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External validation of a serum tumor marker algorithm for early prediction of no durable benefit to immunotherapy in metastastic non-small cell lung carcinoma

  • 0Department of Pulmonology, Radboud University Medical Center, Nijmegen, The Netherlands.
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine +

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March 17, 2025

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March 17, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

The STOP model, using serum markers, accurately predicts non-responders to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) after six weeks. Combining it with RECIST imaging offers earlier identification of patients unlikely to benefit from ICIs.

Area Of Science

  • Oncology
  • Immunotherapy
  • Biomarker Discovery

Background

  • Immune checkpoint inhibitors (ICIs) improve survival in non-small cell lung cancer (NSCLC).
  • Predicting patient response to ICIs remains a clinical challenge.
  • The STOP model, based on serum tumor markers, previously identified ICI non-responders.

Purpose Of The Study

  • To externally validate the predictive performance of the STOP model for ICI non-response in metastatic NSCLC.
  • To evaluate the combined predictive value of the STOP model and radiological response (RECIST criteria).

Main Methods

  • A cohort of 242 metastatic NSCLC patients was analyzed.
  • Serum tumor markers (CYFRA, CEA, NSE) were measured pre-treatment and at 6 weeks.
  • The STOP model's ability to predict no durable benefit (NDB) was assessed using specificity and positive predictive value (PPV).
  • The STOP model was combined with RECIST criteria assessed at 6-8 weeks.

Main Results

  • The STOP model demonstrated high specificity (96%) and PPV (88.1%) for predicting NDB.
  • Combining the STOP model with RECIST improved specificity and PPV to 100%.
  • The combined approach predicted NDB significantly earlier than radiological progression.

Conclusions

  • The blood-based STOP model accurately predicts no durable benefit (NDB) in metastatic NSCLC patients after 6 weeks of ICIs.
  • Combining serological markers with RECIST allows for earlier identification of non-responders.
  • This combined approach may enable timely cessation of ineffective ICI therapy, though sensitivity limitations exist.

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