Addition of HER2 and CD44 to 18F-FDG PET-based clinico-radiomic models enhances prediction of neoadjuvant chemoradiotherapy response in esophageal cancer

Roelof J Beukinga; Da Wang; Arend Karrenbeld; Willemieke P M Dijksterhuis; Hette Faber; Johannes G M Burgerhof; Véronique E M Mul; Riemer H J A Slart; Robert P Coppes; John Th M Plukker

doi:10.1007/s00330-020-07439-8

Addition of HER2 and CD44 to ¹⁸F-FDG PET-based clinico-radiomic models enhances prediction of neoadjuvant chemoradiotherapy response in esophageal cancer

Eur Radiol. 2021 May;31(5):3306-3314. doi: 10.1007/s00330-020-07439-8. Epub 2020 Nov 5.

Authors

Roelof J Beukinga¹, Da Wang^{2

3}, Arend Karrenbeld⁴, Willemieke P M Dijksterhuis², Hette Faber^{3

5}, Johannes G M Burgerhof⁶, Véronique E M Mul⁵, Riemer H J A Slart^{7

8}, Robert P Coppes^{3

5}, John Th M Plukker²

Affiliations

¹ Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, The Netherlands. r.j.beukinga@umcg.nl.
² Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
³ Department of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁵ Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁶ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁷ Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 RB, Groningen, The Netherlands.
⁸ Faculty of Science and Technology, Department of Biomedical Photonic Imaging, University of Twente, Enschede, The Netherlands.

Abstract

Objectives: To assess the complementary value of human epidermal growth factor receptor 2 (HER2)-related biological tumor markers to clinico-radiomic models in predicting complete response to neoadjuvant chemoradiotherapy (NCRT) in esophageal cancer patients.

Methods: Expression of HER2 was assessed by immunohistochemistry in pre-treatment tumor biopsies of 96 patients with locally advanced esophageal cancer. Five other potentially active HER2-related biological tumor markers in esophageal cancer were examined in a sub-analysis on 43 patients. Patients received at least four of the five cycles of chemotherapy and full radiotherapy regimen followed by esophagectomy. Three reference clinico-radiomic models based on ¹⁸F-FDG PET were constructed to predict pathologic response, which was categorized into complete versus incomplete (Mandard tumor regression grade 1 vs. 2-5). The complementary value of the biological tumor markers was evaluated by internal validation through bootstrapping.

Results: Pathologic examination revealed 21 (22%) complete and 75 (78%) incomplete responders. HER2 and cluster of differentiation 44 (CD44), analyzed in the sub-analysis, were univariably associated with pathologic response. Incorporation of HER2 and CD44 into the reference models improved the overall performance (R²s of 0.221, 0.270, and 0.225) and discrimination AUCs of 0.759, 0.857, and 0.816. All models exhibited moderate to good calibration. The remaining studied biological tumor markers did not yield model improvement.

Conclusions: Incorporation of HER2 and CD44 into clinico-radiomic prediction models improved NCRT response prediction in esophageal cancer. These biological tumor markers are promising in initial response evaluation.

Key points: • A multimodality approach, integrating independent genomic and radiomic information, is promising to improve prediction of γpCR in patients with esophageal cancer. • HER2 and CD44 are potential biological tumor markers in the initial work-up of patients with esophageal cancer. • Prediction models combining ¹⁸F-FDG PET radiomic features with HER2 and CD44 may be useful in the decision to omit surgery after neoadjuvant chemoradiotherapy in patients with esophageal cancer.

Keywords: CD44 antigen; Esophageal cancer; Oncogene protein HER-2; Positron emission tomography; Radiomics.

MeSH terms

Chemoradiotherapy
Esophageal Neoplasms* / drug therapy
Esophageal Neoplasms* / therapy
Fluorodeoxyglucose F18*
Humans
Hyaluronan Receptors / therapeutic use
Neoadjuvant Therapy
Positron-Emission Tomography
Radiopharmaceuticals / therapeutic use
Receptor, ErbB-2
Treatment Outcome

Substances

CD44 protein, human
Hyaluronan Receptors
Radiopharmaceuticals
Fluorodeoxyglucose F18
ERBB2 protein, human
Receptor, ErbB-2