Endocervical ultrasound applicator for integrated hyperthermia and HDR brachytherapy in the treatment of locally advanced cervical carcinoma

Abstract

The clinical success of hyperthermia adjunct to radiotherapy depends on adequate temperature elevation in the tumor with minimal temperature rise in organs at risk. Existing technologies for thermal treatment of the cervix have limited spatial control or rapid energy falloff. The objective of this work is to develop an endocervical applicator using a linear array of multisectored tubular ultrasound transducers to provide 3-D conformal, locally targeted hyperthermia concomitant to radiotherapy in the uterine cervix. The catheter-based device is integrated within a HDR brachytherapy applicator to facilitate sequential and potentially simultaneous heat and radiation delivery. Treatment planning images from 35 patients who underwent HDR brachytherapy for locally advanced cervical cancer were inspected to assess the dimensions of radiation clinical target volumes (CTVs) and gross tumor volumes (GTVs) surrounding the cervix and the proximity of organs at risk. Biothermal simulation was used to identify applicator and catheter material parameters to adequately heat the cervix with minimal thermal dose accumulation in nontargeted structures. A family of ultrasound applicators was fabricated with two to three tubular transducers operating at 6.6-7.4 MHz that are unsectored (360 degrees), bisectored (2 x 180 degrees), or trisectored (3 x 120 degrees) for control of energy deposition in angle and along the device length in order to satisfy anatomical constraints. The device is housed in a 6 mm diameter PET catheter with cooling water flow for endocervical implantation. Devices were characterized by measuring acoustic efficiencies, rotational acoustic intensity distributions, and rotational temperature distributions in phantom. The CTV in HDR brachytherapy plans extends 20.5 +/- 5.0 mm from the endocervical tandem with the rectum and bladder typically <8 mm from the target boundary. The GTV extends 19.4 +/- 7.3 mm from the tandem. Simulations indicate that for 60 min treatments the applicator can heat to 41 degrees C and deliver > 5EM(43 degrees C) over 4-5 cm diameter with Tmax < 45 degrees C and 1 kg m(-3) s(-1) blood perfusion. The 41 degrees C contour diameter is reduced to 3-4 cm at 3 kg m(-3) s(-1) perfusion. Differential power control to transducer elements and sectors demonstrates tailoring of heating along the device length and in angle. Sector cuts are associated with a 14-47 degrees acoustic dead zone, depending on cut width, resulting in a approximately 2-4 degrees C temperature reduction within the dead zone below Tmax. Dead zones can be oriented for thermal protection of the rectum and bladder. Fabricated devices have acoustic efficiencies of 33.4%-51.8% with acoustic output that is well collimated in length, reflects the sectoring strategy, and is strongly correlated with temperature distributions. A catheter-based ultrasound applicator was developed for endocervical implantation with locally targeted, 3-D conformal thermal delivery to the uterine cervix. Feasibility of heating clinically relevant target volumes was demonstrated with power control along the device length and in angle to treat the cervix with minimal thermal dose delivery to the rectum and bladder.