State of the Art in Radiation Therapy for Pancreas Cancer

  • Aaron C. Spalding
  • Edgar Ben-Josef
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)

Despite an extraordinary tendency for metastatic spread, radiotherapy may have an important role in the management of locally advanced unresectable cancer of the pancreas. Local control remains a significant clinical problem. In patients with unresectable disease, failure to control local disease is virtually uniform, and in patients undergoing curative resection, the rate of local relapse is 50–85% (1). Failure to control the primary is associated with symptoms such as pain, gastric outlet, and duodenal obstruction, and upper gastrointestinal ulceration and bleeding. Palliation of symptoms with radiotherapy (as the sole modality) is accomplished in nearly half of patients (2). It is almost certain that modern day combined-modality therapy provides even better palliation, but unfortunately solid data on symptom control and quality of life associated with such therapy are not available.

Improved local control not only provides a palliative benefit, but may also impact on survival. Chemotherapy can extend survival of patients with advanced disease by 2–3 months to a median of 5–6 months ( 3, 4 ) and it has been suggested that radiotherapy can also extend survival ( 5 ). The Gastrointestinal Tumor Study Group (GITSG) conducted a prospective phase III trial comparing SMF (streptozotocin, mitomycin, and 5-fluorouracil) chemotherapy alone to SMF plus external-beam radiotherapy to a dose of 54 Gy. They reported a significant benefit in median survival (9.7 months versus 7.4 months) in favor of the combined modality arm. Patients with unresectable disease who are rendered resectable by chemoradiotherapy and undergo surgery, appear to have a survival similar to patients who are surgical candidates at presentation ( 10 ), suggesting that aggressive local therapy may have an impact on survival. Like other fields of oncology (breast cancer and lymphoma, for instance), with the advent of more effective systemic agents, the need for local control and the impact of local control on survival are likely to become more evident.


