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: March 2023

110 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%). CGT was not associated with reduction in OC diagnoses or deaths. Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$4,190.10 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 outcomes, including increased survivorship and reduced BC development. Despite a lack of demonstrated benefit for OC, 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]
Pembrolizumab (Pem) in metastatic castration-resistant prostate cancer (mCRPC): Experience from a comprehensive cancer center.
Authors: Roy Arya Mariam , Farmer Bailey , Muthusamy Kumarasamy Vasanthan , Jatwani Karan , Levine Ellis Glenn , Chatta Gurkamal S. , Gopalakrishnan Dharmesh 
Published: March 2023

113 Background: The prognosis of refractory mCRPC remains poor despite advancements in therapeutic options. KeyNote-199 demonstrated modest activity of Pem in mCRPC with expected safety profile. We present our real-world experience with Pem in mCRPC. Methods: We conducted a retrospective review of mCRPC patients treated with Pem at our institution from 1/1/2017 to 10/1/22. Baseline demographic, clinicopathologic, and genomic characteristics were recorded. PSA and radiographic responses were assessed by the study team, and survival distributions estimated using the Kaplan-Meier method. Results: A total of 39 patients were identified – 97% (37) were White, median age was 71 years, 4% (19/35) had a Gleason Score ≥8; 80% (31) had skeletal and 74% (29) had soft tissue metastases at Pem initiation. Overall, patients were heavily pre-treated (median of 7 prior therapies, range 0-8) - 87% (34) had received taxanes, 82% (32) novel antiandrogens, 23% (9) Ra-223, 21% (8) Sipuleucel-T, and 2% (1) Olaparib. Median duration on Pem was 7 months (range = 1-29). Among the 34 evaluable patients, 2 (6%) achieved CR, 2 (6%) had PR, 5 (15%) had stable disease (SD), and 25 (73%) had progressive disease (PD) on radiographic assessment. PSA reduction ≥ 50% was noted in 7/32 (22%) patients. The 4 patients who had radiographic CR/PR had positive predictive biomarkers – Patient 1: CR – MSI-H, high TMB (17.5/Mb); Patient 2: CR – MSI-indeterminate, germline MSH6 mutation; Patient 3: PR – MSI-H, high TMB (28.8/Mb), germline MSH2 mutation; and Patient 4: PR – MSI-S, high TMB (18.3/Mb), PDL1 TPS 100%, positive neuroendocrine markers. Interestingly, patient 3 was switched to ipilimumab + nivolumab after PD on Pem, and subsequently had a CR. None of the evaluated patients with SD or PD had high MSI, TMB, or PDL1 levels. The median overall survival from Pem initiation was 4.4 months (95% CI 3.0-10.2 months). Three (8%) patients discontinued Pem due to immune-related adverse effects (IRAEs); no treatment-related deaths were reported. The most frequent Gr 3 IRAEs are shown. Conclusions: Single-agent Pem demonstrated modest overall efficacy in mCRPC, restricted only to patients with predictive biomarkers. Given the non-trivial risk of IRAEs, financial toxicity, and potential QoL implications, we suggest using checkpoint inhibitors only in appropriately biomarker-selected patients with mCRPC. [Table: see text]
Real world rates of genetic referrals and germline testing in patients with prostate adenocarcinoma at an academic cancer center in southern New Jersey.
Authors: Ambrogi Christopher , Desai Sahaj , Carhart Randi Zukas , Jenab-Wolcott Jenia , Shih Julia Chia-Ying 
Published: March 2023

