Medical Policy

This document addresses the use of histotripsy to ablate tissue. Histotripsy is an incisionless non-thermal procedure that uses ultrasound to induce mechanical cavitation resulting in the transformation of targeted tissue into acellular debris. The mechanism of action for histotripsy differs from that for high intensity focused ultrasound (HIFU). In HIFU, the heat produced by high intensity focused ultrasound directly destroys tissue and the spread of this heat can damage adjacent tissue. Histotripsy creates microbubbles within tissue and it is the expansion and contraction of these bubbles that destroy cells. Histotripsy is being evaluated as a treatment for malignant tissue, including liver lesions and renal cancer. This treatment has also been proposed for treatment of nonmalignant conditions such as benign prostatic hypertrophy (BPH).

Note: For other documents related to ultrasonic ablation techniques, please see the following:

• CG-MED-81 Ultrasound Ablation for Oncologic Indications
• MED.00057 MRI Guided High Intensity Focused Ultrasound Ablation for Non-Oncologic Indications

Note: For a high-level overview of this document, please see “Summary for Members and Families” below. 

Medically Necessary:

Histotripsy is considered medically necessary when all of the following criteria (A, B, C, and D) are met:

1. Treatment is intended for destruction of liver tumors (primary or metastatic; malignant or nonmalignant); and
2. There is a lack of other available therapies (locoregional therapies, chemotherapy, immunotherapy, targeted therapies) as evidenced by at least one of the following:
   1. Unresponsive to other therapies; or
   2. Relapse following other therapies; or
   3. Intolerant to other available therapies; or
   4. Thermal ablation is not viable due to tumor location (for example, proximity to vital structures or centrally located);
      and
3. Targeted tumor(s) diameter 3 centimeters (cm) or less; and
4. Three or fewer tumors will be treated.

Investigational and Not Medically Necessary:

Histotripsy is considered investigational and not medically necessary when the criteria above are not met.

This document describes clinical studies and expert recommendations, and explains when a treatment called histotripsy is clinically appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Histotripsy is a treatment that destroys tissue without surgery or heat. It uses focused ultrasound waves to create tiny bubbles that break apart targeted tissue. The body then absorbs the treated tissue over time. This treatment may be used for some liver tumors when other treatment options are not suitable. Studies show that histotripsy can destroy targeted liver tumors with good short-term safety and tumor control in carefully selected people. Most side effects are mild and temporary, but serious complications can occur. Better studies with longer follow-up are needed to understand long-term results. Histotripsy has not been proven to improve health for kidney cancer, enlarged prostate, pancreatic cancer, or other uses described in this document.

What the Studies Show

Histotripsy works differently from treatments that destroy tissue with heat or cold. Instead of heating or cooling tissue, it creates tiny bubbles that break apart cells while helping protect nearby healthy tissue. This may make it useful for tumors that are close to important blood vessels or other structures. The treatment does not require an incision.

Studies of liver tumors found that histotripsy successfully treated many tumors and had safety results similar to other local treatments for liver cancer. Most side effects were mild, such as abdominal pain or fever that improved after treatment. A small number of people had serious complications, including infection, bleeding, liver failure, or pain that required hospital care. Researchers are still following people to learn how well the treatment works over many years. For kidney cancer, enlarged prostate, and pancreatic cancer, only information from early studies or ongoing clinical trials is available. Better studies are needed to know if histotripsy improves health for these conditions.

When is Histotripsy Clinically Appropriate?

Histotripsy may be appropriate in these situations:

• The treatment is intended to destroy primary liver cancer or liver tumors that spread from another part of the body; and
• Other treatment options, such as local treatments, chemotherapy, immunotherapy, targeted therapy, or thermal ablation, are not suitable because at least one of the following applies:
  • The tumor did not respond to treatment; or
  • The cancer returned after treatment; or
  • The person could not tolerate other treatment; or
  • Thermal ablation cannot be used because of the tumor's location, such as being close to important structures or in the center of the liver; and
• Each treated tumor is 3 centimeters (cm) or smaller; and
• No more than three tumors will be treated.

When is Histotripsy not Clinically Appropriate?

Histotripsy is not clinically appropriate when the situations listed above are not met. There is not enough evidence to show that it improves health outside those situations. Better studies are needed to know whether histotripsy improves health for kidney cancer, enlarged prostate, pancreatic cancer, and other uses. Unnecessary or unproven treatments can expose people to risks without proven benefit.

