Current Treatment Options in Oncology

, Volume 9, Issue 4–6, pp 343–356

Post-Operative Radiation Therapy (PORT) in Completely Resected Non-Small-Cell Lung Cancer

Lung Cancer

Opinion statement

High-level evidence to guide the optimal postoperative management of patients with completely resected non-small-cell lung cancer (NSCLC) is lacking. Large randomized controlled trials have established postoperative chemotherapy as the standard of care for patients with pathologically involved lymph nodes. Recent retrospective and non-randomized studies provide evidence of the benefit of post-operative radiation therapy (PORT) in patients with mediastinal nodal involvement (N2 stage). A large multi-institutional randomized trial of PORT in this patient population is now underway. Based on currently available data, PORT may be considered for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy. At this point, PORT is not recommended for patients with less than N2 nodal stage. Ideally, modern three-dimensional conformal radiation technique should be used, with attention to normal organ sparing, particularly lung and heart. Appropriate image guidance tools are encouraged to individualize treatment margins, account for breathing-induced motion, and minimize irradiation of normal tissues. The target volume should include at a minimum the bronchial stump, ipsilateral hilum, and involved nodal stations, and covering adjacent mediastinal nodal stations is recommended. A total dose of 50–54 Gy in 1.8–2 Gy fractions is appropriate.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Cerfolio RJ, Bryant AS, Eloubeidi MA. Routine mediastinoscopy and esophageal ultrasound fine-needle aspiration in patients with non-small cell lung cancer who are clinically N2 negative: a prospective study. Chest 2006,130:1791–5. doi:10.1378/chest.130.6.1791.PubMedCrossRefGoogle Scholar
  2. 2.
    Meyers BF, Haddad F, Siegel BA, et al. Cost-effectiveness of routine mediastinoscopy in computed tomography- and positron emission tomography-screened patients with stage I lung cancer. J Thorac Cardiovasc Surg 2006,131:822–9; discussion –9.PubMedCrossRefGoogle Scholar
  3. 3.
    Koike T, Tsuchiya R, Goya T, et al. Prognostic factors in 3315 completely resected cases of clinical stage I non-small cell lung cancer in Japan. J Thorac Oncol 2007,2:408–13. doi:10.1097/01.JTO.0000268674.02744.f9.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee PC, Port JL, Korst RJ, et al. Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer. Ann Thorac Surg 2007,84:177–81. doi:10.1016/j.athoracsur.2007.03.081.PubMedCrossRefGoogle Scholar
  5. 5.
    Herth FJ, Eberhardt R, Krasnik M, Ernst A. Endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes in the radiologically and positron emission tomography-normal mediastinum in patients with lung cancer. Chest 2008,133:887–91. doi:10.1378/chest.07-2535.PubMedCrossRefGoogle Scholar
  6. 6.
    Andre F, Grunenwald D, Pignon JP, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 2000,18:2981–9.PubMedGoogle Scholar
  7. 7.
    Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol 2007,2:603–12. doi:10.1097/JTO.0b013e31807ec803.PubMedCrossRefGoogle Scholar
  8. 8.
    Cerfolio RJ, Bryant AS. Survival of patients with unsuspected N2 (stage IIIA) nonsmall-cell lung cancer. Ann Thorac Surg 2008,86:362–6; discussion 6–7. doi:10.1016/j.athoracsur.2008.04.042.PubMedCrossRefGoogle Scholar
  9. 9.••
    The PORT Meta-analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet 1998,352:257–63. doi:10.1016/S0140-6736(98)06341-7.CrossRefGoogle Scholar
  10. 10.
    Van Houtte P, Rocmans P, Smets P, et al. Postoperative radiation therapy in lung caner: a controlled trial after resection of curative design. Int J Radiat Oncol Biol Phys 1980,6:983–6.PubMedGoogle Scholar
  11. 11.
    The Lung Cancer Study Group. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. N Engl J Med 1986,315:1377–81.CrossRefGoogle Scholar
  12. 12.