114 Background: Prostate adenocarcinoma is the second leading cause of cancer-related death in men in the United States. A major risk factor is family history, with prostate cancer in a first-degree relative effectively doubling a patient’s risk. However, relying on family history alone fails to identify many patients with clinically relevant cancer-related germline mutations, which can have important prognostic and therapeutic implications for patients and their families. In 2018, the NCCN recommended expanding the germline testing to include all men with high risk, very high risk, regional or metastatic prostate cancer. We sought to identify the rate of genetic testing within this patient population at the MD Anderson Cancer Center at Cooper University Hospital. Methods: The institution database was queried to identify patients with the ICD-10 diagnosis of prostate adenocarcinoma between 01-2019 and 12-2020; the inclusion criteria were age 18 years or older, biopsy-proven prostate adenocarcinoma, and qualification to receive germline genetic testing per NCCN guidelines. A total of 201 patients were screened and 97 cases were analyzed. Results: Of the 97 patients who qualified for genetic testing, 53 were referred to genetics (54.6%). 27 of the 53 patients who met with our genetics team underwent testing (50.9%). Of the 27 patients tested, nine patients (33.3%) were found to have clinically relevant cancer-related germline mutations with therapeutic implications for the patient and/or screening recommendations for the patient and their family members. Conclusions: Overall, the proportion of patients who qualified for and completed genetic testing was low at 27.8%. Of those who completed testing, the rate of detection of a significant germline mutation was high at 33.3%, indicating that a significant proportion of those untested may carry a genetic mutation of clinical importance. Based on these results, we developed an electronic Best Practice Alert that notifies providers if a patient qualifies for a genetic risk evaluation based on his prostate cancer risk. We implemented this system, with reported high utilization demonstrating feasibility of this tool. Preliminary data shows improved rates of referral among prostate cancer patients.
Preliminary findings of G8 and G8-modified as screening tools associated with quality of life in elderly patients with prostate, renal or bladder neoplasms in a Brazilian cancer center.
Authors: Modesto Ingrid Felix Felix , Dettino Aldo A. 
Published: March 2023

122 Background: Population aging and cancer increased incidence are a public health challenge, as the elderly vary widely in terms of health status and aging process. Aiming at therapeutic efficacy and minimization of toxicities, treatment should be individualized. To aid in clinical decision and patient (pt) management, screening tools use is recommended, such as the G8 and the G8-modified (G8m), which identify geriatric problems: scored as abnormal when ≤ 14 and ≥6, respectively. These scales include health status self-assessment, which can be investigated by specific tools as EQ-5D-5L. The objective is to compare the G8 and G8m scales as screening tools in Brazilians ≥ 60 years old with urological tumors and describe Quality of Life using the Visual Analogue Scale of EQ-5D-5L (EQ VAS), which scores from 0-100 (higher better). Methods: Sociodemographic data were collected, and scales G8, G8m and EQ-5D-5L were applied to elderly people ≥ 60 years old with urologic cancer diagnosed within 6 months or prior to a change in therapeutic strategy, from Feb to Sep 2022. Statistical analyzes were performed, such as means, median, standard deviation and proportions, as well as comparisons of G8 total score versus G8m, using Kappa Coefficient. Fisher's Exact Test was used to analyze these scores related to sociodemographic data and the Pearson Correlation test to verify the relationship of the scores with the EQ VAS. Results: 43 pt aged ≥ 60 completed G8 with a mean score of 13,7(±2,2), G8m with 7,7 (±6,6) and EQ VAS 81,5 (±14,9). The mean age was 72,7 (±8,7) and 100% were men and 27 (62,8%) were white; furthermore, 9 (20,9%) lived alone. The most frequent cancer type was prostate 34(79,1%), followed by renal 5 (11,6%). 36 (83.7%) pt were changing treatment strategy and 7 (16.3%) had a diagnosis within 6 months. A weak agreement of 72.2% between normal G8 and G8m scores was identified (Kappa = 0.435 and p 0.006). A statistically significant association between normal G8m score and married marital status (p=0.039) was found, however there was no statistically significant association between G8 and G8m scores and comorbidities, smoking or polypharmacy. As well as no statistically significant correlation was found between the G8 and G8m scores with the Quality of Life measured by the EQ VAS. Conclusions: G8 and G8m demonstrated similar results in elderly pt with urologic tumors, identifying pt with frailties that are warranting a complete geriatric evaluation. In addition, this study indicates that it is better to assess quality of life using specific instruments, since the G8 and G8m scores were not correlated with the EQ VAS, although the screening scales included self-rated health. We intend to prospectively evaluate the prognostic power in the short term - 6 months, relating it to the quality of life, by the EQ-5D-5L.
Risk factors for treatment (tx) toxicity and discontinuation among patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) on androgen receptor targeted therapy (ART).
Authors: Chakrani Zakaria , Mellgard George Slade , Mccroskery Stephen , Saffran Nathaniel , Taylor Nicole , Liaw Bobby Chi-Hung , Oh William K. , Tsao Kai , Patel Vaibhav G. 
Published: March 2023

