bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive accuracy of PSA density in the UCSF-CAPRA score.
Authors: Parker Robert , Bell Alexander , Greenberg Scott , Washington Samuel L. , Cowan Janet E. , Cooperberg Matthew R. , Carroll Peter 
Published: February 2022

233 Background: The UCSF-CAPRA score is a validated risk tool that uses patient factors at diagnosis to predict prostate cancer outcomes after radical prostatectomy. This study aims to evaluate whether the substitution of prostate-specific antigen (PSA) density for serum PSA improves the predictive performance of the clinical CAPRA model. Methods: Participants were diagnosed in 2000-2019 with stage T1/T2 cancer, underwent radical prostatectomy (RP) for prostate cancer, and had at least 6 months of post-surgical follow up. We computed the standard CAPRA clinical risk score using diagnostic age, Gleason grade, percentage of positive cores, clinical T stage, and serum PSA, as well as an alternate score based on the same variables but substituting PSA density (incremental categories) for serum PSA. We reported validated CAPRA categories of low (0-2), intermediate (3-5) and high (6-10) risk. Recurrence was defined as 2 consecutive PSA > = 0.2 ng/ml or receipt of salvage treatment. Life table and Kaplan-Meier analysis was used to evaluate recurrence-free survival after prostatectomy. Two Cox proportional hazards regression models were used to test associations of standard or alternate CAPRA component variables with risk of recurrence. Two additional models tested associations between standard CAPRA score or alternate CAPRA score with risk of recurrence. The Cox log-likelihood ratio test (-2 LOG L) was used to assess model accuracy. Results: A total of 2,557 patients had a median age of 61 years (IQR 56-66), GG1 34% and GG2 30%, median PSA 6.3 (IQR 4.8-9.3), and median PSA density 0.19 (IQR 0.13-0.29). Post-surgical follow up was 49 months (IQR 25-86). The alternate CAPRA model was associated with significant shifts in risk scores, with 16% of patients increasing and 6% decreasing (p < 0.01). Recurrence-free survival after RP was 75% at 5 years and 63% at 10 years. Both CAPRA component models were associated with risk of recurrence after RP on Cox regression. Covariate fit statistics showed significantly better fit (low -2 LOG L) for the standard CAPRA model compared to the alternate model (-p < 0.01). Both standard (HR 1.55; 95% CI 1.49-1.61) and alternate (HR 1.52; 95%CI 1.46-1.58) CAPRA scores were associated with risk of recurrence, with better fit for the standard model p < 0.01). Conclusions: In a cohort of 2,557 men followed for a median of 49 months after RP, a alternate CAPRA model using PSA was associated with higher risk of BCR, but did not perform better than the standard CAPRA model at predicting BCR. While PSA density is well established as an independent prognostic variable in the pre-diagnostic setting and for sub-stratifying otherwise low-risk disease, it does not appear to improve predictive accuracy of BCR models when applied across the full range of cancer risk.
A phase I does-escalation and expansion study of epidiolex (cannabidiol) in patients with biochemically recurrent prostate cancer.
Authors: Myint Zin , St.Clair William H. , Strup Stephen , Wang Peng , James Andrew Callaway , Yan Donglin , Ellis Carleton Scott , Otto Danielle E. , DiPaola Robert S. , Arnold Susanne M. , Kolesar Jill 
Published: February 2022

257 Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have anti-tumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients’ prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily; two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in >10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease. Clinical trial information: NCT04428203.
External beam radiation therapy with or without brachytherapy boost for low PSA, high-grade prostate cancer.
Authors: Fischer-Valuck Benjamin Walker , Baumann Brian Christopher , Dhere Vishal Ramesh , Brenneman Randall , Gay Hiram Alberto , Andruska Neal , Brown Simon A. , Hershatter Bruce , Michalski Jeff M. , Patel Sagar Anil 
Published: February 2022