(Return to Description/Scope)

Summary

Histotripsy is a nonthermal, ultrasound-based ablation technique that mechanically destroys tissue through acoustic cavitation, enabling precise, incisionless tumor treatment while sparing surrounding structures. It is considered medically necessary for individuals with up to three liver tumors ≤ 3 cm when other locoregional, systemic, or ablative therapies are not viable. Clinical evidence, including the HOPE4LIVER trial data, demonstrates high technical success, favorable safety, and local tumor control comparable to conventional ablation, with mostly mild, short-term adverse events (AEs).

Histotripsy therapy remains investigational for other indications, including renal malignancy or BPH. Early trials for renal tumors are ongoing, and current National Comprehensive Cancer Network (NCCN) and National Cancer Institute (NCI) guidelines do not endorse its use. Limited pilot studies in BPH show procedural feasibility but lack long-term or comparative data. While promising for nonthermal tissue destruction, further evidence is needed to establish safety, efficacy, and clinical benefit beyond hepatic applications.

Discussion

Histotripsy is a focal ablative therapy that destroys tissue by acoustic cavitation. It has been proposed as an alternative treatment for tumors. The proposed benefits of low-heat focal ablative therapy include avoidance of heat sink effects, which is theorized to allow histotripsy to be used in highly vascular areas (Hendricks-Wenger, 2021).

A phase I trial provided the initial safety and efficacy data regarding the use of histotripsy in individuals with hepatocellular carcinoma and hepatic metastasis (Vidal-Jove, 2022). In this study, 8 individuals with multifocal liver tumors were followed for 8 weeks post-procedure. There were no significant procedure-related events. The study focused on technical safety and did not provide follow-up data on cancer-related outcomes.

On October 6, 2023, the Edison^® System (HistoSonics^®, Ann Arbor, MI) received de novo marketing authorization from the FDA for the non-thermal destruction of liver tumors. On February 14, 2024, an updated Edison system was cleared for use in the non-invasive destruction of liver tumors. The authorization was based in part on the data from two single-arm, non-randomized prospective trials evaluating primary or metastatic liver tumors (NCT04572633, NCT04573881). Interim results have been published for one of those studies (Mendiratta-Lala, 2024). Participants will be followed for 5 years post-procedure (NCT04572633, NCT04573881). On October 1, 2024, the FDA cleared the updated system for the treatment of liver tumors, as “substantially equivalent to the predicate device”.

Liver tumors

Mendiratta-Lala (2024) published the results of a prospective multicenter, single-arm trial (#HOPE4LIVER). Participants with up to 3 tumors smaller than 3 cm in size were treated with histotripsy. Participants included individuals with hepatocellular carcinoma (n=18) or with liver metastases from non-hepatocellular carcinomas (n=26). The co-primary endpoints were technical success, tumor treatment volume being greater than or equal to the targeted volume with complete tumor coverage, and safety, and the absence of procedure-related major complications through 30 days post-procedure. All participants underwent a single session of histotripsy. Technical efficacy at 30 days was 83%. A total of 101 AEs were reported within 30 days postoperatively, with 94 AEs (93.1%) categorized as nonserious. Of the 7 serious AEs, 3 were classified as primary safety end-point failures. These end-point failures included 1 case each of sepsis, pleuritic pain requiring inpatient care, and hepatic failure leading to death 37 days after the procedure. The remaining serious AEs were identified as splenic hematoma, melena, procedural pain, and progression of metastatic colorectal cancer. The study was limited to reporting early endpoints related to performance rather than clinical outcomes. The authors noted that the cohort in this study may not be typical of individuals who receive ablative treatment because many of them had stage IV metastatic disease. Longer-term 12-month data regarding safety and efficacy are being analyzed with plans to publish in the future.

Ziemlewicz (2025) reported on the 1-year clinical outcomes from the #HOPE4LIVER trial. Among 47 participants, the 1-year local tumor control rate was 63% by initial review and 90% after expert reassessment. The investigators attributed this difference to increasing experience interpreting the appearance of tissue disruption caused by the histotripsy treatment. One-year survival was 73% for hepatocellular carcinoma and 49% for metastatic disease. Most treatment zones showed progressive shrinkage (over 95% volume reduction), and nearly all adverse effects occurred within 30 days of treatment. The most common adverse effects were fever and mild abdominal pain. Only six serious device-related events were reported, and no delayed toxicities were found. Overall, histotripsy provided tumor control and safety outcomes within ranges reported for  current local liver therapies 1 year post-procedure.