135 Background: mCRPC is associated with (a/w) increased mortality among prostate cancer pts and new and safe txs are needed. In recent clinical trials, ARTs improved survival outcomes within this population, however, a significant portion will go on to discontinue tx. We aim to describe reasons for ART tx discontinuation and to identify predictors a/w increased risk of tx discontinuation due to tx toxicity or death. Methods: We performed a single-institution retrospective review of mCRPC pts on ART between 2010 and 2021. We screened for demographics, medical history, ART course, and tx side-effects. Our primary aim was to identify risk factors for tx discontinuation due to toxicity or death. Our secondary aim was to describe ART discontinuation among mCRPC. Fisher’s Exact was used to identify significant predictors of tx discontinuation due to toxicity or death. Significant outcomes were included in a multivariate logistic regression to determine odds ratios. Results: 133 pts with mCRPC started and discontinued ARTs. Among this cohort, 27 pts (20.3%) discontinued tx due to death or toxicity. Reasons for tx discontinuation are described in the table below. Significant predictors of tx discontinuation due to toxicity or death on bivariate analysis included pt-reported sepsis, hypertension (htn), weakness, falls, ECOG ≥2, and hospitalization during tx. Adjusting for confounders, pt-reported falls (OR 2.35; [0.91-2.59]; p=0.009), htn (OR 2.06; [0.94-2.21]; p=0.027), and weakness (OR 1.63; [0.59-2.72]; p=0.007) were a/w an increased risk of pt tx discontinuation from toxicity or death. Conclusions: Our results illustrate that the majority of mCRPC pts discontinued tx due to progression of disease. The data also indicates that mCRPC pts reporting new onset htn, falls, or weakness were more likely to discontinue tx due to toxicity or death. Early monitoring of this population is warranted to prolong duration of tx and prevent unnecessary txs. [Table: see text]
Additional cycles of docetaxel in combination with androgen deprivation therapy (D-ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): Efficacy and feasibility analysis.
Authors: Aydogdu Can , Urban Florian , Tamalunas Alexander , Berg Elena , Götz Melanie , Rodler Severin , Heinemann Volker , Stief Christian , Casuscelli Jozefina 
Published: March 2023

185 Background: Several phase III trials have assessed efficacy and safety of 6 cycles of docetaxel combined to androgen deprivation therapy (ADT). This is the current standard of care for a subgroup of patients. We aimed to assess whether treatment beyond 6 cycles of docetaxel prove to be more effective than the standard of care. Methods: We retrospectively analyzed patients with histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease from a large tertiary care center. All patients with mHSPC were treated in first line with ADT in combination with docetaxel (75 mg/m2) (D-ADT) intravenously on the first day of each 21-day cycle. A subset of patients was treated beyond the standard of 6 cycles. Clinical and pathological variables were analyzed, progression free survival on D-ADT (PFS1), progression free survival on subsequent therapy (PFS2) and overall survival (OS) were the endpoints analyzed by log- rank test. Results: Between 2018-2022 a total of 74 mHSPC patients were followed-up for a median time of 13.7 months. Mean age was 66.2 years (range 50.1-82.4), and 79.7% had GS≥8, 73% a CHAARTED high-volume and 76% LATITUDE high risk disease. 43 pts. were treated with ≤ 6 cycles (D-ADTstand) (2.4 % 1-2 cycles; 97.6 % ≥3 cycles; mean 5.3 cycles) and 31 were treated with >6 cycles docetaxel (D-ADTadd) (25.8 % 7-8 cycles; 74.2% ≥9-10 cycles, mean 9.2 cycles). No significant differences were observed in median PFS1 (12.4 vs. 13.7 mos.) and PFS2 (5.4 vs. 9.6 mos.). Median OS in the D-ADTstand group was 39.8 mos., median OS in the D-ADTadd group was not yet reached. Conclusions: While more than 6 cycles of D-ADT in mHSPC proved to be feasible without significant additional toxicity, efficacy is not superior compared to the standard of 6 cycles. Overall survival data is not mature yet, but the benefit of more chemotherapy upfront is debatable and leverages further studies in light of the upcoming triplet combinations in mHSPC, that presumably will render D-ADT obsolete in future. [Table: see text]
Physician-driven artificial intelligence enabled planning for intraprostatic dose escalation in under ten minutes.
Authors: Rayn Kareem , Elliston Carl , Savacool Michelle , Fang Yi , Deutsch Israel , Spina Catherine S. , Kachnic Lisa A. , Yu James B. 
Published: March 2023

