bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of ctDNA findings at the end of life in patients with prostate cancer.
Authors: Gupta Kanika , Caputo Sydney , Casado Crystal , Jang Albert , Sweeney Patrick L , Lanka Sree M , Pocha Olivia , Hawkins Maddie , Lieberman Alexandra , Schwartz Jennifer , Miller Patrick , Jaeger Ellen B. , Barata Pedro C. , Layton Jodi Lyn , Lewis Brian E. , Ledet Elisa M. , Sartor A. Oliver 
Published: March 2023

230 Background: Somatic alterations change over time in response to treatment and disease progression in patients with prostate cancer (PCa). We report ctDNA findings of patients who died from PCa within 3 months of a ctDNA assessment to better characterize patients with fatal disease. Methods: A total of 118 patients with PCa specific mortality who had been treated at Tulane Cancer Center and had ctDNA assessments between 2015 and 2022. The ctDNA was assessed by Guardant360 (Guardent Health, Inc) assays to identify alterations, pathogenic mutations and/or copy number alterations (CNAs) in cancer-related genes. Clinical annotation including treatment history, genetics, and staging were also obtained. Statistical analyses included Fischer’s Exact and Wilcoxon tests. Results: Of the 118 patients with PCa specific mortality, 42% (49/118) had a ctDNA assessment <3 months from death. Of 49 CRPC patients tested within 3 months of death, the median number of life extending therapies (LET) at death was 5 (2-9). Patients had a median of 2 (0-6) LET prior to first ctDNA screening and 3 (0-7) LET in between first and last ctDNA assessment. Of the total gene alterations detected on ctDNA analysis, within 3 months of death, the most common alterations detected were 65.3% (32/49) TP53, 44.9% (22/49) AR, 28.6% (14/49) EGFR, 24.5% (12/49) PIK3CA, 22.4% (11/49) MYC, and 20.4% (10/49) CDK6. In a paired analysis(n= 45) of first and last ctDNA screening, AR (OR= 2.35, 95% C.I. (0.99, 5.62), p= 0.05), CDK6 (OR= 4.00, 95% C.I. (1.02, 15.68), p= 0.04), FGFR1 (OR= 9.51, 95% C.I. (1.14, 79.61), p= 0.03), and EGFR (OR= 9.71, 95% C.I. (2.06, 45.83), p= 0.0009) were significantly more likely to be detected in ctDNA screening within 3 months of death. In addition, ctDNA alterations in general were significantly more likely to be detected at the end-of-life (p=< 0.00001). Other ctDNA gene mutations did not have statistically significant increases. Conclusions: An analysis of patients with PCa mortality showed most frequent gene alterations in TP53, AR, EGFR, PIK3CA, MYC, and CDK6. When comparing patients’ first and last ctDNA, alterations were significantly more likely by time of death in AR, CDK6, EGFR, FGFR and there was a significant increase in overall detection of somatic alterations in ctDNA. These analyses are limited to the genes assessed on the ctDNA panel and may or may not reflect all of the functionally relevant alterations. Further the CNAs reported herein may reflect broad genomic changes rather than specific gene alterations.
Characterizing changes in tumor mutational burden (TMB) by serial circulating tumor DNA (ctDNA) testing in patients with advanced prostate cancer (aPC).
