Real-Time Image Guided Ablative Prostate Cancer Radiation Therapy: Results From the TROG 15.01 SPARK Trial.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy. METHODS AND MATERIALS: Forty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity. RESULTS: Motion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities. CONCLUSIONS: Real-time IGRT is clinically effective for prostate cancer SABR.

A Multi-center Prospective Study for Implementation of an MRI-Only Prostate Treatment Planning Workflow.

Purpose: This project investigates the feasibility of implementation of MRI-only prostate planning in a prospective multi-center study. Method and Materials: A two-phase implementation model was utilized where centers performed retrospective analysis of MRI-only plans for five patients followed by prospective MRI-only planning for subsequent patients. Feasibility was assessed if at least 23/25 patients recruited to phase 2 received MRI-only treatment workflow. Whole-pelvic MRI scans (T2 weighted, isotropic 1.6 mm voxel 3D sequence) were converted to pseudo-CT using an established atlas-based method. Dose plans were generated using MRI contoured anatomy with pseudo-CT for dose calculation. A conventional CT scan was acquired subsequent to MRI-only plan approval for quality assurance purposes (QA-CT). 3D Gamma evaluation was performed between pseudo-CT calculated plan dose and recalculation on QA-CT. Criteria was 2%, 2 mm criteria with 20% low dose threshold. Gold fiducial marker positions for image guidance were compared between pseudo-CT and QA-CT scan prior to treatment. Results: All 25 patients recruited to phase 2 were treated using the MRI-only workflow. Isocenter dose differences between pseudo-CT and QA-CT were -0.04 ± 0.93% (mean ± SD). 3D Gamma dose comparison pass-rates were 99.7% ± 0.5% with mean gamma 0.22 ± 0.07. Results were similar for the two centers using two different scanners. All gamma comparisons exceeded the 90% pass-rate tolerance with a minimum gamma pass-rate of 98.0%. In all cases the gold fiducial markers were correctly identified on MRI and the distances of all seeds to centroid were within the tolerance of 1.0 mm of the distances on QA-CT (0.07 ± 0.41 mm), with a root-mean-square difference of 0.42 mm. Conclusion: The results support the hypothesis that an MRI-only prostate workflow can be implemented safely and accurately with appropriate quality assurance methods.

The accuracy and precision of the KIM motion monitoring system used in the multi-institutional TROG 15.01 Stereotactic Prostate Ablative Radiotherapy with KIM (SPARK) trial.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) allows for real-time image guidance for tracking tumor motion in six-degrees-of-freedom (6DoF) on a standard linear accelerator. This study assessed the geometric accuracy and precision of KIM used to guide patient treatments in the TROG 15.01 multi-institutional Stereotactic Prostate Ablative Radiotherapy with KIM trial and investigated factors affecting accuracy and precision. METHODS: Fractions from 44 patients with prostate cancer treated using KIM-guided SBRT were analyzed across four institutions, on two different linear accelerator models and two different beam models (6 MV and 10 MV FFF). The geometric accuracy and precision of KIM was assessed from over 33 000 images (translation) and over 9000 images (rotation) by comparing the real-time measured motion to retrospective kV/MV triangulation. Factors potentially affecting accuracy, including contrast-to-noise ratio (CNR) of kV images and incorrect marker segmentation, were also investigated. RESULTS: The geometric accuracy and precision did not depend on treatment institution, beam model or motion magnitude, but was correlated with gantry angle. The centroid geometric accuracy and precision of the KIM system for SABR prostate treatments was 0.0 ± 0.5, 0.0 ± 0.4 and 0.1 ± 0.3 mm for translation, and -0.1 ± 0.6°, -0.1 ± 1.4° and -0.1 ± 1.0° for rotation in the AP, LR and SI directions respectively. Centroid geometric error exceeded 2 mm for 0.05% of this dataset. No significant relationship was found between large geometric error and CNR or marker segmentation correlation. CONCLUSIONS: This study demonstrated the ability of KIM to locate the prostate with accuracy below other uncertainties in radiotherapy treatments, and the feasibility for KIM to be implemented across multiple institutions.

Dosimetric impact of intrafraction rotations in stereotactic prostate radiotherapy: A subset analysis of the TROG 15.01 SPARK trial.