187 Background: Intraprostatic radiation dose escalation is an area of clinical interest. Dose escalation within the prostate must be balanced with maintaining acceptable dose to the organs at risk, OAR (bladder, rectum, and urethra). Treatment planning therefore requires simultaneous consideration of multiple competing plan optimization goals, for which iterative, interdisciplinary treatment planning tasks may take significant physician, physicist, and dosimetrist time. Semi-automated treatment planning using artificial intelligence has the potential to significantly reduce treatment planning time for technically complex treatments. Methods: A prostate SBRT planning template was created using the Varian ETHOS treatment planning system (TPS) combined with an in-house RapidPlan SBRT prostate model. Prostate dose was prescribed to 36.25 Gy over 5 fractions with 95% coverage to the PTV. To respect standard SBRT normal tissue toxicity constraints while simultaneously escalating intraprostatic dose, the TPS automatically created an intraprostatic boost structure (PTV_SIB), derived from the PTV by excluding OARs with a pre-determined margin. Physicians were trained to perform treatment planning using the prostate SBRT planning template. Treatment planning was performed on 5 unique patients. The time spent from initiation to end of treatment planning and dosimetric parameters were recorded. Results: For each patient, the ETHOS TPS generated two SBRT plans (9 field static IMRT and 3 VMAT arc) with intraprostatic dose escalation in an average of 9.3 minutes [range 8.4-11.8]. Static field and VMAT plans were comparable. PTV_SIB was escalated to above 50 Gy in all cases. Relevant dosimetry for each patient’s static IMRT plan is shown. Conclusions: Physician-driven ETHOS treatment planning was able to produce boosted internal PTV doses using autosegmented volumes. The ETHOS TPS was able to generate dose-escalated plans that reconciled complex OAR and PTV goals within 8-12 minutes. Hence, the ETHOS TPS opens the possibility of rapid physician-driven treatment planning throughput. [Table: see text]
Effect of early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting on cancer-specific survival in metastatic castrate-resistant prostate cancer.
Authors: Lehner Kelly , Ahmed Mohamed E. , Bole Raevti , Andrews Jack R. , Haloi Rimki , Bold Michael S. , Kendi Ayse T. , Karnes R. Jeffrey , Kwon Eugene D. , Bryce Alan Haruo 
Published: March 2023

