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Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial

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Abstract

Background

CAVE is a single arm, Phase 2 trial, that demonstrated anti-tumor activity of cetuximab rechallenge plus avelumab in patients with RAS wild type (wt) metastatic colorectal cancer (mCRC).

Objective

We conducted a post hoc analysis to identify potential radiomic biomarkers for patients with CRC liver metastasis (LM).

Patients and Methods

Patients with LM that could be measured by enhanced contrast phase computed tomography (CT) imaging at baseline and at first response evaluation were included. Multiple texture parameters were extracted with the LifeX Software. Delta-texture (D-TA) variations were calculated by comparing data at baseline and after treatment.

Results

Overall, 55/77 patients (71%) had LM; 39 met the inclusion criteria for the current analysis. The D-TA parameters that significantly correlated at univariate analysis with median progression-free survival (mPFS) were EntropyHistogram (p = 0.021), HomogeneityGLCM (p < 0.001) and Dissimilarity GLCM (p = 0.002). At multivariate analysis, only HomogeneityGLCM resulted significant for PFS (p = 0.001). Patients (19/39, 48.7%) with reduction of HomogeneityGLCM experienced better mPFS (4.6 vs 2.9 months; HR 0.45; 95% CI 0.23–0.88; p = 0.021) and median overall survival (mOS) (17.3 vs 6.8 months; HR 0.40, 95% CI 0.21–0.80; p = 0.010). A trend to better mPFS, was also observed in patients with RAS/BRAF wt circulating tumor DNA and reduction of HomogeneityGLCM. Overall survival was significantly better in this subgroup of patients with low HomogeneityGLCM: mOS was 17.8 (95% CI 15.5–20.2) versus 6.8 months (95% CI 3.6–10.0) (HR 0.34, 95% CI 0.14–0.81; p = 0.016).

Conclusion

Reduction in the D-TA parameter HomogeneityGLCM by radiomic analysis correlates with improved outcomes in patients with LM receiving cetuximab rechallenge plus avelumab therapy. Larger prospective studies are needed to validate and confirm these findings.

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Acknowledgments

We would like to thank GOIM for the support in conducting the CAVE trial.

Author information

Author notes

  1. Erika Martinelli, Davide Ciardiello, Valerio Nardone, and Alfonso Reginelli have contributed equally.

Authors and Affiliations

  1. Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Erika Martinelli, Giulia Martini, Stefania Napolitano, Sara Del Tufo, Luca D’Ambrosio, Marco De Chiara, Vincenzo Famiglietti, Valeria Nacca, Teresa Troiani, Salvatore Cappabianca, Fortunato Ciardiello, Valerio Nardone & Alfonso Reginelli

  2. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy

    Davide Ciardiello

  3. Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale”, IRCCS, Naples, Italy

    Claudia Cardone & Antonio Avallone

  4. Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy

    Chiara Cremolini

  5. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Chiara Cremolini

  6. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Filippo Pietrantonio

  7. Oncology Unit, IRCCS Foundation Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Evaristo Maiello

  8. Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy

    Vincenza Granata

Authors
  1. Erika Martinelli
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  2. Davide Ciardiello
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  3. Giulia Martini
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  4. Stefania Napolitano
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  7. Marco De Chiara
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  8. Vincenzo Famiglietti
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  9. Valeria Nacca
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  14. Evaristo Maiello
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  15. Vincenza Granata
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  16. Teresa Troiani
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  17. Salvatore Cappabianca
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  18. Fortunato Ciardiello
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  19. Valerio Nardone
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  20. Alfonso Reginelli
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Corresponding authors

Correspondence to Erika Martinelli or Davide Ciardiello.

Ethics declarations

Funding information

This was an academic nonprofit study, conducted in the Gruppo Oncologico dell’Italia Meridionale (GOIM) clinical research network. Cetuximab and avelumab were provided by Merck KGaA, Darmstadt, Germany. Two research grants, that partially covered the costs of the study, were provided by Merck and by Regione Campania (I-Cure Research Project, Grant number: Cup 21C17000030007).

