First-in-human results of the CAIN trial evaluating the HistoSonics system for the treatment of primary renal cancer have demonstrated that histotripsy can be used to safely and effectively target small renal tumours, achieving high technical success and good early efficacy outcomes. Findings were presented at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual congress (13–17 September, Barcelona, Spain).
Presenting the results, principal investigator Tze Min Wah (Leeds Teaching Hospitals NHS Trust, Leeds, UK) explained that histotripsy uses short, high-pressure focused ultrasound pulses to generate cavitation at a precise focal point, enabling non-invasive tissue destruction under ultrasound guidance. Unlike other ablative technologies, histotripsy is non-thermal, does not require needles, and avoids radiation exposure.
CAIN, named in honour of the late Charles Cain, professor of biomedical engineering at the University of Michigan (Ann Arbor, USA) was designed as a prospective, single-centre, single-arm feasibility study with the aim of generating data to inform a subsequent larger pivotal trial.
The research team enrolled 20 patients aged over 18 years with non-metastatic, biopsy-proven renal cancer. Key inclusion criteria included a single tumour ≤3cm in diameter and estimated glomerular filtration rate (eGFR) >/=45ml/min. Exclusion criteria included concurrent cancer treatment within 30 days post histotripsy, genetic predisposition to renal cancer, or tumours overlapping with other vital structures.
Patients were followed up at 36 hours and at one month following treatment. The primary effectiveness endpoint was defined as technical success—complete tumour coverage confirmed by CT or MRI at 36 hours post-procedure—while the primary safety endpoint was freedom from any major complication (Clavien–Dindo grade >/=III) within 30 days.
Of 20 patients initially screened, five were excluded for not meeting inclusion criteria and four were deemed unsuitable at the investigators’ discretion, leaving 11 patients who underwent treatment. Median age was 71 years, the majority were male, and mean tumour size was 2.37cm. Most tumours were of low complexity by RENAL nephrometry score and located in the right kidney, predominantly in interpolar or lower pole positions.
Technical success at 36 hours was achieved in 100% of cases, while 30-day efficacy was reported in 90%. Freedom from major complications at 30 days was 90.9%, with one patient experiencing a grade IIIa event related to prolonged head-down positioning rather than the device itself, which required the patient to be kept overnight in the high dependency unit for oxygen and intravenous fluids, but was discharged uneventfully the following day, Wah states. Minor complications—which were the majority—including transient haematuria, resolved by day five.
“What have we learned through this study?” questioned Wah, who stated that successful ablation depends on “optimising the acoustic window, minimising respiratory motion, and ensuring the tumour is fully encompassed throughout the respiratory cycle”.
During discussion, audience members queried anaesthesia protocols during treatment with histotripsy. Wah described that all patients in this initial series were treated under general anaesthesia, with treatment duration varying depending on tumour depth.
“We don’t use jet-air ventilation for anaesthesia, so there’s a learning curve to work with anaesthetist to ensure good positioning and ensure the tumour is within the planned treatment volume throughout the respiratory cycle,” said Wah, who added that positioning is important to reduce pain in these patients. “It can take up to 83 minutes, so treatment does take a long time—it’s also longer when compared to treatment of the liver with histotripsy,” Wah explained. She continued that, in the future, she would “love to see histotripsy performed without anaesthesia”, ideally as a day-case procedure. “That’s my aspiration,” said Wah.
Wah concluded that CAIN demonstrates the feasibility of using the HistoSonics system to successfully and safely treat small renal tumours with high early efficacy. The speaker underlined that further refinement of respiratory management and acoustic window optimisation will be critical to support broader clinical adoption.
