Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer

Abstract

Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC). Three-dimensional radiotherapy (3DCRT) has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT). IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage conformality, or dose escalation. The most critical step for a radiation oncology department is to strictly evaluate its own technical and physical capabilities to determine the ability of IMRT to deliver an optimal treatment plan. This includes calculating the internal tumor motion (ideally 4DCT or equivalent techniques), treatment planning software with an up-to-date heterogeneity correction algorithm, and daily image guidance. It is crucial to optimise and individualise the therapeutic ratio for each patient during the decision of 3DCRT versus IMRT. The current literature rationalises the increasing use of IMRT, including 4D imaging plus PET/CT, and encourages the applicable knowledge-based and individualised dose escalation using advanced daily image-guided radiotherapy.

Keywords

• 3-D conformal radiotherapy, intensity modulated radiotherapy, lung cancer

References

1. 1. Selek U, Chang JY. Evolution of modern-era radiotherapy strategies for unresectable advanced non-small-cell lung cancer. Lung Cancer Management 2013;2:213-25.[CrossRef]
2. 2. Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. PubMed PMID: 20351327. Epub 2010/03/31. eng.
3. 3. Curran WJ, Jr., Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 2011;103:1452-60. [CrossRef]
4. 4. Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. J Clin Oncol 1996;14:1065-70.
5. 5. Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;17:2692-9.
6. 6. Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 2004;46:87-98. [CrossRef]
7. 7. Fournel P, Robinet G, Thomas P, Souquet PJ, Lena H, Vergnenegre A, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced nonsmall-cell lung cancer: Groupe Lyon-Saint-Etienne d’Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPC 95-01 Study. J Clin Oncol 2005;23:5910-7. [CrossRef]
8. 8. Topkan E, Parlak C, Topuk S, Guler OC, Selek U. Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: retrospective analysis of 89 patients. Lung Cancer 2013;81:226-30. [CrossRef]

9. 9. Machtay M, Bae K, Movsas B, Paulus R, Gore EM, Komaki R, et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: An analysis of the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 2012;82:425-34. [CrossRef]
10. 10. Machtay M, Paulus R, Moughan J, Komaki R, Bradley JE, Choy H, et al. Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma. J Thorac Oncol 2012;7:716-22. [CrossRef]
11. 11. Rengan R, Rosenzweig KE, Venkatraman E, Koutcher LA, Fox JL, Nayak R, et al. Improved local control with higher doses of radiation in large-volume stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004;60:741-7. [CrossRef]
12. 12. Wang L, Correa CR, Zhao L, Hayman J, Kalemkerian GP, Lyons S, et al. The effect of radiation dose and chemotherapy on overall survival in 237 patients with Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2009;73:1383-90. [CrossRef]
13. 13. Tyldesley S, Boyd C, Schulze K, Walker H, Mackillop WJ. Estimating the need for radiotherapy for lung cancer: an evidence-based, epidemiologic approach. Int J Radiat Oncol Biol Phys 2001;49:973-85. [CrossRef]
14. 14. Tyldesley S, Delaney G, Foroudi F, Barbera L, Kerba M, Mackillop W. Estimating the need for radiotherapy for patients with prostate, breast, and lung cancers: verification of model estimates of need with radiotherapy utilization data from British Columbia. Int J Radiat Oncol Biol Phys 2011;79:1507-15. [CrossRef]
15. 15. Yom SS, Liao Z, Liu HH, Tucker SL, Hu CS, Wei X, et al. Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensitymodulated radiotherapy. Int J Radiat Oncol Biol Phys 2007;68:94-102. [CrossRef]
16. 16. Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA, et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 1999;45:323-9. [CrossRef]
17. 17. Marks LB, Bentzen SM, Deasy JO, Kong FM, Bradley JD, Vogelius IS, et al. Radiation dose-volume effects in the lung. Int J Radiat Oncol Biol Phys 2010;76(3 Suppl):S70-6. [CrossRef]
18. 18. Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010;76(3 Suppl):S10-9. [CrossRef]
19. 19. Kong FM, Ritter T, Quint DJ, Senan S, Gaspar LE, Komaki RU, et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol Biol Phys 2011;81:1442-57. [CrossRef]
20. 20. Sundar IK, Mullapudi N, Yao H, Spivack SD, Rahman I. Lung cancer and its association with chronic obstructive pulmonary disease: update on nexus of epigenetics. Curr Opin Pulm Med. 2011;17:279-85. [CrossRef]
21. 21. Semrau S, Klautke G, Fietkau R. Baseline cardiopulmonary function as an independent prognostic factor for survival of inoperable non-smallcell lung cancer after concurrent chemoradiotherapy: a single-center analysis of 161 cases. Int J Radiat Oncol Biol Phys 2011;79:96-104. [CrossRef]
22. 22. Cerfolio RJ, Talati A, Bryant AS. Changes in pulmonary function tests after neoadjuvant therapy predict postoperative complications. Ann Thorac Surg 2009;88:930-5.[CrossRef]
23. 23. Kepka L, Bujko K, Orlowski TM, Jagiello R, Salata A, Matecka-Nowak M, et al. Cardiopulmonary morbidity and quality of life in non-small cell lung cancer patients treated with or without postoperative radiotherapy. Radiother Oncol 2011;98:238-43. [CrossRef]
24. 24. Bradley JD, Bae K, Graham MV, Byhardt R, Govindan R, Fowler J, et al. Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. J Clin Oncol 2010;28:2475-80. [CrossRef]
25. 25. Schild SE, McGinnis WL, Graham D, Hillman S, Fitch TR, Northfelt D, et al. Results of a Phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2006;65:1106-11. [CrossRef]
26. 26. Socinski MA, Rosenman JG, Halle J, Schell MJ, Lin Y, Russo S, et al. Dose-escalating conformal thoracic radiation therapy with induction and concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified phase I/II trial. Cancer 2001;92:1213-23. [CrossRef]
27. 27. Kong FM, Ten Haken RK, Schipper MJ, Sullivan MA, Chen M, Lopez C, et al. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: long-term results of a radiation dose escalation study. Int J Radiat Oncol Biol Phys 2005;63:324-33. [CrossRef]
28. 28. Zhao L, West BT, Hayman JA, Lyons S, Cease K, Kong FM. High radiation dose may reduce the negative effect of large gross tumor volume in patients with medically inoperable early-stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2007;68:103-10. [CrossRef]
29. 29. Yuan S, Sun X, Li M, Yu J, Ren R, Yu Y, et al. A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer. Am J Clin Oncol 2007;30:239-44. [CrossRef]
30. 30. Bradley J, Paulus R, Komaki R, Masters G, Forster K, Schild SE, et al., editors. A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy +/- cetuximab for stage IIIa/IIIb non-small cell lung cancer: Preliminary findings on radiation dose in RTOG 0617 (late-breaking abstract 2). Presented at the 53rd Annual Meeting of the American Society of Radiation Oncology, October 2-6, 2011, Miami, FL.2011.
31. 31. Cox JD. Are the results of RTOG 0617 mysterious? Int J Radiat Oncol Biol Phys 2012;82:1042-4. [CrossRef]