Authors: Childs Daniel S , Kwon Eugene D. , Ahmed Mohamed E. , Mahmoud Ahmed , Rodrigues Pessoa Rodrigo , Nabavizadeh Reza , Tsai Jill , Drusbosky Leylah , Bucheit Leslie 
Published: March 2023

239 Background: In part, TMB guides therapeutic decisions on the use of immune checkpoint inhibitors (ICIs) in aPC. Most patients (pts) with aPC do not have high TMB (TMB-H) at the time of initial assessment. However, TMB changes over time (from treatment pressure) as pts progress through lines of therapy (LOT) has not been extensively explored in aPC. We describe real world data on changes to blood TMB (bTMB) in pts with aPC exposed to several LOT. Methods: Genomic results from pts with aPC who had ≥1 ctDNA test(s) with TMB analyzed (Guardant360, Guardant Health, Inc) as part of clinical care from Oct 2020 – Jun 2022 were retrospectively queried. Clinical factors were extracted from test requisition forms; pts from Mayo Clinic had additional factors, including intervening treatment, extracted from medical records. High bTMB (TMB-H) was defined as ≥13.4 mut/Mb, as previously reported. Proportions were compared using Fisher’s Exact Test. Results: 316 patients with a median age of 72 (range: 44-91) were analyzed. Initial median TMB for the entire cohort was 8.18 mut/Mb (range: 0.01-268.3). On subsequent test, TMB decreased in 122(40%), increased in 173(55%), of whom 29 (17%) became TMB-H; 21 (7%) had unchanged TMB. Median time between tests was 182 days (range: 21-578). 101 patients with 262 tests and a median age of 71 years (range: 46-87) were clinically annotated in the Mayo cohort of whom 58 had >2 consecutive TMB scores: 25 (43%) had TMB increase, of whom 4 (16%) became TMB-H, 23 (40%) had TMB decrease, 10 (17%) had dynamic changes with increases and decreases. Numeric but not statistically significant differences in clinical factors were observed between groups (p>0.05). Conclusions: In this real world cohort, variation in TMB is seen with increasing LOT. Importantly, nearly 1 in 5 patients with increasing tumor mutational burden develop TMB-H, which may be a clinically actionable finding as these pts become eligible for ICI. Findings underscore the importance of repeat genetic testing with time and LOT. [Table: see text]
Evaluation of ctDNA in patients treated with lutetium-177-PSMA-617.
Authors: Lanka Sree M , Jang Albert , Sweeney Patrick L , Gupta Kanika , Caputo Sydney , Casado Crystal , Huang Minqi , Pocha Olivia , Hawkins Maddie , Lieberman Alexandra , Schwartz Jennifer , Jaeger Ellen B. , Miller Patrick , Layton Jodi Lyn , Barata Pedro C. , Lewis Brian E. , Ledet Elisa M. , Sartor A. Oliver 
Published: March 2023

243 Background: Lutetium-177- PSMA-617 (Lu-177) is a radioligand therapy that delivers radiation to PSMA-expressing cells in patients with advanced prostate cancer. In this study, we aimed to analyze ctDNA in responders and non-responders after Lu-177 treatments. Methods: Data was retrospectively collected on 31 heavily pre-treated metastatic CRPC patients who received Lu-177 treatment at Tulane Cancer Center. All patients fulfilled VISION criteria for treatment and all had ctDNA assessment with Guardant 360 within 30 days prior to first treatment with Lu-177. Of the 31 patients, 7 had paired ctDNA assessment both prior initiation of treatment and at the end of treatment. Clinical data such as PSA response (PSA decline 50% or more) to Lu-177, initial diagnosis, pathology, treatment history, and relevant germline genetic data were collected. Results: Of the 31 patients who received Lu-177 treatment, 18 had PSA response to Lu-177 (responders) and 13 did not (non-responders). In ctDNA mutational analyses, there were no significant differences detected prior to treatment between responders and non-responders. There was, however, a significant increase in the presence of copy number amplifications in non-responders (n= 11/13) when compared to responders (n= 7/18) (OR= 8.64, 95% C.I. [1.46, 51.25)], p = 0.0250). Amplification was detected in 10 genes in non-responders, whereas responders only had amplifications in AR (7/18) and EGFR (1/18). The most frequently amplified genes in non-responders were AR (8/13), CCNE1 (6/13), EGFR (4/13), and FGFR1 (4/13). Furthermore, in analysis of the 7 patients with paired ctDNA assessments, amplifications increased during treatment with Lu-177. Conclusions: Radioligand therapy with Lu-177 has been shown to prolong life and reduce disease progression. Our analysis of the cohort of Lu-177 treated patients showed that the presence of gene amplifications in ctDNA may play a role in predicting resistance to treatment with Lu-177.
