Evaluating the efficacy of three carrier screening workflows designed to identify at-risk carrier couples.

OBJECTIVE: To evaluate the efficacy of three different carrier screening workflows designed to identify couples at risk for having offspring with autosomal recessive conditions. METHODS: Partner testing compliance, unnecessary testing, turnaround time, and ability to identify at-risk couples (ARCs) were measured across all three screening strategies (sequential, tandem, or tandem reflex). RESULTS: A total of 314,100 individuals who underwent carrier screening were analyzed. Sequential, tandem, and tandem reflex screening yielded compliance frequencies of 25.8%, 100%, and 95.9%, respectively. Among 14,595 couples tested in tandem, 42.2% of females were screen-negative, resulting in unnecessary testing of the male partner. In contrast, less than 1% of tandem reflex couples included unnecessary male testing. The median turnaround times were 29.2 days (sequential), 8 days (tandem), and 13.3 days (tandem reflex). The proportion of ARCs detected per total number of individual screens were 0.5% for sequential testing and 1.3% for both tandem and tandem reflex testing. CONCLUSION: The tandem reflex strategy simplifies a potentially complex clinical scenario by providing a mechanism by which providers can maximize partner compliance and the detection of at-risk couples while minimizing workflow burden and unnecessary testing and is more efficacious than both sequential and tandem screening strategies.

Catheter-based ultrasound hyperthermia with HDR brachytherapy for treatment of locally advanced cancer of the prostate and cervix.

A clinical treatment delivery platform has been developed and is being evaluated in a clinical pilot study for providing 3D controlled hyperthermia with catheter-based ultrasound applicators in conjunction with high dose rate (HDR) brachytherapy. Catheter-based ultrasound applicators are capable of 3D spatial control of heating in both angle and length of the devices, with enhanced radial penetration of heating compared to other hyperthermia technologies. Interstitial and endocavity ultrasound devices have been developed specifically for applying hyperthermia within HDR brachytherapy implants during radiation therapy in the treatment of cervix and prostate. A pilot study of the combination of catheter based ultrasound with HDR brachytherapy for locally advanced prostate and cervical cancer has been initiated, and preliminary results of the performance and heating distributions are reported herein. The treatment delivery platform consists of a 32 channel RF amplifier and a 48 channel thermocouple monitoring system. Controlling software can monitor and regulate frequency and power to each transducer section as required during the procedure. Interstitial applicators consist of multiple transducer sections of 2-4 cm length × 180 deg and 3-4 cm × 360 deg. heating patterns to be inserted in specific placed 13g implant catheters. The endocavity device, designed to be inserted within a 6 mm OD plastic tandem catheter within the cervix, consists of 2-3 transducers × dual 180 or 360 deg sectors. 3D temperature based treatment planning and optimization is dovetailed to the HDR optimization based planning to best configure and position the applicators within the catheters, and to determine optimal base power levels to each transducer section. To date we have treated eight cervix implants and six prostate implants. 100 % of treatments achieved a goal of >60 min duration, with therapeutic temperatures achieved in all cases. Thermal dosimetry within the hyperthermia target volume (HTV) and clinical target volume (CTV) are reported. Catheter-based ultrasound hyperthermia with HDR appears feasible with therapeutic temperature coverage of the target volume within the prostate or cervix while sparing surrounding more sensitive regions. (NIHR01CA122276).

Catheter-based ultrasound devices and MR thermal monitoring for conformal prostate thermal therapy.

Catheter-based ultrasound applicators have been developed for delivering hyperthermia or high-temperature thermal ablation of cancer and benign disease of the prostate. These devices allow for control of heating along the length and angular expanse during therapy delivery. Four types of transurethral applicators were devised for thermal treatment of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns and rotation; planar and curvilinear devices with narrow heating patterns and rotation; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate these devices and develop treatment delivery strategies. MR thermal imaging was used to monitor temperature and thermal dose in multiple slices through the target volume. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. The sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation under motor control and modulated dwell time can be used to tightly conform thermal ablation to selected regions. Interstitial implants with directional devices can be used to effectively ablate targeted regions of the gland while protecting the rectum. The MR derived 52 degrees C and lethal thermal dose contours (t43=240 min) effectively defined the extent of thermal damage and provided a means for real-time control of the applicators. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast (5-40 min) and precise thermal ablation of prostate.