Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review article: Biomedical intelligence

Vol. 143 No. 2122 (2013)

Stereotactic body radiation therapy in stage I inoperable lung cancer: from palliative to curative options

  • Noureddine Boujelbene
  • Fatma Elloumi
  • Mohamed Ehab Kamel
  • Hamdi Abeidi
  • Oscar Matzinger
  • René-Olivier Mirimanoff
  • Kaouthar Khanfir
DOI
https://doi.org/10.4414/smw.2013.13780
Cite this as:
Swiss Med Wkly. 2013;143:w13780
Published
19.05.2013

Summary

Surgery has historically been the standard of care for operable stage I non-small cell lung cancer (NSCLC). However, nearly one-quarter of patients with stage I NSCLC will not undergo surgery because of medical comorbidity or other factors. Stereotactic ablative radiotherapy (SABR) is the new standard of care for these patients. SABR offers high local tumour control rates rivalling the historical results of surgery and is generally well tolerated by patients with both peripheral and centrally located tumours. This article reviews the history of SABR for stage I NSCLC, summarises the currently available data on efficacy and toxicity, and describes some of the currently controversial aspects of this treatment.

References

  1. Le Chevalier T. Management of early-stage non-small-cell lung cancer (NSCLC). Eur J Cancer. 2011;47(3):S292–3.
  2. Wisnivesky JP, BonomiM, Henschke C, Iannuzzi M, McGinn T. Radiation therapy for the treatment of unresected stage I–II non-small cell lung cancer. Chest. 2005;128(3):1461–7.
  3. Qiao X, Tullgren O, Lax I, Sirzén F, Lewensohn R. The role of radiotherapy in treatment of stage I non-small cell lung cancer. Lung Cancer. 2003;41(1):1–11.
  4. Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, et al. Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lungcancer: can SBRT be comparable to surgery? Int J Radiat Oncol Biol Phys. 2011;81(5):1352–8.
  5. Timmerman RD, Kavanagh BD, Cho LC, Papiez L, Xing L. Stereotactic body radiation therapy in multiple organ sites. J Clin Oncol. 2007;25(8):947–52.
  6. Nagata Y, Wulf J, Lax I, Timmerman R, Zimmermann F, Stojkovski I, et al. Stereotactic radiotherapy of primary lung cancer and other targets: results of consultant meeting of the International Atomic Energy Agency. Int J Radiat Oncol Biol Phys. 2011;79(3):660–9.
  7. Kavanagh BD, McGarry RC, Timmerman RD. Extracranial radiosurgery (stereotactic body radiation therapy) for oligometastases. Semin Radiat Oncol. 2006;16(2):77–84.
  8. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62(740):679–94.
  9. Kirkpatrick JP, Meyer JJ, Marks LB. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol. 2008;18(4):240–3.
  10. Courdi A. High doses per fraction and the linear-quadratic model. Radiother Oncol. 2010;94(1):121–2.
  11. Park C, Papiez L, Zhang S, Story M, Timmerman RD. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70(3):847–52.
  12. Guerrero M, Li XA. Extending the linear-quadratic model for large fraction doses pertinent to stereotactic radiotherapy. Phys Med Biol. 2004;49(20):4825–35.
  13. Timmerman RD, Story M. Stereotactic body radiation therapy: a treatment in need of basic biological research. Cancer J. 2006;12(1):19–20.
  14. Kirkpatrick JP, Dewhirst MW. Analytic solution to steady-state radial diffusion of a substrate with first-order reaction kinetics in the tissue of a Krogh’s cylinder. Radiat Res. 2008;169(3):350–4.
  15. Fuks Z, Kolesnick R. Engaging the vascular component of the tumor response. Cancer Cell. 2005;8(2):89–91.
  16. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, et al. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009;114(3):589–95.
  17. Curiel TJ. Tregs and rethinking cancer immunotherapy. J Clin Invest. 2007;117(5):1167–74.
  18. Benedict SH, Lin PS, Zwicker RD, Huang DT, Schmidt-Ullrich RK. The biological effectiveness of intermittent irradiation as a function of overall treatment time: development of correction factors for linac-based stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 1997;37(4):765–9.
  19. Fowler JF, Welsh JS, Howard SP. Loss of biological effect in prolonged fraction delivery. Int J Radiat Oncol Biol Phys. 2004;59(1):242–9.
  20. Lax I, Blomgren H, Näslund I, Svanström R. Stereotactic radiotherapy of malignancies in the abdomen. Methodological aspects. Acta Oncol. 1994;33(6):677–83.
