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Radiation as an Adjunct to Surgery

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Surgery

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Abstract

Almost one-half of all cancer patients are treated with radiation at some time during the duration of their illness. This chapter focuses on the role of radiotherapy as an adjunct to surgery, both as adjuvant treatment to standard surgery (e.g., in rectal cancer) and as adjuvant therapy to organ-preserving surgery, as a substitute to more radical surgery (e.g., lumpectomy and radiation rather than mastectomy for breast cancer). We begin by briefly reviewing the biological and physical basis for using radiotherapy and the rationale for combining surgery and radiation for the treatment of cancer. It should be noted that radiation is a primary curative modality for several cancer subtypes (e.g., seminoma, lymphoma, head and neck cancer) and has a critical role in the palliation of patients with locally advanced or metastatic disease. The role of radiation in these settings is well addressed in other textbooks.1,2

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References

  1. Halperin EC, Perez CA, Brady LW, Wazer DE, Freeman C. Perez and Brady’s Principles and Practic of Radiation Oncology. Philadelphia: Lippincott Williams and Wilkins, 2007.

    Google Scholar 

  2. DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott Williams & Wilkins, 2004.

    Google Scholar 

  3. Hockel M, Knoop C, Schlenger K, et al. Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993;26(1):45–50.

    Article  PubMed  CAS  Google Scholar 

  4. Hockel M, Schlenger K, Hockel S, Aral B, Schaffer U, Vaupel P. Tumor hypoxia in pelvic recurrences of cervical cancer. Int J Cancer 1998;79(4):365–369.

    Article  PubMed  CAS  Google Scholar 

  5. Vaupel P, Kelleher DK, Hockel M. Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol 2001;28(2 suppl 8):29–35.

    Article  PubMed  CAS  Google Scholar 

  6. Lawrence WT, Zabell A, McDonald HD. The tolerance of skin grafts to postoperative radiation therapy in patients with soft-tissue sarcoma. Ann Plast Surg 1986;16(3):204–210.

    Article  PubMed  CAS  Google Scholar 

  7. Abeloff MAJ, Lichter A, Niederhuber J. Clinical Oncology. New York: Churchill Livingston, 1995.

    Google Scholar 

  8. Blichert-Toft M, Rose C, Andersen JA, et al. Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group. J Natl Cancer Inst Monogr 1992(11):19–25.

    PubMed  Google Scholar 

  9. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347(16):1233–1241.

    Article  PubMed  Google Scholar 

  10. Jacobson JA, Danforth DN, Cowan KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med 1995;332(14):907–911.

    Article  PubMed  CAS  Google Scholar 

  11. Veronesi U, Banfi A, Salvadori B, et al. Breast conservation is the treatment of choice in small breast cancer: long-term results of a randomized trial. Eur J Cancer 1990;26(6):668–670.

    PubMed  CAS  Google Scholar 

  12. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92(14):1143–1150.

    Article  PubMed  Google Scholar 

  13. Arriagada R, Le MG, Rochard F, Contesso G. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol 1996;14(5):1558–1564.

    PubMed  CAS  Google Scholar 

  14. Liljegren G, Holmberg L, Bergh J, et al. 10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol 1999;17(8):2326–2333.

    PubMed  CAS  Google Scholar 

  15. Veronesi U, Marubini E, Mariani L, et al. Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 2001;12(7):997–1003.

    Article  PubMed  CAS  Google Scholar 

  16. Clark RM, Whelan T, Levine M, et al. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group. J Natl Cancer Inst 1996;88(22):1659–1664.

    Article  PubMed  CAS  Google Scholar 

  17. Forrest AP, Stewart FIJ, Everington D, et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group. Lancet 1996;348(9029):708–713.

    Article  PubMed  CAS  Google Scholar 

  18. Renton SC, Gazet JC, Ford HT, Corbishley C, Sutcliffe R. The importance of the resection margin in conservative surgery for breast cancer. Eur J Surg Oncol 1996;22(1):17–22.

    Article  PubMed  CAS  Google Scholar 

  19. Anonymous. Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. Early Breast Cancer Trialists Collaborative Group. N Engl J Med 1995;333(22):1444–1455.