BACKGROUND AND PURPOSE: Accurate delivery of radiotherapy is critical to achieve optimal treatment outcomes. Interfraction translational IGRT is now standard, and intrafraction motion management is becoming accessible. Some platforms can report both translational and rotational movements in real time. This study aims to quantify the dosimetric impact of observed intrafraction rotation of the prostate measured using monitoring software. MATERIALS AND METHODS: A dose grid resampling algorithm was used to model the dosimetric impact of prostate rotations for 20 patients on a SBRT prostate clinical trial. Translations were corrected before and during treatment, but rotations were not. Real time rotation data were acquired using KIM and a cumulative histogram analysis performed. Prostate volumes were rotated by the range of observed angles and used to calculate DVH data. RESULTS: The pitch axis had a higher range of observed rotations resulting in only 7 patients spending at least 90% of the beam on time across all fractions within rotation angles resulting in PTV D95% ≥36 Gy in this axis. The yaw and roll axes saw 17 and 15 patients respectively achieving this criterion. All but one of 20 patients exceeded CTV D98% ≥36 Gy for all observed rotation angles. CONCLUSIONS: Current CTV-PTV margins do not result in compromised CTV dose coverage due to inter and intrafraction prostate rotations in the absence of other uncertainties. Reduced PTV dosing is due to the extremely conformal treatment delivery but is unlikely to be clinically deleterious. Prostate standard IGRT should continue to focus on correcting any observed translational movements. Margin reduction could be explored in conjunction with other uncertainties.

Audiovisual biofeedback guided breath-hold improves lung tumor position reproducibility and volume consistency.

PURPOSE: Respiratory variation can increase the variability of tumor position and volume, accounting for larger treatment margins and longer treatment times. Audiovisual biofeedback as a breath-hold technique could be used to improve the reproducibility of lung tumor positions at inhalation and exhalation for the radiation therapy of mobile lung tumors. This study aimed to assess the impact of audiovisual biofeedback breath-hold (AVBH) on interfraction lung tumor position reproducibility and volume consistency for respiratory-gated lung cancer radiation therapy. METHODS: Lung tumor position and volume were investigated in 9 patients with lung cancer who underwent a breath-hold training session with AVBH before 2 magnetic resonance imaging (MRI) sessions. During the first MRI session (before treatment), inhalation and exhalation breath-hold 3-dimensional MRI scans with conventional breath-hold (CBH) using audio instructions alone and AVBH were acquired. The second MRI session (midtreatment) was repeated within 6 weeks after the first session. Gross tumor volumes (GTVs) were contoured on each dataset. CBH and AVBH were compared in terms of tumor position reproducibility as assessed by GTV centroid position and position range (defined as the distance of GTV centroid position between inhalation and exhalation) and tumor volume consistency as assessed by GTV between inhalation and exhalation. RESULTS: Compared with CBH, AVBH improved the reproducibility of interfraction GTV centroid position by 46% (P = .009) from 8.8 mm to 4.8 mm and GTV position range by 69% (P = .052) from 7.4 mm to 2.3 mm. Compared with CBH, AVBH also improved the consistency of intrafraction GTVs by 70% (P = .023) from 7.8 cm3 to 2.5 cm3. CONCLUSIONS: This study demonstrated that audiovisual biofeedback can be used to improve the reproducibility and consistency of breath-hold lung tumor position and volume, respectively. These results may provide a pathway to achieve more accurate lung cancer radiation treatment in addition to improving various medical imaging and treatments by using breath-hold procedures.

Rectal protection in prostate stereotactic radiotherapy: a retrospective exploratory analysis of two rectal displacement devices.

INTRODUCTION: High rectal doses are associated with increased toxicity. A rectal displacement device (RDD) reduces rectal dose in prostate stereotactic body radiation therapy (SBRT). This study investigates any dosimetric difference between two methods of rectal displacement (Rectafix and SpaceOAR) for prostate SBRT. METHODS: Rectal dosimetry of 45 men who received SBRT within the PROMETHEUS trial was retrospectively examined, across two radiation therapy centres using the two RDD's. Men received a total dose (TD) of 19 or 20 Gy in two fractions followed by 46 Gy in 23 fractions. Centre 1 contributed 16 Rectafix and 10 SpaceOAR patients. Centre 2 contributed 19 Rectafix patients. Rectal dose volume histogram (DVH) data were recorded as a TD percentage at the following volume intervals; V1%, V2%, V5%, V10% and then 10% increments to V80%. As only one centre employed both RDD's, three sequential rectal dosimetry comparisons were performed; (1) centre 1 Rectafix versus centre 1 SpaceOAR; (2) centre 1 Rectafix versus centre 2 Rectafix and (3) centre 1+ centre 2 Rectafix versus centre 1 SpaceOAR. RESULTS: In comparison (1) Rectafix demonstrated lower mean doses at 9 out of 11 measured intervals (P = 0.0012). Comparison (2) demonstrated a moderate difference with centre 2 plans producing slightly lower rectal doses (P = 0.013). Comparison (3) further demonstrated that Rectafix returned lower mean doses than SpaceOAR (P < 0.001). Although all dose levels were in favour of Rectafix, in absolute terms differences were small (2.6-9.0%). CONCLUSIONS: In well-selected prostate SBRT patients, Rectafix and SpaceOAR RDD's provide approximately equivalent rectal sparing.

Real-time in vivo rectal wall dosimetry using MOSkin detectors during linac based stereotactic radiotherapy with rectal displacement.