  21. Wang L, Feigenberg S, Chen L, Pasklev K, Ma CC. Benefit of three-dimensional image-guided stereotactic localization in the hypofractionated treatment of lung cancer. Int J Radiat Oncol Biol Phys. 2006;66(3):738–47.
  22. Murphy MJ. An automatic six-degree-of-freedom image registration algorithm for image-guided frameless stereotaxic radiosurgery. Med Phys. 1997;24(6):857–66.
  23. Nath SK, Sandhu AP, Jensen L, Kim D, Bharne A, Nobiensky PD, et al. Frameless image-guided stereotactic body radiation therapy for lung tumors with 4-dimensional computed tomography or 4-dimensional positron emission tomography/ computed tomography. Clin Lung Cancer. 2011;12(3):180–6.
  24. Wulf J, Hädinger U, Oppitz U, Olshausen B, Flentje M. Stereotactic radiotherapy of extracranial targets: CT-simulation and accuracy of treatment in the stereotactic body frame. Radiother Oncol. 2000;57(2):225–36.
  25. Mageras GS, Yorke E. Deep inspiration breath hold and respiratory gating strategies for reducing organ motion inradiation treatment. Semin Radiat Oncol. 2004;14(1):65–75.
  26. Chen QS, Weinhous MS, Deibel FC, Ciezki JP, Macklis RM. Fluoroscopic study of tumor motion due to breathing: facilitating precise radiation therapy for lung cancer patients. Med Phys. 2001;28(9):1850–6.
  27. Kimura T, Hirokawa Y, Murakami Y, Tsujimura M, Nakashima T, Ohno Y, et al. Reproducibility of organ position using voluntary breath-hold method with spirometer for extracranial stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 2004;60(4):1307–13.
  28. Sharp GC, Jiang SB, Shimizu S, Shirato H. Prediction of respiratory tumour motion for real-time image-guided radiotherapy. Phys Med Biol. 2004;49(3):425–40.
  29. De Ruysscher D, Nestle U, Jeraj R, Macmanus M. PET scans in radiotherapy planning of lung cancer. Lung Cancer. 2012;75(2):141–5.
  30. Timmerman R, Papiez L, McGarry R, Likes L, DesRosiers C, Frost S, et al. Extracranial stereotactic radioablation: results of a phase I study in medically inoperable stage I non-small cell lung cancer. Chest. 2003;124(5):1946–55.
  31. De Ruysscher D, Faivre-Finn C, Nestle U, Hurkmans CW, Le Péchoux C, Price A, et al. European Organisation for Research and Treatment of Cancer recommendations for planning anddelivery of high-dose, high-precision radiotherapy for lung cancer. J Clin Oncol. 2010;28(36):5301–10.
  32. Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA. 2010;303(11):1070–6.
  33. Papiez L, Timmerman R, DesRosiers C, Randall M. Extracranial stereotactic radioablation: physical principles. Acta Oncol. 2003;42(8):882–94.
  34. Liu R, Wagner TH, Buatti JM, Modrick J, Dill J, Meeks SL. Geometrically based optimization for extracranial radiosurgery. Phys Med Biol. 2004;49(6):987–96.
  35. Cardinale RM, Wu Q, Benedict SH, Kavanagh BD, Bump E, Mohan R. Determining the optimal block margin on the planning target volume for extracranial stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 1999;45(2):515–20.
  36. Lim do H, Yi BY, Mirmiran A, Dhople A, Suntharalingam M, D’Souza WD. Optimal beam arrangement for stereotactic body radiation therapy delivery in lung tumors. Acta Oncol. 2010;49(2):219–24.
  37. Timmerman R, Galvin J, Michalski J, Straube W, Ibbott G, Martin E, et al. Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer. Acta Oncol. 2006;45(7):779–86.
  38. Buyyounouski MK, Balter P, Lewis B, D’Ambrosio DJ, Dilling TJ, Miller RC, et al. Stereotactic body radiotherapy for early-stage non-small-cell lung cancer: report of the ASTRO Emerging Technology Committee. Int J Radiat Oncol Biol Phys. 2010;78(1):3–10.
  39. Fakiris AJ, McGarry RC, Yiannoutsos CT, Papiez L, Williams M, Henderson MA, et al. Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospective phase II study. Int J Radiat Oncol Biol Phys. 2009;75(3):677–82.
  40. Grills IS, Mangona VS, Welsh R, Chmielewski G, McInerney E, Martin S, et al. Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. J Clin Oncol. 2010;28(6):928–35.
  41. http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0236
  42. Grimm J, LaCouture T, Croce R, Yeo I, Zhu Y, Xue J. Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J Appl Clin Med Phys. 2011;12(2):3368.
  43. Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, et al. Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol. 2009;27(20):3290–6.
