Histotripsy as a novel adjunct in advanced melanoma treatment

Summary: Abstract Body: Advanced melanoma presents significant treatment challenges due to its diffuse nature and complex microenvironment. Current therapies have shown efficacy but are limited by toxicities, resistance, and incomplete tumor eradication.1,2,3 Histotripsy, a non-invasive focused ultrasound technique, offers a novel approach to tumor disruption and may complement existing treatments.5,6 Studies investigating histotripsy in melanoma or related cancer models, as well as clinical trials, were reviewed. Data on histotripsy's mechanism, efficacy, safety, and combination therapies were analyzed. Histotripsy utilizes high-amplitude focused ultrasound pulses to mechanically disrupt tumor tissue through nonthermal cavitation.5,6 Preclinical studies in murine melanoma and hepatocellular carcinoma models have shown histotripsy to induce local tumor destruction and abscopal effects at untreated tumor sites, stimulate systemic anti-tumor response and enhance checkpoint inhibitor immunotherapy.7,8 A single-arm clinical trial demonstrated histotripsy to be effective in treating primary and metastatic liver tumors with few adverse events, emphasizing its potential as a non-invasive treatment in cases refractory to traditional methods.9 Primary tumor location and nodal metastasis make histotripsy a candidate for adjunctive treatment of advanced melanoma, as these tumors avoid some of the areas in which histotripsy shows weaknesses (e.g., attenuation of ultrasound energy or bone obstruction).10 The technique's non-invasive nature and favorable safety profile in early clinical trials support its potential as a complementary treatment. Additionally, its mechanical mode of action bypasses the limitations of systemic therapies, offering a promising adjunct therapy. Exploring histotripsy in combination with checkpoint inhibitors or other immunomodulators may improve advanced melanoma treatment. Kermanjot S. Sidhu¹, Hamza Kaakarli², Sahil Kapur³, Bryce DeLong³, Meyer Gershater⁴, Craig Burkhart³ 1. Michigan State University College of Human Medicine, Grand Rapids, MI, United States. 2. University of Michigan Medical School, Ann Arbor, MI, United States. 3. The University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States. 4. Wayne State University School of Medicine, Detroit, MI, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance