Stereotactic body radiotherapy for early-stage non-small cell lung cancer: clinical outcomes from a National Patient Registry

Joanne N Davis, Clinton Medbery 3rd, Sanjeev Sharma, David Perry, John Pablo, David J D'Ambrosio, Heidi McKellar, Frank C Kimsey, Paul N Chomiak, Anand Mahadevan, Joanne N Davis, Clinton Medbery 3rd, Sanjeev Sharma, David Perry, John Pablo, David J D'Ambrosio, Heidi McKellar, Frank C Kimsey, Paul N Chomiak, Anand Mahadevan

Abstract

Objectives: Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1-T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting.

Methods: The RSSearch® Patient Registry was screened for T1-T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method.

Results: In total, 723 patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up was 12 months (1-87 months) with a median age of 76 years. Median SBRT dose was 54 Gy (range 10-80 Gy) delivered in a median of 3 fractions (range 1-5), and median biological equivalent dose (BED10) was 151.2 Gy (range 20-240 Gy). Median OS was 30 and 26 months for T1 and T2 tumors, respectively (p = 0.019). LC was associated with higher BED10 for T2 tumors, but not in T1 tumors at a median follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED10 < 105 Gy, BED10 105-149, and BED10 ≥ 150 Gy was 43, 74, and 95 %, respectively (p = 0.011). Local failure rates for T2 tumors treated with BED10 < 105 Gy, 105-149 Gy, and ≥150 Gy were 32, 21, and 8 % (p = 0.029), respectively. Median OS for patients with T2 tumors treated with BED10 < 105 Gy was 17 vs. 32 months for T2 tumors treated with BED10 105-149 Gy (p = 0.062).

Conclusion: SBRT for T1-T2 NSCLC is feasible and effective in the community setting. OS was greater for patients with T1 lesions compared to T2 lesions. An improvement in LC was observed in patients with T2 lesions treated with BED10 > 105 Gy.

Keywords: Lung cancer; Non-small cell lung cancer; Radiosurgery; Registry; Stereotactic body radiotherapy.

Figures

Fig. 1
Fig. 1
Survival curves for T1 and T2 lesions treated with SBRT. Kaplan-Meier analysis of overall survival (a), local control (b), and distant disease control (c) for patients with T1 (solid lines) and T2 (dotted lines) NSCLC treated with SBRT. Ticked marks indicate censored patients. Patients with T1 lesions had greater overall survival compared to T2 lesions (p = 0.019 by log-rank test)
Fig. 2
Fig. 2
Local control (LC) and overall survival (OS) for T1 and T2 lesions treated with BED10 a) and T1 (c) lesions and OS for T2 (b) and T1 (d) lesions treated with BED10 < 105 Gy (dotted line), BED10 105–149 (dashed line), and BED10 ≥ 150 Gy (solid line). Tick marks indicate censored patients. LC improved for T2 lesions treated with BED10 (p = 0.011 by log-rank test), but not T1 lesions. There was a trend for improved OS for T2 lesions treated with BED10105–149 compared to BED10 < 105 although it did not reach statistical significance (p = 0.062 by log-rank test)

