bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cascade genetic testing (CGT) female first-degree relatives (FDR) of men with germline BRCA2 mutations (gBRCA2mut) and prostate cancer (PCa): A cost-effectiveness analysis.
Authors: Carletti Alexie A , Caughey Aaron B , Sokolova Alexandra 
Published: June 2023

e17099 Background: g BRCA2mut are associated with increased risk of PCa, breast cancer (BC), and ovarian cancer (OC). ~5% of men with metastatic PCa have g BRCA2mut. CGT is recommended for their relatives as there are implications for cancer prevention and early detection strategies. Little is known about CGT initiated by men with PCa. Here we evaluate the cost-effectiveness of CGT in FDR of men with PCa and g BRCA2mut. Methods: A decision-analytic model was created with TreeAge software to compare BC and OC outcomes for female FDRs who underwent CGT for g BRCA2mut versus no CGT. Our theoretical cohort contained 100,000 females, a conservative estimate of patients who could benefit from CGT. We used literature derived estimates to determine the percentage of patients that would pursue risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, both surgeries, or surveillance after CGT. Outcomes included BC or OC diagnoses, survivorship, and cancer death. We derived all probabilities, costs, utilities, and life expectancies from the literature and discounted quality adjusted life years (QALYs) at a rate of 3%. Incremental cost-effectiveness (ICER) was calculated to determine the cost per QALY gained and set the willingness-to-pay threshold at $100,000/QALY. We assessed the robustness of the model with sensitivity analyses. Results: In our theoretical cohort, CGT of female FDRs resulted in 12,910 less BC diagnoses and 6,360 less BC deaths. CGT was associated with lower BC death rates (26.1%) compared to no CGT (35.8%). OC survival rates were higher with CGT (73.1%) compared to no CGT (36.4%). Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$7,211.40 per QALY, saving an estimated $595 million. We found that CGT in females was the dominant strategy in 100% of the samples, once uncertainty was incorporated into our model inputs via Monte Carlo simulation. The cost-effectiveness of CGT for male FDRs will be presented at the meeting. Conclusions: In this study, CGT of female FDRs of men with PCa and g BRCA2mut was the dominant strategy to improve BC and OC outcomes, including increased survivorship and reduced BC and OC development. CGT was associated with reduced costs and increased QALYs. CGT for female FDRs of patients with PCa and g BRCA2mut may be a cost-effective approach for identifying and informing individuals with potentially harmful mutations. [Table: see text]
Ten-year outcomes of hypofractionated (45 Gy in 9 fractions) intensity-modulated radiotherapy for localized prostate cancer.
Authors: Zhong Sijin , Liu Yueping , Fang Hui , Tang Ping , Dai Jianrong , Shou Jianzhong , Li Yexiong 
Published: June 2023

e17100 Background: We reported 10-year outcomes of localized prostate cancers treated with hypofractionated intensity-modulated radiotherapy of 45 Gy in 9 consecutive fractions. Methods: From October 2011 to April 2017, thirty patients with localized prostate cancer were enrolled in this prospective trial. The median age of the patients was 72.5 years. According to NCCN recurrence risk criteria, eight patients were at low risk group, 17 at intermediate risk group, 5 at high risk group. All patients were treated with hypofractionated intensity-modulated radiotherapy (IMRT) of 45 Gy in 9 consecutive fractions to their prostate with or without seminal vesicles. Before radiotherapy, three gold fiducials were implanted into the prostate. In order to reduce the rectal high dose irradiation volume , an inflated rectal balloon was placed in the rectum at simulation and every treatment and patients were treated with comfortable full bladder. Static Intensity-modulated radiotherapy (SIMRT) was applied in 1 patient, Volumetric Modulated Arc Therapy (VMAT) in 27 patients, and tomotherapy in 2 patients. Image guided radiotherapy (IGRT) with gold fiducial registration was adopted. Twenty-six patients also received androgen deprivation therapy (ADT). The median time of ADT was 6 months. Progression⁃free survival(PFS) and overall survival(OS) were analyzed using Kaplan-Meier