  44. Ricardi U, Filippi AR, Guarneri A, Giglioli FR, Ciammella P, Franco P, et al. Stereotactic body radiation therapy for early stage non-small cell lung cancer: results of a prospective trial. Lung Cancer. 2010;68(1):72–7.
  45. Lagerwaard FJ, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008;70(3):685–92.
  46. Koto M, Takai Y, Ogawa Y, Matsushita H, Takeda K, Takahashi C, et al. A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer. Radiother Oncol. 2007;85(3):429–34.
  47. Grutters JP, Kessels AG, Pijls-Johannesma M, De Ruysscher D, Joore MA, Lambin P. Comparison of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell lung cancer: a meta-analysis. Radiother Oncol. 2010;95(1):32–40.
  48. Pan H, Simpson DR, Mell LK, Mundt AJ, Lawson JD. A survey of stereotactic body radiotherapy use in the United States. Cancer. 2011;117(19):4566–72.
  49. Nagata Y, Hiraoka M, Mizowaki T, Narita Y, Matsuo Y, Norihisa Y, et al. Survey of stereotactic body radiation therapy in Japan by the Japan 3-D Conformal External Beam Radiotherapy Group. Int J Radiat Oncol Biol Phys. 2009;75(2):343–7.
  50. Palma D, Visser O, Lagerwaard FJ, Belderbos J, Slotman BJ, Senan S. Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non-small-cell lung cancer: a population-based time-trend analysis. J Clin Oncol. 2010;28(35):5153–9.
  51. Inoue T, Shimizu S, Onimaru R, Takeda A, Onishi H, Nagata Y, et al. Clinical outcomes of stereotactic body radiotherapy for small lung lesions clinically diagnosed as primary lung cancer on radiologic examination. Int J Radiat Oncol Biol Phys. 2009;75(3):683–7.
  52. Martini N, Bains MS, Burt ME, Zakowski MF, McCormack P, Rusch VW, et al. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg. 1995;109(1):120–9.
  53. Chi A, Liao Z, Nguyen NP, Xu J, Stea B, Komaki R. Systemic review of the patterns of failure following stereotactic body radiation therapy in early-stage non-small-cell lung cancer: clinical implications. Radiother Oncol. 2010;94(1):1–11.
  54. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. 2001;285(7):914–24.
  55. Andratschke N, Zimmermann F, Boehm E, Schill S, Schoenknecht C, Thamm R, et al. Stereotactic radiotherapy of histologically proven inoperable stage I non-small cell lung cancer: patterns of failure. Radiother Oncol. 2011;101(2):245–9.
  56. Crabtree TD, Denlinger CE, Meyers BF, El Naqa I, Zoole J, Krupnick AS, et al. Stereotactic body radiation therapy versus surgical resection for stage I non-small cell lungcancer. J Thorac Cardiovasc Surg. 2010;140(2):377–86.
  57. Videtic GM, Stephans KL. The role of stereotactic body radiotherapy in the management of non-small cell lung cancer: anemerging standard for the medically inoperable patient? Curr Oncol Rep. 2010;12(4):235–41.
  58. Carey Sampson M, Katz A, Constine LS. Stereotactic body radiation therapy for extracranial oligometastases: does the sword have adouble edge? Semin Radiat Oncol. 2006;16(2):67–76.
  59. Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, et al. Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study. J Thorac Oncol. 2007;2(7 Suppl 3):S94–100.
  60. Powell JW, Dexter E, Scalzetti EM, Bogart JA. Treatment advances for medically inoperable non-small-cell lung cancer: emphasis on prospective trials. Lancet Oncol. 2009;10(9):885–94.
  61. Le QT, Loo BW, Ho A, Cotrutz C, Koong AC, Wakelee H, et al. Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors. J Thorac Oncol. 2006;1(8):802–9.
  62. Song SY, Choi W, Shin SS, Lee SW, Ahn SD, Kim JH, et al. Fractionated stereotactic body radiation therapy for medically inoperable stage I lung canceradjacent to central large bronchus. Lung Cancer. 2009;66(1):89–93.
  63. http://www.clinicaltrials.gov./ct2/results?term=NCT00750269
  64. Bral S, Gevaert T, Linthout N, Versmessen H, Collen C, Engels B, et al. Prospective, risk-adapted strategy of stereotactic body radiotherapy for early-stage non-small-celllung cancer: results of a Phase II trial. Int J Radiat Oncol Biol Phys. 2011;80(5):1343–9.
  65. Jin JY, Kong FM, Chetty IJ, Ajlouni M, Ryu S, Ten Haken R, et al. Impact of fraction size on lung radiation toxicity: hypofractionation may be beneficial in doseescalation of radiotherapy for lung cancers. Int J Radiat Oncol Biol Phys. 2010;76(3):782–8.
