Prognostic Factors Analysis of Metastatic Recurrence in Cervical Carcinoma Patients Treated with Definitive Radiotherapy: A Retrospective Study Using Mixture Cure Model

Author:

Ou Xiaxian1ORCID,You Jing2,Liang Baosheng1ORCID,Li Xiaofan2,Zhou Jiangjie1,Wen Fengyu3,Wang Jingyuan1ORCID,Dong Zhengkun2,Zhang Yibao23

Affiliation:

1. Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, China

2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China

3. Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China

Abstract

Objectives: This study aims to identify prognostic factors associated with metastatic recurrence-free survival of cervical carcinoma (CC) patients treated with radical radiotherapy and assess the cure probability of radical radiotherapy from metastatic recurrence. Methods: Data were from 446 cervical carcinoma patients with radical radiotherapy for an average follow up of 3.96 years. We applied a mixture cure model to investigate the association between metastatic recurrence and prognostic factors and the association between noncure probability and factors, respectively. A nonparametric test of cure probability under the framework of a mixture cure model was used to examine the significance of cure probability of the definitive radiotherapy treatment. Propensity-score-matched (PSM) pairs were generated to reduce bias in subgroup analysis. Results: Patients in advanced stages (p = 0.005) and those with worse treatment responses in the 3rd month (p = 0.004) had higher metastatic recurrence rates. Nonparametric tests of the cure probability showed that 3-year cure probability from metastatic recurrence was significantly larger than 0, and 5-year cure probability was significantly larger than 0.7 but no larger than 0.8. The empirical cure probability by mixture cure model was 79.2% (95% CI: 78.6–79.9%) for the entire study population, and the overall median metastatic recurrence time for uncured patients (patients susceptible to metastatic recurrence) was 1.60 (95% CI: 1.51–1.69) years. Locally advanced/advanced stage was a risk factor but non-significant against the cure probability (OR = 1.078, p = 0.088). The interaction of age and activity of radioactive source were statistically significant in the incidence model (OR = 0.839, p = 0.025). In subgroup analysis, compared with high activity of radioactive source (HARS), low activity of radioactive source (LARS) significantly contributed to a 16.1% higher cure probability for patients greater than 53 years old, while cure probability was 12.2% lower for the younger patients. Conclusions: There was statistically significant evidence in the data showing the existence of a large amount of patients cured by the definitive radiotherapy treatment. HARS is a protective factor against metastatic recurrence for uncured patients, and young patients tend to benefit more than the elderly from the HARS treatment.

Funder

National Natural Science Foundation of China

Beijing Natural Science Foundation

Fundamental Research Funds for the Central Universities

PKU-Baidu Fund

Science Foundation of Peking University Cancer Hospital

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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