The Role of Radiotherapy in Curative-intent Management of Pancreatic Adenocarcinoma

The Role of Radiotherapy in Curative-intent Management of Pancreatic Adenocarcinoma

Abrams Ross A
US Gastroenterology - Volume 4 - Issue I
Published: January 2009
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Nothing comes easily in the management of pancreatic adenocarcinoma. The American Cancer Society (ACS) anticipates 37,680 new cases and 34,290 deaths in 2008,1 implying that approximately 91% of patients in the ‘steady state’ die from their malignancy. This sobering reality is consistent with some well-known harsh realities: surgery is a sine qua non for cure, but most patients (about 80%) present with either locoregionally unresectable or overtly metastatic disease, and most patients resected with curative intent are nevertheless not cured.2 Even so, the context of surgically resectable disease represents the current locus of opportunity for increasing the likelihood of a cure, and it is within this context that this article begins.

There are numerous familiar oncological contexts where curative-intent surgery is augmented by the use of chemotherapy and/or radiotherapy as additional antineoplastic interventions in order to achieve optimal outcomes. Common examples include stage-dependent examples of lung cancer, colorectal cancer, and breast cancer.3–7 In all of these contexts the chemotherapy and radiotherapy supplement the benefits of surgery by addressing subclinical (microscopic) tumor extensions that are not optimally addressed by resection. This paradigm has three clear advantages that are relevant to our discussion. First, chemotherapy is often most effective against microscopic (as opposed to overt) disease burdens.8 Second, the therapeutic ratio for radiotherapy is optimized by reducing the locoregional tumor burden surgically, as radiotherapy in fractions of 180–200cGy to doses of 5,000–6,000cGy is quite reliably capable of eradicating subclinical amounts of in-field residual tumor.9 Third, in situations where there are significant components of both locoregional and systemic failure risk from subclinical disease burden following surgery, the use of chemotherapy and radiotherapy consistently produces better outcomes than chemotherapy alone.3–5,7 The mechanism for this bimodality success following surgery probably relates in part to spatial synergy,10 where the greatest burden of microscopic tumor burden remains locoregional to the area of resection in sufficient quantities to overwhelm the ability of chemotherapy to effect eradication.

