Intact Prostate Cancer Research Articles

SU‐E‐T‐642: PTV Is the Voxel‐Wise Worst‐Case of CTV in Prostate Photon Therapy

Purpose:To examine the adequacy of the planning target volume (PTV) dose distribution as the worst‐case representation of clinical target volume (CTV) dose distribution in prostate volumetric‐modulated arc therapy (VMAT) plans.Methods:Ten intact prostate cancer cases treated by VMAT at our institution were randomly selected. Isocenter was shifted in the three cardinal directions by a displacement equal to the PTV expansion on the CTV (±3 mm) for a total of six shifted plans per original plan. Rotationally‐perturbed plans were generated with a couch rotation of ±1° to simulate patient yaw. The eight perturbed dose distributions were recalculated in the treatment planning system using the same, fixed fluence map as the original plan. The voxel‐wise worst‐case CTV dose distribution was constructed from the minimum value per voxel from the eight perturbed doses. The resulting dose volume histograms (DVH) were evaluated for statistical correlation between the worst‐case CTV and nominal PTV dose distributions based on D95% by Wilcoxon signed‐rank test with significance level p ≤ 0.05.Results:Inspection demonstrates the PTV DVH in the nominal dose distribution is bounded by the CTV DVH in the worst‐case dose distribution. Comparison of D95% for the two dose distributions by Wilcoxon signed‐rank test gives p = 0.131. Therefore the null hypothesis cannot be rejected since the difference in median values is not statistically significant.Conclusion:The assumption that the nominal dose distribution for PTV represents the worst‐case dose distribution for CTV appears valid for the ten plans under examination. Although the worst‐case dose distribution is unphysical since the dose per voxel is chosen independently, it serves as a lower bound for the possible CTV coverage. Furthermore, this is consistent with the unphysical nature of the PTV. Minor discrepancies between the two dose distributions are expected since the dose cloud is not strictly static.Funding Support: NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation

Role of radiation and androgen deprivation therapy for advanced prostate cancer

This article provides details on the following: (1) the addition of hormone therapy to radiotherapy (XRT) and vice versa, (2) the duration and timing of hormone therapy, and (3) ongoing investigations in this active study area. It should be noted that the discussion has been limited to the use of androgen deprivation therapy (ADT) with XRT in locally advanced intact prostate cancer (ie, not postprostatectomy) setting. In addition, the discussion of XRT has been restricted to external beam radiotherapy (EBRT) as opposed to brachytherapy, as EBRT is the primary clinical setting in which combination ADT and XRT has been investigated.

Dosimetric comparison of intensity-modulated solutions for intact prostate cancer

The purpose of this study is intended to investigate the implementation of a modified class solution for intact prostate intensity-modulated radiation therapy (IMRT). The class solution uses 2 additional optimization structures intended to increase target conformity and decrease unnecessary dose to healthy tissue. A total of 10 randomly selected intact prostate IMRT patients were chosen for this retrospective study. Each of the original IMRT plans was compared with a modified class solution. The class solution implemented 2 additional optimization structures. The 95_OPT was intended to increase target conformity, and the Avoidance_3780 was intended to reduce normal tissue. Each plan was evaluated for minimum, maximum, and mean doses to the target. Additionally, mean normal tissue dose, total monitor units (MUs), and segments were investigated. Conformity index and normal healthy index were also compared. All comparisons were evaluated using a paired t-test using GraphPad software. Evaluations of MUs; segments; minimum, maximum, mean target doses; mean normal tissue dose; and conformity index did not demonstrate a significant difference between the modified class solution and the original plans. However, evaluation of healthy tissue conformity index indicated a significant difference. Overall, 70% of the original plans failed to demonstrate a satisfactory score (< 0.6) of properly sparing normal healthy tissue, whereas 70% of the modified plans exhibited a satisfactory score (> 0.6). Most (90%) of the modified plans demonstrated a greater number of segments than the compared original plan. A modified class solution provides a good starting point for planning intact prostate cancer. The addition of the Avoidance_3780 structure increases the healthy tissue conformity index score.

FROGG high-risk prostate cancer workshop: Patterns of practice and literature review

Australian and New Zealand radiation oncologists with an interest in uro-oncology were invited to participate in a pattern-of-practice survey dealing with the management of intact high-risk prostate cancer. Responses from 46 practitioners (representing 73% of all potential respondents) revealed that high-dose radiation therapy is the standard of care. However, there is variability in practice with regard to the methods used to achieve dose escalation, the use of whole-pelvic radiation therapy and the optimal duration of androgen deprivation therapy employed. A review of the literature outlining the current body of knowledge and the planned and ongoing studies in intact high-risk prostate cancer is presented.

Gastrointestinal and Genitourinary Toxicity and Quality of Life After Postprostatectomy Radiation Therapy: Are Normal Tissue DVH Parameters for Intact Prostate Cancer Applicable?

Gastrointestinal and Genitourinary Toxicity and Quality of Life After Postprostatectomy Radiation Therapy: Are Normal Tissue DVH Parameters for Intact Prostate Cancer Applicable?