Pathogenic BRAF mutations in prostate cancer: Frequency and distribution.
Authors: Ledet Elisa M. , Mauer Elizabeth , Chao Calvin Y. , Sartor A. Oliver 
Published: March 2023

257 Background: Human cancers are known to harbor mutations in BRAF, a rare but clinically significant finding. BRAF p. V600E is the most common hot spot mutation and has been well described, however other activating mutations are less well studied. Herein we evaluate the landscape of BRAF pathogenic/likely pathogenic (P/LP) variations in prostate cancer patients. Methods: De-identified records from patients with primary prostate cancer who underwent NGS with Tempus xF (ctDNA, 105 genes) or xT (tissue, DNAseq of 648 genes, 500× coverage, full transcriptome RNAseq for a subset of patients) were analyzed from a real-world dataset. Results: There were 5,902 patients identified with prostate cancer who underwent any Tempus xT testing, of whom 85 (1.4%) harbored a P/LP BRAF mutation. Of these 85 patients, the most prevalent BRAF mutation identified was BRAF K601E (Lys601Glu) (36% of total), followed by Gly469Ala (18%) and Leu597Arg (8%, Table) There were 4,177 patients identified with primary prostate cancer who underwent any Tempus xF testing, of whom 50 (1.2%) harbored a P/LP BRAF mutation. Similarly, the most prevalent BRAF mutation identified was BRAF K601E (26%). Conclusions: This study presents the first large-scale genomic characterization of BRAF mutations in patients with prostate cancer using both tissue and ctDNA NGS analysis. Among thousands of samples from prostate cancer patients, K601E was the most common BRAF mutation. This confirms findings of smaller studies and has implications for developmental therapeutics. Further studies should document the natural history of BRAF K601E in prostate cancer. [Table: see text]
The impact of genomic biomarkers on a validated clinical risk prediction model for upgrading/upstaging among men with low-risk prostate cancer.
Authors: Braun Avery , Cowan Janet E. , Chan June M. , Neuhaus John , Carroll Peter , Cooperberg Matthew R. 
Published: March 2023

262 Background: While active surveillance (AS) is the preferred management strategy for men diagnosed with low-risk prostate cancer (PCa), the inability to distinguish indolent from aggressive tumors in clinically low-risk patients complicates decision-making. Genomic classifiers (GCs) were introduced to improve risk stratification, based on their ability to predict the risk of upgrading or upstaging (UG/US) in this setting. We assessed the impact of GCs on UG/US risk prediction added to a rich clinical model to better guide management decision-making for low-risk patients. Methods: We used multivariate logistic regression and receiver operating characteristic (ROC) curves to develop a prediction model for UG/US in men with low-risk, low-volume intermediate-risk PCa who were potential candidates for AS. The model was developed among 864 men and validated in an independent cohort of 2,267 men with similar risk profiles. After computing areas under the ROC curve (AUC) from these probabilities, we tested the model’s predictive ability with the addition of a series of GCs (OncoType Dx Genomic Prostate Score, Decipher score, and selected Decipher GRID scores) using the logistic model constructed for the development cohort to estimate the predicted probability of UG/US. Results: The prediction model for the development cohort included five diagnostic variables that were significantly associated with risk of UG/US: diagnostic grade (OR 5.83, 95% CI 3.73-9.10), PSA (OR 1.10, 95% CI 1.01-1.20), percent positive cores (OR 1.01, 95% CI 1.01-1.02), TRUS prostate volume (OR 0.98, 95% CI 0.97-0.99), and age (OR 1.05, 95% CI 1.02-1.07). The pooled AUC was 0.72 for 10 iterations of the model. When the addition of GCs was applied to this model, Genomic Prostate Score was independently associated with risk of UG/US (OR 1.42, 95%CI 0.016-0.066, p=0.017). However, the pooled AUC was 0.71, indicating comparable predictive performance to the risk prediction model. Conclusions: The addition of GCs to a validated rich model incorporating detailed clinical variables, when applied to favorable-risk PCa patients, did not substantially improve prediction of UG/US. Our findings suggest that widespread use of biomarkers to guide management or the intensity of follow up may not be supported in men with low-risk, low-volume disease pursuing AS.