    Wang M, Gu XZ, Yin WB, et al. Randomized clinical trial of postoperative irradiation after surgery for non-small cell lung carcinoma. Chin J Radiat Oncol 1994,3: 39–43.Google Scholar
  13. 13.
    Debevec M, Bitenc M, Vidmar S, et al. Postoperative radiotherapy for radically resected N2 non-small-cell lung cancer (NSCLC): randomised clinical study 1988–1992. Lung Cancer 1996,14:99–107. doi:10.1016/0169-5002(95)00515-3.PubMedCrossRefGoogle Scholar
  14. 14.
    Lafitte JJ, Ribet ME, Prévost BM, et al. Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study. Ann Thorac Surg 1996,62:830–4. doi:10.1016/S0003-4975(96)00507-3.PubMedCrossRefGoogle Scholar
  15. 15.
    Stephens RJ, Girling DJ, Bleehen NM, et al. The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party. Br J Cancer 1996,74:632–9.PubMedGoogle Scholar
  16. 16.
    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 1999,86:265–73. doi:10.1002/(SICI)1097-0142(19990715)86:2<265::AID-CNCR10>3.0.CO;2-B.PubMedCrossRefGoogle Scholar
  17. 17.
    Mayer R, Smolle-Juettner FM, Szolar D, et al. Postoperative radiotherapy in radically resected non-small cell lung cancer. Chest 1997,112:954–9. doi:10.1378/chest.112.4.954.PubMedCrossRefGoogle Scholar
  18. 18.
    Feng QF, Wang M, Wang LJ, et al. A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial. Int J Radiat Oncol Biol Phys 2000,47:925–9. doi:10.1016/S0360-3016(00)00509-5.PubMedGoogle Scholar
  19. 19.
    Trodella L, Granone P, Valente S, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncology 2002,62:11–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Perry MC, Kohman LJ, Bonner JA, et al. A phase III study of surgical resection and paclitaxel/carboplatin chemotherapy with or without adjuvant radiation therapy for resected stage III non-small-cell lung cancer: Cancer and Leukemia Group B 9734. Clin Lung Cancer 2007,8:268–72. doi:10.3816/CLC.2007.n.005.PubMedCrossRefGoogle Scholar
  21. 21.
    Machtay M, Lee JH, Shrager JB, et al. Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma. J Clin Oncol 2001,19:3912–7.PubMedGoogle Scholar
  22. 22.
    Keller SM, Adak S, Wagner H, et al. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. Eastern Cooperative Oncology Group. N Engl J Med 2000,343:1217–22. doi:10.1056/NEJM200010263431703.PubMedCrossRefGoogle Scholar
  23. 23.
    Bradley JD, Paulus R, Graham MV, et al. Phase II trial of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage II and IIIA non-small-cell lung cancer: promising long-term results of the Radiation Therapy Oncology Group—RTOG 9705. J Clin Oncol 2005,23:3480–7. doi:10.1200/JCO.2005.12.120.PubMedCrossRefGoogle Scholar
  24. 24.••
    Douillard JY, Rosell R, De Lena M, et al. Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the adjuvant Navelbine International Trialist Association (ANITA) Randomized Trial. Int J Radiat Oncol Biol Phys 2008,72:695–701. doi:10.1016/j.ijrobp.2008.01.044.PubMedGoogle Scholar
  25. 25.••
    Burdett S, Stewart L, PORT Meta-analysis Group. Postoperative radiotherapy in non-small-cell lung cancer: update of an individual patient data meta-analysis. Lung Cancer 2005,47:81–3. doi:10.1016/j.lungcan.2004.09.010.PubMedCrossRefGoogle Scholar
  26. 26.•
    Lally BE, Zelterman D, Colasanto JM, et al. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 2006,24:2998–3006. doi:10.1200/JCO.2005.04.6110.PubMedCrossRefGoogle Scholar
  27. 27.
    Bekelman JE, Rosenzweig KE, Bach PB, Schrag D. Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2006,66:492–9. doi:10.1016/j.ijrobp.2006.04.032.PubMedGoogle Scholar
  28. 28.