    Google Scholar 

  20. Anonymous. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists Collaborative Group. Lancet 2000;355(9217):1757–1770.

    Google Scholar 

  21. Carlson RW, Goldstein LJ, Gradishar WJ, et al. NCCN Breast Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology (Huntingt) 1996;10(11 suppl):47–75.

    CAS  Google Scholar 

  22. Bijker N, Meijnen P, Peterese J, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: ten year results of European Organisation for research and treatment of cancer randomised phase III trial 10853. A study by the EORTC breast cancer cooperative group and EORTC radiotherapy group. J Clin Oncol Vol 2006;24:3381–3387.

    Article  Google Scholar 

  23. Fisher B, Bryant J, Dignam JJ, et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol 2002;20(20):4141–4149.

    Article  PubMed  CAS  Google Scholar 

  24. Fyles AW, McCready DR, Manchul LA, et al. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med 2004;351(10):963–970.

    Article  PubMed  CAS  Google Scholar 

  25. Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 2004;351(10):971–977.

    Article  PubMed  CAS  Google Scholar 

  26. Robertson JM, Clarke DH, Pevzner MM, Matter RC. Breast conservation therapy. Severe breast fibrosis after radiation therapy in patients with collagen vascular disease. Cancer (Phila) 1991;68(3):502–508.

    Article  PubMed  CAS  Google Scholar 

  27. Ross JG, Hussey DH, Mayr NA, Davis CS. Acute and late reactions to radiation therapy in patients with collagen vascular diseases. Cancer (Phila) 1993;71(11):3744–3752.

    Article  PubMed  CAS  Google Scholar 

  28. Griem KL, Henderson IC, Gelman R, et al. The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy. J Clin Oncol 1987;5(10):1546–1555.

    PubMed  CAS  Google Scholar 

  29. Velez-Garcia E, Carpenter JT Jr, Moore M, et al. Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial. Eur J Cancer 1992;28A(11):1833–1837.

    Article  PubMed  CAS  Google Scholar 

  30. Rutqvist LE, Pettersson D, Johansson H. Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up of a randomized clinical trial. Radiother Oncol 1993;26(2):104–110.

    Article  PubMed  CAS  Google Scholar 

  31. Jones JM, Ribeiro GG. Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy. Clin Radiol 1989;40(2):204–208.

    Article  PubMed  CAS  Google Scholar 

  32. Host H, Brennhovd IO, Loeb M. Postoperative radiotherapy in breast cancer: long-term results from the Oslo study. Int J Radiat Oncol Biol Phys 1986;12(5):727–732.

    PubMed  CAS  Google Scholar 

  33. Early Breast Cancer Trialists’ Collaborative Group. Treatment of Early Breast Cancer, vol 1. Worldwide Evidence, 1985–1990. Oxford: Oxford University Press, 1990.

    Google Scholar 

  34. Muss HB, Cooper MR, Brockschmidt JK, et al. A randomized trial of chemotherapy (L-PAM vs. CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial. Breast Cancer Res Treat 1991;19(2):77–84.

    Article  PubMed  CAS  Google Scholar 

  35. Buzdar AU, Blumenschein GR, Smith TL, et al. Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial. Cancer (Phila) 1984;53(3):384–389.

    Article  PubMed  CAS  Google Scholar 

  36. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997;337(14):949–955.

    Article  PubMed  CAS  Google Scholar 

  37. Ragaz J, Olivotto I, Spinelli J, et al. Locoregional radiation therapy in patients with high risk breast cancer receiving adjuvant chemotherapy: 20 year results of the British Columbia randomised trial. J Natl Cancer Inst 2005;97,2:116–126.

    PubMed  Google Scholar 

  38. Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1982;196(3):305–315.

    Article  PubMed  CAS  Google Scholar 

  39. Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14(3):859–868.

    PubMed  CAS  Google Scholar 

  40. Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16(1):197–203.

    PubMed  CAS  Google Scholar 

  41. O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 2002;359(9325):2235–2241.

    Article  PubMed  Google Scholar 

  42. Sindelar WF, Kinsella TJ, Chen PW, et al. Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial. Arch Surg 1993;128(4):402–410.

