The Radiation Target in Small-Cell Lung Cancer

Part of the Medical Radiology book series (MEDRAD)


What constitutes the appropriate target in the treatment of small-cell lung cancer is an area of active investigation. Advances in the last 30 years in radiologic and nuclear imaging as well as in radiotherapy delivery have prompted revision of the classically defined target which was designed to be “tolerable” and encompass visible tumor and potential areas of microscopic disease. Current trends are to minimize normal tissue irradiation and more precisely define the extent of potential microscopic spread in order to optimize target volume. This chapter will review historic trials and ongoing studies to provide a comprehensive understanding on the evolution of the radiotherapy target in small-cell lung cancer.


Positron Emission Tomography Plan Target Volume Clinical Target Volume Gross Tumor Volume Prophylactic Cranial Irradiation 


  1. Aristei C, Falcinelli L, Palumbo B, Tarducci R (2010) PET and PET-CT in radiation treatment planning for lung cancer. Expert Rev Antic Ther 10:571–584CrossRefGoogle Scholar
  2. Arriagada R, Pellae-Cosset B, Ladron de Guevara JC, el Bakry H, Benna F, Martin M, de Cremoux H, Baldeyrou P, Cerrina ML, Le Chevalier T (1991) Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences. Radiother Oncol 20:91–98PubMedCrossRefGoogle Scholar
  3. Auperin A, Arriagada R, Pignon JP, Le Pechoux C, Gregor A, Stephens RJ et al (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic cranial irradiation overview collaborative group. N Engl J Med 341:476–484PubMedCrossRefGoogle Scholar
  4. Baas P, Belderbos JS, Senan S, Kwa HB, van Bochove A, van Tinteren H, Burgers JA, van Meerbeeck JP (2006) Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study. Br J Cancer 94:625–630PubMedGoogle Scholar
  5. Belderbos J, Baas P, Senan S (2007) Reply: patterns of nodal recurrence after omission of elective nodal irradiation for limited-stage small-cell lung cancer. British J Cancer 97:276CrossRefGoogle Scholar
  6. Bleehen NM, Bunn PA, Cox JD, Dombernowsky P, Fox RM, Høst H, Joss R, White JE, Wittes RE (1983) Role of radiation therapy in small cell anaplastic carcinoma of the lung. Cancer Treat Rep 67:11–19PubMedGoogle Scholar
  7. Bogart JA, Herndon JE 2nd, Lyss AP, Watson D, Miller AA, Lee ME, Turrisi AT, Green MR, Cancer and Leukemia Group B study 39808 (2004) 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of cancer and leukemia group B study 39808. Int J Radiat Oncol Biol Phys 59:460–468PubMedCrossRefGoogle Scholar
  8. Bradley JD, Dehdashti F, Mintun MA, Govindan R, Trinkaus K, Siegel BA (2004) Positron emission tomography in limited-stage small-cell lung cancer: a prospective study. J Clin Oncol 22:3248–3254PubMedCrossRefGoogle Scholar
  9. Brodin O, Rikner G, Steinholtz L, Nou E (1990) Local failure in patients treated with radiotherapy and multidrug chemotherapy for small cell lung cancer. Acta Oncol 29:739–746PubMedCrossRefGoogle Scholar
  10. Bunn PA Jr, Lichter AS, Makuch RW, Cohen MH, Veach SR, Matthews MJ, Anderson AJ, Edison M, Glatstein E, Minna JD et al (1987) Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer. A prospective, randomized trial. Ann Intern Med 106:655–662PubMedCrossRefGoogle Scholar
  11. Cooper S, Spiro SG (2006) Small cell lung cancer: treatment review. Respirology 11:241–248PubMedCrossRefGoogle Scholar
  12. Curran WJ Jr (2001) Therapy of limited stage small cell lung cancer. Cancer Treat Res 105:229–252PubMedCrossRefGoogle Scholar
  13. de Ruysscher D, Vansteenkiste J (2000) Chest radiotherapy in limited-stage small cell lung cancer: facts, questions, prospects. Radiother Oncol 55:1–9PubMedCrossRefGoogle Scholar
