To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC).
Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1–2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT.
Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy.
The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Onishi H, Shirato H, Nagata Y et al (2007) Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small-cell lung cancer: updated results of 257 patients in Japanese multi-institutional study. J Thorac Oncol 2(Suppl 3):S94–S100
Takeda A, Sanuki N, Kunieda E et al (2009) Stereotactic body radiotherapy for primary lung cancer at a dose of 50 Gy total in five fractions to the periphery of the planning target volume calculated using a superposition algorithm. Int J Radiat Oncol Biol Phys 73:442–448
Nagata Y, Hiraoka M, Shibata T et al (2015) Prospective trial of stereotactic body radiation therapy for both operable and inoperable T1N0M0 non-small cell lung cancer: Japan Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys 93:989–996
Timmerman R, Rebecca P, Galvin J et al (2010) Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 303:1070–1076
Baumann P, Nyman J, Hoyer M et al (2009) Outcome in a prospective phase II trial of medically inoperable stage I non-small cell lung cancer patients treated with stereotactic body radiotherapy. JCO 27:3290–3296
Matsuo Y, Chen F, Hamaji M et al (2014) Comparison of long-term survival outcomes between stereotactic body radiotherapy and sublobar resection for stage I non-small-cell lung cancer in patients at high risk for lobectomy: a propensity score matching analysis. Eur J Cancer 50:2932–2938
Shirvani SM, Jiang J, Chang JY et al (2014) Lobectomy, sublobar resection, and stereotactic ablative radiotherapy for early-stage non-small cell lung cancers in the elderly. JAMA Surg 149:1244–1253
Verstegen NE, Oosterhuis JW, Palma DA et al (2013) Stage I–II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis. Ann Oncol 24:1543–1548
Chang JY, Senan S, Paul MA et al (2015) Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 16:630–637. doi:10.1016/S1470-2045(15)70168-3
Haasbeek CJ, Lagerwaard FJ, Slotman BJ et al (2011) Outcomes of stereotactic ablative radiotherapy for centrally located early-stage lung cancer. J Thorac Oncol 6:2036–2043
Rowe BP, Boffa DJ, Wilson LD et al (2012) Stereotactic body radiotherapy for central lung tumors. J Thorac Oncol 7:1394–1399
Chang JY, Li QQ, Xu QY et al (2014) Stereotactic ablative radiation therapy for centrally located early stage or isolated parenchymal recurrences of non-small cell lung cancer: how to fly in a “no fly zone”. Int J Radiat Oncol Biol Phys 88:1120–1128
Modh A, Rimner A, Williams E et al (2014) Local control and toxicity in a large cohort of central lung tumors treated with stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 90:1168–1176
Mangona VS, Aneese AM, Marina O et al (2015) Toxicity after central versus peripheral lung stereotactic body radiation therapy: a propensity score matched-pair analysis. Int J Radiat Oncol Biol Phys 91:124–132
Tekatli H, Senan S, Dahele M et al (2015) Stereotactic ablative radiotherapy (SABR) for central lung tumors: plan quality and long-term clinical outcomes. Radiother Oncol 117:64–70
Onimaru R, Shirato H, Shimizu S et al (2003) Tolerance of organs at risk in small volume, hypofractionated, image-guided radiotherapy for primary metastatic lung cancers. Int J Radiat Oncol Biol Phys 56:126–135
Timmerman R, McGarry R, Yiannoutsos C et al (2006) Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. JCO 24:4833–4839
Corradetti MN, Haas AR, Rengan R (2012) Central-airway necrosis after stereotactic body-radiation therapy. NEJM 366:2327–2329
Senthi S, Ullmann EF, Senan S (2013) Pulmonary atelectasis after stereotactic ablative radiotherapy for a central lung tumor. J Thorac Oncol 8:e94–e95
Karlsson K, Nyman J, Baumann P et al (2013) Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree. Int J Radiat Oncol Biol Phys 87:590–595
Adebahr S, Collette S, Shash S et al (2015) LungTech, an EORTC phase II trial of stereotactic body radiotherapy for centrally located lung tumours: a clinical perspective. Br J Radiol 88:20150036
Tekatli H, Haasbeek N, Dahele M et al (2016) Outcomes of hypofractionated high-dose radiotherapy in poor-risk patients with “ultracentral” non-small cell lung cancer. J Thorac Oncol 11:1081–1089
Karasawa K, Kaminuma T, Maezawa N et al (2009) Three dimensional non-coplanar conformal radiation therapy for stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 75:S449–S450
This study was supported in part by a Grant-in-Aid from the Japanese Radiation Oncology Study Group (JROSG), and the authors would like to thank the JROSG staff office for their helpful support.
Conflict of interest
Dr. Harada reports grants from Astrazeneca Co., Chugai Pharmaceutical Co., and Brainlab Co., although they were not received in association with the submitted work.
This work was supported by the Japanese Radiation Oncology Study Group (JROSG).
About this article
Cite this article
Kimura, T., Nagata, Y., Harada, H. et al. Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1). Int J Clin Oncol 22, 849–856 (2017). https://doi.org/10.1007/s10147-017-1125-y
- Phase I
- Non-small cell lung cancer (NSCLC)
- Centrally located stage IA