Browsing by Subject "Prostatic Neoplasms"
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Item Addressing Label Variability in Deep Learning-Based Segmentation for Radiation Therapy(December 2021) Balagopal, Anjali; Wang, Jing; Jiang, Steve B.; Nguyen, Dan; Lin, Mu-Han; Fei, BaoweiAccurate segmentation of tumor and surrounding organs-at-risk (OARs) is important for radiotherapy treatment(RT) planning. Manual segmentation by physicians currently used in clinical practice is time consuming and highly depends on the physicians' skill and experience, leading to large inter-and intra-observer variation. Deep learning(DL) algorithms, such as those used for image recognition, has been promising in the development of automated segmentation tools for medical imaging. Contouring in RT has some specific challenges as opposed to semantic segmentation in other spaces. DL segmentation models are trained with large, annotated datasets. The annotations play such an important role since these labels are the supervisory signals teaching the model how to segment. Majority of the times, a very high-quality dataset is unavailable. The datasets available are usually biased, noisy, and sometimes scarcely annotated. One of the primary sources of noise in RT datasets is annotation variations. This dissertation addresses the challenge of label variability and investigates different methods to deal with various kinds of label variability. The thesis studies the impact that label variability has on automation performance as well as patient outcome and devices ways to reduce or to respect this variability. Computed Tomography based segmentation model for intact and post-operative prostate cancer RT planning are proposed and developed for clinical use. Uncertainty in the automated label prediction for CTV and OARs are evaluated in detail. Impact of inter-physician variability on patient outcome for post-operative prostate cancer is investigated and instead of segmenting a general CTV , PSA-Net is proposed that respects style variations across physicians as well as across institutions. For dealing with systematic label variability in some structures, a prior-guided deep difference meta-learner is proposed that can segment a structure in a new labelling style from just a handful of prior segmented patients. A multi-modality IPA segmentation model is proposed to reduce label variability due to expertise differences among physicians in clinical trials. This model can effectively help inexperienced physicians in producing expert segmentations. The contributions of this thesis are expected to facilitate better understanding of label variability in RT and help in avoiding/respecting label variability when developing deep learning models for RT.Item Anticoagulant Use is Associated with Improved Biochemical Control of High-Risk Prostate Cancer Patients Treated with Radiation Therapy(2013-01-22) Jacobs, Corbin; Kim, D. Nathan; Choe, Kevin; Yan, Jingsheng; Xie, Xian-Jin; Hannan, Raquibul; Pistenmaa, David; Lotan, Yair; Roehrborn, ClausINTRODUCTION: The coagulation system modulates multiple cancer pathways, including tumor proliferation, angiogenesis, host immunologic defense, and metastasis. Prior studies have reported improved survival and freedom from biochemical failure (FFBF) in prostate cancer (PCa) patients taking aspirin and other anticoagulants (ACs). We reviewed the outcomes of patients with high-risk PCa who received ACs and definitive radiation therapy (RT). METHODS: Patients with nonmetastatic high-risk adenocarinoma of the prostate (stage ≥ T3a, or Gleason score (GS) ≥ 8, or prostate-specific antigen (PSA) ≥ 20) treated with definitive RT between 2005-2008 at UTSW were identified. The AC group consisted of patients who had warfarin, clopidogrel, or aspirin recorded on the medication list at any clinical visit. FFBF of patients was determined using the Phoenix definition. Log-rank test was used to correlate FFBF with the ACs. Univariate and multivariate analysis (MVA) of FFBF to pretreatment PSA, GS, stage, hormone use, total RT dose, and ACs was performed. RESULTS: Among the 76 patients identified, 45 (59.2%) comprised the AC group. Within the AC group, 43 were taking aspirin, 8 were taking warfarin, 8 were taking clopidogrel, and 13 were