Molecularly targeted agents as radiosensitizers in cancer therapy--focus on prostate cancer.

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.

Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis.

To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.

Stereotactic body radiation therapy: the report of AAPM Task Group 101.

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

Thoracic irradiation in the elderly.

This article has reviewed radiation treatment of thoracic malignancies in elderly patients. In general the literature suggests that thoracic irradiation is equally efficacious in elderly patients as in younger patients and is associated with increased but acceptable toxicity. Technical advances are allowing a further reduction in morbidity with preliminary results suggestive of stable outcomes. Prospective data from elderly specific trials are needed to determine the optimal treatment of lung cancer and to compare innovative radiation technology with standard therapies.

Transperineal prostate intervention: robot for fully automated MR imaging--system description and proof of principle in a canine model.

The study was approved by the animal care and use committee. The purpose of the study was to prospectively establish proof of principle in vivo in canines for a magnetic resonance (MR) imaging-compatible robotic system designed for image-guided prostatic needle intervention. The entire robot is built with nonmagnetic and dielectric materials and in its current configuration is designed to perform fully automated brachytherapy seed placement within a closed MR imager. With a 3.0-T imager, in four dogs the median error for MR imaging-guided needle positioning and seed positioning was 2.02 mm (range, 0.86-3.18 mm) and 2.50 mm (range, 1.45-10.54 mm), respectively. The robotic system is capable of accurate MR imaging-guided prostatic needle intervention within a standard MR imager in vivo in a canine model.

Comparison of daily couch shifts using MVCT (TomoTherapy) and B-mode ultrasound (BAT System) during prostate radiotherapy.

The purpose of this study was to compare daily couch shifts after prostate localization between megavoltage CT (MVCT, Hi-ART TomoTherapy) and b-mode ultrasound (BAT system). Nine hundred and thirteen couch shifts from 22 consecutive patients treated using MVCT localization were compared to 853 shifts from 23 randomly selected patients treated using b-mode ultrasound prostate localization. Shifts were made in three principal axes based on prostate position after comparing daily images to the initial planning CT. Mean shift for each axis and the shift variability both between and within individual subjects were calculated. Variability was higher for BAT compared to MVCT for vertical and cranial-caudal (CC) shifts (p=0.0084 and 0.01037, respectively), while lateral shifts were significantly greater for MVCT. For each individual, the pairwise correlations between shifts in different axes were calculated. Among all the groups and pairings, only the pairing of vertical and cranial/caudal adjustments in BAT-localized patients showed significant evidence of correlation after adjustment for multiple pairwise comparisons (p=0.0006). When compared to MVCT, the use of BAT for prostate localization results in greater variability of positional adjustments in vertical and CC directions. This likely reflects differences in the ability to precisely align b-mode ultrasound contours to KVCT images, as well as prostate excursion in vertical and CC direction caused by the ultrasound probe. These considerations need to be made when defining treatment volumes, and argue for the use of less disruptive techniques for daily prostate localization.

Radiation therapy for prostate cancer: the role for dose escalation.

Recent technological advances in radiation treatment delivery have allowed relatively higher doses of radiation to be delivered safely to the prostate. Emerging data suggest improvements in disease control with higher doses of radiation in subsets of patients with prostate cancer.

Needle release mechanism enabling multiple insertions with an ultrasound-guided prostate brachytherapy robot.

We present a robotic system for transrectal ultrasound-guided prostate brachytherapy that employs a quick release mechanism to enable multiple needles to be inserted into the prostate prior to plan optimization. The mechanism consists of two actuated fingers that act as needle guides, thereby allowing insertion of both parallel and angled needles. Path planning, including reordering of needles within a batch, is required to avoid collisions with previously inserted needles. We perform two phantom experiments using clinical implant plans. The extra time required for the robotic motions, including finger actuation, is less than three minutes for the entire procedure. Mean position error is measured to be less than 0.5 mm, presumably due to the design of the needle guides, which have a toroidal shape to enable needle angulation.

Deformable registration of X-ray to MRI for post-implant dosimetry in prostate brachytherapy.