  66. Forquer JA, Fakiris AJ, Timmerman RD, Lo SS, Perkins SM, McGarry RC, et al. Brachial plexopathy from stereotactic body radiotherapy in early-stage NSCLC: dose-limitingtoxicity in apical tumor sites. Radiother Oncol. 2009;93(3):408–13.
  67. Andolino DL, Forquer JA, Henderson MA, Barriger RB, Shapiro RH, Brabham JG, et al. Chest wall toxicity after stereotactic body radiotherapy for malignant lesions of the lung and liver. Int J Radiat Oncol Biol Phys. 2011;80(3):692–7.
  68. Bongers EM, Haasbeek CJ, Lagerwaard FJ, Slotman BJ, Senan S. Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy forearly-stage lung cancer. J Thorac Oncol. 2011;6(12):2052–7.
  69. Karmakar MK, Ho AM. Postthoracotomy pain syndrome. Thorac Surg Clin. 2004;14(3):345–52.
  70. Sugiura H, Morikawa T, Kaji M, Sasamura Y, Kondo S, Katoh H. Long-term benefits for the quality of life after video-assisted thoracoscopic lobectomy in patients with lung cancer. Surg Laparosc Endosc Percutan Tech. 1999;9(6):403–8.
  71. Palma D, Senan S. Stereotactic radiation therapy: changing treatment paradigms for stage I nonsmall cell lung cancer. Curr Opin Oncol. 2011;23(2):133–9.
  72. Zimmermann FB, Geinitz H, Schill S, Thamm R, Nieder C, Schratzenstaller U, et al. Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell lung cancer (NSCLC). Acta Oncol. 2006;45(7):796–801.
  73. Baumann P, Nyman J, Lax I, Friesland S, Hoyer M, Rehn Ericsson S, et al. Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. Aretrospective analysis of patients treated in the Nordic countries. Acta Oncol. 2006;45(7):787–95.
  74. Verbakel WF, Senan S, Cuijpers JP, Slotman BJ, Lagerwaard FJ. Rapid delivery of stereotactic radiotherapy for peripheral lung tumors using volumetric intensity-modulated arcs. Radiother Oncol. 2009;93(1):122–4.
  75. Haasbeek CJ, Lagerwaard FJ, de Jaeger K, Slotman BJ, Senan S. Outcomes of stereotactic radiotherapy for a new clinical stage I lung cancer arising postpneumonectomy. Cancer. 2009;115(3):587–94.
  76. Henderson M, McGarry R, Yiannoutsos C, Fakiris A, Hoopes D, Williams M, Timmerman R. Baseline pulmonary function as a predictor for survival and decline in pulmonary function over time in patientsundergoing stereotactic body radiotherapy for the treatment of stage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008;72(2):404–9.
  77. Palma D, Lagerwaard F, Rodrigues G, Haasbeek C, Senan S. Curative treatment of Stage I non-small-cell lung cancer in patients with severe COPD: stereotactic radiotherapyoutcomes and systematic review. Int J Radiat Oncol Biol Phys. 2012;82(3):1149–56.
  78. Kelly P, Balter PA, Rebueno N, Sharp HJ, Liao Z, Komaki R, et al. Stereotactic body radiation therapy for patients with lung cancer previously treated with thoracic radiation. Int J Radiat Oncol Biol Phys. 2010;78(5):1387–93.
  79. http://atc.wustl.edu/protocols/rtog/1021/1021.html
  80. http://clinicaltrials.gov/ct2/results?term=NCT00840749
  81. http://clinicaltrials.gov/ct2/results?term=NCT00687986
  82. http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0618
  83. http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000000063&language=E
  84. Nagata Y, Takayama K, Matsuo Y, Norihisa Y, Mizowaki T, Sakamoto T, et al. Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. Int J Radiat Oncol Biol Phys. 2005;63(5):1427–31.
  85. Xia T, Li H, Sun Q, Wang Y, Fan N, Yu Y, et al. Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2006;66(1):117–25.
  86. Taremi M, Hope A, Dahele M, Pearson S, Fung S, Purdie T, et al. Stereotactic body radiotherapy for medically inoperable lung cancer: prospective, single-center study of 108 consecutive patients. Int J Radiat Oncol Biol Phys. 2012;82(2):967–73.
  87. Timmerman R, McGarry R, Yiannoutsos C, Papiez L, Tudor K, DeLuca J, et al. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol. 2006;24(30):4833–9.
  88. http://www.trog.com.au/Default.aspx?tabid=71#lung
  89. http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0915
  90. http://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0813
  91. Nyman J. SPACE – Stereotactic precision and conventional radiotherapy evaluation. A multicenter randomized phase II study of stereotactic hypofractionated radiotherapy with body frame versus conventionally fractionated radiotherapy for stage I medically inoperable non-small cell lung cancer 2006. [cited 2011 Sep 9]. Available from: http://www.nlcg.no/uploads/space_060717.doc