    Wakelee H, Chhatwani L. Adjuvant chemotherapy for resected non-small cell lung cancer. Seminars in Thoracic and Cardiovascular Surgery 2008,20:198–203. doi:10.1053/j.semtcvs.2008.09.001.PubMedCrossRefGoogle Scholar
  29. 29.
    Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004,350:351–60. doi:10.1056/NEJMoa031644.PubMedCrossRefGoogle Scholar
  30. 30.
    Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005,352:2589–97. doi:10.1056/NEJMoa043623.PubMedCrossRefGoogle Scholar
  31. 31.
    Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. The Lancet Oncology 2006,7:719–27. doi:10.1016/S1470-2045(06)70804-X.PubMedCrossRefGoogle Scholar
  32. 32.
    Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008,26:3552–9. doi:10.1200/JCO.2007.13.9030.PubMedCrossRefGoogle Scholar
  33. 33.
    Lally BE, Detterbeck FC, Geiger AM, et al. The risk of death from heart disease in patients with nonsmall cell lung cancer who receive postoperative radiotherapy: analysis of the Surveillance, Epidemiology, and End Results database. Cancer 2007,110:911–7. doi:10.1002/cncr.22845.PubMedCrossRefGoogle Scholar
  34. 34.
    Matsuguma H, Nakahara R, Ishikawa Y, et al. Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: focusing on an effect of the number of mediastinal lymph node stations involved. Interact Cardiovasc Thorac Surg 2008,7:573–7. doi:10.1510/icvts.2007.174342.PubMedCrossRefGoogle Scholar
  35. 35.
    Wakelee HA, Stephenson P, Keller SM, et al. Post-operative radiotherapy (PORT) or chemoradiotherapy (CPORT) following resection of stages II and IIIA non-small cell lung cancer (NSCLC) does not increase the expected risk of death from intercurrent disease (DID) in Eastern Cooperative Oncology Group (ECOG) trial E3590. Lung Cancer 2005,48:389–97. doi:10.1016/j.lungcan.2004.11.007.PubMedCrossRefGoogle Scholar
  36. 36.
    Sawyer TE, Bonner JA, Gould PM, et al. Effectiveness of postoperative irradiation in stage IIIA non-small cell lung cancer according to regression tree analyses of recurrence risks. Ann Thorac Surg 1997,64:1402–7; discussion 7–8. doi:10.1016/S0003-4975(97)00908-9.PubMedCrossRefGoogle Scholar
  37. 37.
    Scagliotti GV. The ALPI Trial: the Italian/European experience with adjuvant chemotherapy in resectable non-small lung cancer. Clin Cancer Res 2005,11:5011s-6s. doi:10.1158/1078-0432.CCR-05-9009.PubMedCrossRefGoogle Scholar
  38. 38.
    Wind J, Smit EJ, Senan S, Eerenberg JP. Residual disease at the bronchial stump after curative resection for lung cancer. Eur J Cardiothorac Surg 2007,32:29–34.PubMedCrossRefGoogle Scholar
  39. 39.•
    Ettinger DS, Akerley W, Bepler G, et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2008,6:228–69.PubMedGoogle Scholar
  40. 40.
    Watanabe Y, Shimizu J, Tsubota M, Iwa T. Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer. Chest 1990,97:1059–65. doi:10.1378/chest.97.5.1059.PubMedCrossRefGoogle Scholar
  41. 41.
    Kotoulas CS, Foroulis CN, Kostikas K, et al. Involvement of lymphatic metastatic spread in non-small cell lung cancer accordingly to the primary cancer location. Lung Cancer 2004,44:183–91. doi:10.1016/j.lungcan.2003.10.012.PubMedCrossRefGoogle Scholar
  42. 42.
    Cerfolio RJ, Bryant AS. Distribution and likelihood of lymph node metastasis based on the lobar location of nonsmall-cell lung cancer. Ann Thorac Surg 2006,81:1969–73; discussion 73. doi:10.1016/j.athoracsur.2005.12.067.PubMedCrossRefGoogle Scholar
  43. 43.