  14. de Ruysscher D, Bremer RH, Koppe F, Wanders S, van Haren E, Hochstenbag M, Geeraedts W, Pitz C, Simons J, ten Velde G, Dohmen J, Snoep G, Boersma L, Verschueren T, van Baardwijk A, Dehing C, Pijls M, Minken A, Lambin P (2006) Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial. Radiother Oncol 80:307–312PubMedCrossRefGoogle Scholar
  15. Emami B (1996) Three-dimensional conformal radiation therapy in bronchogenic carcinoma. Semin Radiat Oncol 6:92–97PubMedCrossRefGoogle Scholar
  16. European Organisation for Research and Treatment of Cancer (EORTC) trial (2007) A randomized controlled trial of concurrent chemo-radiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small celllung cancer (SCLC) and good performance status. Accessed 13 Mar 2011
  17. Faivre-Finn C, Lee LW, Lorigan P, West C, Thatcher N (2005a) Thoracic radiotherapy forlimited-stage small-cell lung cancer: controversies and future developments. Clin Oncol (R Coll Radiol) 17:591–598CrossRefGoogle Scholar
  18. Faivre-Finn C, Lorigan P, West C, Thatcher N (2005b) Thoracic radiation therapy for limited-stage small-cell lung cancer: unanswered questions. Clin Lung Cancer 7:23–29PubMedCrossRefGoogle Scholar
  19. Fried DB, Morris DE, Poole C, Rosenman JG, Halle JS, Detterbeck FC, Hensing TA, Socinski MA (2004) Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22:4785–4793CrossRefGoogle Scholar
  20. Huncharek M, McGarry R (2004) A meta-analysis of the timing of chest irradiation in the combined modality treatment of limited-stage small cell lung cancer. Oncologist 9:6665–6672CrossRefGoogle Scholar
  21. International Commission on Radiation Units and Measurements (1993) Prescribing, recording, and reporting photon beam therapy, ICRU Report 50, MD, USAGoogle Scholar
  22. International Commission on Radiation Units and Measurements (1999) Prescribing, recording, and reporting photon beam therapy (Supplement to ICRU Report 50). ICRU Report 62, MD, USAGoogle Scholar
  23. Jeremic B (2006) Timing of concurrent radiotherapy and chemotherapy in limited-disease small-cell lung cancer: “Meta-analysis of meta-analyses”. Int J Radiat Oncol Biol Phys 64:981–982PubMedCrossRefGoogle Scholar
  24. Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S (1997) Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. J Clin Oncol 15:893–900PubMedGoogle Scholar
  25. Jeremic B, Shibamoto Y, Nikolic N, Milicic B, Milisavljevic S, Dagovic A, Aleksandrovic J, Radosavljevic-Asic G (1999) Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol 17:2092–2099PubMedGoogle Scholar
  26. Kamel EM, Zwahlen D, Wyss MT, Stumpe KD, von Schulthess GK, Steinert HC (2003) Whole-body (18) F-FDG PET improves the management of patients with small cell lung cancer. J Nucl Med 44:1911–1917PubMedGoogle Scholar
  27. Kies MS, Mira JG, Crowley JJ, Chen TT, Pazdur R, Grozea PN, Rivkin SE, Coltman CA Jr, Ward JH, Livingston RB (1987) Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a southwest oncology group study. J Clin Oncol 5:592–600PubMedGoogle Scholar
  28. Kong FM, Gaspar LE, Komaki R, Sun A, Bonner JA, Choy H, Wang L, Morris D, Sandler HM, Movsas B (2007) Patterns of practice in radiation dose prescription and treatment planning for patients with lung cancer among members of American society of therapeutic radiology and oncology. Int J Radiat Oncol Biol Phys 69(Suppl 1):S483CrossRefGoogle Scholar
  29. Lee CB, Morris DE, Fried DB et al (2006) Current and evolving treatment options for limited stage small cell lung cancer. Curr Opin Oncol 18:162–172PubMedCrossRefGoogle Scholar
