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. 2024 Sep 30:14:1429343.
doi: 10.3389/fonc.2024.1429343. eCollection 2024.

Evaluating the feasibility and predictive accuracy of biodynamic imaging to platinum-based chemotherapy response in esophageal adenocarcinoma

Ali Ajrouch  1 , Ben Krempley  1 , Ahmad Karkash  1 , John M Dewitt  2 , Mohammad Al-Haddad  2 , Dawith Lim  3 , David Nolte  3 , John Turek  3 , Susan M Perkins  4 , Shadia I Jalal  1
Affiliations

Evaluating the feasibility and predictive accuracy of biodynamic imaging to platinum-based chemotherapy response in esophageal adenocarcinoma

Ali Ajrouch et al. Front Oncol. .

Abstract

Background: Esophageal cancer management lacks reliable response predictors to chemotherapy. In this study we evaluated the feasibility and accuracy of Biodynamic Imaging (BDI), a technology that employs digital holography as a rapid predictor of chemotherapy sensitivity in locoregional esophageal adenocarcinoma.

Methods: Pre-treatment endoscopic pinch biopsies were collected from patients with esophageal adenocarcinoma during standard staging procedures. BDI analyzed the tumor samples and assessed in vitro chemotherapy sensitivity. BDI sensitivity predictions were compared to patients' pathological responses, the gold standard for determining clinical response, in the surgically treated subset (n=18).

Result: BDI was feasible with timely tissue acquisition, collection, and processing in all 30 enrolled patients and successful BDI analysis in 28/29 (96%) eligible. BDI accurately predicted chemotherapy response in 13/18 (72.2%) patients using a classifier for complete, marked, and partial/no-response. BDI technology had 100% negative predictive value for complete pathological response hence identifying patients unlikely to respond to treatment.

Conclusion: BDI technology can potentially predict patients' response to platinum chemotherapy. Additionally, this technology represents a promising step towards optimizing treatment strategies for esophageal adenocarcinoma patients by pre-emptively identifying non-responders to conventional platinum-based chemotherapy.

Keywords: biodynamic imaging; chemotherapy response prediction; digital holography; esophageal adenocarcinoma; patient-specific modeling; platin agents; precision oncology.

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Conflict of interest statement

Employment and Shareholding: Both DN and JT are employed by and hold shares in Animated Dynamics, Inc. Founders and Advisory Roles: In addition to their employment, DN and JT are founders of Animated Dynamics, Inc. and serve on its Scientific Advisory Board. Patent Holdings: The authors hold a total of eight patents related to the technology discussed in this research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Outline of the study design. Bolded areas represent study interventions.
Figure 2
Figure 2
A schematic diagram of the Mach-Zehnder interferometer used to perform biodynamic imaging (BDI). The reference arm contains a 180° reflector mounted on a motorized stage to control the coherence depth for the optical sectioning. The object arm contains a series of optical Fourier transforms with spatial filters (apertures). The object and reference beams are recombined with a slight angle offset at the beam splitter (BS3) and projected onto the camera located on the Fourier plane, where the interferogram is recorded.
Figure 3
Figure 3
A visual summary of the data processing steps involved in biodynamic imaging. (A) the raw hologram captured by the camera, showing the interference fringes and speckle pattern; (B) 2D digital Fourier transform of the hologram showing the zeroth order terms (spatial autocorrelation) in the center, the object field and its phase conjugate offset from the center; (C) an averaged power spectrum; (D) differential spectrogram showing the change in power spectral weights over the course of the experiment for one sample.
Figure 4
Figure 4
Three-class likelihoods for graded patients as well as for the patients without outcomes. Grades 2 and 3 are grouped into a single class. Respectively, Grade 0 signifies tissue sensitivity to chemotherapy and Complete Response clinically, Grade 1 signifies a mixed response to chemotherapy and a Marked Response clinically, finally Grade 2 or 3 signify Partial/No Response to chemotherapy as in the tissue is resistant to chemotherapy and tumor regression is not expect clinically.
Figure 5
Figure 5
Two-class performance. (A) Receiver operator curves (ROCs) plotting true positive rate against false positive rate for three cases comparing groups of grades (0 vs 2&3, 0&1 vs 2&3, and 0 vs 1&2&3) with the respective values for areas under the curve (AUC). (B) Class distribution functions for Grade 0&1 versus Grades 2&3 (black curve in part a). The horizontal axis is the mean value of the likelihoods for non-response (-1) and response (+1). Respectively, Grade 0 signifies tissue sensitivity to chemotherapy and Complete Response clinically, Grade 1 signifies a mixed response to chemotherapy and a Marked Response clinically, finally Grade 2 or 3 signify Partial/No Response to chemotherapy as in the tissue is resistant to chemotherapy and tumor regression is not expect clinically.
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