taking multiple ACs. Median follow up was 61.2 months (range 3.1-89.4) for the AC group and 55.1 months (range 6.5-88.9) for the non-AC group. Patients receiving ACs exhibited significantly improved FFBF compared to the control group (p=0.0018; log-rank test). The estimated 4-year FFBF was 83.7% and 63.2% for the AC and non-AC groups, respectively. Among the patients taking a single AC, only aspirin showed significantly improved FFBF (p=0.0037). The hazard ratio for T-stage was 1.18 (95% CI 0.75, 1.85; p=0.4672) in the AC group and 1.67 (95% CI 1.09, 2.58; p=0.0196) in the non-AC group, implying a benefit from taking the AC. Aspirin use, T-stage, and N-stage remained significantly correlated to FFBF (p=0.0002, p=0.0056, and p=0.0040, respectively). The early and late grade 2 toxicity rates for rectal bleeding were 7.7% in patients on multiple ACs and 0% for patients on a single AC or no AC. No patients experienced grade 3 rectal toxicity. CONCLUSION: Use of ACs in high-risk PCa patients improved the FFBF after definitive RT without increasing rates of rectal bleeding. This suggests that daily use of a single anticoagulant, especially aspirin, in high-risk PCa patients treated with definitive RT decreases biochemical failure and may improve outcome. Large prospective data are needed to validate the findings of this study.Item Benign prostatic hyperplasia: the quest for a medical therapy(1990-12-06) Wilson, Jean D.Item Determination of the Optimal Targeted Prostate Biopsy Strategy(2021-05-01T05:00:00.000Z) Subramanian, Naveen Gopal; Costa, Daniel N.; Pedrosa, Ivan; Yokoo, TakeshiBACKGROUND: Prostate cancer is one of the leading causes of cancer-related mortality in men and is treated in different ways based on the aggressiveness of the disease. The traditional method of diagnosis has been the systematic biopsy, which frequently underestimates or completely misses the disease. Recently, targeted prostate biopsies using pre-biopsy multiparametric MRI (mpMRI) have increased the detection of clinically significant disease. Of these methods, the two most sophisticated types are the MRI-TRUS fusion biopsy and the direct in-bore biopsy. Data comparing the diagnostic accuracy of these approaches and optimization of the biopsy procedure are lacking. OBJECTIVE: To compare the diagnostic accuracy of in-bore biopsy and MRI-TRUS fusion biopsy at accurately determining the index lesion grade group compared to radical prostatectomy (Aim 1), and to establish the optimal number of cores taken during in-bore biopsies to maximize detection of clinically significant disease while minimizing duration of the biopsy (Aim 2). METHODS: In Aim 1, patients that had at least one prostate lesion with abnormal mpMRI (at least one PI-RADS score 3 lesion) followed by targeted biopsy between April 2017 and January 2019 were included. The decision of what biopsy method to use for each patient was made by the ordering provider. The index lesion was defined as the largest lesion that exhibited the highest grade group (GG) and/or stage. The reference standard was the highest GG obtained from the radical prostatectomy specimen. In Aim 2, patients with abnormal mpMRI followed by in-bore biopsy between May 2017 and December 2019 were included. The endpoints of the study were the detection rate of clinically significant disease (defined as a GG of at least 2) and the GG upgrade (defined as the increase in the cumulative maximum GG with each additional core). RESULTS: In Aim 1, there was a statistically significant difference in the number of GG upgrades between the two biopsy types, with the in-bore biopsy having fewer (14%) upgrades than the fusion biopsy (30%; p=0.012). The mean net GG change was also significantly lower in the in-bore cohort (-0.11) compared to the fusion cohort (+0.16; p=0.0085). The GG concordance of the in-bore cohort (61%) was higher than the fusion cohort (53%) when compared to radical prostatectomy. In Aim 2, clinically significant cancers were detected by the first biopsy core in 78% of cases, the second core in 13% of cases, and the third core in 8.1% of cases. Only two lesions had the fourth core find csPCa. GG upgrade from insignificant to significant disease was also higher in the second and third cores (3%) compared to the