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Erschienen in: Strahlentherapie und Onkologie 2/2020

29.11.2019 | Original Article

Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies

verfasst von: Xiao Hu, Bing Xia, Yong Bao, Yu-jin Xu, Jin Wang, Hong-lian Ma, Fang Peng, Ying Jin, Min Fang, Hua-rong Tang, Meng-yuan Chen, Bai-qiang Dong, Jia-nan Jin, Xiao-long Fu, Ming Chen

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 2/2020

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Abstract

Purpose

The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT.

Methods

Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model.

Results

Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1‑ and 2‑year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4–40.1) and 22.0 (95% CI 16.4–27.5), while the 1‑year, 3‑year, and 5‑year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20–0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32–0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29–0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003).

Conclusion

Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.
Literatur
1.
Zurück zum Zitat Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24:4539–4544CrossRef Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24:4539–4544CrossRef
2.
Zurück zum Zitat van Meerbeeck JP, Fennell DA, De Ruysscher DK (2011) Small-cell lung cancer. Lancet 2011(378):1741–1755CrossRef van Meerbeeck JP, Fennell DA, De Ruysscher DK (2011) Small-cell lung cancer. Lancet 2011(378):1741–1755CrossRef
3.
Zurück zum Zitat Turrisi AT, Kim K, Blum R et al (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340:265–271CrossRef Turrisi AT, Kim K, Blum R et al (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340:265–271CrossRef
4.
Zurück zum Zitat Aupérin A, Arriagada R, Pignon JP et al (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 341:476–484CrossRef Aupérin A, Arriagada R, Pignon JP et al (1999) Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 341:476–484CrossRef
5.
Zurück zum Zitat Faivre-Finn C, Snee M, Ashcroft L et al (2017) 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. Lancet Oncol 18:1116–1125CrossRef Faivre-Finn C, Snee M, Ashcroft L et al (2017) 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. Lancet Oncol 18:1116–1125CrossRef
6.
Zurück zum Zitat Grønberg BH, Halvorsen TO, Fløtten Ø et al (2016) Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer. Acta Oncol 55:591–597CrossRef Grønberg BH, Halvorsen TO, Fløtten Ø et al (2016) Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer. Acta Oncol 55:591–597CrossRef
7.
Zurück zum Zitat Xia B, Hong LZ, Cai XW et al (2015) Phase 2 study of accelerated hypofractionated thoracic radiation therapy and concurrent chemotherapy in patients with limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 91:517–523CrossRef Xia B, Hong LZ, Cai XW et al (2015) Phase 2 study of accelerated hypofractionated thoracic radiation therapy and concurrent chemotherapy in patients with limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 91:517–523CrossRef
8.
Zurück zum Zitat Hu X, Bao Y, Zhang L et al (2012) Omitting elective nodal irradiation and irradiating postinduction versus preinduction chemotherapy tumor extent for limited-stage small cell lung cancer: interim analysis of a prospective randomized noninferiority trial. Cancer 118:278–287CrossRef Hu X, Bao Y, Zhang L et al (2012) Omitting elective nodal irradiation and irradiating postinduction versus preinduction chemotherapy tumor extent for limited-stage small cell lung cancer: interim analysis of a prospective randomized noninferiority trial. Cancer 118:278–287CrossRef
9.
Zurück zum Zitat Pijls-Johannesma M, De Ruysscher D, Vansteenkiste J et al (2007) Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta—analysis of randomised controlled trials. Cancer Treat Rev 33:461–473CrossRef Pijls-Johannesma M, De Ruysscher D, Vansteenkiste J et al (2007) Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta—analysis of randomised controlled trials. Cancer Treat Rev 33:461–473CrossRef
10.
Zurück zum Zitat De Ruysscher D, Pijls-Johannesma M, Bentzen SM et al (2006) Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 24:1057–1063CrossRef De Ruysscher D, Pijls-Johannesma M, Bentzen SM et al (2006) Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 24:1057–1063CrossRef