Post-implant dosimetric assessment in prostate brachytherapy is typically performed using CT as the standard imaging modality. However, poor soft tissue contrast in CT causes significant variability in target contouring, resulting in incorrect dose calculations for organs of interest. CT-MR fusion-based approach has been advocated taking advantage of the complementary capabilities of CT (seed identification) and MRI (soft tissue visibility), and has proved to provide more accurate dosimetry calculations. However, seed segmentation in CT requires manual review, and the accuracy is limited by the reconstructed voxel resolution. In addition, CT deposits considerable amount of radiation to the patient. In this paper, we propose an X-ray and MRI based post-implant dosimetry approach. Implanted seeds are localized using three X-ray images by solving a combinatorial optimization problem, and the identified seeds are registered to MR images by an intensity-based points-to-volume registration. We pre-process the MR images using geometric and Gaussian filtering. To accommodate potential soft tissue deformation, our registration is performed in two steps, an initial affine transformation and local deformable registration. An evolutionary optimizer in conjunction with a points-to-volume similarity metric is used for the affine registration. Local prostate deformation and seed migration are then adjusted by the deformable registration step with external and internal force constraints. We tested our algorithm on six patient data sets, achieving registration error of (1.2±0.8) mm in < 30 sec. Our proposed approach has the potential to be a fast and cost-effective solution for post-implant dosimetry with equivalent accuracy as the CT-MR fusion-based approach.

Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation.

PURPOSE: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients. METHODS AND MATERIALS: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. RESULTS: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). CONCLUSIONS: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.

Transurethral light delivery for prostate photoacoustic imaging.

Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

Stereotactic body radiation therapy. Rationale, techniques, applications, and optimization.

Stereotactic body radiation therapy (SBRT) is a rapidly evolving cancer treatment method in which concepts and techniques previously developed for brain tumor radiosurgery are adapted to eradicate tumors elsewhere in the body. The spatial accuracy, conformality, and steep radiation dose gradients of radiosurgery, which have been critical to its success in the treatment of intracranial tumors, are applied in SBRT to treat a variety of extracranial tumors. Early results demonstrate excellent response rates and low toxicity with a variety of hypofractionated dose regimens and localization/immobilization techniques. This article provides an overview of the rationale and results of SBRT for specific indications, descriptions of some methods of treatment delivery, and discussion of potential areas of future investigation.

In vivo visualization of prostate brachytherapy seeds with photoacoustic imaging.

We conducted a canine study to investigate the in vivo feasibility of photoacoustic imaging for intraoperative updates to brachytherapy treatment plans. A fiber coupled to a 1064-nm Nd:YAG laser was inserted into high-dose-rate brachytherapy needles, which diffused light spherically. These needles were inserted through the perineum into the prostate for interstitial light delivery and the resulting acoustic waves were detected with a transrectal ultrasound probe. Postoperative computed tomography images and ex vivo photoacoustic images confirmed seed locations. Limitations with insufficient light delivery were mitigated with short-lag spatial coherence (SLSC) beamforming, providing a 10-20 dB contrast improvement over delay-and-sum (DAS) beamforming for pulse energies ranging from 6.8 to 10.5 mJ with a fiber-seed distance as large as 9.5 mm. For the same distance and the same range of energy densities, signal-to-noise ratios (SNRs) were similar while the contrast-to-noise ratio (CNR) was higher in SLSC compared to DAS images. Challenges included visualization of signals associated with the interstitial fiber tip and acoustic reverberations between seeds separated by ≤ 2 mm. Results provide insights into the potential for clinical translation to humans.

An image-guidance system for dynamic dose calculation in prostate brachytherapy using ultrasound and fluoroscopy.

PURPOSE: Brachytherapy is a standard option of care for prostate cancer patients but may be improved by dynamic dose calculation based on localized seed positions. The American Brachytherapy Society states that the major current limitation of intraoperative treatment planning is the inability to localize the seeds in relation to the prostate. An image-guidance system was therefore developed to localize seeds for dynamic dose calculation. METHODS: The proposed system is based on transrectal ultrasound (TRUS) and mobile C-arm fluoroscopy, while using a simple fiducial with seed-like markers to compute pose from the nonencoded C-arm. Three or more fluoroscopic images and an ultrasound volume are acquired and processed by a pipeline of algorithms: (1) seed segmentation, (2) fiducial detection with pose estimation, (3) seed matching with reconstruction, and (4) fluoroscopy-to-TRUS registration. RESULTS: The system was evaluated on ten phantom cases, resulting in an overall mean error of 1.3 mm. The system was also tested on 37 patients and each algorithm was evaluated. Seed segmentation resulted in a 1% false negative rate and 2% false positive rate. Fiducial detection with pose estimation resulted in a 98% detection rate. Seed matching with reconstruction had a mean error of 0.4 mm. Fluoroscopy-to-TRUS registration had a mean error of 1.3 mm. Moreover, a comparison of dose calculations between the authors' intraoperative method and an independent postoperative method shows a small difference of 7% and 2% forD90 and V100, respectively. Finally, the system demonstrated the ability to detect cold spots and required a total processing time of approximately 1 min. CONCLUSIONS: The proposed image-guidance system is the first practical approach to dynamic dose calculation, outperforming earlier solutions in terms of robustness, ease of use, and functional completeness.