In a multicenter retrospective case series, Wehrle (2025b) reported on the safety data of the first 230 individuals who underwent histotripsy. Nearly half of treated tumors were colorectal metastases and disease biology heterogeneity was not analyzed in the safety analysis. Although this study only reported 30-day safety outcomes and did not report long-term tumor control effects, there were no device-related interventions, supporting early safety across diverse liver tumor types and locations. The overall complication rate was 5.2%. The 1.3% major-event rate compares favorably to published 30-day major-complication rates of TACE (≈5-10%), MWA/RFA (≈2-4%), or hepatic resection (≈10-20%). Industry involvement may have introduced a source of bias to this voluntary retrospective registry study.

A single-center cohort (Mabud, 2025) which included 26 individuals with 56 tumors described short-term safety and imaging findings after histotripsy treatment of liver metastases. Participants were ineligible for alternative NCCN-recommended locoregional therapy or were unfit for anesthesia. The imaging data were incomplete and heterogeneous: 1-month post-treatment tumor ablation zone volume and tumor long-axis dimension were reported for 21 participants while only 2 participants had corresponding 3-month data. There was no blinding or independent radiology review. Based on imaging, treatment was considered technically successful for 97% of the participants. Mild treatment-related AEs were reported for 15% of the participants and 1 participant experienced bacteremia that was judged to be a major AE. Industry involvement represents a potential source of bias in this voluntary retrospective registry study with incomplete follow-up. The authors stated that “This study is limited by its retrospective nature, small heterogeneous cohort, single study center, and limited and non-standardized follow-up protocols, precluding robust conclusions regarding outcomes.”

Wehrle (2025a) conducted a retrospective, multicenter cohort study evaluating the early safety and local tumor control of histotripsy in individuals undergoing curative-intent treatment for primary and secondary liver tumors. The study included 47 participants with 91 liver tumors treated at 4 U.S. centers. While nearly all participants were treated for malignant disease, one individual was treated for a hepatic adenoma. Radiographic response was assessed at 30 and 90 days using mRECIST for hepatocellular carcinoma and standardized ablation response criteria for other tumor types. At 30 days, 95% (86/91) of treated tumors demonstrated complete radiographic response with no evidence of viable tumor, while 5 tumors, including the hepatic adenoma, showed residual viable disease. Two participants, 1 with hepatocellular carcinoma and the individual with the hepatic adenoma, underwent repeat histotripsy between postoperative days 30 and 90, and both achieved a complete response after retreatment without AEs. No major complications occurred. Interpretation of the findings is limited by the retrospective, uncontrolled study design and the short 90-day follow-up period.

Renal Cancer

Histotripsy is proposed for use to treat renal cancer; however, there are no peer-reviewed published studies evaluating the use of histotripsy for this indication. There are two prospective, multi-center, single-arm clinical trials underway to evaluate the safety and effectiveness of the device in treating renal tumors.

The prospective, single-arm CAIN feasibility trial (NCT05432232) evaluated histotripsy for the treatment of primary solid renal tumors at a single UK center. Although the study was originally designed to enroll up to 20 participants, results have currently been posted for an interim cohort of 11 treated participants. Technical success, defined as complete tumor coverage on CT or MRI within 36 hours, was achieved in 100% (11/11) of treated tumors (95% confidence interval [CI], 71.5%-100.0%). The primary safety endpoint, freedom from procedure-related major complications (Clavien-Dindo grade III or higher) through 30 days, was achieved in 90.9% (10/11) of participants (95% CI, 58.7%-99.8%). No outcome data were reported for the planned 90-day technique efficacy endpoints. No deaths occurred during the 30-day follow-up; however, 3 participants experienced serious AEs, including vomiting, postoperative urinary retention, emphysema, and obstructive airway disorder. As of July 2026, these results have been posted on ClinicalTrials.gov but have not yet been published as a peer-reviewed report of the complete trial cohort. Consequently, interpretation is limited by the small sample size, single-arm design, lack of a comparator group, incomplete reporting of planned efficacy outcomes, and short duration of follow-up, precluding conclusions regarding long-term oncologic efficacy, durability of local tumor control, renal function preservation, or comparative effectiveness.