BACKGROUND: MOSFET dosimetry is a method that has been used to measure in-vivo doses during brachytherapy treatments and during linac based radiotherapy treatment. Rectal displacement devices (RDDs) allow for safe dose escalation for prostate cancer treatment. This study used dual MOSkin detectors to assess real-time in vivo rectal wall dose in patients with an RDD in place during a high dose prostate stereotactic body radiation therapy (SBRT) boost trial. METHODS: The PROMETHEUS study commenced in 2014 and provides a prostate SBRT boost dose with a RDD in place. Twelve patients received two boost fractions of 9.5-10 Gy each delivered to the prostate with a dual arc volumetric modulated arc therapy (VMAT) technique. Two MOSkins in a face-to-face arrangement (dual MOSkin) were used to decrease angular dependence. A dual MOSkin was attached to the anterior surface of the Rectafix and read out at 1 Hz during each treatment. The planned dose at each measurement point was exported from the planning system and compared with the measured dose. The root mean square error normalised to the total planned dose was calculated for each measurement point and treatment arc for the entire course of treatment. RESULTS: The average difference between the measured and planned doses over the whole course of treatment for all arcs measured was 9.7% with a standard deviation of 3.6%. The cumulative MOSkin reading was lower than the total planned dose for 64% of the arcs measured. The average difference between the final measured and final planned doses for all arcs measured was 3.4% of the final planned dose, with a standard deviation of 10.3%. CONCLUSIONS: MOSkin detectors were an effective tool for measuring dose delivered to the anterior rectal wall in real time during prostate SBRT boost treatments for the purpose of both ensuring the rectal doses remain within acceptable limits during the treatment and for the verification of final rectal doses.

Audiovisual Biofeedback Improves Cine-Magnetic Resonance Imaging Measured Lung Tumor Motion Consistency.

PURPOSE: To assess the impact of an audiovisual (AV) biofeedback on intra- and interfraction tumor motion for lung cancer patients. METHODS AND MATERIALS: Lung tumor motion was investigated in 9 lung cancer patients who underwent a breathing training session with AV biofeedback before 2 3T magnetic resonance imaging (MRI) sessions. The breathing training session was performed to allow patients to become familiar with AV biofeedback, which uses a guiding wave customized for each patient according to a reference breathing pattern. In the first MRI session (pretreatment), 2-dimensional cine-MR images with (1) free breathing (FB) and (2) AV biofeedback were obtained, and the second MRI session was repeated within 3-6 weeks (mid-treatment). Lung tumors were directly measured from cine-MR images using an auto-segmentation technique; the centroid and outlier motions of the lung tumors were measured from the segmented tumors. Free breathing and AV biofeedback were compared using several metrics: intra- and interfraction tumor motion consistency in displacement and period, and the outlier motion ratio. RESULTS: Compared with FB, AV biofeedback improved intrafraction tumor motion consistency by 34% in displacement (P=.019) and by 73% in period (P<.001). Compared with FB, AV biofeedback improved interfraction tumor motion consistency by 42% in displacement (P<.046) and by 74% in period (P=.005). Compared with FB, AV biofeedback reduced the outlier motion ratio by 21% (P<.001). CONCLUSIONS: These results demonstrated that AV biofeedback significantly improved intra- and interfraction lung tumor motion consistency for lung cancer patients. These results demonstrate that AV biofeedback can facilitate consistent tumor motion, which is advantageous toward achieving more accurate medical imaging and radiation therapy procedures.

A prospective study of nomogram-based adaptation of prostate radiotherapy target volumes.

BACKGROUND: A prospective clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer (HRPC) through the use of a nomogram to tailor radiotherapy target volumes. METHODS: Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015. A set of validated prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center (MSKCC) prostate cancer nomogram to estimate risk of loco-regional spread (LRS). The nomogram risk estimates for extra-capsular extension (ECE), seminal vesicles involvement (SVI), and pelvic lymph nodes involvement (LNI) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases. A planning guide was used to delineate target volumes and organs at risk (OAR). Up to three dose levels were administered over 28 fractions; 70Gy for gross disease in the prostate +/- seminal vesicles (2.5Gy/fraction), 61.6Gy for subclinical peri-prostatic disease (2.2Gy/fraction) and 50.4Gy to pelvic nodes (1.8Gy/fraction). Data regarding protocol adherence, nomogram use, radiotherapy dose distribution, and acute toxicity were collected. RESULTS: Nomogram use 100 % of patients were treated for ECE, 88.9 % for SVI, and 70.4 % for LNI. The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases. The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis. Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % (159/171). Compliance with protocol for small bowel contouring was poor (59.3 %). Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % (191/196). Compliance with dose constraints for OAR was 88.2 % (285/323). Acute toxicity There were no grade 3 acute toxicities observed. 20/27 (74.1 %) and 6/27 (22.2 %) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively. CONCLUSIONS: We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC. This study has identified key learning points regarding this approach, including the importance of standardization and updating of risk quantification tools, and the utility of an observer to verify their correct use. TRIAL REGISTRATION: ClincialTrials.gov identifier NCT01418040 . Hunter New England Human Research Ethics Committee (HNEHREC) reference number 12/08/15/4.02.