analysis. All grade ≥1 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using Common Terminology Criteria for Adverse Event version 5.0 (CTCAE 5.0) and Radiation Therapy Oncology Group (RTOG) late morbidity criteria , and GU and GI toxicities were cumulatively calculated. Results: After a median follow-up of 102 months (65~131 months), the 10-year OS was 90.0%(95% confidence interval, 83.3%-96.7%), and the 10-year PFS was 86.5% (95% confidence interval, 79.1%-93.9%). According to CTCAE 5.0, grade 1 acute gastrointestinal (GI) toxicity developed in 12 patients, grade 2 in 2 patients, grade 3 in 2 patients, and grade 1 acute genitourinary (GU) toxicity developed in 12 patients, grade 2 in 2 patients, and no grade 3 or higher toxicity occurred. According to RTOG late morbidity criteria, late (≥3 months after radiotherapy) grade 1 GI toxicity developed in 4 patients (13.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%), and late grade 1 GU toxicity occurred in 1 patient (3.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%). No grade 4 or higher GI and GU toxicities developed. Only one grade 3 GI and one grade 2 GU toxicities were observed for the maximum toxicity at the last follow-up. The potency was not evaluated. Conclusions: The 10-year oncologic outcomes of this shortened hypofractionated IMRT regimen for mainly low/intermediate risk prostate cancer patients is favorable with acceptable acute and late toxicities.
Exploring the efficacy of a continuous form of the histologic grade in prostate cancer prognosis prediction.
Authors: Kwak Tae-Yeong , Lee JaeHeon , Cho Joonyoung , Kim Sun Woo , Chang Hyeyoon 
Published: June 2023

e17105 Background: Adenocarcinoma of the prostate is the second most common type of cancer among men worldwide. The Gleason grading system remains the gold standard for evaluating the prognosis of prostate cancer by assessing the cancer morphology. However, the current discretized Gleason pattern regime limits the depiction of fine-grained histomorphological changes. We evaluated the efficacy of the algorithm-generated continuous histologic grade value in prostate cancer prognosis prediction. Methods: Whole-slide images of H&E prostatectomy tissue, along with the follow-up data including new tumor event (NTE) and biochemical recurrence (BCR), were obtained for the cases diagnosed as prostate cancer during 2000-2013 from The Cancer Genome Atlas (TCGA) database. Cases with missing data were excluded, resulting in a total of 308 and 397 cases being used for the analysis of NTE and BCR, respectively. Our study utilized a deep learning-based algorithm that performs Gleason scoring as follows. First, it computes per-pixel likelihood values for each of the 4 classes: benign, Gleason 3, 4, and 5. Then, the per-pixel class with the highest likelihood value and the slide-wise ISUP grade group (GG-AI) is successively determined. We tweaked the algorithm to aggregate the likelihood-weighted Gleason grade assigned to each pixel into a continuous form of the histologic grade (c-HG). We compared the prognostic performance of c-HG with that of the original ISUP grade group in TCGA (GG) and that of algorithm-generated GG-AI in predicting the risk of NTE as well as BCR. The Cox regression analysis was conducted, setting the cases from one of three donating institutions (EJ, HC, KK) as the target, fitting the Cox model with the cases from the other institutions, and evaluating the fitted model on the target. Results: The median follow-up duration in months was 32 for NTE and 29 for BCR, respectively. The number of cases with NTE was 51, while the one with BCR was 82. The table presents the c-index values obtained from each institution for GG, GG-AI, and c-HG. Note that the number of cases in each institution is different for NTE and BCR, due to the different number of removed cases with missing data. c-HG showed the best average performance in both NTE and BCR risk predictions. It is also notable that c-HG showed a stable performance for varying institutions. Conclusions: We proposed an algorithm-based method of representing histologic grade as a continuous value, which may give better predictions in disease progression for prostate adenocarcinoma. [Table: see text]
Impact of COVID-19 pandemic on the treatment of prostate cancer in the Brazilian public health system.