The pivotal #HOPE4KIDNEY trial (NCT05820087) completed enrollment in December 2024 with results expected midyear in 2030.

The preferred treatment of renal cancer is partial or radical nephrectomy. For individuals with small tumors or for individuals who are not candidates for surgery, ablative therapies, such as RFA, cryoablation or stereotactic ablative body radiation therapy are considered standard alternative therapies (NCI, Renal Cancer Treatment, 2025; NCCN, Kidney cancer V1.2027). Histotripsy is not mentioned as a potential treatment of renal tumors in any current guidelines.

BPH

Schuster (2018) presented the results of a prospective cohort study in which 25 individuals with BPH were treated with histotripsy to relieve urinary obstruction. The primary study endpoint was safety as reflected by the rate of AEs. There was 1 serious AE (urinary retention requiring catheterization for 8 days) and 26 other AEs including catheter-related pain (n=8), dysuria (n=5), bladder spasm (n=5), urinary retention (n=3), minor anal abrasion (n=1), microhematuria (n=1), and local reaction at the catheter site (n=3). The authors describe this as a limited pilot study. Larger controlled studies with longer follow up are needed to evaluate outcomes of histotripsy compared to more established therapies for BPH.

Pancreatic Cancer

Published studies evaluating histotripsy in treating pancreatic cancer are limited to pre-clinical studies in porcine models (Gannon, 2026; Hendricks-Wenger, 2021). Clinical trials evaluating histotripsy safety and effectiveness in treating pancreatic cancer are underway. The GANNON study (NCT06282809) is a prospective multi-center, single-arm, feasibility trial which includes participants with Stage 3 (unresectable locally advanced) or Stage 4 (oligometastatic) disease. Participants will be followed for up to 180 days. The estimated study completion date is August 2028. The NCCN clinical practice guidelines (CPGs) for treatment of pancreatic adenocarcinoma (V3.2026) do not address histotripsy.

Histotripsy is sometimes compared to HIFU, but the treatments are fundamentally different. HIFU is a thermal treatment that uses continuous or long bursts of ultrasound to induce heat resulting in tissue destruction. In contrast, histotripsy is a non-thermal treatment that employs “short ultrasound bursts with higher peak pressure amplitudes” to cause mechanical cavitation and tissue destruction (Verma, 2024). The treated tissue is liquefied and reabsorbed within 1-2 months post-treatment (Xu, 2024).

Histotripsy devices consist of a treatment head and probe linked to a touchscreen interface for real-time visualization and control. Tumor margins are mapped and the probe generates bubble clouds in specific locations within the target area to confirm margins and determine the energy needed for cavitation. In histotripsy, focal volumes are stacked together to treat the target volume. This has the proposed benefit of sparing surrounding tissues, unlike thermal ablation. Robotic assistance can be incorporated to ensure precise positioning of the treatment arm over the tumor.

Histotripsy works differently in solid tissues compared to tissue-fluid interfaces. In solid tissue, histotripsy transforms tissue into a liquid, entirely removing cellular structures and creating clear acellular zones. In tissue-fluid interfaces, histotripsy erodes the tissue surface, causing the shedding of micrometer-sized cell debris and progressively thinning the tissue until it completely perforates. Acoustic wave propagation may also be affected by tissue heterogeneity, intervening structures, and organ motion.

Histotripsy is theorized to induce antitumor immune responses that may contribute to tumor regression and potentially enhance the effectiveness of immunotherapy. One hypothesized manifestation of this immune activation is the abscopal effect, in which localized treatment is associated with regression of untreated distant tumors. Clinical evidence of immune activation in humans remains preliminary and observational, consisting primarily of tumor marker changes, cytokine profiling, and isolated case reports of possible abscopal responses, rather than prospective, controlled clinical trials with prespecified immune endpoints.

The benefits of non-thermal focal ablative therapy over other ablative therapies include tissue destruction in the targeted area and avoidance of heat sink effects which is theorized to allow histotripsy to be used in highly vascular areas (Hendricks-Wenger, 2021). Treatment success depends on precise targeting and reliable cavitation generation, requiring accurate image guidance, acoustic parameter optimization, and real-time monitoring to ensure complete ablation while avoiding injury to surrounding tissues. Histotripsy is a threshold-dependent therapy. Effective tissue fractionation occurs only when sufficient acoustic pressure is achieved, making consistent energy delivery critical. Limitations of histotripsy include decreased effectiveness with increased target depths, potential risks in gas-filled organs, and a theoretical risk of metastasis due to tissue fragmentation (Verma, 2024).