TH-A-116-04: A Universal Predictive DVH Modeling Toolkit

Purpose: The goal of this work was to develop an efficient DICOM-based tool to create predictive DVH (pDVH) models for treatment plan automation and knowledge-based IMRT quality control (QC) independent of treatment planning system (TPS). Methods: The tool was implemented in MATLAB. RT dose and structure files exported from different TPSs including Eclipse, Pinnacle, and Tomotherapy were used as the input to the pDVH DICOM tool. pDVH models based on the correlation of expected dose to the distance from a voxel to the PTV surface in a cohort of patients were created for multiple treatment sites (intact prostate, prostate bed, head-and-neck, endometrial, cervical). To accelerate the computation of a distance vector field for efficient model building, multiple techniques were employed including GPUs acceleration and parallel computation using multiple CPU cores. The tool has a full GUI and can also run in batch mode with minimal user interaction. It automatically identifies outliers for treatment plan quality control and pDVH model refinement. Identified outliers can be replanned and reimported to refine the accuracy of the DVH prediction. Results: The inclusion of GPUs reduces computation time by 200 times, requiring <1 second to compute an OAR vector field and only a few seconds to build a pDVH model. The pDVH DICOM tool has been used by multiple institutions and pDVH models for intact prostate and cervical cancer were created in less than one hour without GPU acceleration. Conclusion: We developed a universal DICOM-based tool that provides clinicians a novel and highly efficient plan quality control mechanism by predicting OAR DVHs based on local institutional best practices. This technology can be used to asses inter-institutional and inter-TPS plan quality based on aggregate clinical data instead of contrived benchmark planning sets. Supported by a research agreement with Varian Medical Systems.

MO‐A‐137‐01: BEST IN PHYSICS (THERAPY) ‐ Predictive DVH Models Developed at a Large Institution Impact Clinically Relevant DVH Parameters in IMRT Plans at An Unrelated Radiotherapy Facility

Purpose: The purpose of this work was to investigate the impact of a predictive DVH (pDVH) model developed at one institution on IMRT plan quality control (QC) at an unrelated radiotherapy facility. Methods: DICOM‐RT datasets for twenty randomly selected intact prostate cancer patients treated at a small clinic were analyzed with knowledge based pDVH models developed at a larger institution. Previously validated rectum and bladder pDVH models used in this study were derived based on the correlation of expected dose to the distance from a voxel to the PTV surface. A sum of residuals (SR) metric quantifying the integrated difference between clinical DVHs and the pDVHs was used to rank the 20 evaluated plans. The 5 plans with greatest deviation from the prediction were replanned by the small clinic to evaluate the ability to achieve rectum and bladder DVH predictions while maintaining PTV quality metrics per institutional standard. Metrics used to evaluate plan quality (V65 and V40) quantified the clinical gains in the rectum and bladder DVHs. The pDVHs were compared to the replan DVHs using dV65=V65(replan)‐V65(pred), dV40=V40(replan) ‐ V40(pred), and mean SR to measure DVH prediction accuracy. Results: The significance of IMRT QC using pDVHs was demonstrated by an average reduction in V65 and V40 in the 5 replanned patients of 4.8% ± 2.3% and 17.9% ± 10.3% for the rectum and 3.4% ± 2.1% and 6.0% ± 2.8% for the bladder, respectively. The pDVH models demonstrated excellent prediction accuracy with an average dV65 and dV40 of 0.9% ± 1.1% and 0.7% ± 1.4% for the rectum and 0.4% ± 0.5% and 0.6% ± 0.9% for the bladder, respectively. Conclusion: DICOM‐based pDVH modeling methods based on patient geometry accurately predict achievable rectum and bladder DVH parameters that are clinically relevant and may facilitate improved IMRT plan quality across multiple institutions. L.Appenzoller, S. Mutic, K. Moore: Patent Application # 13, 486,809 : Developing Predictive Dose‐Volume Relationships for a Radiotherapy Treatment.

Abstract PR2: Optimization and applications of a tissue slice culture model of the normal and malignant human prostate

