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Development, internal validation and calibration of a risk score to predict survival in patients with EGFR-mutant non-small cell lung cancer
  1. Isaac KS Ng1,
  2. Nesaretnam Barr Kumarakulasinghe2,
  3. Nicholas L Syn1,
  4. Ross Andrew Soo2
  1. 1 Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  2. 2 Department of Hematology-Oncology, National University Cancer Institute, Singapore
  1. Correspondence to Dr Ross Andrew Soo, Department of Hematology-Oncology, National University Cancer Institute, Singapore 119074, Singapore; ross_soo{at}


Aims EGFR tyrosine kinase inhibitors (TKIs) are first-line molecularly targeted therapies in patients with advanced non-small cell lung cancer (NSCLC) who carry sensitising EGFR mutations, due to its superior survival outcomes compared with conventional chemotherapy regimens. In this study, we sought to identify clinical, immune and biochemical variables with prognostic significance in this patient subgroup and incorporate them into a nomogram-based risk score.

Methods A total of 199 patients with EGFR mutation-positive, advanced NSCLC (defined as stage IV at initial diagnosis or incurable disease recurrence) treated with first-line EGFR TKI therapy were retrospectively profiled. Univariable and multivariable survival analyses were conducted, with variables from the multivariable model with the highest Harrell’s Concordance (C) Index selected for inclusion in the subsequent survival nomogram. Internal validation and internal calibration of our prognostic nomogram were also performed.

Results Serum lactate dehydrogenase (LDH) and lung/pleural metastasis were independent predictors of unfavourable overall survival in all three multivariable models. A survival nomogram was generated based on the multivariable model with the highest Harrell’s C Index, incorporating the following 11 variables: white cell count, haemoglobin, LDH, neutrophil/lymphocyte ratio, ethnicity (Chinese vs non-Chinese), Karnofsky-Performance Status (score of ‘90–100’ or ‘70–80’ vs ‘0–60’), Charlson Comorbidity Index (≥3, or 2, or 1 vs 0), neurological symptoms, brain, lung/pleural and adrenal metastases.

Conclusion We identified serum LDH as an independent predictor of unfavourable clinical outcomes in patients with advanced, EGFR mutation-positive NSCLC. We further developed a robust nomogram-based risk score that incorporates clinical, biochemical and immune variables that can provide more targeted prognostication and management in this patient subgroup.

  • biomarkers, tumour
  • lung neoplasms
  • neoplasm metastasis

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  • Handling editor Runjan Chetty.

  • Contributors IKSN wrote the manuscript. All authors contributed to study design, data analysis and interpretation. All authors reviewed and approved the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RAS has received honoraria from Astra-Zeneca, BMS, Boehringer Ingelheim, Celgene, Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, and Yuhan; and research funding from Astra-Zeneca and Boehringer Ingelheim.

  • Patient consent for publication Not required.

  • Ethics approval Institutional Review Board, National Healthcare Group Domain Specific Review Board (reference number 2014/00079).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement The dataset analysed in this study is available from the corresponding author, upon reasonable request.