    PubMed  CAS  Google Scholar 

  43. Chang AE, Kinsella T, Glatstein E, et al. Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity. J Clin Oncol 1988;6(9):1491–1500.

    PubMed  CAS  Google Scholar 

  44. Van Houtte P, Rocmans P, Smets P, et al. Postoperative radiation therapy in lung cancer: a controlled trial after resection of curative design. Int J Radiat Oncol Biol Phys 1980;6(8):983–986.

    PubMed  Google Scholar 

  45. Bangma PJ. Postoperative radiotherapy. In: Deeley TJ (ed) Carcinoma of the Bronchus: Modern Radiotherapy. New York: Appleton-Century-Crofts, 1972:163–170.

    Google Scholar 

  46. Paterson R, Russell MH. Clinical trial in malignant disease. IV. Lung cancer. Value of postoperative radiotherapy. Clin Radiol 1962;13:141–144.

    Article  PubMed  CAS  Google Scholar 

  47. Smolle-Juettner FM, Mayer R, Pinter H, et al. “Adjuvant” external radiation of the mediastinum in radically resected non-small cell lung cancer. Eur J Cardiothorac Surg 1996;10(11):947–950.

    Article  PubMed  CAS  Google Scholar 

  48. Anonymous. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. The Lung Cancer Study Group. N Engl J Med 1986;315(22):1377–1381.

    Google Scholar 

  49. Choi NC, Carey RW, Daly W, et al. Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer. J Clin Oncol 1997;15(2):712–722.

    PubMed  CAS  Google Scholar 

  50. Astudillo J, Conill C. Role of postoperative radiation therapy in stage Ilia non-small cell lung cancer. Ann Thorac Surg 1990;50(4):618–623.

    PubMed  CAS  Google Scholar 

  51. Chung CK, Stryker JA, O’Neill M Jr, DeMuth WE Jr. Evaluation of adjuvant postoperative radiotherapy for lung cancer. Int J Radiat Oncol Biol Phys 1982;8(11):1877–1880.

    PubMed  CAS  Google Scholar 

  52. Israel L Bonadonna G, Sylvester R. Controlled study with adjuvant radiotherapy, chemotherapy, immunotherapy, and chemo-immunotherapy in operable squamous cell carcinoma of the lung. In: Muggia FM, Rozencweig M, eds. Lung Cancer: Progress in Therapeutic Research. New York: Raven Press, 1979:443–452.

    Google Scholar 

  53. Stephens RJ, Girling DJ, Bleehen NM, Moghissi K, Yosef HM, Machin D. The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged Tl-2, Nl-2, MO disease. Medical Research Council Lung Cancer Working Party. Br J Cancer 1996;74(4):632–639.

    PubMed  CAS  Google Scholar 

  54. Anonymous. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet 1998;352(9124):257–263.

    Google Scholar 

  55. Dautzenberg B, Arriagada R, Chammard AB, et al. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Groupe d’Etude et de Traitement des Cancers Bronchiques. Cancer (Phila) 1999;86(2):265–273.

    Article  PubMed  CAS  Google Scholar 

  56. Dautzenberg B, Chastang C, Arriagada R, et al. Adjuvant radiotherapy versus combined sequential chemotherapy followed by radiotherapy in the treatment of resected nonsmall cell lung carcinoma. A randomized trial of 267 patients. GETCB (Groupe d’Etude et de Traitement des Cancers Bronchiques). Cancer (Phila) 1995;76(5):779–786.

    Article  PubMed  CAS  Google Scholar 

  57. Anonymous. The benefit of adjuvant treatment for resected locally advanced non-small-cell lung cancer. The Lung Cancer Study Group. J Clin Oncol 1988;6(1):9–17.

    Google Scholar 

  58. Trakhtenberg A, Kiseleva ES, Pitskhelauri VG, et al. Preoperative radiotherapy in the combined treatment of lung cancer patients. Neoplasma 1988;35(4):459–465.

    PubMed  Google Scholar 

  59. Okubo K, Wada H, Fukuse T, et al. Treatment of Pancoast tumors. Combined irradiation and radical resection. Thorac Cardiovasc Surg 1995;43(5):284–286.