Competing Interests

Prof. Martinelli reported receiving travel grants from AstraZeneca and Pierre Fabre and being an advisory board member for AstraZeneca, Bayer, Amgen, Merck KGaK, Roche, Sanofi, Servier and Pierre Fabre outside the submitted work. Dr. D Ciardiello, reported receiving travel grants from Sanofi, BMS and Merck KGaA outside the submitted work. Dr. Martini reported honoraria from Servier and Incyte outside the submitted work. Dr. Napolitano reported that received travel grants from Amgen and Merck KGaA outside the submitted work. Dr. Cardone reported receiving personal fees from Bayer outside the submitted work. Dr. Avallone reported receiving personal fees for consulting from Amgen, AstraZeneca, MSD and Eisai and being an advisory board member for Amgen and Servier outside the submitted work. Prof. Cremolini reported receiving honoraria from Amgen, Bayer, Merck, Pierre Fabre, Roche and Servier. Consulting or advisory role for Amgen, Bayer, MSD, Nordic Pharma, Roche, Takeda. Speakers’ Bureau for Amgen, Pierre Fabre, MSD, Servier. Research funding from Amgen, Bayer, Merck, Servier. Dr. Pietrantonio reported receiving research grants from Incyte, Lilly, Bristol Myers Squibb, Amgen, Agenus and AstraZeneca and honoraria from Bristol Myers Squibb, Amgen, Merck Serono, Bayer, Takeda, GSK, Ipsen, Astellas, Servier, MSD, and Pierre Fabre outside the submitted work. Dr. Maiello has served as advisor and speaker for AstraZeneca, Eli Lilly, Servier, Sanofi Genzyme, Roche, Merck, Eisai, Pfizer outside the submitted work. Prof. Troiani reported receiving travel grants from AstraZeneca and Pierre Fabre and being an advisory board member for AstraZeneca, Bayer, Amgen, Merck KGaK, Roche, Sanofi, Servier and Pierre Fabre outside the submitted work. Prof. Ciardiello F reported serving on the advisory board for Amgen and Servier during the conduct of the study and serving on the advisory board for MSD, Merck KGaA, Roche, Pfizer, Bayer, Pierre Fabre and Eisai outside the submitted work. All other authors declare no competing interests.

Ethics Approval

The CAVE-mCRC trial was approved by the Ethic Committee of Università degli Studi della Campania Luigi Vanvitelli, Azienda Ospedaliera Universitaria-AORN “Ospedali dei Colli”, Napoli, Italy. CAVE-mCRC trial is registered with Eudract.ema.europa.eu, EudraCT number: 2017-004392-32 and ClinicalTrial.gov identifier: NCT04561336.

Consent to Participate

All patients provided written informed consent before entering the trial.

Consent for Publication

Not applicable.

Availability of Data and Material

The data that support the findings of our study and further information are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

Authors' Contributions

Prof. E. Martinelli, Dr. D. Ciardiello, Dr. V. Nardone, Prof. F. Ciardiello, had full access to all of the data in the study and are accountable for the integrity and the accuracy of the data analysis. Conception and Design of the Trial Conceptualization: Martinelli E, Ciardiello D, Nardone V, Martini G, Ciardiello F and Reginelli A. Financial support: Ciardiello. Acquisition, analysis and interpretation of the clinical data: all authors. Data curation: all authors. Statistical formal analysis: Nardone V, Famiglietti. Translational research data analysis and interpretation: Martinelli E, Ciardiello D, Ciardiello F. Writing of the manuscript-original draft: Martinelli E, Ciardiello D, Ciardiello F, and Nardone V. Final approval of the manuscript Writing – review and editing: all authors. The work reported in the paper has been performed by the authors, unless clearly specified in the text.

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Martinelli, E., Ciardiello, D., Martini, G. et al. Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial. Clin Drug Investig (2024). https://doi.org/10.1007/s40261-024-01372-0

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