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References:
  1. American Cancer Society, 2008 Cancer facts and Figures, www.cancer.org
  2. Willet CG, Czito BG, Bendell JC, Adjuvant Therapy of Pancreatic Cancer, The Cancer J, 2007;13:185–91.
  3. Ragaz J, Jackson SM, Le N, et al., Adjuvant radiotherapy and chemotherapy in node positive premenopausal women with breast cancer, N Engl J Med, 1997;337(14):956–62.
  4. Overgaard M, Hansen PS, Overgaard J, et al., Postoperative radiotherapy in high risk premenopausal women with breast cancer who received chemotherapy, N Engl J Med, 1997;337(14):949–55.
  5. Warde P, Payne D, Does thoracic irradiation improve survival and local control in limited stage small cell carcinoma of the lung? A meta analysis, J Clin Oncol, 1992;10:890–95.
  6. Pignon JP, Arriagada R, Ihde DC, et al., A metaanalysis of thoracic radiotherapy for small cell lung cancer, N Engl J Med, 1992;327:1618–24.
  7. National Institutes of Health Consensus Conference, Adjuvant therapy for patients with colon and rectal cancer, JAMA, 1990;264:1444–50.
  8. Heidelberger C, Griesbach L, Montag BJ, et al., Studies on fluorinated pyrmidines II. Effects on transplanted tumors, Cancer Res, 1958;18:305–17.
  9. Fletcher GH, Basic principles of radiotherapy. In: Fletcher GH (ed.), Textbook of Radiotherapy, Philadelphia: Lea & Febiger, 1980;196.
  10. Steel GG, Peckham MJ, Exploitable mechanisms in combined radiotherapy-chemotherapy: The concept of additivity, Int J Radiat Oncol Biol Phys, 1979;5:85–91.
  11. Wolff RA, Chemotherapy for pancreatic cancer:from metastatic disease to adjuvant therapy, Cancer J, 2007;13:175–84.
  12. Abrams RA, Comment on “adjuvant therapy in pancreatic cancer: a critical appraisal”, Drugs, 2007;67:2481–5.
  13. Regine WF, Winter KA, Abrams RA, et al., Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma—a randomized controlled trial, JAMA, 2008;299:1019–26.
  14. Macdonald JS, Smalley SR, Benedetti J, et al., Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction, N Engl J Med, 2001;345:725–30.
  15. Hofstetter W, Swisher SG, Correa AM, et al., Treatment outcomes of resected esophageal cancer, Ann Surg, 2002;236:376–85.
  16. Cooper JS, Pajak TF, Forastiere AA, et al., Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous cell carcinoma of the head and neck, N Engl J Med, 2004;350:1937–44.
  17. Robinson LA,Wagner H, Ruckdeschel JC, Treatment of IIIA non small cell lung cancer, Chest, 2003;123:202–20.
  18. Griffin JF, Smalley SR, Jewell W, et al., Patterns of failure after curative resection of pancreatic adenocarcinomas, Cancer, 1990;66:56–61.
  19. Hishinuma S, Ogata Y, Tomikawa M, Patterns of recurrence after curative resection of pancreatic cancer based on autopsy findings, J Gastrointest Surgery, 2006;10:511–18.
  20. Kalser MH, Ellenberg SS, Pancreatic Cancer. Adjuvant combined radiation and chemotherapy following curative resection, Arch Surg, 1985;120:899–903.
  21. Yeo CJ, Abrams RA, Grochow LB, et al., Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival: a prospective, single institution experience, Ann Surg, 1997;225:621–36.
  22. Klinkenbijl J, Jeekel J, Sahmound T, 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, Ann Surg, 1999;230:776–84.
  23. Smeenk HG, van Eijck CHJ, Hop WC, et al., Long term survival and metastatic pattern of pancreatic and perimapullary cancer after adjuvant chemoradiation or observation – long term results of EORTC trial 40891, Ann Surg, 2007;246:734–40.
  24. Neoptolemos J, Dunn JA, Stocken DD, et al., Adjuvant chemoradiotherapy and chemotherapy in respectable pancreatic cancer: a randomized controlled trial, Lancet, 2001;358: 1576–85.
  25. Neoptolemos J, Stocken D, Friess H, et al., A randomized trial of chemoradiotheapy and chemotherapy after resection of pancreatic cancer, N Engl J Med, 2004;350:1200–8.
  26. Oettle H, Post S, Neuhaus P, et al., Adjuvant chemotherapy with gemcitabine versus observation in patients undergoing curative intent resection of pancreatic cancer. A multicenter randomized controlled trial, JAMA, 2007;297:267–77.
  27. Abrams RA, Lillemoe KD, Piantadosi S, Continuing controversy over adjuvant therapy of pancreatic cancer, Lancet, 2001;358: 1565–6.
  28. Letters to the Editor (multiple) re EORTC Trial, Ann Surg, 2000;232:726–7.
  29. Letters to the Editor re EORTC trial, Ann Surg, 2006;244:332–3.
  30. Abbruzzese JL, Adjuvant therapy for surgically resected pancreatic adenocarcinoma, JAMA, 2008;299:1066–7.
  31. Oettle H, Neuhaus P, Adjuvant therapy in pancreatic cancer: a critical appraisal, Drugs, 2007;67(16):2293–2310.
  32. Brennan MF, Kattan MW, Klimstra D, et al., Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas, Ann Surg, 2004;240:293–8.
  33. Ferrone CR, Finkelstein DM, Thayer SP, Perioperative CA19-9 Levels Can Predict Stage and Survival in Patients With Resectable Pancreatic Adenocarcinoma, J Clin Oncol, 2006;24:2897–2902.
  34. Boeck S, Stieber P, Holdenrieder S, et al., Prognostic and Therapeutic Significance of Carbohydrate Antigen 19-9 as Tumor Marker in Patients with Pancreatic Cancer, Oncology, 2006;70: 255–64.
  35. Regine WF, Garcia M, Berger AC, et al., Post-resectional ca 19-9 values >90 are associated with significantly worse survival in patients with pancreatic carcinoma treated with adjuvant therapy on RTOG 9704 -implications for current and future trials, Int J Rad Oncol Biol Phys, 2007;69(Suppl.):S78.
  36. EVA Finlayson, Birkmeyer JD, Effects of hospital volume on life expectancy after selected cancer operations in older adults: a decision analysis, J Am Coll Surg, 2003;196:410–17.
  37. Birkmeyer JD, Stukel TA, Siewers AE, et al., Surgeon volume and operative mortality in the United States, N Engl J Med, 2003;349:2117–27.
  38. Abrams RA, Winter KA, Regine WF, et al., RTOG 9704 – Radiotherapy Quality Assurance (QA) Review and Survival, Int J Radiat Oncol Biol Phys, 2006;66(Suppl. 3):S22.
  39. Picozzi VM, Personal communication, 2007.

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