Association of exposure of Camp Lejeune contaminated water and prostate cancer outcomes.
Authors: Deshler Leah N. , Morgan Kylie M. , Duran Elizabeth A. , Nelson Tyler J. , Guram Kripa , Rose Brent S 
Published: March 2023

265 Background: There is evidence that exposure to contaminated water while serving at Camp Lejeune is associated with the development of genitourinary cancers including kidney and bladder; however, there is a lack of literature regarding prostate cancer (PC). We investigated disease severity at diagnosis, overall survival, and cumulative incidence of metastases for PC patients within the Veterans Health Administration (VHA) who served at Camp Lejeune. Methods: The cohort included men diagnosed with PC between 1999 and 2022 within the VHA Database. Patients who were housed at or had one or more Military Service Episodes between August 1, 1953 and December 31, 1987 at Camp Lejeune were considered to have exposure. Camp Lejeune exposure status and baseline characteristics were ascertained through the VHA electronic health records. Logistic regressions were used to analyze associations between Camp Lejeune exposure and adverse diagnostic characteristics, adjusted for demographic covariates. The outcome of metastases was identified through natural language processing from cancer or radiology documents. Time to metastases was defined as the time from PC diagnosis to metastases, with other causes of death considered as competing risks. The hazard ratio for the association between Camp Lejeune exposure and metastatic disease was calculated with a Cox regression model, controlling for covariates. The difference in overall survival was assessed with the Kaplan-Meier method and log-rank test. Results: The cohort included 6,918 men with PC, 1,635 (23.6%) of which had Camp Lejeune exposure and 5,283 (76.4%) without. Median age at diagnosis was 65 years. Logistic regression models indicated patients with Camp Lejeune exposure have similar odds of having Gleason Score ≥8 at diagnosis (odds ratio (OR) 0.97, p=0.62) and metastasis at diagnosis (OR 1.00, p=0.997), and slightly lower odds of PSA >20 ng/mL at diagnosis (OR 0.78, p=0.02).There were 803 patients with metastatic disease, 159 of which had Camp Lejeune exposure in comparison to the 644 that did not. The 10-year cumulative incidence of metastases for those with Camp Lejeune exposure was 11.9% (CI: 9.9-13.9%), while for those without exposure it was 14.0% (CI: 12.8-15.1%). The Cox proportional hazards model indicated that those with Camp Lejeune exposure had a similar risk of developing metastases (hazard tatio (HR) 0.93, p=0.43) compared to those without exposure. The 10-year overall survival was similar for those with Camp Lejeune exposure (83.3% [CI: 80.7-85.9%]) compared to those without exposure (82.5% [CI: 81.1-83.9%]) (p=0.2). Conclusions: In contrast to kidney and bladder cancers, Camp Lejeune exposure is not associated with worse outcomes for PC. Further research should be conducted to test whether Camp Lejeune exposure affects the risk of developing PC. However, these data do not support Camp Lejeune exposure playing a large role in PC outcomes.
Oncologist-driven development of an electronic health record (EHR) clinical data visualization tool for prostate cancer.
Authors: Ganta Teja , Anker Jonathan Forrest , Miller Eric James , Kannry Joseph , Bhardwaj Aarti Sonia , Tsao Kai , Oh William K. 
