Techniques to Improve Gynecological High-Dose-Rate Brachytherapy Treatments

The thesis has two parts. The first project relates to real time dosimetry in Gynecological (GYN) High Dose Rate (HDR) Brachytherapy Treatments and the second part investigates a new workflow for Image Guided Brachytherapy (IGBT) for centers that do not have access to MRI with applicator in-situ.

Project 1: Real-time Dosimetry in HDR Brachytherapy using the Duke designed NanoFOD dosimeter: Limits of Error Detection in Clinical Applications

Purpose: Previously, an optical fiber radiation detector system was shown to be capable of identifying potential high dose rate (HDR) brachytherapy delivery errors in real time. The purpose of this work is to determine this detector’s limits of error detection in vaginal cylinder and tandem and ovoid-type HDR gynecological brachytherapy treatments.

Method and Materials: The system consists of a scintillating nanoparticle-terminated fiber-optic dosimeter (NanoFOD) and a LabView platform (Versions 2015 and 2017; National Instruments Corporation, Austin, TX) which displays the real-time voltages measured by the NanoFOD during HDR treatment delivery. The platform allows for the measured voltage to be overlaid on the expected detector signal. To test the limitation of error detectability in vaginal cylinder brachytherapy, the NanoFOD was taped 1.5-cm from the tip of a 3-cm diameter Varian manufactured stump cylinder. This setup was

imaged using CT to localize the NanoFOD, and a plan was generated based on one of the institutional 3-cm stump cylinder templates with 9 dwell positions. For each dwell position, the expected voltage and doses were calculated using the dose distribution exported from the treatment planning system (TPS), a previously obtained distance-based calibration curve for the NanoFOD and TG-229 along and away table. The voltage values were imported to the LabView for real time monitoring. With a known location of the NanoFOD tip, the expected doses from the NanoFOD at each dwell position were calculated for all applicators for: 1) the clinical plan; 2) wrong source guide tube (SGT); 3) wrong cylinder; 4) wrong treatment template; 5) wrong step size, as well as 6) incorrect positioning of the cylinder insert. Measurements of voltage from each delivered plan were converted to dose per dwell and compared to the expected dose values.

In addition to experiments, a simulation-based limit of error detection with cylinder was studied and the results obtained from simulation were compared to experimental results. Simulation was done by modifying the applicator parameters and the incorrect plans were generated for 1) wrong SGT lengths 5-mm to 70-mm longer than correct length with a 5-mm interval; 2) wrong cylinder; 3) wrong treatment template; 4) wrong step size, as well as 5) incorrect positioning of the cylinder insert. Doses per dwell were also calculated and compared to the doses from correct plan.

Furthermore, simulations-only for T&O plans were also performed. Two representative clinical T&O-based plans with extra needles were used to establish the simulation-based limits of error detectability of the NanoFOD system. With a known location of the NanoFOD tip, the expected doses from the NanoFOD at each dwell position were calculated for all applicators for: 1) the clinical plan; 2) wrong treatment lengths (TL); 3) wrong connection to afterloader; 4) wrong digitization direction; and 5) wrong step size.

From previous work, it has been determined that the overall uncertainty in dose of this system in HDR brachytherapy is 20%. The percent difference (PD) between expected and measured doses and, between the simulated doses from correct and incorrect plans was calculated and compared to 20% to determine if a certain potential error can be detected with the NanoFOD system.

Results: For the cylinder experiments, when the correct treatment was delivered, the median PD over 9 dwells between measured and expected dose from each dwell was 11%. When the wrong SGT, wrong cylinder size, or wrong clinical template was used, the system detected PD values of -91.6%, -71.4% and -29.6% at the first dwell. With wrong step, the system showed large discrepancies starting at the third dwell position (58.6%). When incorrect cylinder insert length was 0.5cm, 1.0cm and 1.5cm, the significant PD values captured were -29.4%, -28.1% and -22.5% at 3rd, 2nd and 1st dwell, respectively.

In TPS simulations for the cylinder applicator, PD from wrong SGT, wrong cylinder size and wrong template and were -93.6%, -90.8% and -57.8% at first dwell. For wrong step size, the simulation predicted the PD to be greater than 20% (47.2%) starting at first dwell. For all incorrect insert length, simulation predicted greater than 20% PD (-38.6%, -34.9%, -38.6%) at first dwell. For incorrect SGT lengths range from 5mm to 70mm, simulation-based PD was from -28.0% to -82.3% at the first dwell, indicating the NanoFOD caught this error when the SGT was only 5-mm longer.