11.
Zurück zum Zitat De Ruysscher D, Lueza B, Le Péchoux C et al (2016) Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis. Ann Oncol 27:1818–1828CrossRef De Ruysscher D, Lueza B, Le Péchoux C et al (2016) Impact of thoracic radiotherapy timing in limited-stage small-cell lung cancer: usefulness of the individual patient data meta-analysis. Ann Oncol 27:1818–1828CrossRef
12.
Zurück zum Zitat Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346CrossRef Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346CrossRef
13.
Zurück zum Zitat Schild SE, Bonner JA, Hillman S et al (2007) Results of a phase II study of high-dose thoracic radiation therapy with concurrent cisplatin and etoposide in limited-stage small-cell lung cancer (NCCTG 95-20-53). J Clin Oncol 25:3124–3129CrossRef Schild SE, Bonner JA, Hillman S et al (2007) Results of a phase II study of high-dose thoracic radiation therapy with concurrent cisplatin and etoposide in limited-stage small-cell lung cancer (NCCTG 95-20-53). J Clin Oncol 25:3124–3129CrossRef
14.
Zurück zum Zitat Tomita N, Kodaira T, Hida T et al (2010) The impact of radiation dose and fractionation on outcomes for limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 76:1121–1126CrossRef Tomita N, Kodaira T, Hida T et al (2010) The impact of radiation dose and fractionation on outcomes for limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 76:1121–1126CrossRef
15.
Zurück zum Zitat Xia B, Chen GY, Cai XW et al (2011) The effect of bioequivalent radiation dose on survival of patients with limited-stage small-cell lung cancer. Radiat Oncol 6:50CrossRef Xia B, Chen GY, Cai XW et al (2011) The effect of bioequivalent radiation dose on survival of patients with limited-stage small-cell lung cancer. Radiat Oncol 6:50CrossRef
16.
Zurück zum Zitat Zhu L, Zhang S, Xu X et al (2016) Increased biological effective dose of radiation correlates with prolonged survival of patients with limited-stage small cell lung cancer: a systematic review. PLoS ONE 11:e156494CrossRef Zhu L, Zhang S, Xu X et al (2016) Increased biological effective dose of radiation correlates with prolonged survival of patients with limited-stage small cell lung cancer: a systematic review. PLoS ONE 11:e156494CrossRef
17.
Zurück zum Zitat Choi NC, Herndon JE 2nd, Rosenman J et al (1998) Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer. J Clin Oncol 16:3528–3536CrossRef Choi NC, Herndon JE 2nd, Rosenman J et al (1998) Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer. J Clin Oncol 16:3528–3536CrossRef
18.
Zurück zum Zitat Bogart JA, Herndon JE 2nd, Lyss AP et al (2004) 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys 59:460–468CrossRef Bogart JA, Herndon JE 2nd, Lyss AP et al (2004) 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys 59:460–468CrossRef
19.
Zurück zum Zitat Miller AA, Wang XF, Bogart JA et al (2007) Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002. J Thorac Oncol 2:645–651CrossRef Miller AA, Wang XF, Bogart JA et al (2007) Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002. J Thorac Oncol 2:645–651CrossRef
20.
Zurück zum Zitat Kelley MJ, Bogart JA, Hodgson LD et al (2013) Phase II study of induction cisplatin and irinotecan followed by concurrent carboplatin, etoposide, and thoracic radiotherapy for limited-stage small-cell lung cancer, CALGB 30206. J Thorac Oncol 8:102–108CrossRef Kelley MJ, Bogart JA, Hodgson LD et al (2013) Phase II study of induction cisplatin and irinotecan followed by concurrent carboplatin, etoposide, and thoracic radiotherapy for limited-stage small-cell lung cancer, CALGB 30206. J Thorac Oncol 8:102–108CrossRef
21.
Zurück zum Zitat Salama JK, Hodgson L, Pang H et al (2013) A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy (CALGB 30904). J Thorac Oncol 8:1043–1049CrossRef Salama JK, Hodgson L, Pang H et al (2013) A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy (CALGB 30904). J Thorac Oncol 8:1043–1049CrossRef
22.
Zurück zum Zitat El Sharouni SY, Kal HB, Battermann JJ (2003) Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy. Br J Cancer 89:2184–2189CrossRef El Sharouni SY, Kal HB, Battermann JJ (2003) Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy. Br J Cancer 89:2184–2189CrossRef
23.