Published: March 2023

267 Background: Clinical information management is a burdensome process for oncology providers owing to the complexity of modern cancer data. The results that a clinician needs to review are often spread across several areas within the EHR, making it cumbersome to sense a broad overview of patient status. The purpose of this study is to describe a framework for oncologist-driven development of a data visualization tool to trend cancer biomarkers and assess the feasibility of this tool to query and display EHR data relevant for the treatment of prostate cancer. Methods: A clinical sponsor is selected to identify data elements necessary to make treatment decisions for patients receiving therapy for prostate cancer and to provide rapid feedback for the clinical tool interface. The commercial EHR database is queried to determine identifying codes for relevant laboratory tests, medications, and procedures. Data elements are assembled using the EHR platform for clinical synopsis and the clinical tool is made available to five genitourinary medical oncologists for initial pilot. Results: Oral prostate cancer medications were queried based on medication therapeutic and pharmaceutical class. In addition, androgen deprivation therapy (ADT) injections were separately identified based on route of administration. Prostate specific antigen (PSA) and testosterone result values were queried using laboratory base and/or common name codes. However, many duplicate entities are found varying by hospital/laboratory site and test assay. The assembled clinical data visualization tool can overlay temporal trends in PSA and testosterone over medication start/stop dates to convey treatment response and signs of early medication resistance. The clinician also has the option to overlay vital signs or other laboratory information to visualize treatment related adverse events (ex. weight gain related to ADT, anemia related to PARP inhibitor therapy, etc.) Lastly, the tool can also highlight the dates of the patient’s last imaging tests to allow clinicians to determine if the patient is due for any follow up imaging. Conclusions: The EHR can support novel data visualization tools for cancer biomarkers that can reasonably support clinical workflows. Development requires an intimate knowledge of EHR data but may still be limited by duplicate or erroneous codes for laboratory results. This issue may be addressed by using standard nomenclature for laboratory results such as LOINC codes but is not currently supported by the commercial EHR. Future work in this area will include formal usability testing from the perspective of oncology providers and patients.
Racial impact (Asian vs. White) on the prognosis of patients with de novo mCSPC: An analysis on LATITUDE, SEER and NCDB.
Authors: Ni Xudong , Luu Michael , Ma Weiwei , Freedland Stephen J. , Daskivich Timothy , Yao Zhu 
Published: March 2023

27 Background: Little is known about the impact of race (Asian or White) on the long-term survival outcomes of men with de novo mCSPC treated with different methods. Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. Methods: This multiple-cohort study included individual patient-level data of men with de novo mCSPC from the following 3 cohorts: LATITUDE clinical trial data (LATITUDE [n=1199]); Surveillance, Epidemiology, and End Results (SEER [n=5496]); and the National Cancer Database (NCDB [n=10366]). Key efficacy outcomes were overall survival (OS) in LATTITUDE and NCDB as well as OS and cancer-specific survival (CSS) in SEER. Kaplan-Meier analysis with propensity score matching (PSM) was used for survival analysis. Hazard ratios were calculated using a multivariate Cox proportional-hazard model. Results: Across all three cohorts, Asian patients diagnosed with de novo mCSPC had better OS and CSS than White patients. In LATITUDE, median OS was significantly longer in Asian than in White men in the ADT+Abiraterone+Prednisone group (not reached vs. 43.8 months, HR 0.47, 95%CI 0.28–0.77, P=0.003 for Cox analysis) as well as in the ADT+placebo group (57.6 months vs. 32.7 months, HR 0.49, 95%CI 0.32–0.75, P=0.001 for cox analysis). In SEER, among all patients diagnosed with de novo mCSPC, median OS was significantly longer in Asian than in White men (53 months vs. 42 months, HR 0.76, 95%CI 0.68–0.85, P<0.001 for Cox analysis). When analyses were restricted to patients who received chemotherapy, Asian men again had longer OS (67 months vs. 41 months, HR 0.70 95% CI 0.51–0.95, P=0.02 for Cox analysis). Using CSS data in SEER resulted in similar conclusions as OS. In NCDB, Asians also had longer OS than White men (whole cohort: 38 months vs. 26 months, HR 0.73, 95%CI 0.63–0.84, P=0.02 for Cox analysis; ADT subgroup: 41 months vs. 26 months, HR 0.75, 95%CI 0.63–0.89, P<0.001 for Cox analysis; Chemotherapy subgroup: 34 months vs. 27 months, HR 0.80, 95%CI 0.69–0.94, P=0.005 for Cox analysis). Conclusions: Asian men had better OS and CSS than White men with mCSPC across different treatment regimens in all datasets examined and should be considered as an independent prognostic factor. This racial difference should also be considered when designing multiregional clinical trials. Further studies including biological analyses are needed to understand the etiology of the apparent survival advantage for Asian men. [Table: see text]
Radiographic-pathologic concordance in the workup of locally radiorecurrent prostate cancer.
