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Molecular Diagnostics

Prediction of response to neoadjuvant chemo-immunotherapy in patients with esophageal squamous cell carcinoma by a rapid breath test

British Journal of Cancer volume 130, pages 694–700 (2024)Cite this article

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Abstract

Background

Neoadjuvant chemo-immunotherapy combination has shown remarkable advances in the management of esophageal squamous cell carcinoma (ESCC). However, the identification of a reliable biomarker for predicting the response to this chemo-immunotherapy regimen remains elusive. While computed tomography (CT) is widely utilized for response evaluation, its inherent limitations in terms of accuracy are well recognized. Therefore, in this study, we present a novel technique to predict the response of ESCC patients before receiving chemo-immunotherapy by testing volatile organic compounds (VOCs) in exhaled breath.

Methods

This study employed a prospective-specimen-collection, retrospective-blinded-evaluation design. Patients’ baseline breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Subsequently, patients were categorized as responders or non-responders based on the evaluation of therapeutic response using pathology (for patients who underwent surgery) or CT images (for patients who did not receive surgery).

Results

A total of 133 patients were included in this study, with 91 responders who achieved either a complete response (CR) or a partial response (PR), and 42 non-responders who had stable disease (SD) or progressive disease (PD). Among 83 participants who underwent both evaluations with CT and pathology, the paired t-test revealed significant differences between the two methods (p < 0.05). For the breath test prediction model using breath test data from all participants, the validation set demonstrated mean area under the curve (AUC) of 0.86 ± 0.06. For 83 patients with pathological reports, the breath test achieved mean AUC of 0.845 ± 0.123.

Conclusions

Since CT has inherent weakness in hollow organ assessment and no other ideal biomarker has been found, our study provided a noninvasive, feasible, and inexpensive tool that could precisely predict ESCC patients’ response to neoadjuvant chemo-immunotherapy combination using breath test based on HPPI-TOFMS.

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Fig. 1: The flow chart shows recruitment and allocation process.
Fig. 2: Sample collection and VOCs detection.
Fig. 3: Prediction model construction based on breath test.

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Acknowledgements

This work is partially supported by the National Natural Science Foundation of China (82303567, 82173386), Peking University People’s Hospital Research and Development Founds (RDH2021-07 and RZ2022-04), Beijing Nova Program (20230484314) and Research Project of Shenzhen Second People’s Hospital (20213357024).

Author information

Author notes

  1. These authors contributed equally: Qi Huang, Zheng Liu, Yipei Yu.

Authors and Affiliations

  1. Department of Thoracic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450003, China

    Qi Huang, Teng Mu, Jilun Li, Jia Zhao & Xiangnan Li

  2. Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, 100044, China

    Zheng Liu, Peiyu Wang, Shaodong Wang, Xiang Yan & Mantang Qiu

  3. Thoracic Oncology Institute, Peking University People’s Hospital, Beijing, 100044, China

    Zheng Liu, Peiyu Wang & Mantang Qiu

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

    Yipei Yu, Zhiwei Rong & Yan Hou

  5. Department of Thoracic Surgery, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518000, China

    Hao Wu

  6. Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China

    William C. Cho

  7. Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing, 100074, China

    Mantang Qiu

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Contributions

MQ: Conceptualization, Methodology, Supervision, Writing- Reviewing and Editing, Funding acquisition. QH: Resources, Data curation, Writing- Original draft preparation. ZL: Writing – Original draft preparation, Investigation, Visualization. YY: Formal analysis, Software, Validation. ZR: Data curation, Software. PW: Data curation. SW: Resources. HW: Clinical interpretation, Editing. XY: Writing- Reviewing and Editing, Methodology. WCC: Writing – Reviewing and Editing. TM: Data curation. JL: Data curation. JZ: Data curation. XL: Conceptualization, Methodology, Supervision. YH: Conceptualization, Methodology, Supervision.

Corresponding authors

Correspondence to Mantang Qiu, Yan Hou or Xiangnan Li.

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The authors declare no conflict of interest.

Ethics approval

This study has been approved by the Ethic Committee of the First Affiliated Hospital of Zhengzhou University and has been registered in the Chinese Clinical Trial Registry (www.chictr.org.cn, registry ID: hiCTR2000040966). A written signed informed consent was obtained from all patients before entering any study procedure. The study was performed in accordance with the Declaration of Helsinki.

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Huang, Q., Liu, Z., Yu, Y. et al. Prediction of response to neoadjuvant chemo-immunotherapy in patients with esophageal squamous cell carcinoma by a rapid breath test. Br J Cancer 130, 694–700 (2024). https://doi.org/10.1038/s41416-023-02547-w

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