In TPS simulations with two T&O-based plans, with incorrect treatment length (TL, 5mm-70mm), the PD ranges for the two patients were 26.4%-26.8%, 20.4%-30.9%, and 30.9%-57% in 10mm TL tandem, 5mm TL ovoid and 10mm TL needle at first dwell. PD values were -44.1% to -36.4%, -75.3% to 96.4%, and -39.6% to 298.1% respectively at the first dwell when connections between tandem and left ovoid, left needle and left ovoid, left needle and tandem were swapped. When the two needles were switched, PD values were 43.1% and 63.6% at the 1st and 3rd dwell for patient A and patient B. Switching connection between the two ovoids did not produce significant PD for patient A because the two ovoids were identically loaded. For patient B, the PD was 87.5% when ovoids were swapped. Incorrect direction of digitization made the signal too low to be detected, an indication that treatment should be stopped. With wrong step size in tandem, ovoid and needle, simulation-based PD range in dose for two patients were 25.8%-34.9%, 34.3%-37.4%, and 20.7%-81.5%, respectively at 3rd, 2nd and 1st dwell for both patients.

Conclusion:

Using the 20% error detection threshold, the NanoFOD system was able to detect errors in real time cylinder tests when the wrong cylinder size, wrong SGT and wrong template were used, all at the first dwell position. For subtle errors such as small incorrect catheter insertions, the real-time system can detect errors starting with the second or third dwell position. The Labview interface is a good tool to use for real time tracking of the delivery.

TPS simulation predicted comparable discrepancies to PD obtained from experimental measurements when wrong cylinder size and wrong source guide tube was used. The disagreement between simulation-based PD and experiment-based PD is due to uncertainty in positioning during the experiment, as the nanoFOD in current form does not have a radio opaque marker to help with easy identification. TPS simulation was thus used for more complex applicators, knowing that simulations and experiments match.

With the 20% PD as an indication of wrong treatment in T&O-based HDR cases, the NanoFOD can capture all simulated gross errors within the first few dwells into the treatment, indicating it is capable of real-time verification of T&O HDR brachytherapy. Although the two T&O plans were different, the NanoFOD was able to capture the errors at similar dwell positions regardless of the difference in planning. Overall, the NanoFOD can catch, in real time, potential gross errors in clinical HDR.

Project 2: Investigation of Contour-based Deformable Image Registration (cbDIR) of pre-brachytherapy MRI (pbMRI) for target definition in HDR cervical cancer treatments

Purpose: While MRI-guided brachytherapy has been considered the gold standard for IGBT treatment for cervical cancer, practical factors such as cost, MRI access and clinical flow efficiency have limited the use of MRI for brachytherapy treatments. However, a pre-brachytherapy MRI (pbMRI) is usually taken before the brachytherapy to assess the tumor regression after external beam treatments. The purpose of this project is to investigate the role of contour-based deformable image registration of the pbMRI in target definition for high dose rate (HDR) cervical cancer treatments.

Method and Materials: Thirty-five patients with locally advanced cervical cancer treated at Duke University with Tandem and Ovoids (T&O) applicators were studied. A pbMRI was acquired for all patients. Each patient also had MRI and CT taken with applicator in situ at the time of the first fraction. The uterus structure contoured on pbMRI was deformed using contour-based (cb) and hybrid contour-based (hcb) DIR to the same structure contoured on the CT of first HDR fraction (MIM Software Inc., v 6.7.3 and v 6.8.11). The deformation matrix was used to deform the dHRCTV, which was then compared with the ground truth HRCTV (gtHRCTV) obtained on the MRI of 1st HDR fraction. Dice Similarity Coefficients (DSC) and Hausdorff Distance (med_HD, max_HD) were used to evaluate the overlap and mismatch at boundaries between the deformed HRCTV and gtHRCTV using both DIR methods. The process of generating dHRCTV requires user’s manual input. Therefore, inter- and intra-user variability using cbDIR, as well as the difference in the two DIR methods were investigated.

Results: The pbMRI scan was acquired on average 5.9+/-3.8 days before first HDR fraction. Median DSC for uterus was 0.9 (IQR 0.88-0.93) and 0.93 (IQR 0.92-0.94), and for HRCTV was 0.64 (IQR 0.52-0.71) and 0.68 (IQR 0.59-0.72) for cbDIR and hcbDIR, respectively. The median med_HD for uterus was 0.09cm (IQR 0.08-0.1cm) and 0.08cm (IQR 0.06-0.09cm). The median max_HD for HRCTV was 1.37cm (IQR 1.1-2.3cm) and 1.39cm (IQR 1.1-1.6cm) with cbDIR and hcbDIR respectively. Limited inter-user, intra-user, and DSC variability between DIR versions were found (p=0.53, p=0.77, p=0.18, respectively).

Conclusion: Contour-based DIR based on uterus/cervix structure is proven to be relatively user independent, improves when hybrid contoured based DIR algorithms are used, and is expected to serve as a good starting point for HRCTV definition for HDR planning in the absence of MRI with applicators in-situ.