fourth and fifth cores. The fourth and fifth cores only detected 0.3% of clinically significant tumors and resulted in only 1.2% of GG upgrades. CONCLUSION: Direct in-bore MRI-guided biopsy has greater diagnostic accuracy and a lower incidence of GG upgrades compared to MRI-TRUS fusion biopsy. Three cores per lesion was determined to offer the optimal balance between increasing the detection of clinically significant cancers and minimizing biopsy duration. Future work will center around cost-effective analyses and the impact on long-term patient outcomes.Item Improved Detection of Higher Risk Prostate Cancer by MRI-Targeted Versus Standard Template Ultrasound-Guided Biopsy(2018-01-23) Wong, Daniel; Shakir, Nabeel; Passoni, NiccoloIMPORTANCE: The majority of new prostate cancer (PCa) diagnoses made in the United States occur via transrectal ultrasound (TRUS) guided systematic template prostate biopsy ("standard biopsy"). Since this modality depends on random sampling of the organ, which may lead to undersampling of aggressive disease in addition to detection of low-risk PCa with concomitant harms of overtreatment, there is a demand for more reliable and accurate diagnostic methods. Multiparametric magnetic resonance imaging (MP-MRI) of the prostate can identify lesions suspicious for PCa, and platforms using software fusion of pre-acquired MRI with real-time TRUS ("MRI-targeted biopsy") are now FDA-approved. OBJECTIVE: To assess whether MRI-targeted biopsy detects a significantly greater proportion of higher-grade, clinically-significant disease as compared to standard biopsy ("upgrading") in patients who underwent both approaches. DESIGN: Prospective cohort study of men undergoing both MRI-targeted and standard biopsy from the National Cancer Institute (NCI) and UT Southwestern from 2007 to 2017. Pathology was categorized by the International Society of Urological Pathology grading scheme and compared between targeted biopsy and concurrent standard biopsy with McNemar's test. Parameters associated with upgrading, determined by threshold p<0.15, were evaluated in multivariable logistic regression models where significance was defined as p<0.05. INTERVENTIONS: Following referral for elevated serum prostate-specific antigen (PSA), patients underwent MP-MRI. Men with lesions suspicious for PCa on MRI underwent a single biopsy session during which targeted biopsy and standard biopsy were performed concurrently. RESULTS: Of 1913 men in the study, 1235 were diagnosed with PCa by either standard or targeted biopsy. Patients between the two centers were matched by age and PSA (Table 1) but differed by history of previous biopsy, MRI prostate volume, and racial distribution. 408 patients had intermediate to high grade prostate cancer diagnosed by either targeted or standard biopsy (Table 2), of whom 194 (47%) had concordant targeted and standard biopsy results. 151 (37%) men had intermediate to high grade disease missed or downgraded relative to targeted biopsy by standard biopsy, and 63 men (15%) were missed or downgraded relative to standard biopsy by targeted biopsy (p<0.0001). On multivariable analysis of upgrading by targeted biopsy, when controlling for potentially confounding factors, increasing age, MRI prostate volume, number of targets and PSA remained significantly associated, whereas the performing center was not predictive. CONCLUSIONS: MRI-targeted prostate biopsy results in greater detection of clinically significant higher-grade PCa as compared to standard biopsy. Whether MRI-targeted biopsy can be performed instead of standard biopsy, versus being performed in selected risk-stratified populations or as a supplemental technique, requires additional study.Item Long Term Follow-up of Prostate Cancer Patients Who Fail Salvage Radiation Therapy and Radical Prostatectomy(2014-02-04) Ying, James; Yan, Jingsheng; Xie, Xian-Jin; Roehrborn, Claus; Lotan, Yair; Liauw, Stanley; Pistenmaa, David; Kim, NathanPURPOSE/OBJECTIVES: Salvage radiation therapy (SRT) is an effective treatment for prostate cancer (PCa) that has recurred after radical prostatectomy. Long term follow up in men who developed biochemical recurrence (BCR) after SRT is less well described in literature. This study follows the natural history of patients