258 Background: Radiation dose escalation with the addition of a brachytherapy boost (BT) to external beam radiation therapy (EBRT) may be associated with improved survival in certain men with Gleason grade 5 (GG5) prostate cancer (PCa). However, low PSA, high-grade PCa has much worse outcomes, is associated with neuroendocrine genomic features, and may be more resistant to androgen suppression. It is unclear whether the addition of a BT boost in men with this disease subgroup is associated with a survival benefit and is the subject of this analysis. Methods: Men diagnosed with node-negative, non-metastatic GG5 PCa and treated with (1) EBRT plus ADT or (2) EBRT plus BT plus ADT between 2004 and 2015 were identified in the National Cancer Database (NCDB). The EBRT cohort received conventionally fractionated ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy x 20-28 fractions) EBRT. EBRT plus BT cohort received external beam doses of conventionally fractionated ≥45 Gy or moderately hypofractionated (2.5 Gy x 15 – 18 fractions) radiation, and either LDR or HDR BT. Men receiving chemotherapy, immunotherapy, or any form of surgery were excluded. Patients were stratified into two groups based on whether the presenting PSA was above or below the normal threshold (≤4 and > 4 ng/mL). OS was compared using the Kaplan-Meier and log-rank test. Multivariable analysis (MVA) using Cox proportional hazards regression modeling was performed, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, treatment facility type, Gleason Score (9 versus 10), and clinical T-stage. Results: 8,260 men met study inclusion criteria of which 658 (8%) presented with PSA ≤4. 572 (87%) patients were treated with EBRT monotherapy and 86 (13%) patients were treated with EBRT + BT. 5-year OS for EBRT versus EBRT plus BT was 79.7 +/- 2.3% versus 86.9 +/- 5.0%, respectively (P = 0.49). On MVA analysis, EBRT plus BT was not associated with improved OS versus EBRT (adjusted HR 0.90, 95% CI 0.52-1.87; P = 0.62). In comparison, for men with PSA > 4 and GG5 disease [EBRT: 6,780 patients (89.2%) & EBRT plus BT: 822 patients (10.8%)], EBRT plus BT was associated with improved OS versus EBRT (adjusted HR 0.85, 95% CI 0.66-0.99; P = 0.044). Conclusions: Receipt of dose-escalated prostate radiation by means of a BT boost was not associated with improved survival in men with PSA ≤4 ng/mL and GG5 prostate cancer. By contrast, an association with improved survival was observed in men with GG5 disease and higher initial PSA. This low PSA, high-grade subgroup may represent a unique risk tier for which current treatment paradigms need further investigation, including study of escalated systemic therapy.
M2 macrophage increase in prostate adenocarcinoma after high-dose rate brachytherapy.
Authors: Kundu Palak , Kane Nathanael , Lim Andrew , Ma Ting Martin , Li Yunfeng , Huang Rong Rong , Ye Huihui , Lee Alan , Nickols Nicholas George , Chang Albert 
Published: February 2022

271 Background: Brachytherapy delivers high doses of hypofractionated radiation (RT) internally within the prostate tumor. While radiation has been shown to exhibit immunomodulatory effects, the success of combining radiation and immunotherapy in prostate cancer has been limited. M2 macrophages can contribute to an immunosuppressive tumor environment, and we therefore hypothesize that radiation may increase the abundance of M2 macrophage in the prostate tumor immune infiltrate. Methods: 10 Patients with intermediate risk prostate cancer (age 51-78; 7 GS 3+4, 3 GS 4+3) underwent high-dose rate brachytherapy (2 implants, 13.5Gy per implant, 1 week apart). Patients consented to biopsies before each fraction at the first and second implant. Bulk RNA-seq gene expression was performed on formalin-fixed, paraffin-embedded pre- vs. post-RT tumor samples, and then analyzed with a machine learning deconvolution model to resolve immune cell abundances. CD68+CD163+ M2 macrophages were analyzed with multiplex immunohistochemistry and quantified with tissue analysis software. Paired t-test was used to compare M2 macrophage abundance pre- versus post-RT. Results: Bulk RNA-seq deconvolution demonstrated that the most prevalent immune cell types in the pre-RT samples were resting CD4 memory T cells (39.7%), resting mast cells (38.5%), and M2 macrophages (30.4%), while those in the post-RT samples were M2 Macrophages (78.7%), resting mast cells (58.1%), and resting CD4 memory T cells (48%). M2 macrophages demonstrated the greatest increase, which was corroborated by multiplex IHC: average CD68+CD163+ cell counts were significantly elevated after RT (pre-RT 63.7 vs. post-RT 200.1 per mm2, p=0.015). Conclusions: Hypofractionated radiation increases the immunosuppressive M2 macrophage population in prostate cancer, which may present a therapeutic target to augment the efficacy of radiation and immunotherapy combinations.
Patient-reported experience of diagnosis, management, and burden of renal cell carcinomas: Results >2,000 patients in 41 countries, with focus on older patients.
Authors: Giles Rachel H. , Marconi Lorenzo , Martinez Robin , Maskens Deborah , Kastrati Karin , Castro Carlos , Julian Mauro Juan Carlo , Bick Robert , Heng Daniel Yick Chin , Larkin James , Bex Axel , Jonasch Eric , Maclennan Sara Jane , Jewett Michael A.S. 
Published: February 2022