    Article  PubMed  CAS  Google Scholar 

  60. Perry MC, Herndon JE III, Eaton WL, Green MR. Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083. J Clin Oncol 1998;16(7):2466–2467.

    PubMed  CAS  Google Scholar 

  61. Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341(7):476–484.

    Article  PubMed  CAS  Google Scholar 

  62. Anonymous. Prolongation of the disease-free interval in surgically treated rectal carcinoma. Gastrointestinal Tumor Study Group. N Engl J Med 1985;312(23):1465–1472.

    Google Scholar 

  63. Fisher B, Wolmark N, Rockette H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988;80(1):21–29.

    Article  PubMed  CAS  Google Scholar 

  64. Bentzen SM, Balslev I, Pedersen M, et al. Time to loco-regional recurrence after resection of Dukes’ B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis. Br J Cancer 1992;65(1):102–107.

    PubMed  CAS  Google Scholar 

  65. Balslev I, Pedersen M, Teglbjaerg PS, et al. Postoperative radiotherapy in Dukes’ B and C carcinoma of the rectum and rectosigmoid. A randomized multicenter study. Cancer (Phila) 1986;58(1):22–28.

    Article  PubMed  CAS  Google Scholar 

  66. Arnaud JP, Nordlinger B, Bosset JF, et al. Radical surgery and postoperative radiotherapy as combined treatment in rectal cancer. Final results of a phase III study of the European Organization for Research and Treatment of Cancer. Br J Surg 1997;84(3):352–357.

    Article  PubMed  CAS  Google Scholar 

  67. Anonymous. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Medical Research Council Rectal Cancer Working Party. Lancet 1996;348(9042):1610–1614.

    Google Scholar 

  68. Treurniet-Donker AD, van Putten WL, Wereldsma JC, et al. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands. Cancer (Phila) 1991;67(8):2042–2048.

    Article  PubMed  CAS  Google Scholar 

  69. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324(11):709–715.

    PubMed  CAS  Google Scholar 

  70. Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 1988;13(4):245–252.

    Article  PubMed  CAS  Google Scholar 

  71. Wolmark N, Wieand HS, Hyams DM, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000;92(5):388–396.

    Article  PubMed  CAS  Google Scholar 

  72. Goldberg PA, Nicholls RJ, Porter NH, Love S, Grimsey JE. Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure. Eur J Cancer 1994;30A(11):1602–1606.

    Article  PubMed  CAS  Google Scholar 

  73. Higgins GA, Humphrey EW, Dwight RW, Roswit B, Lee LE Jr, Keehn RJ. Preoperative radiation and surgery for cancer of the rectum. Veterans Administration Surgical Oncology Group Trial II. Cancer (Phila) 1986;58(2):352–359.

    Article  PubMed  CAS  Google Scholar 

  74. Reis Neto JA, Quilici FA, Reis JA Jr. A comparison of nonop-erative vs. preoperative radiotherapy in rectal carcinoma. A 10-year randomized trial. Dis Colon Rectum 1989;32(8):702–710.

    Article  PubMed  CAS  Google Scholar 

  75. Rider WD, Palmer JA, Mahoney LJ, Robertson CT. Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial. Can J Surg 1977;20(4):335–338.

    PubMed  CAS  Google Scholar 

  76. Anonymous. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl JMedl 997;336(14):980–987.

    Google Scholar 

  77. Anonymous. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Medical Research Council Rectal Cancer Working Party. Lancet 1996;348(9042):1605–1610.

    Google Scholar 

  78. Anonymous. Randomized study on preoperative radiotherapy in rectal carcinoma. Stockholm Colorectal Cancer Study Group. Ann Surg Oncol 1996;3(5):423–430.

    Google Scholar 

  79. Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer (Phila) 1995;75(9):2269–2275.

    Article  PubMed  CAS  Google Scholar 

  80. Anonymous. Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Rectal Cancer Study Group. Cancer (Phila) 1990;66(1):49–55.

    Google Scholar 

  81. Marsh PJ, James RD, Schofield PF. Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial. Dis Colon Rectum 1994;37(12):1205–1214.