treated with SRT > 13 years ago. MATERIALS/METHODS: 61 patients with PCa treated with SRT during 1992-2000 at UT Southwestern were identified. Survival was calculated using the Kaplan-Meier method. Log-rank test and Cox regression were used to determine significance of clinical parameters with outcome. RESULTS: Median follow-up for the 61 patients was 126 months (3-238). Median age at SRT was 62 (46-83), 15% of patients had pathologic Gleason score (pGS) 8-10 disease, 14% had pre-surgical PSA > 20, 63% had pT3+ disease, 59% had positive margin at time of surgery. Of 61 patients, 34 (56%) had treatment failure after SRT. 5 y and 10 y freedom from PSA failure (FFPF) were 51% and 33% respectively. pGS significantly correlated with FFPF (p=.0042) and overall survival (OS) (p=.0022). Seminal vesicle invasion (p=.0357, HR 2.07, 1.0-4.2), lymphovascular invasion (p=.035, HR 5.28, 0.9-32.2), and pre-SRT PSA (p=.015, HR 2.27, 1.14-4.5) were associated with decreased FFPF. For the 34 patients who had BCR, median follow-up was 157.5 months (13-238). Median time to BCR following SRT was 30 months (3-138). 19 (56%) received androgen deprivation therapy (ADT). Median time from BCR to initiating ADT was 48 months (0-151). Outcome after BCR is as follows. OS at 5 and 10 y were 79% and 59% (median 13.6 y). PCa-specific survival (PCSS) at 5 and 10 y were 89% and 73%. Distant metastasis free survival at 5 and 10 y were 75%. Castration resistant free survival at 5 and 10 y were 81% and 70%. Time to BCR after SRT < 1 year (p=.0005, HR 3.92, 2.7-33.6) and < 2 years (p=.021, HR 2.52, 1.2-9.2) significantly correlated with decreased OS, compared to < 3 years (p=.054) and < 5 years (p=.073). CONCLUSIONS: Clinical parameters predictive of treatment failure after SRT are presented. Unfortunately, 25% of patients who fail SRT developed distant metastases within 5 yrs of failure. 56% of those who failed eventually also required ADT. Such events could have significant emotional impact, affect quality of life, and lead to morbidity related to salvage therapy. However, while up to 27% of patients died from PCa after BCR at 10 years, only patients who failed SRT in less than 2 years had a significantly worse OS. Overall, patients who fail SRT treatment can have a prolonged median overall survival of 13.6 years.Item Mechanisms of prostate cancer progression to androgen independence(2008-11-14) McPhaul, Michael J.Item [News](1978-06-19) Land, ChrisItem Parameters that Predict for High Grade Rectal Toxicity in Prostate Cancer Patients Undergoing Stereotactic Body Radiation Therapy- Analysis of Phase I/II at UT Southwestern(2013-01-22) Straka, Christopher; Kim, D. Nathan; Pistenmaa, David; Lotan, Yair; Xie, Xian-Jin; Timmerman, RobertINTRODUCTION: Conventional radiation therapy (CRT) is a well-accepted option for PCa treatment with high disease control rate, and low (< 3-5%) risk of rectal toxicity. SBRT, unlike CRT, delivers higher doses of radiation in 1-5 fractions, reducing treatment time significantly (from 8-9 weeks to ~ 2 weeks). Benefits of SBRT include improved patient convenience, significant healthcare cost reduction, and it has strong biologic rationale. A dose escalation phase I study (Boike et. al, JCO 2011) established 45-50 Gy in 5 treatments as effective and safe. Phase II study at 50 Gy was recently completed. Interim analysis unexpectedly revealed a significant number of grade 3+ delayed rectal events. We performed a rigorous analysis to determine potential etiology and methods to avoid occurrence of such rectal events. METHODS: Clinical parameters evaluated include tumor stage, Gleason grade, prostate volume, comorbid conditions (diabetes, smoking history, immunosuppression), race, age, and baseline bowel function score. Treatment planning parameters collected and evaluated included rectal wall volume receiving high doses of radiation, target volume size, rectal wall size, and degree of circumferential radiation to the rectal wall. Uni/multivariate analysis and correlative studies were conducted. RESULTS: 59 low/intermediate risk Pca patients were enrolled in this phase I/II study at UTSW. Median follow-up for all patients is 25.5 months. Tumor control rate is 99% to date. No patients experienced high grade rectal toxicity at 45 