  30. Liengswangwong V, Bonner JA, Shaw EG, Foote RL, Frytak S, Eagan RT, Jett JR, Richardson RL, Creagan ET, Su JQ (1994) Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy. J Clin Oncol 12:496–502PubMedGoogle Scholar
  31. Mira JG, Livingston RB (1980) Evaluation and radiotherapy implications of chest relapse patterns in small cell lung carcinoma treated with radiotherapy-chemotherapy: study of 34 cases and review of the literature. Cancer 46:2557–2565PubMedCrossRefGoogle Scholar
  32. Mira JG, Livingston RB, Moore TN, Chen T, Batley F, Bogardus CR Jr, Considine B Jr, Mansfield CM, Schlosser J, Seydel HG (1982) Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A southwest oncology group study. Cancer 50:1266–1272PubMedCrossRefGoogle Scholar
  33. Murray N, Coy P, Pater JL, Hodson I, Arnold A, Zee BC, Payne D, Kostashuk EC, Evans WK, Dixon P et al (1993) Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The national cancer institute of Canada clinical trials group. J Clin Oncol 11:336–344PubMedGoogle Scholar
  34. Perez CA, Krauss S, Bartolucci AA, Durant JR, Lowenbraun S, Salter MM, Storaalsi J, Kellermeyer R, Comas F (1981) Thoracic and elective brain irradiation with concomitant or delayed multiagent chemotherapy in the treatment of localized small cell carcinoma of the lung: a randomized prospective study by the southeastern cancer study group. Cancer 47:2407–2413PubMedCrossRefGoogle Scholar
  35. Perez CA, Einhorn L, Oldham RK, Greco FA, Cohen HJ, Silberman H, Krauss S, Hornback N, Comas F, Omura G, et al (1984) Randomized trial of radiotherapy to the thorax in limited small-cell carcinoma of the lung treated with multiagent chemotherapy and elective brain irradiation: a preliminary report. J Clin Oncol 2:1200–1208PubMedGoogle Scholar
  36. Perry MC, Eaton WL, Propert KJ, Ware JH, Zimmer B, Chahinian AP, Skarin A, Carey RW, Kreisman H, Faulkner C et al (1987) Chemotherapy with or without radiation therapy in limited small-cell carcinoma of the lung. N Engl J Med 316:912–918PubMedCrossRefGoogle Scholar
  37. Phase III randomized study of three different thoracic radiotherapy regimens in patients with limited-stage small cell lung cancer receiving cisplatin and etoposide. Accessed 13 Mar 2011
  38. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, Brodin O, Joss RA, Kies MS, Lebeau B et al (1992) A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 327:1618–1624PubMedCrossRefGoogle Scholar
  39. Pijls-Johannesma M, de Ruysscher D, Vansteenkiste J, Kester A, Rutten I, Lambin P (2007) Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta-analysis of randomised controlled trials. Cancer Treat Rev 33:461–473PubMedCrossRefGoogle Scholar
  40. Rusch VW (2005) Mediastinoscopy: an endangered species? J Clin Oncol 23:8283–8285PubMedCrossRefGoogle Scholar
  41. Samson DJ, Seidenfeld J, Simon GR, Turrisi AT 3rd, Bonnell C, Ziegler KM, Aronson N American College of Chest Physicians (2007) Evidence for management of small cell lung cancer: ACCP evidence-based clinical practice guidelines, 2nd edn. Chest 132(3 Suppl):314S–323SGoogle Scholar
  42. Schild SE, Bonner JA, Hillman S et al (2007) Results of a phase II study of high-dose thoracic radiation therapy with concurrent cisplatin and etoposide in limited-stage small-cell lung cancer (NCCTG 95–20-53). J Clin Oncol 25:3124–3129PubMedCrossRefGoogle Scholar
  43. Senan S, de Ruysscher D (2005) Critical review of PET-CT for radiotherapy planning in lung cancer. Crit Rev Oncol Hematol 56:345–351PubMedCrossRefGoogle Scholar
  44. Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G (2001) Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic cooperative oncology group (HeCOG). Ann Oncol 12:1231–1238PubMedCrossRefGoogle Scholar