306 Background: Renal cell carcinoma (RCC) is increasing in global prevalence, thereby increasing burden to health systems, and most of all, to individual patients and their families. Little is known about the variations in patient experience and best practices among countries. Here, we report on the second biennial Global Patient Survey on the diagnosis, management, and burden of Renal Cell Carcinomas conducted by the International Kidney Coalition (IKCC) worldwide in 13 languages. The aim of the survey was to improve collective understanding and to contribute toward the reduction of the burden of kidney cancer around the world. Methods: A 35-question survey on the diagnosis, management, and burden of RCC was designed by a multi-country steering committee to identify geographic variations in 6 topics: patient education, experience and awareness, access to care and clinical trials, best practices, quality of life, and unmet psychosocial needs. The survey was distributed to patients with kidney cancer and their caregivers in 13 languages, through IKCC’s 46 Affiliate Organisations and social media from 29 Oct 2020 to 5 Jan 2021. Results: 2,012 responses came from 41 countries. Survey results were analysed using cross-tabulations by an independent third-party organisation. The full global report is publicly available, as well as 7 individual country reports where at least 100 responses were received. 42% reported that the likelihood of surviving their cancer beyond 5 years was not explained Just over half (51%) reported that they were involved as much as they wanted to be in developing their treatment plan. 56% experienced barriers to their treatment 41% indicated that “No one” discussed cancer clinical trials with them 31% were invited to take part in a clinical trial 45% self-reported that they were insufficiently active 50% indicated that they ‘very often’ or ‘always’ experienced disease-related anxiety. 26% ‘very often’ or ‘always’ experienced stress related to financial issues 55% indicated that they ‘very often’ or ‘always’ experienced a fear of recurrence 52% reported having talked to their doctor/healthcare professional about their concerns 48% had been offered a biopsy in the past with only 3% refusing; 47% would be willing to undergo biopsy in the future Patients aged ≤65 experienced more barriers to quality care, understood their disease less well, and experienced a longer time to diagnosis. Conclusions: The IKCC and its global affiliates will be using the results to ensure that patients’ voices are heard. Actionable points will suggest future projects. Individual countries can use their reports to advance their understanding of patient experiences and to improve local care.
Characteristics associated with common reasons to pursue genomic profiling among patients with metastatic genitourinary cancers.
Authors: Malhotra Jasnoor , Philip Errol James , Govindarajan Ameish , Salgia Sabrina , Meza Luis A , Zengin Zeynep Busra , Muddasani Ramya , Chawla Neal Shiv , Castro Daniela , Chehrazi-Raffle Alex , Dizman Nazli , Bergerot Paulo Gustavo , Hsu Joann , Dorff Tanya B. , Pal Sumanta K. , Bergerot Cristiane Decat 
Published: February 2022

327 Background: Patients with cancer may possess limited knowledge of emerging modalities in oncology, including genomic profiling (GP) tests, which can create barriers to shared decision making. Effective provider communication can address such barriers but little is understood regarding patients’ perceptions of GP. Methods: In this cross-sectional study, patients who were diagnosed with advanced genitourinary cancers (bladder, renal, and prostate cancers), and were referred for GP responded to a survey to assess reasons to pursue such testing. Clinicopathologic characteristics were collected via chart review. Kolmogorov-Smirnov tests were used to assess associations between reasons to pursue GP and patient characteristics. Results: Data was obtained from a sample of 126 patients (gender: 75% M, 25% F; average age: 67; marital status: 78% married; education: 76% some college; histology: 67% renal cell carcinoma, 19% urothelial, and 14% prostate). The most common reasons to pursue GP by patient response were: to guide treatment (73%), to improve treatment response (32%), to follow physician’s indication (27%), to predict treatment response (23%), to learn about their disease (19%), and to contribute to the science (12%). Notably, older age was significantly associated with three reasons (guide treatment, P = 0.001; physician’s indication, P = 0.03; contribute to the science, P = 0.001). No association was found among younger patients. A higher level of education was associated with the desire to guide treatment (P = 0.001). In contrast, a lower level of education was associated with physician’s indication (P = 0.002). Conclusions: This study highlights important associations between reasons to pursue GP and age and level of education. Differing strategies for information delivery could be considered when communicating GP benefits to older patients and to patients with lower levels of education.
Rare intrascrotal tumors in a tertiary cancer center: A retrospective case series.
Authors: Cunha Mateus Trinconi , Cardoso Camila , Fialho de Freitas Guilherme , Silva Jamile Almeida , Muniz David Queiroz Borges , Bastos Diogo Assed , Cardili Leonardo , Mota Jose Mauricio 
Published: February 2022