Absorbable hydrogel spacer use in men undergoing prostate cancer radiotherapy: 12 month toxicity and proctoscopy results of a prospective multicenter phase II trial.

BACKGROUND: Radiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial. METHODS: Fifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of 78 Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS). RESULTS: Of the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months. CONCLUSION: The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

AAPM and GEC-ESTRO guidelines for image-guided robotic brachytherapy: report of Task Group 192.

In the last decade, there have been significant developments into integration of robots and automation tools with brachytherapy delivery systems. These systems aim to improve the current paradigm by executing higher precision and accuracy in seed placement, improving calculation of optimal seed locations, minimizing surgical trauma, and reducing radiation exposure to medical staff. Most of the applications of this technology have been in the implantation of seeds in patients with early-stage prostate cancer. Nevertheless, the techniques apply to any clinical site where interstitial brachytherapy is appropriate. In consideration of the rapid developments in this area, the American Association of Physicists in Medicine (AAPM) commissioned Task Group 192 to review the state-of-the-art in the field of robotic interstitial brachytherapy. This is a joint Task Group with the Groupe Européen de Curiethérapie-European Society for Radiotherapy & Oncology (GEC-ESTRO). All developed and reported robotic brachytherapy systems were reviewed. Commissioning and quality assurance procedures for the safe and consistent use of these systems are also provided. Manual seed placement techniques with a rigid template have an estimated in vivo accuracy of 3-6 mm. In addition to the placement accuracy, factors such as tissue deformation, needle deviation, and edema may result in a delivered dose distribution that differs from the preimplant or intraoperative plan. However, real-time needle tracking and seed identification for dynamic updating of dosimetry may improve the quality of seed implantation. The AAPM and GEC-ESTRO recommend that robotic systems should demonstrate a spatial accuracy of seed placement ≤1.0 mm in a phantom. This recommendation is based on the current performance of existing robotic brachytherapy systems and propagation of uncertainties. During clinical commissioning, tests should be conducted to ensure that this level of accuracy is achieved. These tests should mimic the real operating procedure as closely as possible. Additional recommendations on robotic brachytherapy systems include display of the operational state; capability of manual override; documented policies for independent check and data verification; intuitive interface displaying the implantation plan and visualization of needle positions and seed locations relative to the target anatomy; needle insertion in a sequential order; robot-clinician and robot-patient interactions robustness, reliability, and safety while delivering the correct dose at the correct site for the correct patient; avoidance of excessive force on radioactive sources; delivery confirmation of the required number or position of seeds; incorporation of a collision avoidance system; system cleaning, decontamination, and sterilization procedures. These recommendations are applicable to end users and manufacturers of robotic brachytherapy systems.

Current standards and future directions for prostate cancer radiation therapy.

Definitive radiation therapy is a well-recognized curative treatment option for localized prostate cancer. A suitable technique, dose, target volume and the option of a combination with androgen deprivation therapy need to be considered. An optimal standard external beam radiotherapy currently includes intensity-modulated and image-guided radiotherapy techniques with total doses of ≥76-78 Gy in conventional fractionation. Protons or carbon ions are alternatives available only in specific centers. Data from several randomized studies increasingly support the rationale for hypofractionated radiotherapy. A simultaneous integrated boost with dose escalation focused on a computed tomography/PET- or MRI/magnetic resonance spectroscopy-detected malignant lesion is one option to increase tumor control, with potentially no additional toxicity. The application of a spacer is a promising concept for optimal protection of the rectal wall.

A Dynamic Dosimetry System for Prostate Brachytherapy.

The lack of dynamic dosimetry tools for permanent prostate brachytherapy causes otherwise avoidable problems in prostate cancer patient care. The goal of this work is to satisfy this need in a readily adoptable manner. Using the ubiquitous ultrasound scanner and mobile non-isocentric C-arm, we show that dynamic dosimetry is now possible with only the addition of an arbitrarily configured marker-based fiducial. Not only is the system easily configured from accessible hardware, but it is also simple and convenient, requiring little training from technicians. Furthermore, the proposed system is built upon robust algorithms of seed segmentation, fiducial detection, seed reconstruction, and image registration. All individual steps of the pipeline have been thoroughly tested, and the system as a whole has been validated on a study of 25 patients. The system has shown excellent results of accurately computing dose, and does so with minimal manual intervention, therefore showing promise for widespread adoption of dynamic dosimetry.