Authors: Carvalhal Gustavo , Morbeck Igor Alexandre Protzner , Herchenhorn Daniel , Sasse Andre Deeke , McKay Rana R. , Rose Brent Shane , Maluf Fernando Cotait , Monteiro Fernando Sabino Marques , Carrera Vinicius , Soares Andrey , Jardim Denis L. , Bastos Diogo Assed , Firminiano Elcio , Valverde Douglas Andreas , James Nick 
Published: June 2023

e17106 Background: COVID-19 pandemic reached Brazil in the beginning of 2020 causing a profound impact in economic and social activities, up to the end of 2021. In Brazil, there is universal access to the public health system (BPHS-SUS); however, during the pandemic public resources were directed mainly to the management of COVID-19 infected patients. We evaluated the impact of the 2020/2021 pandemic on the treatment of prostate cancer in the BPHS-SUS. Methods: we compared data regarding the number of radical prostatectomies, radiotherapy treatments, and hormonal and chemotherapy treatments administered in the time frame from March 1st, 2020 (when lockdown measures were initially adopted in Brazil) to February 29th, 2022, with that of the two most recent pre-pandemic years (March 1st, 2018, to February 28th, 2020). A large proprietary healthcare data science platform offered by TECHTRIALSÒ was surveyed. Results: in the two pandemic years, 15,196 radical prostatectomies were performed in the BPHS, with a cost of U$ 14,271,297; there was a 23.3% reduction in the number of surgeries compared with the two pre-pandemic years (19,818 radical prostatectomies, with a cost of U$ 18,056,470). In the pandemic, 34,982 men were treated with radiation therapy, with a cost of U$ 39,616,736; this meant a 18.7% reduction in the number of patients treated with radiation therapy as compared with the two pre-pandemic years (43,013 men, with a cost of U$ 44,148,190). Regarding hormonal treatments, numbers were similar: 116,490 men were treated during the pandemic (cost of U$ 74,834,615); in the pre-pandemic timeframe, 115,949 patients received hormonal therapy (cost of U$ 75,179,674). As to chemotherapy for hormone-resistant disease, in the pandemic 14,946 men were treated (cost of U$ 23,402,947) compared with 12,695 men treated in the two pre-pandemic years (cost of U$ 19,239,099). Conclusions: there was a significant reduction in the number of radical prostatectomies and of radiation therapy treatments during the pandemic years in the BPHS-SUS. Abrupt reductions of potentially curative therapies will probably affect stage migration, costs to the public system and patients’ survival in the ensuing years. The number of systemic therapies (first- and second-line hormonal therapies, and chemotherapies) were slightly increased, probably reflecting the BPHS-SUS policy of maintaining systemic treatments active during the pandemic.
Deep learning-based histomorphological pattern profiles for effective risk stratification in prostate cancer.
Authors: Lee JaeHeon , Kwak Tae-Yeong , Cho Joonyoung , Kim Sun Woo , Chang Hyeyoon 
Published: June 2023

e17107 Background: Prostate cancer affects millions of men globally and biochemical recurrence (BCR) is an important indicator of its progression. With the increasing use of computational techniques, there has been a growing interest in utilizing whole slide images (WSIs) of H&E stained prostate tissue to evaluate the patients’ clinical risks. Our study aimed to develop a novel method for predicting BCR by performing clustering on features extracted from deep learning models, thereby capturing morphological characteristics. Methods: The WSIs and clinical information were collected from The Cancer Genome Atlas (TCGA, from 2000 to 2013) dataset, for 321 patients (43 patients with BCR) who were not treated with any adjuvant therapies, with 2.5 years of median follow-up time. 356 collected WSIs were split into 1024 x 1024 patches at 5x magnification for the deep learning-based analysis. We used an ImageNet-pretrained deep learning-based clustering model (SwAV) to extract features from each patch and applied additional K-means clustering to assign the patches into one of 16 clusters. We tested both the cosine similarity and Euclidean distance as the clustering measure. After excluding the dissimilar patches under specific thresholds, the proportion of each cluster was calculated per slide to describe the distribution of morphological patterns as a 16-dimensional vector. To evaluate the predictability, we trained Cox models with the proportion vectors and assessed their performance via the concordance index (c-index). We repeated a stratified 5-fold cross-validation process 100 times to achieve robustness. As a reference, we conducted the same experiment with a BCR prediction nomogram published by MSKCC. Moreover, with the median proportion of each cluster, we separated two patient groups, drawed Kaplan-Meier curves, performed the log-rank test for significance, and we obtained the hazard ratio (HR) of each cluster from the trained Cox model of each fold. Results: We explored several thresholds to find ones yielding the best performance. When using the similarity, the best c-index was 0.704 with the threshold value of 0.25. With the distance value of 0.60, the c-index was 0.701. When using the MSKCC nomogram that incorporates clinical features, the average c-index was 0.717. The table contains the results of statistical analysis for selected clusterings that were significant in the log-rank test. Particularly in cluster B, the patches showed high-risk patterns including perineural invasion, high grade cancer, and necrosis in agreement with the high HR. Conclusions: Our results suggest that the histomorphological pattern profiles depicted by the deep learning model have the potential for effective risk stratification in prostate cancer. [Table: see text]
Perioperative safety and outcomes following radical prostatectomy in setting of locally advanced, node positive, and metastatic prostate cancer.
