Real-time detection of surgery-provoked metastasis development
Summary
Most cancer deaths (up to 90%) are related to metastasis due to hematogenous dissemination of circulating tumor cells (CTCs) shed from the tumor. Our UAMS team already demonstrated using ultrasensitive in vivo photoacoustic (PA) flow cytometry (PAFC) in a melanoma-bearing mouse model that palpation, incisional biopsy, and tumor resection can significantly (10-50–fold) increase CTC counts. This suggests that common treatment (e.g., surgery), while providing initial improvement can trigger the release of CTC from the tumor to circulation. In turn, this can increase the risk of deadly metastases as elongated adverse effects. No relevant clinical studies have been performed because of the absence appropriate diagnostic tool and limitations in the detection of CTCs in operating room. Additionally, despite significant efforts, existing CTC assays are not in clinical use due to their low sensitivity.
The goal of this proposal is to bridge this gap by developing an innovative portable and wearable PA probe to test the feasibility for controlling surgery-induced CTCs in melanoma patients. We hypothesize that this our novel diagnostic tool can provide rapid detection of CTCs during surgery. To achieve our goal, we will pursue the following Aims:
Specific Aim 1 . Develop the novel, clinically relevant fiber-based PA probes. We will build a PA probe integrating a ”round-to-linear” fiber bundle and ultrasound transducers. Its main parameters will be tested in vitro using a dynamic vessel phantom with moving mimic CTCs.
Specific Aim 2 . Explore the diagnostic potential of the new PA probe in melanoma patients in vivo. We will explore the feasibility of the PAFC prototype using the modified probe (Aim 1) to test melanoma patients (N=20) before and after surgery. The IRB protocol #133965 was already approved for 4 visits, and the FDA determined that the PAFC is a Non-Significant Risk device; the Investigational Device Exemption (IDE) regulation can be applied.
Our newly established interdisciplinary group is uniquely positioned to accomplish our goal because the synergy in biological engineering, medicine and clinical research lead by experienced PI (Dr. Zharov, PhD, DSc), Dr. Sunde, MD (surgical oncologist) and Dr. Shalin, MD, PhD (dermatopathology). Dr. Sunde will be involved in the surgical treatment of melanoma patients and Dr. Shalin will review of the pathology specimens with focus on resected tumor and lymph-vascular intravascular cancer cells. Yadem, UALR PhD student with a biophotonics background will develop the PA probe and assist with melanoma patient testing (two years clinical experience in UAMS).
This work will result in the submission of a patent associated with the new PA probe and/or method to prevent metastases by immediate treatment of released CTCs. Two grants will be submitted to a) Melanoma Research Alliance (MRA), PI-Zharov (developing of technical platform); and b) NCI, R01, PIs- Drs. Sunder and Makhoul. We plan in the future to establish a Melanoma Center in UAMS using P01 grant mechanism. We expect that new PAFC-based CTC assay after commercialization will be used in most operation room to alarm of CTC release during surgery (like oximetry and ECG).
Keywords:
- Health Care
- Cancer, metastasis, early diagnosis, circulating tumor cells, in vivo flow cytometry, photoacoustics
Researchers:
- Vladimir Zharov (Author)
- Sara Shalin
- Jumin Sunde