Significance of radiation esophagitis: Conditional survival assessment in patients with non-small cell lung cancer

Hao Yu; Ka-On Lam; Michael D Green; Huanmei Wu; Li Yang; Weili Wang; Jianyue Jin; Chen Hu; Yang Wang; Shruti Jolly; Feng-Ming Spring Kong

doi:10.1016/j.jncc.2021.02.003

Significance of radiation esophagitis: Conditional survival assessment in patients with non-small cell lung cancer

J Natl Cancer Cent. 2021 Feb 18;1(2):31-38. doi: 10.1016/j.jncc.2021.02.003. eCollection 2021 Jun.

Authors

Hao Yu^{1

2}, Ka-On Lam^{3

4}, Michael D Green^{5

6}, Huanmei Wu², Li Yang⁴, Weili Wang⁷, Jianyue Jin⁷, Chen Hu⁸, Yang Wang¹, Shruti Jolly⁶, Feng-Ming Spring Kong^{3

4

7}

Affiliations

¹ Biomedical Engineering, Shenzhen Polytechnic, Shenzhen, China.
² BioHealth Informatics, School of Informatics and Computing, IUPUI, Indianapolis, IN, USA.
³ Department of Clinical Oncology, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
⁴ Clinical Oncology Center, the University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
⁵ Radiation Oncology, Ann Arbor VA Health Care, Ann Arbor, MI, USA.
⁶ Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁷ University Hospitals/Cleveland Medical Center, Seidman Cancer Center and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
⁸ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Purpose: This study aimed to examine the effect of radiation esophagitis (RE) and the dynamics of RE on subsequent survival in non-small cell lung cancer (NSCLC) patients who underwent radiotherapy.

Experimental design: Patients with NSCLC treated with fractionated thoracic radiotherapy enrolled in prospective trials were eligible. RE was graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 per protocol requirement weekly during-RT and 1 month after RT. This study applied conditional survival assessment which has advantage over traditional survival analysis as it assesses the survival from the event instead of from the baseline. P-value less than 0.05 was considered to be significant. The primary endpoint is overall survival.

Results: A total of 177 patients were eligible, with a median follow-up of 5 years. The presence of RE, the maximum RE grade, the evolution of RE and the onset timing of RE events were all correlated with subsequent survival. At all conditional time points, patients first presented with RE grade1 (initial RE1) had significant inferior subsequent survival (multivariable HRs median: 1.63, all P-values<0.05); meanwhile those with RE progressed had significant inferior subsequent survival than those never develop RE (multivariable HRs median: 2.08, all P-values<0.05). Multivariable Cox proportional-hazards analysis showed significantly higher C-indexes for models with inclusion of RE events than those without (all P-values<0.05).

Conclusion: This study comprehensively evaluated the impact of RE with conditional survival assessment and demonstrated that RE is associated with inferior survival in NSCLC patients treated with RT.

Keywords: Conditional survival; Non-small cell lung cancer; Radiation esophagitis; Radiotherapy.