A current review of dose-escalated radiotherapy in locally advanced non-small cell lung cancer

Ma, Li; Men, Yu; Feng, Lingling; Kang, Jingjing; Sun, Xin; Yuan, Meng; Jiang, Wei; Hui, Zhouguang

doi:10.2478/raon-2019-0006

Abstract

Background

The mainstay therapy for locally advanced non-small cell lung cancer is concurrent chemoradiotherapy. Loco-regional recurrence constitutes the predominant failure patterns. Previous studies confirmed the relationship between increased biological equivalent doses and improved overall survival. However, the large randomized phase III study, RTOG 0617, failed to demonstrate the benefit of dose-escalation to 74 Gy compared with 60 Gy by simply increasing fraction numbers.

Conclusions

Though effective dose-escalation methods have been explored, including altered fractionation, adapting individualized increments for different patients, and adopting new technologies and new equipment such as new radiation therapy, no consensus has been achieved yet.

References

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; 28: 2181-90. doi: 10.1200/JCO.2009.26.2543
Open DOI Search in Google Scholar Back to article
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: 425-44. doi: 10.1016/j.ijrobp.2010.09.004
Open DOI Search in Google Scholar Back to article
Schild SE, Stella PJ, Geyer SM, Bonner JA, Marks RS, McGinnis WL, et al. Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2002; 54: 370-8. doi: 10.1016/S0360-3016(02)02930-9
Open DOI Search in Google Scholar Back to article
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: 2692-99. doi: 10.1200/JCO.1999.17.9.2692
Open DOI Search in Google Scholar Back to article
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 non-small-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. doi: 10.1200/JCO.2005.03.070
Open DOI Search in Google Scholar Back to article
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. doi: 10.1016/j.lungcan.2004.03.004
Open DOI Search in Google Scholar Back to article
Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol 2005; 23: 5883-91. doi: 10.1200/JCO.2005.55.405
Open DOI Search in Google Scholar Back to article
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. doi: 10.1093/jnci/djr325
Open DOI Search in Google Scholar Back to article
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. doi: 10.1200/JCO.2009.27.1205
Open DOI Search in Google Scholar Back to article
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. doi: 10.1016/j.ijrobp.2006.02.046
Open DOI Search in Google Scholar Back to article
Lee CB, Stinchcombe TE, Moore DT, Morris DE, Hayes DN, Halle J, et al. Late complications of high-dose (>/=66 Gy) thoracic conformal radiation therapy in combined modality trials in unresectable stage III non-small cell lung cancer. J Thorac Oncol 2009; 4: 74-9. doi: 10.1097/JTO.0b013e3181915028
Open DOI Search in Google Scholar Back to article
Blackstock AW, Ho C, Butler J, Fletcher-Steede J, Case LD, Hinson W, et al. Phase Ia/Ib chemo-radiation trial of gemcitabine and dose-escalated thoracic radiation in patients with stage III A/B non-small cell lung cancer. J Thorac Oncol 2006; 1: 434-40. doi: 10.1016/S1556-0864(15)31608-7
Open DOI Search in Google Scholar Back to article
Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 2015; 16: 187-99. doi: 10.1016/S1470-2045(14)71207-0
Open DOI Search in Google Scholar Back to article
Belderbos J, Walraven I, van Diessen J, Verheij M, de Ruysscher D. Radiotherapy dose and fractionation for stage III NSCLC. Lancet Oncol 2015; 16: e156-7. doi: 10.1016/S1470-2045(15)70121-X
Open DOI Search in Google Scholar Back to article