Short-lag spatial coherence beamforming of photoacoustic images for enhanced visualization of prostate brachytherapy seeds.

Prostate brachytherapy, administered by implanting tiny radioactive seeds to treat prostate cancer, currently relies on transrectal ultrasound imaging for intraoperative visualization of the metallic seeds. Photoacoustic (PA) imaging has been suggested as a feasible alternative to ultrasound imaging due to its superior sensitivity to metal surrounded by tissue. However, PA images suffer from poor contrast when seeds are distant from the light source. We propose a transperineal light delivery method and investigate the application of a short-lag spatial coherence (SLSC) beamformer to enhance low-contrast photoacoustic signals that are distant from this type of light source. Performance is compared to a conventional delay-and-sum beamformer. A pure gelatin phantom was implanted with black ink-coated brachytherapy seeds and the mean contrast was improved by 3-25 dB with the SLSC beamformer for fiber-seed distances ranging 0.6-6.3 cm, when approximately 10% of the receive aperture elements were included in the short-lag sum. For fiber-seed distances greater than 3-4 cm, the mean contrast-to-noise ratio (CNR) was approximately doubled with the SLSC beamformer, while mean signal-to-noise ratios (SNR) were mostly similar with both beamformers. Lateral resolution was decreased by 2 mm, but improved with larger short-lag values at the expense of poorer CNR and SNR. Similar contrast and CNR improvements were achieved with an uncoated brachytherapy seed implanted in ex vivo tissue. Results indicate that the SLSC beamformer has potential to enhance the visualization of prostate brachytherapy seeds that are distant from the light source.

An overlap-volume-histogram based method for rectal dose prediction and automated treatment planning in the external beam prostate radiotherapy following hydrogel injection.

PURPOSE: Hydrogel injected between the rectum and prostate prior to radiotherapy provides a possible means of increased dose sparing to the rectum. Here the authors evaluate the overlap volume histogram (OVH) metric as a means to predict the rectal dose following hydrogel injection. Whether OVH predicted dose can serve as the dose objective or constraint for automated treatment planning was also investigated. METHODS: Treatment planning was performed on 21 prostate cancer patients both pre- and posthydrogel injection, with five-field IMRT delivering 78 Gy to the planning target volume (PTV). The authors quantify the geometrical relationship between the rectum and the prostate PTV using an OVH metric which determines the fractional volume of the rectum that is within a specified distance of the PTV. For an OVH distance the authors selected, L(20), the PTV expansion distance at which 20% of the rectum overlaps. The authors calculated the rectal dose, D(20), received by 20% of the rectum volume on the dose volume histogram. Linear regression was used to examine the correlation between the L(20) and D(20), and between ΔL(20) and ΔD(20) (i.e., the change of L(20) and D(20) posthydrogel injection). Additionally, rectal dose D(15), D(25), D(35), D(50), and bladder dose D(15) were predicted from the OVH (L(15), L(25), L(35), L(50), for rectum and L(15) for bladder) by the L(x)-D(x) linear regression. The predicted doses were applied to the objectives for automated treatment planning of ten plans from five patients. Automatically generated plans were compared with plans manually generated on trial-and-error basis. RESULTS: The rectal L(20) was increased and dose D(20) decreased due to the enlarged separation of rectum caused by the hydrogel injection. Linear regression showed an inverse linear correlation between L(20) and D(20), and between ΔL(20) and ΔD(20) (r(2) = 0.77, 0.60, respectively; p < 0.0001). The increase in rectal sparing (ΔD(20)) is only weakly correlated with the volume of injected hydrogel (r(2) = 0.17; p = 0.07), indicating OVH is a more predictive indicator of rectal sparing than the volume of hydrogel itself. Application of the predicted rectum and bladder doses to automated planning produced acceptable treatment plans, with rectal dose reduced for eight of ten plans. CONCLUSIONS: The OVH metric can predict the rectal dose in the external beam prostate radiotherapy for patients with hydrogel injection. The predicted doses can be applied to the objectives of optimization in automated treatment planning to produce acceptable treatment plans.