Abstract Current in vitro and in vivo models for prostate cancer do not accurately recapitulate many critical aspects of prostate cancer biology. In vitro cell culture systems lack tissue architecture, complex cellular interactions, and the prostate microenvironment. Neither xenograft nor transgenic models generate authentic prostate pathobiology, and genetic and molecular fidelity is often a concern both in vitro and in vivo. Ex vivo organotypic culture systems have been used as valuable research models for several tissue types. Our lab has recently established a tissue slice graft model for prostate cancer in vivo using precision-cut 300 micron slices of radical prostatectomy tissue implanted under the mouse renal capsule. We have also developed a complimentary in vitro tissue slice culture (TSC) model that we have used for a variety of studies, including evaluation of the DNA damage response in normal cell types of the prostate. The main challenges for normal prostate TSC are maintaining luminal cell integrity beyond 48 hours and preventing hyperproliferation of basal cells. Less is known about the maintenance of cancer in TSCs. We have compared several culture conditions and can maintain normal prostate structure and function up to 4 days using PFMR-4A media supplemented with cholera toxin, epidermal growth factor, bovine pituitary extract, phosphoethanolamine, hydrocortisone, selenium, gentamycin, retinoic acid, insulin, vitamin E, and androgen R1881. Dose-response and time-course experiments revealed that the optimal concentration of R1881 for luminal cell integrity is 50nM. We verified expression of luminal and basal cell-specific markers by immunofluorescence of frozen sections, and we observed secretion of PSA by ELISA. In addition, confocal microscopy is a useful technology for visualizing the 3-dimensional architecture of TSCs. With robust survival of TSCs up to 4 days in vitro, we have a wide range of ongoing and future experimental directions including drug delivery and cell targeting, invasion and migration studies, and metabolic and molecular profiling. Furthermore, we are poised for collaboration with those who want to test their experimental methods in an intact prostate cancer model in vitro. The prostate TSC model is undoubtedly more authentic than current in vitro models, and we are optimizing its utility with the goal of executing more realistic pre-clinical studies. This abstract is also presented as Poster A69. Citation Format: Sophia Lisette Maund, Rosalie Nolley, Donna Peehl. Optimization and applications of a tissue slice culture model of the normal and malignant human prostate [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR2.

Endorectal MRI And Treatment Planning Considerations In Intact Prostate Cancer: Which Patients Are At Greatest Risk For Radiographic Seminal Vesicle Involvement?

Endorectal MRI And Treatment Planning Considerations In Intact Prostate Cancer: Which Patients Are At Greatest Risk For Radiographic Seminal Vesicle Involvement?

Prostate-Specific Membrane Antigen-Based Therapeutics

Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with 177Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.

Dosimetric and Radiobiologic Comparison of 3D Conformal Versus Intensity Modulated Planning Techniques for Prostate Bed Radiotherapy

Adjuvant radiotherapy for locally advanced prostate cancer improves biochemical and clinical disease-free survival. While comparisons in intact prostate cancer show a benefit for intensity modulated radiation therapy (IMRT) over 3D conformal planning, this has not been studied for post-prostatectomy radiotherapy (RT). This study compares normal tissue and target dosimetry and radiobiological modeling of IMRT vs. 3D conformal planning in the postoperative setting. 3D conformal plans were designed for 15 patients who had been treated with IMRT planning for salvage post-prostatectomy RT. The same computed tomography (CT) and target/normal structure contours, as well as prescription dose, was used for both IMRT and 3D plans. Normal tissue complication probabilities (NTCPs) were calculated based on the dose given to the bladder and rectum by both plans. Dose-volume histogram and NTCP data were compared by paired t-test. Bladder and rectal sparing were improved with IMRT planning compared to 3D conformal planning. The volume of the bladder receiving at least 75% (V75) and 50% (V50) of the dose was significantly reduced by 28% and 17%, respectively ( p = 0.002 and 0.037). Rectal dose was similarly reduced, V75 by 33% and V50 by 17% ( p = 0.001 and 0.004). While there was no difference in the volume of rectum receiving at least 65 Gy (V65), IMRT planning significant reduced the volume receiving 40 Gy or more (V40, p = 0.009). Bladder V40 and V65 were not significantly different between planning modalities. Despite these dosimetric differences, there was no significant difference in the NTCP for either bladder or rectal injury. IMRT planning reduces the volume of bladder and rectum receiving high doses during post-prostatectomy RT. Because of relatively low doses given to the bladder and rectum, there was no statistically significant improvement in NTCP between the 3D conformal and IMRT plans.

Detection of intact prostate cancer cells in the blood of men with prostate cancer

Objectives. To develop a procedure to be used to find, identify, and characterize the living prostate cancer cells in the blood of patients with prostate cancer. Methods. The procedure is based on a negative selection approach that removes most of the blood cells and collects the remaining prostate cancer cells, which are identified and characterized by fluorescent in situ hybridization with deoxyribonucleic acid probes and by indirect fluorescent immunocytochemical staining. The blood cells are removed via density gradient centrifugation. Results. Using the prostate cancer LNCaP cells as a model, the recovery rate of the added prostate cancer cells to 10 mL of blood was about 85%, with a dilution of 1 LNCaP cell to 10,000 white blood cells or more. Blood samples varying from 9 to 27 mL were collected and analyzed from 8 men aged 54 to 79 years who had varying levels of PSA in serum. In one blood sample, prostate cancer cells were not found; in the seven other samples, the number of prostate cancer cells found per milliliter of blood varied from 1 to 20. Prostate cancer cells were not found in 7.5 to 15-mL blood samples from 3 healthy younger men. The prostate cells were found to be aneuploid for chromosomes 7 and 8, highly suggestive that these cells were cancerous. Conclusions. Using a negative selection approach, prostate cells can be found in the blood of patients with prostate cancer, as identified by prostate cell-specific probes and antibodies. These cells were found to be aneuploid