Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer

Haiyan Zeng, Rui Li, Chen Hu, Guoqin Qiu, Hong Ge, Huiming Yu, Kaixian Zhang, Miaomiao Hu, Peng Zeng, Dan Xiao, Chuanwang Miao, Chuqing Wei, Meng Ni, Jingyi Shen, Hui Li, Jinbo Yue, Heming Lu, Bingjie Fan, Hui Zhu, Xudong Hu & 3 others Feng Ming Spring Kong, Jinming Yu, Shuanghu Yuan

Research output: Contribution to journalArticle

Abstract

Importance: Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown. Objective: To investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer. Design, Setting, and Participants: In this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision. Exposures: The ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions. Main Outcomes and Measures: The primary end point was brain metastases. Secondary end points included progression-free survival and overall survival. Results: Of the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8%) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0% vs 16.9%; hazard ratio, 1.55; 95% CI, 1.06-2.26; P = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8%) experienced brain metastases, with a rate at 3 years of 14.9% in the ODRT group vs 26.0% in the TDRT group (hazard ratio, 1.71; 95% CI, 1.02-2.88; P = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95% CI, 0.99-2.01; P = .06). Conclusions and Relevance: In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.

Original languageEnglish (US)
Pages (from-to)e190103
JournalJAMA network open
Volume2
Issue number5
DOIs
StatePublished - May 3 2019

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Small Cell Lung Carcinoma
Radiotherapy
Neoplasm Metastasis
Brain
Cranial Irradiation
Thorax
Disease-Free Survival
China
Propensity Score
Survival

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Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer. / Zeng, Haiyan; Li, Rui; Hu, Chen; Qiu, Guoqin; Ge, Hong; Yu, Huiming; Zhang, Kaixian; Hu, Miaomiao; Zeng, Peng; Xiao, Dan; Miao, Chuanwang; Wei, Chuqing; Ni, Meng; Shen, Jingyi; Li, Hui; Yue, Jinbo; Lu, Heming; Fan, Bingjie; Zhu, Hui; Hu, Xudong; Kong, Feng Ming Spring; Yu, Jinming; Yuan, Shuanghu.

In: JAMA network open, Vol. 2, No. 5, 03.05.2019, p. e190103.

Research output: Contribution to journalArticle

Zeng, H, Li, R, Hu, C, Qiu, G, Ge, H, Yu, H, Zhang, K, Hu, M, Zeng, P, Xiao, D, Miao, C, Wei, C, Ni, M, Shen, J, Li, H, Yue, J, Lu, H, Fan, B, Zhu, H, Hu, X, Kong, FMS, Yu, J & Yuan, S 2019, 'Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer', JAMA network open, vol. 2, no. 5, pp. e190103. https://doi.org/10.1001/jamanetworkopen.2019.0103
Zeng, Haiyan ; Li, Rui ; Hu, Chen ; Qiu, Guoqin ; Ge, Hong ; Yu, Huiming ; Zhang, Kaixian ; Hu, Miaomiao ; Zeng, Peng ; Xiao, Dan ; Miao, Chuanwang ; Wei, Chuqing ; Ni, Meng ; Shen, Jingyi ; Li, Hui ; Yue, Jinbo ; Lu, Heming ; Fan, Bingjie ; Zhu, Hui ; Hu, Xudong ; Kong, Feng Ming Spring ; Yu, Jinming ; Yuan, Shuanghu. / Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer. In: JAMA network open. 2019 ; Vol. 2, No. 5. pp. e190103.
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abstract = "Importance: Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown. Objective: To investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer. Design, Setting, and Participants: In this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision. Exposures: The ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions. Main Outcomes and Measures: The primary end point was brain metastases. Secondary end points included progression-free survival and overall survival. Results: Of the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8{\%}) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0{\%} vs 16.9{\%}; hazard ratio, 1.55; 95{\%} CI, 1.06-2.26; P = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8{\%}) experienced brain metastases, with a rate at 3 years of 14.9{\%} in the ODRT group vs 26.0{\%} in the TDRT group (hazard ratio, 1.71; 95{\%} CI, 1.02-2.88; P = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95{\%} CI, 0.99-2.01; P = .06). Conclusions and Relevance: In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.",
author = "Haiyan Zeng and Rui Li and Chen Hu and Guoqin Qiu and Hong Ge and Huiming Yu and Kaixian Zhang and Miaomiao Hu and Peng Zeng and Dan Xiao and Chuanwang Miao and Chuqing Wei and Meng Ni and Jingyi Shen and Hui Li and Jinbo Yue and Heming Lu and Bingjie Fan and Hui Zhu and Xudong Hu and Kong, {Feng Ming Spring} and Jinming Yu and Shuanghu Yuan",
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TY - JOUR

T1 - Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer

AU - Zeng, Haiyan

AU - Li, Rui

AU - Hu, Chen

AU - Qiu, Guoqin

AU - Ge, Hong

AU - Yu, Huiming

AU - Zhang, Kaixian

AU - Hu, Miaomiao

AU - Zeng, Peng

AU - Xiao, Dan

AU - Miao, Chuanwang

AU - Wei, Chuqing

AU - Ni, Meng

AU - Shen, Jingyi

AU - Li, Hui

AU - Yue, Jinbo

AU - Lu, Heming

AU - Fan, Bingjie

AU - Zhu, Hui

AU - Hu, Xudong

AU - Kong, Feng Ming Spring

AU - Yu, Jinming

AU - Yuan, Shuanghu

PY - 2019/5/3

Y1 - 2019/5/3

N2 - Importance: Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown. Objective: To investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer. Design, Setting, and Participants: In this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision. Exposures: The ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions. Main Outcomes and Measures: The primary end point was brain metastases. Secondary end points included progression-free survival and overall survival. Results: Of the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8%) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0% vs 16.9%; hazard ratio, 1.55; 95% CI, 1.06-2.26; P = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8%) experienced brain metastases, with a rate at 3 years of 14.9% in the ODRT group vs 26.0% in the TDRT group (hazard ratio, 1.71; 95% CI, 1.02-2.88; P = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95% CI, 0.99-2.01; P = .06). Conclusions and Relevance: In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.

AB - Importance: Although thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown. Objective: To investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer. Design, Setting, and Participants: In this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision. Exposures: The ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions. Main Outcomes and Measures: The primary end point was brain metastases. Secondary end points included progression-free survival and overall survival. Results: Of the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8%) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0% vs 16.9%; hazard ratio, 1.55; 95% CI, 1.06-2.26; P = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8%) experienced brain metastases, with a rate at 3 years of 14.9% in the ODRT group vs 26.0% in the TDRT group (hazard ratio, 1.71; 95% CI, 1.02-2.88; P = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95% CI, 0.99-2.01; P = .06). Conclusions and Relevance: In this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.

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