    Article  PubMed  CAS  Google Scholar 

  82. Roswit B, Higgins GA, Keehn RJ. Preoperative irradiation for carcinoma of the rectum and rectosigmoid colon: report of a National Veterans Administration randomized study. Cancer (Phila) 1975;35(6):1597–1602.

    Article  PubMed  CAS  Google Scholar 

  83. Duncan W. Adjuvant radiotherapy in rectal cancer: the MRC trials. Br J Surg 1985;72(suppl):S59–S62.

    Article  PubMed  Google Scholar 

  84. Dahl O, Horn A, Morild I, et al. Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway. Cancer (Phila) 1990;66(11):2286–2294.

    Article  PubMed  CAS  Google Scholar 

  85. Gerard A, Buyse M, Nordlinger B, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC). Arm Surg 1988;208(5):606–614.

    CAS  Google Scholar 

  86. Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: a metaanalysis. JAMA 2000;284(8):1008–1015.

    Article  PubMed  CAS  Google Scholar 

  87. Anonymous. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001;358(9290):1291–1304.

    Google Scholar 

  88. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345(9):638–646.

    Article  PubMed  CAS  Google Scholar 

  89. Boulis-Wassif S, Gerard A, Loygue J, Camelot D, Buyse M, Duez N. Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-fluorouracil, followed by radical surgery. Trial of the European Organization on Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. Cancer (Phila) 1984;53(9):1811–1818.

    Article  PubMed  CAS  Google Scholar 

  90. Gerard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers:results of FFCD 9203.J Clin Oncol 2006;24(28):4620–4625

    Article  PubMed  Google Scholar 

  91. Pahlman L, Glimelius B. Pre-or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 1990;211(2):187–195.

    Article  PubMed  CAS  Google Scholar 

  92. Sauer Rolf BH, Hohenberger W, Rodel C, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–1740.

    Article  PubMed  CAS  Google Scholar 

  93. Cummings BJ, Keane TJ, O’Sullivan B, Wong CS, Catton CN. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys 1991;21(5):1115–1125.

    PubMed  CAS  Google Scholar 

  94. Bosset JF, Roelofsen F, Morgan DA, et al. Shortened irradiation scheme, continuous infusion of 5-fluorouracil and fractionation of mitomycin C in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer. Radiotherapy and Gastrointestinal Cooperative Groups. Eur J Cancer 2003;39(1):45–51.

    Article  PubMed  CAS  Google Scholar 

  95. Peiffert D, Bey P, Pernot M, et al. Conservative treatment by irradiation of epidermoid cancers of the anal canal: prognostic factors of tumoral control and complications. Int J Radiat Oncol Biol Phys 1997;37(2):313–324.

    PubMed  CAS  Google Scholar 

  96. Gerard JP, Ayzac L, Hun D, et al. Treatment of anal canal carcinoma with high dose radiation therapy and concomitant fluorouracil-cisplatinum. Long-term results in 95 patients. Radiother Oncol 1998;46(3):249–256.

    Article  PubMed  CAS  Google Scholar 

  97. Anonymous. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996;348(9034):1049–1054.

    Google Scholar 

  98. Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997;15(5):2040–2049.

    PubMed  CAS  Google Scholar 

  99. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemo-radiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996;14(9):2527–2539.

    PubMed  CAS  Google Scholar 

  100. al-Sarraf M, Martz K, Herskovic A, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol 1997;15(1):277–284.

    PubMed  CAS  Google Scholar 

  101. Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326(24):1593–1598.

    PubMed  CAS  Google Scholar 

  102. Teniere P, Hay JM, Fingerhut A, Fagniez PL. Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet 1991;173(2):123–130.

    PubMed  CAS  Google Scholar 

  103. Fok M, Sham JS, Choy D, Cheng SW, Wong J. Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study. Surgery (St. Louis) 1993;113(2):138–147.

    PubMed  CAS  Google Scholar 

  104. Zieren HU, Muller JM, Jacobi CA, Pichlmaier H, Muller RP, Staar S. Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: a prospective randomized study. World J Surg 1995;19(3):444–449.

    Article  PubMed  CAS  Google Scholar 

  105. Huang G. Combined Irradiation and Surgery for Esophageal Carcinoma. St. Louis: Mosby, 1988.

    Google Scholar 

  106. Arnott SJ, Duncan W, Kerr GR, et al. Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial. Radiother Oncol 1992;24(2):108–113.