Authors: Wang Kerith Ruoyao , Simhal Rishabh , Shah Yash , Mark James Ryan , Shah Mihir S , Gomella Leonard G. , Lallas Costas D. , Chandrasekar Thenappan 
Published: June 2023

e17108 Background: Historically, definitive surgical management with radical prostatectomy (RP) has only been considered an option for the treatment of localized prostate cancer (PCa). However, recent data may suggest a role for RP in advanced PCa treatment. Currently, there is limited data on the safety and perioperative outcomes of RP in this setting. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) new procedure targeted database. Methods: RP procedures performed between 2019-2020 were identified. Patients were stratified to compare the effect of locally advanced disease (T3-4), node-positivity (N+), and metastasis (M+) against patients with localized (T1-2 N0 M0) PCa. Baseline demographics and 30-day outcomes, including operative time, hospital length-of-stay, 30-day mortality, readmissions, reoperations, major complications, minor complications, and surgery-specific complications, were compared between groups. Results: Pathologic staging data was available for 9,276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor-complications in the locally-advanced cohort, but no significant difference in major-complications, 30-day-mortality, readmissions, or rectal injuries. In comparison, while node-positivity was associated with longer operative time, LOS, and incidence of 30-day renal failure, it was not associated with a higher rate of any major, minor or surgery-specific complication. Similarly, RP for metastatic cases appeared to be comparably safe to those with M0 disease, although they were associated with a slightly higher rate of bleeding, prolonged-NG-tube use, and ureteral obstruction. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to localized prostate cancer. Given the previously demonstrated survival benefit in treating the primary tumor in advanced disease with radiation therapy, there may be a role for the RP in treating advanced PCa. Further studies are needed to better characterize the risks and benefits of surgery in these patients.
Biochemical recurrence (BCR) among patients (pts) with prostate cancer (PC) after radiation therapy (RT).
Authors: Spratt Daniel Eidelberg , McKay Rana R. , Khan Nasreen , Constantinovici Niculae , Chen Guifang , Ortiz Jorge A. , Srinivasan Shankar , Vassilev Zdravko , Xu Julie , Shore Neal D. 