Kerr KM, Lamb D. Actual growth rate and tumour cell proliferation in human pulmonary neoplasms. Br J Cancer 1984; 50: 343-9. PMID: 6087867
Search in Google Scholar Back to article
Trott KR. Cell repopulation and overall treatment time. Int J Radiat Oncol Biol Phys 1990; 19: 1071-5. doi: 10.1016/0360-3016(90)90036-J
Open DOI Search in Google Scholar Back to article
Machtay M, Hsu C, Komaki R, Sause WT, Swann RS, Langer CJ, et al. Effect of overall treatment time on outcomes after concurrent chemoradiation for locally advanced non-small-cell lung carcinoma: analysis of the Radiation Therapy Oncology Group (RTOG) experience. Int J Radiat Oncol Biol Phys 2005; 63: 667-71. doi: 10.1016/j.ijrobp.2005.03.037
Open DOI Search in Google Scholar Back to article
Fowler JF, Chappell R. Non-small cell lung tumors repopulate rapidly during radiation therapy. Int J Radiat Oncol Biol Phys 2000; 46: 516-7. doi: 10.1016/S0360-3016(99)00364-8
Open DOI Search in Google Scholar Back to article
Brower JV, Amini A, Chen S, Hullett CR, Kimple RJ, Wojcieszynski AP, et al. Improved survival with dose-escalated radiotherapy in stage III non-small-cell lung cancer: analysis of the National Cancer Database. Ann Oncol. 2016; 27: 1887-94. doi: 10.1093/annonc/mdw276
Open DOI Search in Google Scholar Back to article
Yamoah K, Showalter TN, Ohri N. Radiation therapy intensification for solid tumors: a systematic review of randomized trials. Int J Radiat Oncol Biol Phys 2015; 93: 737-45. doi:10.1016/j.ijrobp.2015.07.2284
Open DOI Search in Google Scholar Back to article
Ramroth J, Cutter DJ, Darby SC, Higgins GS, McGale P, Partridge M, et al. Dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer: meta-analysis of randomized trials. Int J Radiat Oncol Biol Phys 2016; 96: 736-47. doi: 10.1016/j.ijrobp.2016.07.022
Open DOI Search in Google Scholar Back to article
Mehta M, Scrimger R, Mackie R, Paliwal B, Chappell R, Fowler J. A new approach to dose escalation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2001; 49: 23-33. doi: 10.1016/S0360-3016(00)01374-2
Open DOI Search in Google Scholar Back to article
Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet 1997; 350: 161-5. doi: 10.1016/S0140-6736(97)06305-8
Open DOI Search in Google Scholar Back to article
Baumann M, Herrmann T, Koch R, Matthiessen W, Appold S, Wahlers B, et al. Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC). Radiother Oncol 2011; 100: 76-85. doi: 10.1016/j.radonc.2011.06.031
Open DOI Search in Google Scholar Back to article
Mauguen A, Le Pechoux C, Saunders MI, Schild SE, Turrisi AT, Baumann M, et al. Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol 2012; 30: 2788-97. doi: 10.1200/JCO.2012.41.6677
Open DOI Search in Google Scholar Back to article
Din OS, Harden SV, Hudson E, Mohammed N, Pemberton LS, Lester JF, et al. Accelerated hypo-fractionated radiotherapy for non small cell lung cancer: results from 4 UK centres. Radiother Oncol 2013; 109: 8-12. doi: 10.1016/j. radonc.2013.07.014
Open DOI Search in Google Scholar Back to article
Sun LM, Leung SW, Wang CJ, Chen HC, Fang FM, Huang EY, et al. Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study. Int J Radiat Oncol Biol Phys 2000; 47: 413-8. doi: 10.1016/S0360-3016(00)00429-6
Open DOI Search in Google Scholar Back to article
Kaster TS, Yaremko B, Palma DA, Rodrigues GB. Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer 2015; 16: 71-9. doi: 10.1016/j.cllc.2014.08.002
Open DOI Search in Google Scholar Back to article
Cannon DM, Mehta MP, Adkison JB, Khuntia D, Traynor AM, Tome WA, et al. Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer. J Clin Oncol 2013; 31: 4343-8. doi: 10.1200/JCO.2013.51.5353