Pancreatic Cancer Planning Target Volume Dose Distribution Radiat Oncol Biol Phys Intensity Modulate Radiotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Evans DB, Rich TA. 1997, Cancer of the pancreas. In: DeVita HS, Rosenberg SA (eds.) Cancer: principles and practice of oncology. Lippincott-Raven, Philadelphia. 1059–1060.Google Scholar
  2. 2.
    Haslam JB, Cavanaugh PJ, Stroup SL.1973, Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer 32(6):1341–1345.CrossRefPubMedGoogle Scholar
  3. 3.
    G limelius B, 1996, Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 7(6):593–600.Google Scholar
  4. 4.
    Palmer KR, 1994, Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Surg 81(6):882–885.CrossRefPubMedGoogle Scholar
  5. 5.
    Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988, 80(10):751–755.CrossRefGoogle Scholar
  6. 6.
    Jain S, 2005, Carcinoma of the pancreas with portal vein involvement—our experience with a modified technique of resection. Hepatogastroenterology 52(65):1596–1600.PubMedGoogle Scholar
  7. 7.
    Geer RJ, Brennan MF. 1993, Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 165(1):68–72; discussion 72-73.CrossRefPubMedGoogle Scholar
  8. 8.
    Bold RJ, 1999, Major vascular resection as part of pancreaticoduodenectomy for cancer: radiologic, intraoperative, and pathologic analysis. J Gastrointest Surg 3(3):233–243.CrossRefPubMedGoogle Scholar
  9. 9.
    Lygidakis NJ, 2004, Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepatogastroenterology 51(56):427–433.PubMedGoogle Scholar
  10. 10.
    Ammori JB, 2003, Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas. J Gastrointest Surg 7 (6):766–772.CrossRefPubMedGoogle Scholar
  11. 11.
    Fortner JG, 1996, Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg 223(2):147–153.CrossRefPubMedGoogle Scholar
  12. 12.
    Kayahara M, 1992, Lymphatic flow in carcinoma of the head of the pancreas. Cancer 70(8):2061–2066.CrossRefPubMedGoogle Scholar
  13. 13.
    Kayahara M, 1995, Surgical strategy for carcinoma of the pancreas head area based on clinico-pathologic analysis of nodal involvement and plexus invasion. Surgery 117(6):616–623.CrossRefPubMedGoogle Scholar
  14. 14.
    Nagakawa T, 1993, The pattern of lymph node involvement in carcinoma of the head of the pancreas. A histologic study of the surgical findings in patients undergoing extensive nodal dissections.Int J Pancreatol 13(1):15–22.PubMedGoogle Scholar
  15. 15.
    Nagakawa T, 1993, A clinical study on lymphatic flow in carcinoma of the pancreatic head area—peripancreatic regional lymph node grouping. Hepatogastroenterology 40(5):457–462.PubMedGoogle Scholar
  16. 16.
    Nakao A, 1997, Lymph node metastasis in carcinoma of the body and tail of the pancreas. Br J Surg 84(8):1090–1092.CrossRefPubMedGoogle Scholar
  17. 17.
    Fortner JG, 1977, Regional pancreatectomy: en bloc pancreatic, portal vein and lymph node resection. Ann Surg 186(1):42–50.PubMedCrossRefGoogle Scholar
  18. 18.
    Nagakawa T, 1993, Perineural invasion of carcinoma of the pancreas and biliary tract. Br J Surg 80(5):619–621.CrossRefPubMedGoogle Scholar
  19. 19.
    Nakao A, 1996, Clinical significance of carcinoma invasion of the extrapancreatic nerve plexus in pancreatic cancer. Pancreas 12(4):357–361.CrossRefPubMedGoogle Scholar
  20. 20.
    Takahashi T, 1997, Perineural invasion by ductal adenocarcinoma of the pancreas. J Surg Oncol 65(3):164–170.CrossRefPubMedGoogle Scholar
  21. 21.
    Yoshioka H, Wakabayashi T. 1958, Therapeutic neurotomy on head of pancreas for relief of pain due to chronic pancreatitis: a new technical procedure and its results. AMA Arch Surg 76 (4):546–554.PubMedGoogle Scholar
  22. 22.
    Yi SQ, 2003, Innervation of the pancreas from the perspective of perineural invasion of pan-creatic cancer. Pancreas 27(3):225–229.CrossRefPubMedGoogle Scholar
  23. 23.
    Nagakawa T, 1992, A clinicopathologic study on neural invasion in cancer of the pancreatic head. Cancer 69(4):930–935.CrossRefPubMedGoogle Scholar
  24. 24.
    Hirai I, 2002, Perineural invasion in pancreatic cancer. Pancreas 24(1):15–25.CrossRefPubMedGoogle Scholar
  25. 25.
    Foo M, Gunderson L, Urrutia R. 2000, Pancreatic cancer. In: Gunderson L, Tepper JE (eds.) Clinical radiation oncology. Churchill Livingstone, Philadelphia, 700–702.Google Scholar
  26. 26.
    Burris HA 3rd, 1997, I mprovements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreatic cancer: a randomized trial. J Clin Oncol 15 (6):2403–2413.PubMedGoogle Scholar