and 47.5 Gy, but at 50 Gy 10.8% experienced ≥ grade 3 rectal toxicity. Significant parameters were rectal volume receiving 50 Gy, HR of 2.67 (1.25, 5.71), p=.0113; rectal circumference irradiated by 24 Gy, 39 Gy and 50 Gy, HR of 1.1 (1.01,1.2) (p=.03), 1.2 (1.01, 1.38) (p=.04), and 1.22 (1.01, 1.47) (p=.04) respectively; and possibly diabetes HR 6.86 (0.83, 56.8) (p=.074). All 4 patients with grade 3+ rectal toxicity had > 3.5 cm3 rectal wall irradiated by 50 Gy. All patients without rectal toxicity had < 3.5 cm3 rectal wall irradiated by 50 Gy. DISCUSSION: We have determined the absolute threshold dose volume constraint to avoid rectal toxicity for SBRT of Pca. These findings contribute significantly to the radiobiology of bowel tolerance. If anatomy does not permit safe rectal dose constraints, dose reduced SBRT or alternatively CRT should be considered. When rectal constraints are met, or when 45-47.5 Gy prescription dose is used, SBRT seems to be a potent, safe, convenient and cost effective treatment for patients with low/intermediate risk PCa.Item Prostate cancer screening argument: does it really enhance outcome?(1996-08-29) Sheehan, Richard G.Item [Southwestern News](2001-10-11) Beeson, TraciItem [Southwestern News](1992-08-06) Doremus, DavidItem [Southwestern News](1995-05-25) Donovan, JenniferItem [Southwestern News](2003-06-24) Horton, RachelItem [Southwestern News](2001-07-18) Baxter, MindyItem Targeted Molecular Imaging: A Guide to Combination Therapy(2006-12-20) Ren, Gang; Öz, Orhan K.Recombinant adenovirus is widely used to deliver genes for cancer gene therapy. Coxsackie and Adenovirus' Receptor (CAR) is the primary receptor for recombinant adenovirus. Little attention has been paid to determine CAR protein expression and promoter activity in vivo. This study tested the hypothesis that targeted molecular imaging of CAR could predict the tissue receptivity to viral infection and the response to treatment with histone deacetylases inhibitor (HDACi). To image CAR protein expression, human prostate cancer xenografts were established in nu/nu mice. The ability of iodinated anti-CAR intact, F(ab')2 fragments and control F(ab')2 fragments to distinguish CAR (+) tumors was tested by biodistribution, gamma camera scintigraphy and validated by western blot. Tumor susceptibility to infection was tested with adenoviruses carrying the reporter β-galactosidase. To assess CAR promoter activity, a sodium iodide symporter (NIS) reporter construct containing the NIS open reading frame driven by the CAR promoter (CAR-NIS), was constructed by directional cloning. Tumor cell lines stably expressing CAR-NIS or empty vector were established. NIS protein function was assessed by intracellular accumulation of 99mTcO4- and mRNA level was tested by RT-PCR. The inductivity of the CAR promoter by HDACi in vivo was tested by imaging CAR-NIS tumors after administration of 99mTcO4- using a gamma camera. A replication-deficient recombinant adenovirus coding CAR-NIS was constructed to deliver the reporter construct to cells and tumors to permit radionuclide imaging. Radiolabeled anti-CAR F(ab')2 fragments more effectively distinguished CAR(+) from CAR(-) tumors at early time points. Tumors with greater retention of radiolabeled anti-CAR showed higher levels of CAR protein expression by western blot and ß-galactosidase activity after adenoviral infection. Stable CAR-NIS transfectants showed 16-fold to180-fold increase of 99mTcO4- accumulation after HDACi treatment in PC3 prostate cancer cells or TCC bladder cancer cells, respectively (p<0.001). Ad-CAR-NIS effectively delivered the HDACi inducible CAR-NIS into target cells in a dose dependent manner. The transgene CAR-NIS expression was imaged in vivo using gamma camera scintigraphy. Molecular imaging approaches to image CAR protein expression and assess CAR promoter activity in vivo can predict tissue receptivity to adenoviral infection and have potential to direct combination of gene delivery and chemotherapy.Item [UT Southwestern Medical Center News](2008-06-15) Piloto, ConnieItem [UT Southwestern Medical Center News](2011-07-25) Russell, RobinItem [UT Southwestern Medical Center News](2007-09-20) Piloto, ConnieItem [UT Southwestern Medical Center News](2010-02-02) Morales, Katherine