Open DOI Search in Google Scholar Back to article
Grills IS, Hope AJ, Guckenberger M, Kestin LL, Werner-Wasik M, Yan D, et al. A collaborative analysis of stereotactic lung radiotherapy outcomes for early-stage non-small-cell lung cancer using daily online cone-beam computed tomography image-guided radiotherapy. J Thorac Oncol 2012; 7: 1382-93. doi: 10.1097/JTO.0b013e318260e00d
Open DOI Search in Google Scholar Back to article
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: S94-100. doi: 10.1097/JTO.0b013e318074de34
Open DOI Search in Google Scholar Back to article
Feddock J, Arnold SM, Shelton BJ, Sinha P, Conrad G, Chen L, et al. Stereotactic body radiation therapy can be used safely to boost residual disease in locally advanced non-small cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys 2013; 85: 1325-31. doi: 10.1016/j.ijrobp.2012.11.011
Open DOI Search in Google Scholar Back to article
Karam SD, Horne ZD, Hong RL, McRae D, Duhamel D, Nasr NM. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer. Radiat Oncol 2013; 8: 179. doi: 10.1186/1748-717X-8-179
Open DOI Search in Google Scholar Back to article
Higgins KA, Pillai RN, Chen Z, Tian S, Zhang C, Patel P, et al. Concomitant chemotherapy and radiotherapy with SBRT boost for unresectable stage III non-small cell lung cancer: a phase I study. J Thorac Oncol 2017; 12: 168795. doi: 10.1016/j.jtho.2017.07.036
Open DOI Search in Google Scholar Back to article
Hepel JT, Leonard KL, Safran H, Ng T, Taber A, Khurshid H, et al. Stereotactic body radiation therapy boost after concurrent chemoradiation for locally advanced non-small cell lung cancer: a phase 1 dose escalation study. Int J Radiat Oncol Biol Phys 2016; 96: 1021-7. doi: 10.1016/j. ijrobp.2016.08.032
Open DOI Search in Google Scholar Back to article
van Baardwijk A, Reymen B, Wanders S, Borger J, Ollers M, Dingemans AM, et al. Mature results of a phase II trial on individualised accelerated radiotherapy based on normal tissue constraints in concurrent chemo-radiation for stage III non-small cell lung cancer. Eur J Cancer 2012; 48: 2339-46. doi: 10.1016/j.ejca.2012.04.014
Open DOI Search in Google Scholar Back to article
Abramyuk A, Tokalov S, Zophel K, Koch A, Szluha Lazanyi K, Gillham C, et al. Is pre-therapeutical FDG-PET/CT capable to detect high risk tumor subvolumes responsible for local failure in non-small cell lung cancer? Radiother Oncol 2009; 91: 399-404. doi: 10.1016/j.radonc.2009.01.003
Open DOI Search in Google Scholar Back to article
van Elmpt W, De Ruysscher D, van der Salm A, Lakeman A, van der Stoep J, Emans D, et al. The PET-boost randomised phase II dose-escalation trial in non-small cell lung cancer. Radiother Oncol 2012; 104: 67-71. doi: 10.1016/j.radonc.2012.03.005
Open DOI Search in Google Scholar Back to article
Salem A, Asselin MC, Reymen B, Jackson A, Lambin P, West CML, et al. Targeting hypoxia to improve non-small cell lung cancer outcome. J Natl Cancer Inst 2018; 110: 14-30. doi: 10.1093/jnci/djx160
Open DOI Search in Google Scholar Back to article
Vera P, Thureau S, Chaumet-Riffaud P, Modzelewski R, Bohn P, Vermandel M, et al. Phase II study of a radiotherapy total dose increase in hypoxic lesions identified by (18)F-misonidazole PET/CT in patients with non-small cell lung carcinoma (RTEP5 Study). J Nucl Med 2017; 58: 1045-53. doi: 10.2967/jnumed.116.188367
Open DOI Search in Google Scholar Back to article
Kong FM, Frey KA, Quint LE, Ten Haken RK, Hayman JA, Kessler M, et al. A pilot study of [18F]fluorodeoxyglucose positron emission tomography scans during and after radiation-based therapy in patients with non small-cell lung cancer. J Clin Oncol 2007; 25: 3116-23. doi: 10.1200/JCO.2006.10.3747