189 Background: The objective of this study is to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in the post-chemotherapy setting in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 75 m-CRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized into two groups based on first PSA within 3 months after initiation of therapy: PSA reduction ≥ 50% (Group A) and PSA reduction < 50% (Group B). The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Results: There were 75 patients (52 in group A, 23 in group B) in the analytic cohort. Baseline clinical and demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. PSA reduction ≥50% was significantly associated with decreased risk of radiographic disease progression (HR 0.41, 95%CI 0.21-0.80, p = 0.0113) as well as decreased risk of cancer-specific mortality (HR 0.29, 95%CI 0.09-0.87, p = 0.0325). Conclusions: PSA reduction ≥50% within 3 months of starting 2nd HT for patients with mCRPC who have failed first-line docetaxel is associated with significantly improved 3-year cancer-specific mortality and progression free survival. Our data supports the use of PSA as an early prognosticating marker for patient outcomes on this second line therapy. [Table: see text]
The effect of statin use on survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor targeted therapies (ART).
Authors: Mellgard George Slade , Saffran Nathaniel , Chakrani Zakaria , Mccroskery Stephen , Taylor Nicole , Liaw Bobby Chi-Hung , Galsky Matt D. , Tsao Kai , Patel Vaibhav G. 
Published: March 2023

194 Background: Statins may reinforce and provide a compounded effect on ART by decreasing cholesterol levels thus decreasing de novo androgen synthesis. We aim to investigate the clinical effect of concurrent statin and ART use on outcomes of mCRPC patients. Methods: We conducted a retrospective analysis on mCRPC patients receiving ART from a single institution. Relevant demographic and clinical data was collected in addition to ART treatment course, statin treatment, and survival outcomes. Our primary outcome was PSA progression free survival (PFS) and our secondary outcomes were overall survival (OS) and associated prognostic factors for both PSA PFS and OS. Chi-squared test and Wilcoxon signed ranked test were used to compare baseline characteristics, and a Cox proportional hazards regression model was used to estimate hazard ratios (HR) with 95% confidence interval (CI) for overall survival (OS) and PSA PFS. Results: 153 patients were included in the analysis between 2010 and 2021. 67 patients (mean age 73.8 years) received concurrent statins and 86 patients (mean age 67.6 years) did not. Median PSA PFS was 37.4 months for patients that received concurrent statins and 17.4 months for patients that did not receive statins. On univariate and multivariate analyses, there was no statistically significance difference between groups for PSA PFS (HR 0.7; CI 0.44-1.1; p=0.122). Median OS was 35.6 months for patients that received concurrent statins and 24.0 months for patients who did not. There was no statistical significance between groups for OS on univariate or multivariate analyses (HR 0.67; CI 0.42-1.06; p=0.087). Conclusions: Although results were not statistically significant, our study illustrates that concurrent statin use exhibits improved time to PSA progression and OS in mCRPC patients. Larger multi-center and further prospective studies are warranted to elucidate the relationship between statin use and overall outcomes in this population.
Impact of vaccination against SARS-CoV-2 on the risk of hospital admission and death among infected patients with urologic cancers: A population-based study in northern Italy.
Authors: Fratino Lucia , Gobbato Michele , Clagnan Elena , Taborelli Martina , Del Zotto Stefania , Toffolutti Federica , Burba Ivana , Tosolini Francesca , Polimeni Joseph , Serraino Diego 
Published: March 2023

205 Background: Background: Hospital admission and death of infected cancer patients were investigated according to SARS-CoV-2 vaccination status. Methods: Population-based observational study on 1874 SARS-CoV-2 infected patients with prostate (n=1276), kidney (n=327), and bladder (n=271) cancers. Hazard ratios (HR) and their 95% confidence intervals (CI), adjusted for sex and age, were computed to assess the risk of hospital admission and death of unvaccinated patients as compared to vaccinated ones. Results: 24.5% of patients with prostate, 26.9% with kidney and 29.5% with bladder cancer were unvaccinated. As compared to vaccinated ones, a statistically significant excess risk of hospital admission emerged for unvaccinated ones with prostate (HR=3.33, 95% CI: 2.50-4.55), and kidney (HR=4.35, 95% CI: 2.33-8.33) cancer. The 312 unvaccinated prostate cancer patients were also at a nearly 3-fold higher risk of death than vaccinated ones (HR=2.98, 95% CI:1.89-4.70). Conclusions: Study findings stress the importance of SARS-CoV-2 vaccines in reducing hospital admission and death in patients with urologic cancers, particularly prostate cancer.