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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.
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PURPOSE: As cancer survivorship increases, there is a need for simple tools to measure and promote healthy behaviors. We created a wellness behavioral tool (the SMILE Scale) to encourage self-monitoring of wellness behaviors. This study aimed to determine the feasibility of collecting daily self-reported SMILE Scale data and weekly quality of life data among patients with cancer. We also aimed to measure the association between SMILE Scale responses and validated health-related quality of life (HRQOL) tools (PROMIS-29 + 2 and SymTrak-8) as a pilot test of the hypothesis that increased wellness behaviors may impact quality of life. METHODS: We surveyed 100 patients with cancer at the Indiana University Simon Comprehensive Cancer Center. Participants were asked to complete daily SMILE Scale assessments over a two-week period, as well as weekly PROMIS-29 + 2 and SymTrak-8 surveys. The primary endpoint was the SMILE Scale completion rate. Secondary endpoints in this single-arm pilot study included correlations between the SMILE Scale and other HRQOL tools. RESULTS: Daily completion rate of the SMILE Scale ranged from 57% to 65% of participants over a 14-day period. Among the 61% of participants who completed SMILE on day 1, 87% completed SMILE on 10 of 14 days. By end of study, participants who self-reported more wellness behaviors (i.e., higher daily SMILE scores) demonstrated significantly higher PROMIS physical health (p = 0.003), higher PROMIS mental health (p = 0.008), and lower (better) SymTrak total symptom burden (p = 0.006). Further, among those who completed at least 1 of 14 daily SMILE assessments, quality of life significantly improved over the two-week period for PROMIS mental health (p = 0.018) and SymTrak total symptom burden (p = 0.014). CONCLUSION: The SMILE Scale completion rate did not satisfy our pre-planned ≥70% threshold for feasibility; however, the rate for completing SMILE at least once during the 14 days (77%) met this threshold. Participants with higher average daily SMILE scores had significantly better scores across other validated HRQOL tools. While these results may be correlative and not causative, this suggests a potential physical and mental health benefit for delivering the SMILE Scale in clinical practice to help encourage healthy behaviors and warrants testing the SMILE Scale's impact in future studies.
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Nearly half of cancer patients who receive standard-of-care treatments fail to respond to their first-line chemotherapy, demonstrating the pressing need for improved methods to select personalized cancer therapies. Low-coherence digital holography has the potential to fill this need by performing dynamic contrast OCT on living cancer biopsies treated ex vivo with anti-cancer therapeutics. Fluctuation spectroscopy of dynamic light scattering under conditions of holographic phase stability captures ultra-low Doppler frequency shifts down to 10 mHz caused by light scattering from intracellular motions. In the comparative preclinical/clinical trials presented here, a two-species (human and canine) and two-cancer (esophageal carcinoma and B-cell lymphoma) analysis of spectral phenotypes identifies a set of drug response characteristics that span species and cancer type. Spatial heterogeneity across a centimeter-scale patient biopsy sample is assessed by measuring multiple millimeter-scale sub-samples. Improved predictive performance is achieved for chemoresistance profiling by identifying red-shifted sub-samples that may indicate impaired metabolism and removing them from the prediction analysis. These results show potential for using biodynamic imaging for personalized selection of cancer therapy.