Genetic-pathological prediction for timing and site-specific recurrence pattern in resected lung adenocarcinoma


Deng Chaoqiang123ORCID,Zhang Yang123,Fu Fangqiu123ORCID,Ma Xiangyi123ORCID,Wen Zhexu123,Ma Zelin123,Wang Shengping234,Li Yuan235,Chen Haiquan123ORCID


1. Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China

2. Institute of Thoracic Oncology, Fudan University, Shanghai, China

3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

4. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China

5. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China


Abstract OBJECTIVES We aimed to describe accurately the timing and site-specific recurrence pattern for surgical resected lung adenocarcinoma and develop genetic-pathological risk prediction models to guide individual postoperative surveillance strategies. METHODS We retrospectively analysed radiological, pathological and sequencing data concerning 9 common oncogenic driver mutations from 1531 patients with resected lung adenocarcinoma between 2008 and 2015. The first recurrence site and time-to-recurrence were recorded. Independent risk factors were identified by multivariable regression analysis and consequently incorporated into prediction models. RESULTS With a median follow-up of 53.2 months, postoperative recurrences were noted in 483 (31.5%) patients. Bone and brain recurrence tended to occur early (median 11.7 and 17.0 months, respectively) while thorax recurrence occurred later (median 22.2 months), which was validated across different tumour stages. EGFR mutation was an independent predictor for brain and bone recurrence and KRAS mutation for early recurrence. Both internal and external validation of the nomograms for brain and bone recurrence prediction showed optimal discrimination (concordance index: internal, 0.75 and 0.81, respectively; external, 0.77 and 0.84, respectively) and calibration. Recurrence occurred relatively evenly during the follow-up period in low-risk groups but mainly occurred within 2 years in high-risk groups. CONCLUSIONS Unique biological differences exist among lung adenocarcinoma leading to distinct patterns of recurrence. These user-friendly genetic-pathological nomograms may help physicians to better stratify patients and make individual postoperative follow-up plans.


National Natural Science Foundation of China

Shanghai Municipal Science and Technology Major Project

Shanghai Municipal Key Clinical Specialty Project

Pilot Project of Fudan University


Oxford University Press (OUP)


Cardiology and Cardiovascular Medicine,Pulmonary and Respiratory Medicine,General Medicine,Surgery

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