Open DOI Search in Google Scholar Back to article
Kong FM, Ten Haken RK, Schipper M, Frey KA, Hayman J, Gross M, et al. Effect of midtreatment PET/CT-adapted radiation therapy with concurrent chemotherapy in patients with locally advanced non-small-cell lung cancer: a phase 2 clinical trial. JAMA Oncol 2017; 3: 1358-65. doi: 10.1001/jamaoncol.2017.0982
Open DOI Search in Google Scholar Back to article
Scott JG, Berglund A, Schell MJ, Mihaylov I, Fulp WJ, Yue B, et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol 2017; 18: 202-11. doi: 10.1016/S1470-2045(16)30648-9
Open DOI Search in Google Scholar Back to article
Vinogradskiy Y, Tucker SL, Bluett JB, Wages CA, Liao Z, Martel MK. Prescribing radiation dose to lung cancer patients based on personalized toxicity estimates. J Thorac Oncol 2012; 7: 1676-82. doi: 10.1097/JTO.0b013e318269410a
Open DOI Search in Google Scholar Back to article
Chang JY, Zhang X, Wang X, Kang Y, Riley B, Bilton S, et al. Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2006; 65: 1087-96. doi: 10.1016/j.ijrobp.2006.01.052
Open DOI Search in Google Scholar Back to article
Kanai T, Endo M, Minohara S, Miyahara N, Koyama-ito H, Tomura H, et al. Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy. Int J Radiat Oncol Biol Phys 1999; 44: 201-10. doi: 10.1016/S0360-3016(98)00544-6
Open DOI Search in Google Scholar Back to article
Higgins KA, O’Connell K, Liu Y, Gillespie TW, McDonald MW, Pillai RN, et al. National Cancer Database analysis of proton versus photon radiation therapy in non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2017; 97: 128-37. doi: 0.1016/j.ijrobp.2016.10.001
Open DOI Search in Google Scholar Back to article
Chang JY, Verma V, Li M, Zhang W, Komaki R, Lu C, et al. Proton beam radiotherapy and concurrent chemotherapy for unresectable stage III non-small cell lung cancer: final results of a phase 2 study. JAMA Oncol 2017; 3: e172032. doi: 10.1001/jamaoncol.2017.2032
Open DOI Search in Google Scholar Back to article
Liao Z, Lee JJ, Komaki R, Gomez DR, O’Reilly MS, Fossella FV, et al. Bayesian adaptive randomization trial of passive scattering proton therapy and intensity-modulated photon radiotherapy for locally advanced non-small-cell lung cancer. J Clin Oncol 2018; 36: 1813-22. doi: 10.1200/JCO.2017.74.0720
Open DOI Search in Google Scholar Back to article
Takahashi W, Nakajima M, Yamamoto N, Yamashita H, Nakagawa K, Miyamoto T, et al. A prospective nonrandomized phase I/II study of carbon ion radiotherapy in a favorable subset of locally advanced non-small cell lung cancer (NSCLC). Cancer 2015; 121: 1321-7. doi: 10.1002/cncr.29195
Open DOI Search in Google Scholar Back to article
Karube M, Yamamoto N, Shioyama Y, Saito J, Matsunobu A, Okimoto T, et al. Carbon-ion radiotherapy for patients with advanced stage non-small-cell lung cancer at multicenters. J Radiat Res 2017; 58: 761-4. doi: 10.1093/jrr/rrx037
Open DOI Search in Google Scholar Back to article
Shirai K, Kawashima M, Saitoh JI, Abe T, Fukata K, Shigeta Y, et al. Clinical outcomes using carbon-ion radiotherapy and dose-volume histogram comparison between carbon-ion radiotherapy and photon therapy for T2b-4N0M0 non-small cell lung cancer - a pilot study. PLoS One. 2017; 12: e0175589. doi: 10.1371/journal.pone.0175589
Open DOI Search in Google Scholar Back to article

A current review of dose-escalated radiotherapy in locally advanced non-small cell lung cancer

Abstract

Background

Conclusions

Paradigm

My account