High intensity focused ultrasound—potential for cancer treatment

Abstract

The prospect of being able to use "minimally invasive" surgical techniques is of great interest today, particularly for reasons of health economics, patient acceptability and reduced morbidity. High intensity focused ultrasound (HIFU) has long been known to offer the potential of very precise "trackless lesioning" but has only recently, with the advent of high quality methods of medical imaging, become a practicable possibility. High intensity beams can readily be achieved using either bowel or lens focusing procedures and, by choice of a suitable acoustic frequency, regions of tissue destruction--"lesions"--can be induced at depths of up to at least 10 cm with exposure times of the order of 1 s. Theoretical and experimental evidence indicates that the primary mechanism of damage is thermal, i.e. "cooking" of the tissues. Both conventional cavitation and boiling of tissue water may complicate the situation. Furthermore, substantial non-linear behaviour is involved. On histological appearance the lesions have a spatially sharp demarcation between regions of normal and dead cells. When attempts are made to ablate a block of tissue, by creating an array of adjacent elementary lesions, a phenomenon is observed of inhibition of formation of a lesion whose placing is too close to that of a neighbour. Provided that this problem is dealt with, complete ablation of an extended block of tissue can be achieved. For animal tumours in particular, this observation is reinforced by evidence both of in vitro cell survival and of tumour growth delay experiments. Clinically, the sites accessible for HIFU treatment will be limited by the need for a suitably wide acoustic window that either is available naturally or can be provided by a relatively minor surgical procedure. Tumour sites which thus offer a realistic prospect for local control (and some of which are already the subject of phase 1 trials) include liver, bladder, kidney, prostate, breast and brain. There is also considerable interest in non-cancer applications in these and other sites.

High intensity focused ultrasound-induced gene activation in sublethally injured tumor cells in vitro

“…In comparison, heat shock profile is more relevant for HIFU therapy, in which the initial (5 s) temperature rise becomes dominant. Because of the high ultrasound intensity and short exposure time, a local thermal equilibrium cannot be reached before the end of HIFU exposure (Lizzi and Ostromogilsky, 1987;Hill and ter Haar, 1995).…”

New approaches to surgery for breast cancer.

“…Ablation fields of 3-5 cm are theoretically possible, but the clinical usefulness of this approach has yet to be verified. Focused ultrasound as described by Harari and colleagues (1991) and by Hill & ter Haar (1995) was used in a pilot study involving patients with inoperable breast tumors (Gianfelice et al 1999), but results in this study were not verified histologically. A study currently in progress at the M D Anderson Cancer Center is using MRI-guided focused ultrasound for the treatment of early stage breast lesions <2 cm in diameter.…”

Minimally Invasive Approaches for Diagnosis and Treatment of Early-Stage Breast Cancer

“…The only reported adverse effects were pain and minimal skin bruising [34]. For breast cancer, several groups investigated FUS in pilot studies including patients with inoperable tumors, but the results were not verified on surgical specimens [35,36].…”