Histotripsy therapy in other locations, such as the pancreas, poses anatomical and technical challenges. The retroperitoneal location of the pancreas and its close proximity to the stomach, bowel, bile duct, and major blood vessels complicate acoustic targeting and increase the risk of off-target injury. In addition, overlying bowel gas, respiratory motion, and the dense desmoplastic stroma characteristic of pancreatic ductal adenocarcinoma can impair ultrasound visualization, acoustic energy delivery, and treatment uniformity. To minimize pancreatic motion and maintain accurate targeting, histotripsy typically requires anesthesia with respiratory control to establish an adequate acoustic window. Successful treatment also depends on precise acoustic parameter optimization and real-time image guidance, both of which remain areas of ongoing technological development (Hendricks-Wenger, 2021; Lee, 2026; Sears, 2026).

Warnings

Renal impairment following histotripsy has been reported in the FDA Manufacturer and User Facility Device Experience (MAUDE) database (Bhutta, 2026). In addition to incidences of acute kidney injury (AKI), additional warnings regarding liver reserves and adjacent structures have been included in the user guide:

Histotripsy is used to destroy targeted liver tumors. Consequently, histotripsy should only be considered in patients with sufficient functional liver reserve to withstand the destruction of the planned volume of liver tissue. Functional liver capacity can be impacted by multiple factors, including prior focal therapies, chemotherapies and/or immunotherapies. Loss of liver function below a critical threshold can lead to patient harm, including liver failure and death.

Consider patient-specific risk factors for acute kidney injury (AKI) and/or renal failure based on clinical history and procedural scenarios that could increase stress on kidney function, including but not limited to hydration status, planned treatment volume and expected use of imaging contrast agents. Consistent with other liver-directed therapies, treatments involving large treatment volumes or multiple treatment sessions may be associated with an increased risk of AKI. Evaluate renal risk and monitor for signs of AKI before and after treatment.

Since sufficient functional liver reserve following treatment is a requirement for any focal liver therapy, patients who are Child-Pugh class C or have decompensated liver cirrhosis prior to treatment should not be considered candidates for histotripsy. Histotripsy of the liver has only been evaluated in patients who are Child-Pugh class A and B, without evidence of decompensated cirrhosis.

Mechanical injury to critical structures (e.g., vascular structures, liver capsule, bile ducts) may occur when these structures are within the PTV [planned treatment volume]. The likelihood of bleeding and/or mechanical injury may also increase with additional and/or subsequent treatments within a treatment session or across follow-up treatments.

When any of the following occur, cumulative thermal exposure will increase, elevating the risk of thermal injury to the skin, body wall, or other tissues: (excerpt)

• Anatomical or other structures (e.g., ribs, lung, bowel) located anywhere within the acoustic pathway - including post-focal - with higher absorption and/or reflection
•  Anatomy or obstructions (e.g., bowel gas) within the pre-focal acoustic pathway that require higher voltage settings to sustain the bubble cloud
•  Multiple treatments within the same procedure when acoustic pathways may intersect and/or pass through previously treated zones

Note the following system behaviors, which further inform energy delivery considerations related to cumulative thermal exposure: (excerpt)

• While the mechanism of action is non-thermal, localized temperature rise within the acoustic pathway will occur during energy delivery/deposition—particularly in transition zones such as the skin, body wall, or in tissues that absorb/obstruct ultrasound energy, such as bone

Ablation: The destruction of a body part or tissue or its function. Ablation may be achieved by surgery, hormones, drugs, radiofrequency, heat, or other methods.

Abscopal effect: Regression of untreated tumors at sites distant from the treated lesion, hypothesized to result from treatment-induced activation of systemic antitumor immune responses.

Acoustic cavitation: Cavitation produced by focused ultrasound waves that generate rapidly expanding and collapsing microscopic bubbles capable of mechanically disrupting tissue.

Cavitation: The formation, oscillation, and collapse of microscopic gas or vapor bubbles in response to acoustic pressure. In histotripsy, controlled mechanical cavitation generates forces that disrupt cells and fragment targeted tissue without relying on thermal injury.