415 Background: Given their rarity, the literature on non-germ cell testicular tumors and paratesticular malignancies is still scarce. The objective of this study is to describe clinical and pathological features, as well as treatment patterns and outcomes, of patients with non-germ cell intrascrotal malignancies. Methods: Patients (pts) with benign or malignant non-germ cell intrascrotal tumors who were older than 18 years-old were deemed eligible. Electronic health records (EHR) were reviewed to assess pts clinical features, and disease characteristics and outcomes. Descriptive statistics was used to report data. RECIST 1.1 was used to determine radiological response to treatment. Time-to-event variables were estimated by the Kaplan-Meier method. Results: EHR of 885 pts with a primary diagnosis of ICD-10 C62 treated in a tertiary cancer center from January 2009 to June 2020 were reviewed for eligibility. 29 pts fulfilled eligibility criteria (Sertoli cell tumors, N = 3; Leydig cell tumors, N = 6; granulosa cell tumor, N = 1; testicular tumor of the androgenital syndrome, N = 1; mesotheliomas, N = 3; liposarcomas, N = 3; leiomyosarcomas N = 2; rhabdomyosarcomas, N = 3; spindle cell sarcomas, N = 3; lymphomas, N = 2; carcinoma of the rete testis, N = 1; primary neuroendocrine tumor of the testis, N = 1). The majority of pts (N = 25) had non-metastatic disease at diagnosis, and underwent upfront orchiectomy. The remaining four patients had metastatic disease at diagnosis (lymphoma, N = 1; sarcomas, N = 3), all positive for lymph node (LN) involvement; one with concurrent visceral metastasis. Six other pts posteriorly developed metastatic disease after a median follow-up of 13 months (IQR: 5.8–33.1 months) (Leydig tumor, N = 1; mesothelioma, N = 2; sarcomas, N = 3). The most common metastatic sites were LN (N = 8, 80%), lung (N = 4, 40%), bone (N = 3, 30%), adrenal gland (N = 2, 20%), peritoneum (N = 1, 10%), and skin (N = 1, 10%). Nine pts (90%) received systemic treatment: vincristine, doxorubicin and cyclophosphamide for rhabdomyosarcomas (N = 3), cisplatin plus pemetrexed for mesotheliomas (N = 2), doxorubicin for liposarcomas (N = 2), doxorubicin plus ifosfamide for liposarcoma (N = 1) and doxorubicin, vincristine, cyclophosphamide, and prednisone plus rituximab for lymphoma (N = 1). Of those, 2 pts achieved partial response and 2 had stable disease. Metastasectomy of a single lung metastasis was performed in a patient with metastatic Leydig cell tumor. Median overall survival was 51.2 and 24.5 months for patients with localized and metastatic disease, respectively. Conclusions: Paratesticular and non-germ cell testicular tumors are extremely rare entities with relatively good prognosis if treated at early stages depending on the underlying histology. Most metastatic disease cases were due to paratesticular sarcomas.
Role of preoperative albumin in predicting risk of postoperative complications in patients undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Badia Rohit , Jafri Farzan , Baky Fady , Howard Jeffrey , Woldu Solomon L. , Margulis Vitaly , Bagrodia Aditya 
Published: February 2022

416 Background: Testicular cancer with retroperitoneal metastases is often treated with chemotherapy, with subsequent post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) performed for residual masses after chemotherapy. While the cure rate is high, the surgery is associated with significant morbidity. Unlike in other genitourinary cancers, perioperative nutritional optimization is typically not prioritized as most patients are young, otherwise healthy men. Albumin is a systemic marker of nutritional status and has been shown to predict adverse outcomes in other urological cancers. We sought to assess whether preoperative albumin level is associated with postoperative outcomes in patients undergoing PC-RPLND. Methods: A database of patients who received PC-RPLND at our institution between 2007 and 2019 was created. Pre-RPLND albumin was obtained and correlated with postoperative outcomes using univariate and multivariable regression models. The primary outcome was the presence of major (Clavien-Dindo grade ≥ III) complications within 90 days of surgery. Results: Of 76 patients who underwent PC-RPLND, 70 patients had preoperative albumin values available. The median age (IQR) of patients at the time of surgery was 26 years (22 - 32) and median (IQR) preoperative albumin level was 4.4 g/dL (4.1 - 4.6). Patients with major postoperative complications had lower median preoperative albumin than those without a complication (4.1 g/dL vs. 4.4 g/dL; p = 0.03). Greater albumin level (per g/dL) was associated with a lower risk of major postoperative complications on multivariable logistic regression (OR = 0.12; p = 0.03). Other preoperative serum markers such as hemoglobin and creatinine did not associate with postoperative complications. Conclusions: To our knowledge, this is the first study to demonstrate that preoperative albumin is an independent predictor of major postoperative complications in patients undergoing PC-RPLND. This finding demonstrates the importance of nutritional optimization even in young, otherwise healthy individuals prior to undergoing this morbid surgery. Additional studies are warranted to more reliably predict which patients may experience complications.