    Article  PubMed  CAS  Google Scholar 

  107. Gignoux M, Roussel A, Paillot B, et al. The value of preoperative radiotherapy in esophageal cancer: results of a study of the E. O.R.T.C. World J Surg 1987;11(4):426–432.

    Article  PubMed  CAS  Google Scholar 

  108. Nygaard K, Hagen S, Hansen HS, et al. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World J Surg 1992;16(6):1104–1109;discussion 1110.

    Article  PubMed  CAS  Google Scholar 

  109. Launois B, Delarue D, Campion JP, Kerbaol M. Preoperative radiotherapy for carcinoma of the esophagus. Surg Gynecol Obstet 1981;153(5):690–692.

    PubMed  CAS  Google Scholar 

  110. Wang M, Gu XZ, Yin WB, Huang GJ, Wang LJ, Zhang DW. Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients. Int J Radiat Oncol Biol Phys 1989;16(2):325–327.

    PubMed  CAS  Google Scholar 

  111. Arnott SJ, Duncan W, Gignoux M, et al. Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group). Int J Radiat Oncol Biol Phys 1998;41(3):579–583.

    Article  PubMed  CAS  Google Scholar 

  112. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335(7):462–467.

    Article  PubMed  CAS  Google Scholar 

  113. Le Prise E, Etienne PL, Meunier B, et al. A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus. Cancer (Phila) 1994;73(7):1779–1784.

    Article  PubMed  Google Scholar 

  114. Bosset JF, Gignoux M, Triboulet JP, et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 1997;337(3):161–167.

    Article  PubMed  CAS  Google Scholar 

  115. Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19(2):305–313.

    PubMed  CAS  Google Scholar 

  116. Schlag PM. Randomized trial of preoperative chemotherapy for squamous cell cancer of the esophagus. The Chirurgische Arbeitsgemeinschaft Fuer Onkologie der Deutschen Gesellschaft Fuer Chirurgie Study Group. Arch Surg 1992;127(12):1446–1450.

    PubMed  CAS  Google Scholar 

  117. Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg 2003;185(6):538–543.

    Article  PubMed  Google Scholar 

  118. Kaiser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 1985;120(8):899–903.

    Google Scholar 

  119. Anonymous. Further evidence of adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer (Phila) 1987;59:2006–2010.

    Google Scholar 

  120. Bakkevold KE, Arnesjo B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater-results of a controlled, prospective, randomised multicentre study. Eur J Cancer 1993;29A(5):698–703.

    Article  PubMed  CAS  Google Scholar 

  121. Klinkenbijl JH, Jeekel J, Sahmoud 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(6):776–782;discussion 82–84.

    Article  PubMed  CAS  Google Scholar 

  122. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350(12):1200–1210.

    Article  PubMed  CAS  Google Scholar 

  123. Knaebel HP, Marten A, Schmidt J et al. Phase III trial of postoperative cisplatin, interferon alpha 2b, and 5FU combined with external radiation treatment versus 5FU alone for patients with resected pancreatic adenocarcinoma: CapRI study protocol. BMC Cancer 2005;5:37

    Article  PubMed  CAS  Google Scholar 

  124. Hoffman JP, Weese JL, Solin LJ, et al. A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas. Am J Surg 1995;169(1):71–77;discussion 77–78.

    Article  PubMed  CAS  Google Scholar 

  125. Allum WH, Hallissey MT, Ward LC, Hockey MS. A controlled, prospective, randomised trial of adjuvant chemotherapy or radiotherapy in resectable gastric cancer: interim report. British Stomach Cancer Group. Br J Cancer 1989;60(5):739–744.

    PubMed  CAS  Google Scholar 

  126. Fielding JW, Fagg SL, Jones BG, et al. An interim report of a prospective, randomized, controlled study of adjuvant chemotherapy in operable gastric cancer: British Stomach Cancer Group. World J Surg 1983;7(3):390–399.

    Article  PubMed  CAS  Google Scholar 

  127. Hallissey MT, Dunn JA, Ward LC, Allum WH. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up. Lancet 1994;343(8909):1309–1312.