Authors: Valle Luca Faustino , Calais Jeremie , Marks Leonard S. , Raman Steven , Reiter Robert Evan , Rettig Matthew , Shen John , Czernin Johannes , Weiner Adam B , Steinberg Michael L. , Nickols Nicholas George , Chang Albert J , Boutros Paul Christopher , Ye Huihui , Hotta Masatoshi , Huang Rong Rong , Kishan Amar Upadhyaya 
Published: March 2023

313 Background: Advanced molecular PET/CT (mPET) studies are increasingly being utilized in conjunction with multiparametric MRI (mpMRI) to evaluate the burden of radiorecurrent disease in men who develop a biochemical recurrence following definitive radiotherapy (RT) for prostate cancer (PCa). However, radiographic concordance with pathologic confirmation of radiorecurrent disease in this setting is poorly described. We sought to conduct a patient-level analysis comparing concordance of radiographic and pathologic findings between mpMRI and mPET. Methods: Men who had previously undergone definitive RT for PCa and subsequently experienced treatment failure defined by the Phoenix definition were enrolled in a prospective registry study wherein radiographically identified local PCa recurrences were biopsied using mpMRI or mPET fusion (Artemis) with real-time ultrasound. Prior to biopsy, men underwent diagnostic imaging with mpMRI, advanced mPET (68Ga-PSMA-11 or 18F-FACBC), or both in order to identify a biopsy target. At least one imaging modality had to reveal a recurrent lesion based on PIRADS or PROMISE imaging classifications in order to prompt biopsy. Radiographic and pathologic findings were classified as either “treatment effect” or “recurrent disease”. Using biopsy as the reference standard, positive predictive value (PPV) was evaluated for mpMRI and mPET modalities separately. Results: Of 28 patients with radiographic recurrence on mpMRI or mPET, 10/28 (35.7%) exhibited treatment effect without evidence of active cancer on biopsy confirmation. Prostate adenocarcinoma was identified in 17/28 patient biopsies, whereas small cell prostate cancer was present in 1 patient. All 28 men underwent mpMRI prior to biopsy and 23/28 (82.1%) additionally underwent mPET; 19/23 (82.6%) underwent 68Ga-PSMA-11 and 4/23 (17.4%) were imaged with 18F-FACBC. Concordance in the assessment of recurrent disease between mpMRI and mPET was achieved in 12/23 (52.2%) men who underwent both imaging modalities. Among the 28 men who underwent mpMRI, PPV was 0.84, whereas PPV for the 23 men who underwent mPET was 0.70. Conclusions: In patients for whom clinical suspicion of radiorecurrence was high enough to warrant a biopsy, pre-biopsy mpMRI outperforms mPET in terms of PPV for detecting pathologically confirmed locally radiorecurrent PCa. Used in tandem, mpMRI and mPET might better select appropriate candidates for biopsy than either radiographic modality alone. While advanced mPET remains promising for detecting distant recurrences at the time of RT failure, biopsy confirmation following radiographic detection of local radiorecurrence remains essential for evaluating the true burden of local recurrence.