Heat sink effect: Reduction in the effectiveness of thermal ablation caused by blood flow through adjacent vessels, which dissipates heat and may prevent complete tissue destruction.

Histotripsy: A non-thermal focused ultrasound technique that destroys targeted tissue through controlled acoustic cavitation rather than heat.

Local tumor control: Prevention of tumor progression or recurrence within the treated area during follow-up.

Thermal ablation: Destruction of tissue through the application of heat or extreme cold, including techniques such as radiofrequency ablation, microwave ablation, cryoablation, and high-intensity focused ultrasound.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the codes listed above when criteria are not met or for all other diagnoses, for the following procedure codes, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Bhutta S, Wanchoo R, Sakhiya V, et al. AKI after hepatic histotripsy. Kidney Int Rep. 2026; 11(7):106603.
2. Gannon J, Paul T, Imran KM, et al. Non-invasive pancreas ablation using histotripsy: pre-clinical safety study in an in vivo porcine model. Ultrasound Med Biol. 2026; 52(1):62-71.
3. Hendricks-Wenger A, Sereno J, Gannon J, et al. Histotripsy ablation alters the tumor microenvironment and promotes immune system activation in a subcutaneous model of pancreatic cancer. IEEE Trans Ultrason Ferroelectr Freq Control. 2021; 68(9):2987-3000.
4. Hendricks-Wenger A, Weber P, Simon A, et al. Histotripsy for the treatment of cholangiocarcinoma liver tumors: in vivo feasibility and ex vivo dosimetry study. IEEE Trans Ultrason Ferroelectr Freq Control. 2021; 68(9):2953-2964.
5. Jahangiri S, Yu F. Fundamentals and applications of focused ultrasound-assisted cancer immune checkpoint inhibition for solid tumors. Pharmaceutics. 2024; 16(3):411.
6. Khokhlova VA, Fowlkes JB, Roberts WW, et al. Histotripsy methods in mechanical disintegration of tissue: towards clinical applications. Int J Hyperthermia. 2015; 31(2):145-162.
7. Lee JY, Lafon C, Mouratidis P, et al. Focused ultrasound as a therapeutic adjunct in pancreatic cancer: from thermal and mechanical effects to immune modulation. Ultrasonography. 2026; 45(3):195-204.
8. Mabud TS, Vergara M, Du J, et al. Histotripsy of liver metastases: short-term safety and imaging findings. Cardiovasc Intervent Radiol. September 28, 2025. Online ahead of print.
9. Mendiratta-Lala M, Wiggermann P, Pech M, et al. The #HOPE4LIVER single-arm pivotal trial for histotripsy of primary and metastatic liver tumors. Radiology. 2024; 312(3):e233051.
10. Sandilos G, Butchy MV, Koneru M, et al. Histotripsy - hype or hope? Review of innovation and future implications. J Gastrointest Surg. 2024; 28(8):1370-1375.
11. Schuster TG, Wei JT, Hendlin K, et al. Histotripsy treatment of benign prostatic enlargement using the vortx rx system: initial human safety and efficacy outcomes. Urology. 2018; 114:184-187.
12. Sears O, Zhang H, Blatz N, et al. Focused ultrasound in pancreatic ductal adenocarcinoma: mechanisms, preclinical evidence, and emerging clinical applications. Cancers (Basel). 2026; 18(4):574.
13. Verma Y, Perera Molligoda Arachchige AS. Advances in tumor management: harnessing the potential of histotripsy. Radiol Imaging Cancer. 2024; 6(3):e230159.
14. Vidal-Jove J, Serres X, Vlaisavljevich E, et al. First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study. Int J Hyperthermia. 2022; 39(1):1115-1123.
15. Wehrle CJ, Burns K, Mabud T, et al. Local tumor control of liver tumors after histotripsy: a preliminary national multicenter study. JCO Oncol Pract. 2025a: OP2500550.
16. Wehrle CJ, Burns K, Ong E, et al. The first international experience with histotripsy: a safety analysis of 230 cases. J Gastrointest Surg. 2025b; 29(4):102000.
17. Xu Z, Hall TL, Vlaisavljevich E, Lee FT Jr. Histotripsy: the first noninvasive, non-ionizing, non-thermal ablation technique based on ultrasound. Int J Hyperthermia. 2021b; 38(1):561-575.
18. Xu Z, Khokhlova TD, Cho CS, Khokhlova VA. Histotripsy: a method for mechanical tissue ablation with ultrasound. Annu Rev Biomed Eng. 2024; 26(1):141-167.
19. Ziemlewicz TJ, Critchfield JJ, Mendiratta-Lala M, et al. The #HOPE4LIVER single-arm pivotal trial for histotripsy of primary and metastatic liver tumors: 1-year update of clinical outcomes. Ann Surg. 2025; 282(6):908-916.