Zurück zum Zitat Chen CP, Weinberg VK, Jahan TM, Jablons DM, Yom SS (2011) Implications of delayed initiation of radiotherapy: accelerated repopulation after induction chemotherapy for stage III non-small cell lung cancer. J Thorac Oncol 6:1857–1864CrossRef Chen CP, Weinberg VK, Jahan TM, Jablons DM, Yom SS (2011) Implications of delayed initiation of radiotherapy: accelerated repopulation after induction chemotherapy for stage III non-small cell lung cancer. J Thorac Oncol 6:1857–1864CrossRef
24.
Zurück zum Zitat Yom SS (2015) Accelerated repopulation as a cause of radiation treatment failure in non-small cell lung cancer: review of current data and future clinical strategies. Semin Radiat Oncol 25:93–99CrossRef Yom SS (2015) Accelerated repopulation as a cause of radiation treatment failure in non-small cell lung cancer: review of current data and future clinical strategies. Semin Radiat Oncol 25:93–99CrossRef
25.
Zurück zum Zitat Murray N, Coy P, Pater JL et al (1993) Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11:336–344CrossRef Murray N, Coy P, Pater JL et al (1993) Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11:336–344CrossRef
26.
Zurück zum Zitat Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S (1997) Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. J Clin Oncol 15:893–900CrossRef Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S (1997) Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. J Clin Oncol 15:893–900CrossRef
27.
Zurück zum Zitat Work E, Nielsen OS, Bentzen SM, Fode K, Palshof T (1997) Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group. J Clin Oncol 15:3030–3037CrossRef Work E, Nielsen OS, Bentzen SM, Fode K, Palshof T (1997) Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group. J Clin Oncol 15:3030–3037CrossRef
28.
Zurück zum Zitat Skarlos DV, Samantas E, Briassoulis E et al (2001) Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 12:1231–1238CrossRef Skarlos DV, Samantas E, Briassoulis E et al (2001) Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 12:1231–1238CrossRef
29.
Zurück zum Zitat Fried DB, Morris DE, Poole C et al (2004) Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22:4837–4845CrossRef Fried DB, Morris DE, Poole C et al (2004) Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22:4837–4845CrossRef
30.
Zurück zum Zitat Spiro SG, James LE, Rudd RM et al (2006) Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis. J Clin Oncol 24:3823–3830CrossRef Spiro SG, James LE, Rudd RM et al (2006) Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis. J Clin Oncol 24:3823–3830CrossRef
31.
Zurück zum Zitat Sun JM, Ahn YC, Choi EK et al (2013) Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol 2013(8):2088–2092CrossRef Sun JM, Ahn YC, Choi EK et al (2013) Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol 2013(8):2088–2092CrossRef
32.
Zurück zum Zitat Chen M, Jiang GL, Fu XL et al (2000) The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer. Cancer Treat Res 28:11–19 Chen M, Jiang GL, Fu XL et al (2000) The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer. Cancer Treat Res 28:11–19
33.
Zurück zum Zitat Mauguen A, Le Péchoux C, Saunders MI et al (2012) Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol 30:2788–2797CrossRef Mauguen A, Le Péchoux C, Saunders MI et al (2012) Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol 30:2788–2797CrossRef
34.
Zurück zum Zitat Shirvani SM, Juloori A, Allen PK et al (2013) Comparison of 2 common radiation therapy techniques for definitive treatment of small cell lung cancer. Int J Radiat Oncol Biol Phys 87:139–147CrossRef Shirvani SM, Juloori A, Allen PK et al (2013) Comparison of 2 common radiation therapy techniques for definitive treatment of small cell lung cancer. Int J Radiat Oncol Biol Phys 87:139–147CrossRef
35.
Zurück zum Zitat Owonikoko TK, Behera M, Chen Z et al (2012) A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol 7:866–872CrossRef Owonikoko TK, Behera M, Chen Z et al (2012) A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol 7:866–872CrossRef
Metadaten
Titel
Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies
verfasst von
Xiao Hu
Bing Xia
Yong Bao
Yu-jin Xu
Jin Wang
Hong-lian Ma
Fang Peng
Ying Jin
Min Fang
Hua-rong Tang
Meng-yuan Chen
Bai-qiang Dong
Jia-nan Jin
Xiao-long Fu
Ming Chen
Publikationsdatum
29.11.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 2/2020
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-019-01539-1

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