggruen S, Yaghmai V. Morphological analysis of pancreatic adenocarcinoma on multidetector row computed tomography: implications for treatment response evaluation. Pancreas. 2009;38:799–803. CrossRef
- White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg. 2001;5:626–33. CrossRef
- Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.
- Huang PI, Chao Y, Li CP, et al. Efficacy and factors affecting outcome of gemcitabine concurrent chemoradiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2009;73:159–65.
- Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46. CrossRef
- Igarashi H, Ito T, Kawabe K, et al. Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer. World J Gastroenterol. 2008;14:5311–5. CrossRef
- Spry N, Harvey J, Macleod C, et al. 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. Int J Radiat Oncol Biol Phys. 2008;70:1438–46.
- Blackstock AW, Bernard SA, Richards F, et al. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol. 1999;17:2208–12.
- Waldmann A, Dreckschmidt J, Pritzkuleit R, Katalinic A. Test-retest reliability of the OVIS questionnaire—an instrument to evaluate oncological care from a patient’s point of view. Gesundheitswesen. 2010;[Epub ahead of print].
- Laenen A, Alonso A. The Functional Living Index—Cancer: estimating its reliability based on clinical trial data. Qual Life Res. 2010;19:103–9. CrossRef
- McGinn CJ, Zalupski MM, Shureiqi I, et al. Phase I trial of dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2001;19:4202–8.
- Wilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP. 2006;7:349–60.
- Sa Cunha A, Rault A, Laurent C, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg. 2005;201:359–65. CrossRef
- Wanebo HJ, Glicksman AS, Vezeridis MP, et al. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg. 2000;135:81–7. CrossRef
- Maximous DW, Abdel-Wanis ME, El-Sayed MI, Abd-Elsayed AA. Preoperative gemcitabine based chemo-radiotherapy in locally advanced non metastatic pancreatic adenocarcinoma. Int Arch Med. 2009;2:7. CrossRef
- Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer. 2000;89:314–27. CrossRef
- Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration
Annals of Surgical Oncology
Volume 17, Issue 8 , pp 2092-2101
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Author Affiliations
- 1. Department of Surgery, San Bortolo Hospital, Vicenza, Italy
- 7. Department of Medical and Surgical Emergencies, Dolo Hospital, Dolo, Venice, Italy
- 2. Clinical Radiological Institute, University of Florence, Florence, Italy
- 3. Service of Medicine Applied Physics, San Bortolo Hospital, Vicenza, Italy
- 4. Section of Radiotherapy, San Bortolo Hospital, Vicenza, Italy
- 5. Department of Oncology, Fatebenefratelli Hospital, Benevento, Italy
- 6. School of General Surgery, University of Padua, Padua, Italy