    Article  PubMed  CAS  Google Scholar 

  128. Dent DM, Werner ID, Novis B, Cheverton P, Brice P. Prospective randomized trial of combined oncological therapy for gastric carcinoma. Cancer (Phila) 1979;44(2):385–391.

    Article  PubMed  CAS  Google Scholar 

  129. Moertel CG, Childs DS, O’Fallon JR, Holbrook MA, Schutt AJ, Reitemeier RJ. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. J Clin Oncol 1984;2(11):1249–1254.

    PubMed  CAS  Google Scholar 

  130. 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(10):725–730.

    Article  PubMed  CAS  Google Scholar 

  131. Coppin CM, Gospodarowicz MK, James K, et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1996;14(11):2901–2907.

    PubMed  CAS  Google Scholar 

  132. Kachnic LA, Kaufman DS, Heney NM, et al. Bladder preservation by combined modality therapy for invasive bladder cancer. J Clin Oncol 1997;15(3):1022–1029.

    PubMed  CAS  Google Scholar 

  133. Shipley WU, Winter KA, Kaufman DS, et al. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol 1998;16(11):3576–3583.

    PubMed  CAS  Google Scholar 

  134. Shahab N. Bladder preservation trial: Radiation Therapy Oncology Group 89-03. J Clin Oncol 1999;17(4):1327–1328.

    PubMed  CAS  Google Scholar 

  135. Sell A, Jakobsen A, Nerstrom B, Sorensen BL, Steven K, Barlebo H. Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group. Scand J Urol Nephrol Suppl 1991;138:193–201.

    PubMed  CAS  Google Scholar 

  136. Bloom HJ, Hendry WF, Wallace DM, Skeet RG. Treatment of T3 bladder cancer: controlled trial of pre-operative radiotherapy and radical cystectomy versus radical radiotherapy. Br J Urol 1982;54(2):136–151.

    Article  PubMed  CAS  Google Scholar 

  137. Bolla M, van Poppel H, Collette L, et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 2005;366(9485):572–578.

    Article  PubMed  Google Scholar 

  138. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer. A randomised clinical trial. JAMA 2006;296(19):2329–2335.

    Article  PubMed  CAS  Google Scholar 

  139. Anonymous. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 1991;324(24):1685–1690.

    Google Scholar 

  140. Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996;88(13):890–899.

    Article  PubMed  CAS  Google Scholar 

  141. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349(22):2091–2098.

    Article  PubMed  CAS  Google Scholar 

  142. Kramer S, Gelber RD, Snow JB, et al. Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the Radiation Therapy Oncology Group. Head Neck Surg 1987;10(1):19–30.

    Article  PubMed  CAS  Google Scholar 

  143. Peters LJ, Goepfert H, Ang KK, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Int J Radiat Oncol Biol Phys 1993;26(1):3–11.

    PubMed  CAS  Google Scholar 

  144. Lavertu P, Adelstein DJ, Saxton JP, et al. Management of the neck in a randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage HI and IV squamous cell head and neck cancer. Head Neck 1997;19(7):559–566.

    Article  PubMed  CAS  Google Scholar 

  145. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350(19):1945–1952.

    Article  PubMed  CAS  Google Scholar 

  146. 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(19):1937–1944.

    Article  PubMed  Google Scholar 

  147. Kristiansen K, Hagen S, Kollevold T, et al. Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer (Phila) 1981;47(4):649–652.

    Article  PubMed  CAS  Google Scholar 

  148. Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 1978;49(3):333–343.

    Article  PubMed  CAS  Google Scholar 

  149. Bleehen NM, Stenning SP. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. Br J Cancer 1991;64(4):769–774.

    PubMed  CAS  Google Scholar 

  150. Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 1979;5(10):1725–1731.

    PubMed  CAS  Google Scholar 

  151. Chang CH, Horton J, Schoenfeld D, et al. Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study. Cancer (Phila) 1983;52(6):997–1007.

    Article  PubMed  CAS  Google Scholar 

  152. Laperriere NJ, Leung PM, McKenzie S, et al. Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma. Int J Radiat Oncol Biol Phys 1998;41(5):1005–1011.

