Abstract
Background
Anti-programmed death-1 (PD-1) antibody changed the treatment of non-small cell lung cancer (NSCLC), however, reliable predictive markers were lacking. We aimed to explore factors associated with response and survival, and develop predictive models.
Methods
This multicenter retrospective study included a training cohort (n = 92) and validation cohort (n = 111) with NSCLC patients received anti-PD-1 antibody monotherapy in eight Chinese hospitals, and a control cohort (n = 124) with NSCLC patients received chemotherapy. Logistic and Cox models were used to identify factors associated with response and survival respectively. Nomograms were developed based on significant factors, and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve.
Result
In training cohort, smoking history (P = 0.027) and higher absolute lymphocyte count (P = 0.038) were associated with response. Female (P < 0.001), age ≥ 65 years (P = 0.004) and higher lactate dehydrogenase (LDH, P < 0.001) were associated with shorter progression-free survival (PFS). Higher LDH (P < 0.001) and derived neutrophil-to-lymphocyte ratio (P = 0.035) were associated with poorer overall survival (OS). While these factors were nonsignificant in chemotherapy cohort. Three nomograms to predict response at 6-week after treatment, PFS and OS at 6-, 12- and 18-months were developed, and validated in validation cohort. The C-indices of each nomogram in both cohorts were as follow (training vs validation): 0.706 vs 0.701; 0.728 vs 0.701; 0.741 vs 0.709; respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions.
Conclusion
We developed predictive nomograms based on easily available factors to help clinicians early assess response and prognosis for NSCLC patients received anti-PD-1 antibody.
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Data availability
All data is collected from medical record and is available.
Code availability
Not applicable.
Abbreviations
- AEC:
-
Absolute eosinophil count
- ALC:
-
Absolute lymphocyte count
- ALK:
-
Anaplastic lymphoma kinase
- AMC:
-
Absolute monocyte count
- ANC:
-
Absolute neutrophil count
- AUC:
-
Area under the curve
- C-index:
-
Concordance index
- CRP:
-
C-reactive protein
- DDR:
-
DNA damage repair
- dNLR:
-
Derived neutrophil-to-lymphocyte ratio
- ECOG PS:
-
Eastern Cooperative Oncology Group performance status
- EGFR:
-
Epidermal growth factor receptor
- IDO:
-
Indoleamine2,3-dioxygenase
- IQR:
-
Interquartile ranges
- KRAS:
-
Kirsten rat sarcoma
- LDH:
-
Lactate dehydrogenase
- mOS:
-
Median overall survival
- mPFS:
-
Median progression-free survival
- MSI:
-
Microsatellite instability
- NLR:
-
Neutrophil-to-lymphocyte ratio
- NSCLC:
-
Non-small cell lung cancer
- ORR:
-
Objective response rate
- OS:
-
Overall survival
- PD:
-
Progressive disease
- PD-1:
-
Programmed death-1
- PD-L1:
-
Programmed death-1-ligand 1
- PFS:
-
Progression-free survival
- PNI:
-
Prognostic nutritional index
- PR:
-
Partial response
- SD:
-
Stable disease
- TILs:
-
Tumor infiltrating lymphocytes
- TMB:
-
Tumor mutation burden
- WBC:
-
White blood cell count
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Acknowledgements
We gratefully acknowledge Shaojun **n, Fei Yu and Jiangnan Chen for their data collection. And we also would like to acknowledge Yanzhong Wang for proof reading the article.
Funding
Project supported by the National Natural Science Foundation of China (Grant No. 81972012). None of the funders had any role in the study design and the collection, analysis, and interpretation of data or in the writing of the article and the decision to submit it for publication. The researchers confirm their independence from funders and sponsors.
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JZ, XX and HL conceived the idea, developed the theory, and JZ interpret the results. SY, LS, LY, LL and LC carried out the data collection. And JZ also supervised the data collection. YX conducted the statistical analysis. SY wrote the manuscript with support from YX. All authors discussed the results and contributed to the final manuscript.
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Yuan, S., **a, Y., Shen, L. et al. Development of nomograms to predict therapeutic response and prognosis of non-small cell lung cancer patients treated with anti-PD-1 antibody. Cancer Immunol Immunother 70, 533–546 (2021). https://doi.org/10.1007/s00262-020-02710-9
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DOI: https://doi.org/10.1007/s00262-020-02710-9