  45. Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S (2007) EORTC radiation oncology group and lung cancer group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357:664–672PubMedCrossRefGoogle Scholar
  46. Socinski MA, Bogart JA (2007) Limited-stage small-cell lung cancer: the current status of combined-modality therapy. J Clin Oncol 25:4137–4145PubMedCrossRefGoogle Scholar
  47. Spiro SG, James LE, Rudd RM, Trask CW, Tobias JS, Snee M, Gilligan D, Murray PA, Ruiz de Elvira MC, O’Donnell KM, Gower NH, Harper PG, Hackshaw AK, London Lung Cancer Group (2006) Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London lung cancer group multicenter randomized clinical trial and meta-analysis. J Clin Oncol 24:3823–3830PubMedCrossRefGoogle Scholar
  48. Tada T, Minakuchi K, Koda M, Masuda N, Matsui K, Kawase I, Nakajima T, Nishioka M, Fukuoka M, Kozuka T (1998) Limited-stage small cell lung cancer: local failure after chemotherapy and radiation therapy. Radiology 208:511–515PubMedGoogle Scholar
  49. Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N (2002) Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan clinical oncology group study 9104. J Clin Oncol 20:3054–3060PubMedCrossRefGoogle Scholar
  50. Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340:265–2671PubMedCrossRefGoogle Scholar
  51. van Baardwijk A, Baumert BG, Bosmans G, van Kroonenburgh M, Stroobants S, Gregoire V, Lambin P, de Ruysscher D (2006) The current status of FDG-PET in tumour volume definition in radiotherapy treatment planning. Cancer Treat Rev 32:245–260PubMedCrossRefGoogle Scholar
  52. van Loon J, de Ruysscher D, Wanders R, Boersma L, Simons J, Oellers M, Dingemans AM, Hochstenbag M, Bootsma G, Geraedts W, Pitz C, Teule J, Rhami A, Thimister W, Snoep G, Dehing-Oberije C, Lambin P (2010) Selective nodal irradiation on basis of (18)FDG-PET scans in limited-disease small-cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys 77:329–336PubMedCrossRefGoogle Scholar
  53. van Overhagen H, Brakel K, Heijenbrok MW, van Kasteren JH, van de Moosdijk CN, Roldaan AC, van Gils AP, Hansen BE (2004) Metastases in supraclavicular lymph nodes in lung cancer: assessment with palpation, US, and CT. Radiology 232:75–80PubMedCrossRefGoogle Scholar
  54. Videtic GM, Belderbos JS, Spring Kong FM, Kepka L, Martel MK, Jeremic B (2008) Report from the international atomic energy agency (IAEA) consultants’ meeting on elective nodal irradiation in lung cancer: small-cell lung cancer (SCLC). Int J Radiat Oncol Biol Phys 72:327–334PubMedCrossRefGoogle Scholar
  55. Warde P, Payne D (1992) Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 10:890–895PubMedGoogle Scholar
  56. Watkins JM, Wahlquist AE, Zauls AJ, Shirai K, Garrett-Mayer E, Aguero EG, Silvestri GA, Sherman CA, Sharma AK (2010) Involved-field radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer: disease control, patterns of failure and survival. J Med Imaging Radiat Oncol 54:483–489PubMedCrossRefGoogle Scholar
  57. White JE, Chen T, McCracken J, Kennedy P, Seydel HG, Hartman G, Mira J, Khan M, Durrance FY, Skinner O (1982) The influence of radiation therapy quality control on survival, response and sites of relapse in oat cell carcinoma of the lung: preliminary report of a southwest oncology group study. Cancer 50:1084–1090PubMedCrossRefGoogle Scholar
  58. Work E, Nielsen OS, Bentzen SM, Fode K, Palshof T (1997) Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus lung cancer group. J Clin Oncol 15:3030–3037PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Radiation Oncology/T28Taussig Cancer Institute, Cleveland Clinic FoundationClevelandUSA

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