[an error occurred while processing this directive] | [an error occurred while processing this directive]
Simultaneous integrated boost vs. routine IMRT in limited-stage small-cell lung cancer:an open-label,non-inferiority,randomized, phase 3 trial
Zhan Tianyou, Zhang Tao, Zhou Zongmei, Yan Wenbin, Zhai Yirui, Deng Lei, Wang Wenqing, Bi Nan, Wang Jianyang, Wang Xin, Liu Wenyang, Xiao Zefen, Feng Qinfu, Chen Dongfu, Lyu Jima, Hui Zhouguang, Liang Jun, Wang Lyuhua
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
AbstractObjective Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy. Methods Patients diagnosed with treatment-naiveand confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1:1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2Gy/2.15Gy/28F,PTV 50.4Gy/1.8Gy/28F) or conventional fractionated radiotherapy (PTV 60Gy/2Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity. Results Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95%CI:35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%(HR=1.22,95%CI:0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%(HR=1.35,95%CI:0.90-2.04,P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%(HR=0.98,95%CI:0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups (HR=1.69,95%CI:1.18-2.41,P=0.003;HR=1.72,95%CI:1.09-2.70,P=0.018;HR=1.66,95%CI:1.01-2.73,P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64,95%CI:1.15-11.57,P=0.028). The most common grade 3–4 adverse events were myelosuppression (21.7% vs. 15.4%,P=0.83),radiation pneumonitis (4.7% vs. 2.7%,P=0.44) and radiation esophagitis (3.8% vs. 1.8%,P=0.51). Conclusions Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.
[1] Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer[J]. Lancet, 2021, 398(10299):535-554. DOI:10.1016/S0140-6736(21)00312-3. [2] Nicholson AG, Chansky K, Crowley J, et al. The international association for the study of lung cancer lung cancer staging project:proposals for the revision of the clinical and pathologic staging of small cell lung cancer in the forthcoming eighth edition of the TNM classification for lung cancer[J]. J Thorac Oncol, 2016, 11(3):300-311. DOI:10.1016/j.jtho.2015.10.008. [3] Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide[J]. N Engl J Med, 1999, 340(4):265-271. DOI:10.1056/NEJM199901283400403. [4] Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT):an open-label, phase 3, randomised, superiority trial[J]. Lancet Oncol, 2017, 18(8):1116-1125. DOI:10.1016/S1470-2045(17)30318-2. [5] Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic cranial irradiation overview collaborative group[J]. N Engl J Med, 1999, 341(7):476-484. DOI:10.1056/NEJM199908123410703. [6] Grønberg BH, Killingberg KT, FløttenØ,et al. High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer:an open-label, randomised, phase 2 trial[J]. Lancet Oncol, 2021, 22(3):321-331. DOI:10.1016/S1470-2045(20)30742-7. [7] Videtic GM, Belderbos JS, Spring Kong FM, et al. Report from the international atomic energy agency (IAEA) consultants' meeting on elective nodal irradiation in lung cancer:small-cell lung cancer (SCLC)[J]. Int J Radiat Oncol Biol Phys, 2008, 72(2):327-334. DOI:10.1016/j.ijrobp.2008.03.075. [8] Farrell MJ, Yahya JB, Degnin C, et al. Elective nodal irradiation for limited-stage small-cell lung cancer:survey of US radiation oncologists on practice patterns[J]. Clin Lung Cancer, 2020, 21(5):443-449.e4. DOI:10.1016/j.cllc.2020.02.020. [9] Withers HR, Peters LJ, Taylor JM. Dose-response relationship for radiation therapy of subclinical disease[J]. Int J Radiat Oncol Biol Phys, 1995, 31(2):353-359. DOI:10.1016/0360-3016(94)00354-N. [10] Han D, Qin Q, Hao S, et al. Feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy in patients with limited-disease small cell lung cancer[J]. Radiat Oncol, 2014, 9:280. DOI:10.1186/s13014-014-0280-9. [11] Liu Z, Wang J, Yuan Z, et al. Preliminary results about application of intensity-modulated radiotherapy to reduce prophylactic radiation dose in limited-stage small cell lung cancer[J]. J Cancer, 2018, 9(15):2625-2630. DOI:10.7150/jca.24976. [12] Qiu B, Li Q, Liu J, et al. Moderately hypofractionated once-daily compared with twice-daily thoracic radiation therapy concurrently with etoposide and cisplatin in limited-stage small cell lung cancer: a multicenter, phase II, randomized trial[J]. Int J Radiat Oncol Biol Phys, 2021, 111(2): 424-435. DOI: 10.1016/j.ijrobp.2021.05.003. [13] Levy A, Hendriks L, Le Péchoux C, et al. Current management of limited-stage SCLC and CONVERT trial impact:results of the EORTC lung cancer group survey[J]. Lung Cancer, 2019, 136:145-147. DOI:10.1016/j.lungcan.2019.08.007. [14] De Ruysscher D, Lueza B, Le Péchoux C, et al. Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer:usefulness of the individual patient data meta-analysis[J]. Ann Oncol, 2016, 27(10):1818-1828. DOI:10.1093/annonc/mdw263. [15] Farrell MJ, Yahya JB, Degnin C, et al. Timing of thoracic radiation therapy with chemotherapy in limited-stage small-cell lung cancer:survey of US radiation oncologists on current practice patterns[J]. Clin Lung Cancer, 2018, 19(6):e815-e821. DOI:10.1016/j.cllc.2018.04.007.
2022, Vol. 31 