    Kelsey CR, Light KL, Marks LB. Patterns of failure after resection of non-small-cell lung cancer: implications for postoperative radiation therapy volumes. Int J Radiat Oncol Biol Phys 2006,65:1097–105. doi:10.1016/j.ijrobp.2006.02.007.PubMedGoogle Scholar
  44. 44.
    Senan S, Le Pechoux C, Spoelstra FO, et al. Lack of consensus on post-operative radiotherapy (PORT) fields used in non-small cell lung cancer NSCLC Abstract. Journal of Clinical Oncology 2007,25:7658–00. doi:10.1200/JCO.2006.09.8178.CrossRefGoogle Scholar
  45. 45.
    Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991,21:109–22.PubMedGoogle Scholar
  46. 46.
    Kimsey FC, Mendenhall NP, Ewald LM, et al. Is radiation treatment volume a predictor for acute or late effect on pulmonary function? A prospective study of patients treated with breast-conserving surgery and postoperative irradiation. Cancer 1994,73:2549–55. doi:10.1002/1097-0142(19940515)73:10<2549::AID-CNCR2820731016>3.0.CO;2-N.PubMedCrossRefGoogle Scholar
  47. 47.
    Abratt RP, Morgan GW. Lung toxicity following chest irradiation in patients with lung cancer. Lung Cancer 2002,35:103–9. doi:10.1016/S0169-5002(01)00334-8.PubMedCrossRefGoogle Scholar
  48. 48.
    Inoue A, Kunitoh H, Sekine I, et al. Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis. Int J Radiat Oncol Biol Phys 2001,49:649–55. doi:10.1016/S0360-3016(00)00783-5.PubMedGoogle Scholar
  49. 49.
    Hernando ML, Marks LB, Bentel GC, et al. Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys 2001,51:650–9. doi:10.1016/S0360-3016(01)01685-6.PubMedGoogle Scholar
  50. 50.
    Bradley JD, Hope A, El Naqa I, et al. A nomogram to predict radiation pneumonitis, derived from a combined analysis of RTOG 9311 and institutional data. Int J Radiat Oncol Biol Phys 2007,69:985–92. doi:10.1016/j.ijrobp.2007.04.077.PubMedGoogle Scholar
  51. 51.
    Wang S, Liao Z, Wei X, et al. Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). Int J Radiat Oncol Biol Phys 2006,66:1399–407. doi:10.1016/j.ijrobp.2006.07.1337.PubMedGoogle Scholar
  52. 52.
    Yom SS, Liao Z, Liu HH, et al. Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2007,68:94–102. doi:10.1016/j.ijrobp.2006.12.031.PubMedGoogle Scholar
  53. 53.
    Pan T, Lee TY, Rietzel E, Chen GT. 4D-CT imaging of a volume influenced by respiratory motion on multi-slice CT. Medical physics 2004,31:333–40. doi:10.1118/1.1639993.PubMedCrossRefGoogle Scholar
  54. 54.
    Maxim PG, Loo BW, Shirazi H, et al. Quantification of motion of different thoracic locations using four-dimensional computed tomography: implications for radiotherapy planning. Int J Radiat Oncol Biol Phys 2007,69:1395–401. doi:10.1016/j.ijrobp.2007.05.016.PubMedGoogle Scholar
  55. 55.
    Keall P, Vedam S, George R, et al. The clinical implementation of respiratory-gated intensity-modulated radiotherapy. Med Dosim 2006,31:152–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Korreman SS, Juhler-Nøttrup T, Fredberg Persson G, et al. The role of image guidance in respiratory gated radiotherapy. Acta Oncol 2008,47:1390-6. doi:10.1080/02841860802282786.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Medicine, Division of OncologyStanford UniversityStanfordUSA
  2. 2.Department of Radiation OncologyStanford UniversityStanfordUSA

Personalised recommendations