Published: June 2023

e17111 Background: RT is a frequent primary treatment for pts with clinically localized PC. Despite its frequent success, 30-50% of pts eventually present with BCR, defined as rising prostate-specific antigen (PSA). BCR is associated with a higher risk of developing distant metastasis and ultimately death from PC. Understanding BCR occurrence and its impact on clinical outcomes is important for optimizing diagnostic and therapeutic strategies for recurrent disease. Methods: This is a retrospective cohort study using nationally representative Electronic Medical Records (EMR) data from Optum© from 1/2010-9/2021. Eligible pts were adults who underwent RT after PC diagnosis, had ≥ 3 available PSA values after initiating RT, and had EMR activity for at least 6 mo before and 12 mo after RT. Pts with a history of prior malignancy except nonmelanoma skin cancers and pts with metastatic PC (mPC) at baseline (BL) or within 3 months after RT were excluded. The BL period was 6 mo before RT initiation. Primary outcome was frequency of BCR, defined as rising PSA (PSA ≥ nadir + 2 ng/mL); secondary analyses included % of pts who progressed to mPC, castration-resistant PC (CRPC), and death after BCR and factors impacting time to BCR. Results: 9,292 RT pts were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 69.0 (40-88) y, 83.2% of pts were White, and 13.4% were Black. Median PSA nadir was 0.11 ng/mL, 32.5% of pts had received androgen deprivation therapy (ADT) during BL period, and median (Q1-Q3) follow-up from RT initiation was 3.8 (2.4-5.7) y. Overall, 10.2% of pts developed BCR. Among BCR pts (n = 949), 51.2% had a PSA doubling time (PSADT) < 6 mo and 16.9% had a PSADT between 6-10 mo; 35.0% developed mPC, 30.2% developed CRPC, and 23.4% died. In multivariate Cox regression models, the BL factor associated with the highest risk of developing BCR was PSA ≥ 20 ng/mL. Conversely, the risk of developing BCR was lower for pts who received ADT during BL. Conclusions: This real-world (RW) study evaluates BCR occurrence in pts who underwent RT with a curative intent from a large US database. The study confirms BL PSA as an important prognostic marker for BCR, while use of ADT before RT is associated with a lower risk of BCR. A considerable % of pts with BCR developed mPC (35%) or died (23%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC in pts with high-risk localized disease. [Table: see text]
Biochemical recurrence (BCR) and outcomes in patients (pts) with prostate cancer (PC) following radical prostatectomy (RP).
Authors: Khan Nasreen , McKay Rana R. , Spratt Daniel Eidelberg , Constantinovici Niculae , Chen Guifang , Ortiz Jorge A. , Srinivasan Shankar , Vassilev Zdravko , Xu Julie , Shore Neal D. 
Published: June 2023

e17112 Background: RP is often the primary treatment option for pts with clinically localized PC. Despite its frequent success, more than 30% of pts eventually present with BCR, defined as detectable prostate-specific antigen (PSA) after RP. BCR is associated with a higher risk of developing distant metastasis and ultimately death. Current patterns of BCR and the impact of BCR on treatment choice and clinical outcomes are not well characterized. Methods: This retrospective cohort study uses nationally representative Optum© Electronic Medical Records (EMR) data from 1/2010 to 9/2021. Eligible pts were adults who underwent RP after PC diagnosis, had ≥ 3 available PSA values after RP, and had EMR activity for at least 6 mo before and 12 mo after RP. Pts with prior malignancy except nonmelanoma skin cancers and pts with metastatic PC at baseline (BL) or within 3 months after RP were excluded. The BL period was 6 mo before RP. Primary outcome was frequency of BCR (defined as PSA ≥ 0.2 ng/mL); secondary analyses included % of pts who progressed to metastasis, castration-resistant PC (CRPC), and death after BCR, and factors associated with time to BCR. Results: 15,198 pts who underwent RP were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 63.0 (36-88) y, 85.9% of pts were White, and 10.0% were African American. Median (Q1-Q3) follow-up was 3.9 (2.4-5.7) y, and 14.3% of pts had subsequent adjuvant/salvage radiation therapy (RT). Overall, 19.8% of all pts and 61.4% of the subgroup of 2,178 pts with subsequent RT developed BCR. Among pts with BCR (n = 3,016), 16.3% had a PSA doubling time ≤ 10 mo, 17.1% developed metastasis, 13.8% developed CRPC, and 9.7% died. In multivariate Cox regression models (Table), the BL factors associated with an increased risk of developing BCR were PSA 10- < 20 or ≥ 20 ng/mL, Charlson comorbidity index (CCI) > 0, age ≥ 65, African American race, public insurance, and living in the US South region. Conclusions: This real-world (RW) study evaluates the occurrence of BCR in pts who underwent RP with a curative intent from a large US database. This study confirms BL PSA as an important prognostic marker for BCR. A considerable % of pts with BCR developed metastatic PC (17%) or died (10%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC among pts with high-risk localized disease. [Table: see text]