Boiling Histotripsy as a Non-Invasive Non-Thermal Approach for Treatment of Human Colon Cancer Tumors: An Ex Vivo Proof-of-Concept.

[OBJECTIVES] Colorectal cancer (CRC) is the third most common cancer globally and is frequently diagnosed at metastatic stages. As an alternative to the current standard of care, a novel high-intensity-focused ultrasound (HIFU)-based boiling histotripsy (BH) method has the potential to provide an ultrasound (US)-guided approach for non-invasive mechanical fractionation of CRC metastases and enhancement of anti-tumor immune response for inoperable primary CRC.

[METHODS] Young's modulus of the autopsy human sigmoid colon cancer was first measured using shear wave elastography. Volumetric BH lesion was then produced in the cancer sample ex vivo using a 2-MHz 9-element annular array (67.5° focusing angle) targeting a 3D-grid (5 × 5 foci across 2 transverse layers with 1-mm spacing) under B-mode US guidance. Each focus received 150 pulses of 1-ms duration (peak positive/negative pressures and shock amplitude P+/P/A = 91/-13/78 MPa, acoustic power and initial intensity within the pulse W = 125.5 W and I = 2.7 W/cm) delivered at 0.1-s intervals (1% duty cycle). The obtained lesion was analyzed via B-mode imaging and histologically with hematoxylin-eosin and Masson's trichrome.

[RESULTS] Young's modulus of the autopsy CRC sample was 38 ± 10 kPa and aligned with clinical values for rectal adenocarcinomas. BH treatment was successfully guided in real-time using B-mode US: the treated area was hyperechoic during BH and hypoechoic post-treatment. Histology confirmed the presence of intact mucinous colon carcinoma outside the BH lesion, and fractionated cells and damaged stroma with disrupted collagen fibers within the lesion.

[CONCLUSIONS] This ex vivo pilot study demonstrates the potential of BH for non-invasive non-thermal US-guided treatment for CRC and metastases.