References

    1. Smythe WR. Treatment of stage I non-small cell lung carcinoma. Chest. 2003;123(1 Suppl):181S–187S. doi: 10.1378/chest.123.1_suppl.181S.
    1. Armstrong JG, Minsky BD. Radiation therapy for medically inoperable stage I and II non-small cell lung cancer. Cancer Treat Rev. 1989;16(4):247–255. doi: 10.1016/0305-7372(89)90044-3.
    1. Qiao X, Tullgren O, Lax I, Sirzen F, Lewensohn R. The role of radiotherapy in treatment of stage I non-small cell lung cancer. Lung Cancer. 2003;41(1):1–11. doi: 10.1016/S0169-5002(03)00152-1.
    1. Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, Drugge N, Ekberg L, Friesland S, Johansson KA, Lund JA, Morhed E, Nilsson K, Levin N, Paludan M, Sederholm C, Traberg A, Wittgren L, Lewensohn R. 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 Off J Am Soc Clin Oncol. 2009;27(20):3290–3296. doi: 10.1200/JCO.2008.21.5681.
    1. Grills IS, Hope AJ, Guckenberger M, Kestin LL, Werner-Wasik M, Yan D, Sonke JJ, Bissonnette JP, Wilbert J, Xiao Y, Belderbos J. 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 Off Publ Int Assoc Stud Lung Cancer. 2012;7(9):1382–1393.
    1. Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Niibe Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, Takeda A, Ouchi A, Hareyama M, Kokubo M, Hara R, Itami J, Yamada K, Araki T. 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 Off Publ Int Assoc Stud Lung Cancer. 2007;2(7 Suppl 3):S94–S100.
    1. Timmerman R, Paulus R, Galvin J, Michalski J, Straube W, Bradley J, Fakiris A, Bezjak A, Videtic G, Johnstone D, Fowler J, Gore E, Choy H. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA J Am Med Assoc. 2010;303(11):1070–1076. doi: 10.1001/jama.2010.261.
    1. Haasbeek CJ, Lagerwaard FJ, Antonisse ME, Slotman BJ, Senan S. Stage I nonsmall cell lung cancer in patients aged > or =75 years: outcomes after stereotactic radiotherapy. Cancer. 2010;116(2):406–414. doi: 10.1002/cncr.24759.
    1. Chang JY, Liu H, Balter P, Komaki R, Liao Z, Welsh J, Mehran RJ, Roth JA, Swisher SG. Clinical outcome and predictors of survival and pneumonitis after stereotactic ablative radiotherapy for stage I non-small cell lung cancer. Radiat Oncol. 2012;7:152. doi: 10.1186/1748-717X-7-152.
    1. Fakiris AJ, McGarry RC, Yiannoutsos CT, Papiez L, Williams M, Henderson MA, Timmerman R. 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):677–682. doi: 10.1016/j.ijrobp.2008.11.042.
    1. 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):685–692. doi: 10.1016/j.ijrobp.2007.10.053.
    1. Nagata Y, Takayama K, Matsuo Y, Norihisa Y, Mizowaki T, Sakamoto T, Sakamoto M, Mitsumori M, Shibuya K, Araki N, Yano S, Hiraoka M. 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):1427–1431. doi: 10.1016/j.ijrobp.2005.05.034.
    1. Senthi S, Lagerwaard FJ, Haasbeek CJ, Slotman BJ, Senan S. Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. Lancet Oncol. 2012;13(8):802–809. doi: 10.1016/S1470-2045(12)70242-5.
    1. Crabtree TD, Denlinger CE, Meyers BF, El Naqa I, Zoole J, Krupnick AS, Kreisel D, Patterson GA, Bradley JD. Stereotactic body radiation therapy versus surgical resection for stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2010;140(2):377–386. doi: 10.1016/j.jtcvs.2009.12.054.
    1. Grills IS, Mangona VS, Welsh R, Chmielewski G, McInerney E, Martin S, Wloch J, Ye H, Kestin LL. Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(6):928–935. doi: 10.1200/JCO.2009.25.0928.
    1. Verstegen NE, Oosterhuis JW, Palma DA, Rodrigues G, Lagerwaard FJ, van der Elst A, Mollema R, van Tets WF, Warner A, Joosten JJ, Amir MI, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. 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 Off J Eur Soc Med Oncol ESMO. 2013;24(6):1543–1548. doi: 10.1093/annonc/mdt026.
    1. (NCCN) NCCN National comprehensive practice guidelines in oncology: non-small cell lung cancer. Natl Compr Netw. 2013;2:2014.
    1. Davis JN, Medbery Iii C, Sharma S, Danish A, Mahadevan A. The RSSearch™ Registry: patterns of care and outcomes research on patients treated with stereotactic radiosurgery and stereotactic body radiotherapy. Radiat Oncol. 2013;8(1):275. doi: 10.1186/1748-717X-8-275.
    1. Lagerwaard FJ, Verstegen NE, Haasbeek CJ, Slotman BJ, Paul MA, Smit EF, Senan S. Outcomes of stereotactic ablative radiotherapy in patients with potentially operable stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2012;83(1):348–353. doi: 10.1016/j.ijrobp.2011.06.2003.
    1. Salazar OM, Sandhu TS, Lattin PB, Chang JH, Lee CK, Groshko GA, Lattin CJ. Once-weekly, high-dose stereotactic body radiotherapy for lung cancer: 6-year analysis of 60 early-stage, 42 locally advanced, and 7 metastatic lung cancers. Int J Radiat Oncol Biol Phys. 2008;72(3):707–715. doi: 10.1016/j.ijrobp.2008.01.054.
    1. van der Voort van Zyp NC, Prevost JB, Hoogeman MS, Praag J, van der Holt B, Levendag PC, van Klaveren RJ, Pattynama P, Nuyttens JJ. Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: clinical outcome. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2009;91(3):296–300. doi: 10.1016/j.radonc.2009.02.011.
    1. Rosenzweig KE, Fox JL, Yorke E, Amols H, Jackson A, Rusch V, Kris MG, Ling CC, Leibel SA. Results of a phase I dose-escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma. Cancer. 2005;103(10):2118–2127. doi: 10.1002/cncr.21007.
    1. Sibley GS. Radiotherapy for patients with medically inoperable Stage I nonsmall cell lung carcinoma: smaller volumes and higher doses—a review. Cancer. 1998;82(3):433–438. doi: 10.1002/(SICI)1097-0142(19980201)82:3<433::AID-CNCR2>;2-Q.
    1. Stephans KL, Djemil T, Reddy CA, Gajdos SM, Kolar M, Mason D, Murthy S, Rice TW, Mazzone P, Machuzak M, Mekhail T, Videtic GM. A comparison of two stereotactic body radiation fractionation schedules for medically inoperable stage I non-small cell lung cancer: the Cleveland Clinic experience. J Thorac Oncol Off Publ Int Assoc Stud Lung Cancer. 2009;4(8):976–982.
    1. Le QT, Loo BW, Ho A, Cotrutz C, Koong AC, Wakelee H, Kee ST, Constantinescu D, Whyte RI, Donington J. Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors. J Thorac Oncol Off Publ Int Assoc Stud Lung Cancer. 2006;1(8):802–809.
    1. Nuyttens JJ, van der Voort van Zyp NC, Praag J, Aluwini S, van Klaveren RJ, Verhoef C, Pattynama PM, Hoogeman MS. Outcome of four-dimensional stereotactic radiotherapy for centrally located lung tumors. Radiother Oncol J Eur Soc Ther Radiol Oncol. 2012;102(3):383–387. doi: 10.1016/j.radonc.2011.12.023.
    1. Onimaru R, Fujino M, Yamazaki K, Onodera Y, Taguchi H, Katoh N, Hommura F, Oizumi S, Nishimura M, Shirato H. Steep dose-response relationship for stage I non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy. Int J Radiat Oncol Biol Phys. 2008;70(2):374–381. doi: 10.1016/j.ijrobp.2007.06.043.
    1. Jeppesen SS, Schytte T, Jensen HR, Brink C, Hansen O. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer: an updated retrospective study on local failure and survival rates. Acta Oncol. 2013;52(7):1552–1558. doi: 10.3109/0284186X.2013.813635.

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