  27. 27.
    Shewach DS, 1994, Metabolism of 2',2'-difluoro-2'-deoxycytidine and radiation sensitization of human colon carcinoma cells. Cancer Res 54(12):3218–3223.PubMedGoogle Scholar
  28. 28.
    Lawrence TS, 1996, Radiosensitization of pancreatic cancer cells by 2',2'-difluoro-2'-deoxy-cytidine. I nt J Radiat Oncol Biol Phys 34 (4): 867–872.CrossRefGoogle Scholar
  29. 29.
    Crane CH, 2002, Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer? Int J Radiat Oncol Biol Phys 52 (5): 1293–1302.CrossRefPubMedGoogle Scholar
  30. 30. Scalliet PGC, Galdermans D, Meerbeek J, et al. GEMZAR (trade) (Gemcitabine) with thoracic radiotherapy—a phase II pilot study in chemonaive patients with advanced nonsmall cell lung cancer (NSCLC). Proc Am Soc Clin Oncol, 1998, 1923.Google Scholar
  31. 31. Groen HGA, van Putten J, van der Leest A, et al. Phase I study of gemcitabine (G) and high-dose thoracic radiation (RTf) in stage III non-small lung cancer (NSCLC). Proc Am Soc Clin Oncol 2000, 2123.Google Scholar
  32. 32.
    Vokes EE, 2002, Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. J Clin Oncol 20 (20):4191–4198.CrossRefPubMedGoogle Scholar
  33. 33.
    Niemierko A. 1997, Reporting and analyzing dose distributions: a concept of equivalent uniform dose. Med Phys 24 (1): 103–110.CrossRefPubMedGoogle Scholar
  34. 34.
    Niemierko A, 1999, A generalized concept of equivalent uniform dose (EUD) (Abstract). Med Phys 26: 1100.Google Scholar
  35. 35.
    Murphy MJ, 2002, The effectiveness of breath-holding to stabilize lung and pancreas tumors during radiosurgery. Int J Radiat Oncol Biol Phys 53 (2): 475–482.PubMedGoogle Scholar
  36. 36.
    Gierga DP, 2004, Quantification of respiration-induced abdominal tumor motion and its impact on IMRT dose distributions. I nt J Radiat Oncol Biol Phys 58 (5): 1584–1595.CrossRefGoogle Scholar
  37. 37.
    Bussels B, 2003, Respiration-induced movement of the upper abdominal organs: a pitfall for the three-dimensional conformal radiation treatment of pancreatic cancer. Radiother Oncol 68 (1):69–74.CrossRefPubMedGoogle Scholar
  38. 38.
    Dobelbower RR Jr, 1986, 125I interstitial implant, precision high-dose external beam therapy, and 5-FU for unresectable adenocarcinoma of pancreas and extrahepatic biliary tree. Cancer 58 (10):2185–2195.CrossRefPubMedGoogle Scholar
  39. 39.
    Mohiuddin M, 1992, Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas. Int J Radiat Oncol Biol Phys 23 (2): 305–311.PubMedGoogle Scholar
  40. 40.
    Roldan GE, 1988, External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer. Cancer 61(6):1110–1116.CrossRefPubMedGoogle Scholar
  41. 41.
    Mohiuddin M, 1995, Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. J Clin Oncol 13(11):2764–2768.PubMedGoogle Scholar
  42. 42.
    Ceha HM, 2000, Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma. Cancer 89(11):2222–2229.CrossRefPubMedGoogle Scholar
  43. 43.
    Landry JC, 2002, Treatment of pancreatic cancer tumors with intensity-modulated radiation therapy (IMRT) using the volume at risk approach (VARA): employing dose-volume histo-gram (DVH) and normal tissue complication probability (NTCP) to evaluate small bowel toxicity. M ed Dosim 27(2):121–129.CrossRefGoogle Scholar
  44. 44.
    Ben-Josef E, 2004, Intensity-modulated radiotherapy (IMRT) and concurrent capecitabine for pancreatic cancer. Int J Radiat Oncol Biol Phys 59 (2): 454–459.PubMedGoogle Scholar
  45. 45.
    Wu Q, 2002, Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose. Int J Radiat Oncol Biol Phys 52 (1): 224–235.PubMedGoogle Scholar
  46. 46.
    Schwarz M, 2004, Sensitivity of treatment plan optimisation for prostate cancer using the equivalent uniform dose (EUD) with respect to the rectal wall volume parameter. Radiother Oncol 73(2):209–218.CrossRefPubMedGoogle Scholar
  47. 47.
    Rancati T, 2004, Fitting late rectal bleeding data using different NTCP models: results from an Italian multi-centric study (AIROPROS0101). Radiother Oncol 73 (1): 21–32.CrossRefPubMedGoogle Scholar
  48. 48.
    Ghilezan M, 2004, Online image-guided intensity-modulated radiotherapy for prostate cancer: how much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery. Int J Radiat Oncol Biol Phys 60 (5): 1602–1610.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Aaron C. Spalding
    • 1
  • Edgar Ben-Josef
    • 1
  1. 1.Department of Radiation OncologyUniversity of MichiganAnn ArborUSA

Personalised recommendations