    PubMed  CAS  Google Scholar 

  153. Roa W, Brasher PM, Bauman G, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 2004;22(9):1583–1588.

    Article  PubMed  CAS  Google Scholar 

  154. Stupp R, Mason WP, Van Den Bent MJ, et al. Concomitant and adjuvant temozolamide (TMZ) and radiotherapy (RT) for newly diagnosed glioblastoma multiforme (GBM). Proc Am Soc Clin Oncol 2004;23:1.

    Google Scholar 

  155. Karim AB, Afra D, Cornu P, et al. Randomized trial on the efficacy of radiotherapy for cerebral low-grade glioma in the adult: European Organization for Research and Treatment of Cancer Study 22845 with the Medical Research Council study BR04: an interim analysis. Int J Radiat Oncol Biol Phys 2002;52(2):316–324.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Toronto/Princess Margaret Hospital, Toronto, Ontario, Canada

    Barbara-Ann Millar MBChB (Assistant Professor) & Laura A. Dawson MD (Assistant Professor)

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  1. Barbara-Ann Millar MBChB
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  2. Laura A. Dawson MD
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Editors and Affiliations

  1. Department of Surgery, Stanford University Medical Center, Stanford, CA, USA

    Jeffrey A. Norton MD, FACS (Robert L. and Mary Ellenburg Professor, Chief) (Robert L. and Mary Ellenburg Professor, Chief)

  2. Divisions of Surgical Oncology and General Surgery, Department of Surgery, Stanford University Medical Center, Stanford, CA, USA

    Jeffrey A. Norton MD, FACS (Robert L. and Mary Ellenburg Professor, Chief) (Robert L. and Mary Ellenburg Professor, Chief)

  3. Departments of Surgery and Public Health, New York-Presbyterian Hospital/Weill Cornell Medical College, New York, NY, USA

    Philip S. Barie MD, MBA, FCCM, FACS (Professor, Chief) (Professor, Chief)

  4. Division of Critical Care and Trauma, NewYork-Presbyterian Hospital/Weill Cornell Medical College, New York, NY, USA

    Philip S. Barie MD, MBA, FCCM, FACS (Professor, Chief) (Professor, Chief)

  5. Departments of Surgery and Immunology, Duke University Medical Center, Durham, NC, USA

    R. Randal Bollinger MD, PhD, FACS (Professor) (Professor)

  6. Division of Surgical Oncology, Department of Surgery, University of Michigan, Comprehensive Cancer Center, Ann Arbor, MI, USA

    Alfred E. Chang MD, FACS (Chief, Hugh Cabot Professor of Surgery) (Chief, Hugh Cabot Professor of Surgery)

  7. Department of Surgery, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

    Stephen F. Lowry MD, MBA, FACS (Professor and Chairman) (Professor and Chairman)

  8. Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    Stephen F. Lowry MD, MBA, FACS (Professor and Chairman) (Professor and Chairman)

  9. Department of Surgery, The University of Utah, Salt Lake City, UT, USA

    Sean J. Mulvihill MD, FACS (Professor and Chair, Senior Director of Clinical Affairs) (Professor and Chair, Senior Director of Clinical Affairs)

  10. Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT, USA

    Sean J. Mulvihill MD, FACS (Professor and Chair, Senior Director of Clinical Affairs) (Professor and Chair, Senior Director of Clinical Affairs)

  11. Departments of Cardiothoracic Surgery and Surgery, New York University Medical Center, New York, NY, USA

    Harvey I. Pass MD, FACS (Professor) (Professor)

  12. Radiology, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA

    Robert W. Thompson MD, FACS (Professor of Surgery (Section of Vascular Surgery), Vice-Chairman for Research) (Professor of Surgery (Section of Vascular Surgery), Vice-Chairman for Research)

  13. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Robert W. Thompson MD, FACS (Professor of Surgery (Section of Vascular Surgery), Vice-Chairman for Research) (Professor of Surgery (Section of Vascular Surgery), Vice-Chairman for Research)

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Millar, BA., Dawson, L.A. (2008). Radiation as an Adjunct to Surgery. In: Norton, J.A., et al. Surgery. Springer, New York, NY. https://doi.org/10.1007/978-0-387-68113-9_96

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