Government Agency, Medical Society, and Other Authoritative Publications:

1. HistoSonics, Inc. The HistoSonics Edison^™ System for treatment of pancreatic adenocarcinoma using histotripsy (GANNON). NLM Identifier: NCT06282809. Last updated on July 9, 2026. Available at: https://clinicaltrials.gov/study/NCT06282809?term=histosonics&aggFilters=status:rec%20act&rank=3. Accessed on August 13, 2026.
2. HistoSonics, Inc. The HistoSonics Edison^™ System for Treatment of Primary Solid Renal Tumors Using Histotripsy (#HOPE4KIDNEY). NLM Identifier: NCT05820087. Last updated on June 23, 2026. Available at: https://clinicaltrials.gov/study/NCT05820087?term=NCT05820087&limit=10&rank=1. Accessed on July 7, 2026.
3. HistoSonics, Inc. The HistoSonics Investigational System for treatment of primary solid renal tumors using histotripsy (CAIN). NLM Identifier: NCT05432232. Last updated on December 2, 2025. Available at: https://clinicaltrials.gov/study/NCT05432232?term=NCT05432232&rank=1. Accessed on July 7, 2026.
4. National Cancer Institute (NCI). PDQ^® Cancer Information for Health Professionals. Available at: https://www.cancer.gov/publications/pdq. Accessed on July 6, 2026.
   • Pancreatic Cancer Treatment. Updated February 12, 2025.
   • Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment. Updated May 9, 2025.
   • Primary Liver Cancer Treatment. Updated April 17, 2025.
   • Prostate Cancer Treatment. Updated May 14, 2025.
   • Renal Cell Cancer Treatment. Updated May 13, 2025.
5. National Comprehensive Cancer Network^® (NCCN) Practice Guidelines in Oncology^™. ^©2026 National Comprehensive Cancer Network, Inc. For additional information, visit the NCCN website: http://www.nccn.org. Accessed on August 13, 2026.
   • Biliary Tract Cancer. V1.2026. Revised March 10, 2026.
   • Colon Cancer. V2.2026. Revised April 7, 2026.
   • Hepatocellular Carcinoma. V1.2026. Revised March 10, 2026.
   • Kidney Cancer. V1.2027. Revised July 1, 2026.
   • Neuroendocrine and Adrenal Tumors. V1.2026. Revised April 21, 2026.
   • Pancreatic Adenocarcinoma. V3.2026. Revised August 6, 2026.
6. Solbiati, L. Humanitas Hospital. The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER). NCT04573881. Last updated on January 12, 2026. Available at: https://clinicaltrials.gov/ct2/show/study/NCT04573881?term=%23HOPE4LIVER&draw=1&rank=1. Accessed on July 7, 2026.
7. U.S. Food and Drug Administration (FDA). 510(k) Premarket Notification Database. Histosonics Edison System Summary of Safety and Effectiveness. Rockville, MD: FDA. Accessed on July 7, 2026.
   • No. K233466. March 13, 2024. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K233466.
   • No. K241902. October 1, 2024. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf24/K241902.pdf.
8. U.S. Food and Drug Administration (FDA). De Novo Classification. Histosonics Edison System. DEN220087. December 2, 2022. Available at: https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN220087.pdf. Accessed on August 13, 2026.
9. Ziemlewicz T, Cho C. The HistoSonics System for Treatment of Primary and Metastatic Liver Tumors Using Histotripsy (#HOPE4LIVER US). NCT04572633. Last updated on November 19, 2025. Available at: https://clinicaltrials.gov/ct2/show/study/NCT04572633?term=%23HOPE4LIVER&draw=1&rank=2. Accessed on July 1, 2026.

Acoustic cavitation
Edison^® System
HistoSonics
Histotripsy

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