bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential metastasis-directed therapy (MDT) for oligometastatic prostate cancer (Oligo PCa) assessed by PET-based imaging.
Authors: Carretero-González Alberto , Kwon Daniel , Shakhnazaryan Nonna , Hong Julian C. , Mohamad Osama , Feng Mary Uan-Sian , de Kouchkovsky Ivan , Borno Hala , Bose Rohit , Chou Jonathan , Desai Arpita , Fong Lawrence , Friedlander Terence W. , Koshkin Vadim S , Feng Felix Y , Aggarwal Rahul Raj , Hope Thomas A. , Small Eric Jay 
Published: June 2023

5032 Background: Prostate specific membrane antigen (PSMA) and F-18-Fluciclovine PET imaging have high sensitivity for the detection of prostate cancer (PCa) metastases. MDT with stereotactic body radiation therapy (SBRT) to PET-detected Oligo PCa has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT). However, in those patients (pts) who ultimately develop oligoprogressive disease following MDT, the utility of subsequent courses of MDT has not been well defined. Methods: A single institution retrospective review was undertaken to describe outcomes following ≥2 courses of PET-guided SBRT in pts with Oligo PCa. Pts included in this analysis had undergone initial SBRT for ≤5 PCa lesions detected on PSMA or Fluciclovine PET, and subsequently underwent ≥1 additional course of SBRT at progression. Baseline data collected included stage, PSA level, Gleason Score, tracer type, and concurrent systemic therapy. Endpoints collected for each SBRT course included PSA decline ≥50% (PSA50), PFS, and systemic therapy change free survival (RxFS) (initiation of ADT, or for pts already on ADT, addition of an androgen signaling inhibitor). Association of factors with PFS after SBRT2 were analyzed using multivariable Cox proportional-hazards models. Results: 34 pts underwent ≥2 courses of MDT (SBRT1, SBRT2). At SBRT2, progression was identified by PSMA-PET in 26 (77%) pts, and by Fluciclovine-PET in 8 (23%). With SBRT2, 18 (53%) had a concurrent systemic therapy change; 10 (29%) did not receive any systemic therapy. 12 pts subsequently underwent SBRT3. Progression was detected by PSMA PET in 9 (75%) and Fluciclovine PET in 3 (25%). Clinical outcomes are summarized in the table. In the multivariable analysis, predictors associated with PFS following SBRT2 were 1) PSA decline at SBRT1 (HR 1.10, 95% CI 1.05-1.16, P<0.001) and 2) PSA doubling time (PSADT) < 12 months at the time of SBRT2 (HR 11.52, 95% CI 1.36-97.38, P 0.025). Overall, from SBRT1 to last follow-up (median 25.2 months), 23 (68%) pts remained ADT-free (14 after SBRT2; 9 after SBRT3). Conclusions: Serial MDT for Oligo PCa detected on PSMA or Fluciclovine PET is feasible and results in PSA declines, independent of change in systemic therapy. There is a persistent but diminishing benefit of MDT over successive courses. Overall, 2/3 of pts were able to postpone the use of ADT. PSA decline at SBRT1 and PSADT at SBRT2 may be biomarkers for SBRT2 benefit. Despite the retrospective nature of this study and cohort heterogeneity, these data provide a rationale for serial SBRT in Oligo PCA, and the need for larger, prospective studies of this strategy. [Table: see text]
Genetic ancestry associations with somatic mutations in a real-world cohort of over 3,000 patients with prostate cancer.
Authors: De La Vega Francisco M , Rhead Brooke , Pouliot Yannick , Guinney Justin , Craig David W , Carpten John D. 
Published: June 2023

5034 Background: Disparities in incidence and outcomes of prostate cancer among racial groups have been reported. Black men have a higher incidence of prostate cancer compared to White men and are more likely to be diagnosed at a later stage, resulting in poorer outcomes. These differences are likely due to a combination of genetic, socioeconomic, and healthcare access factors. Furthermore, evidence has revealed racial differences in molecular profiles of prostate cancer, such as a higher incidence of ERF mutations and increased transcriptional activation of the androgen receptor signaling and inflammatory pathways in tumors derived from Black men compared to White men, suggesting that underlying biology may contribute to these disparities. Here, we aimed to identify differences in the mutational profiles of prostate cancers by race and genetic ancestry in a de-identified real-world cohort of 3,804 patients that underwent the Tempus xT 648-gene NGS tumor profiling test. Methods: We used 654 ancestry-informative markers to estimate continental ancestry likelihoods for five regions: Africa (AFR), Americas (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS). We imputed Asian (ASN, n=122), Hispanic/Latino/Native American (HLN, n=300), Non-Hispanic Black (NHB, n=619) and Non-Hispanic White (NHW, n=2,679) categories using genetic ancestry thresholds based on literature and validated with available metadata. Associations between either race/ethnicity categories or continental ancestry proportions and somatic variants (copy number alterations (CNAs), small nonsynonymous, OncoKB L1/2 & R1, and predicted driver somatic mutations) were assessed for 109 prostate cancer-related genes using logistic regression models. Likelihood ratio tests were used to compare models with and without race/ethnicity or ancestry terms, and the Benjamini-Hochberg method was used to adjust p-values and control the FDR at 5%. Results: NHB and ASN men had lower odds of having a PTEN CNA compared to NHW men (OR=0.58 and 0.40, p=0.0001 and 0.009, respectively). Confirming this finding was a positive association between EUR ancestry and PTEN CNAs (OR=1.07 per doubling of EUR ancestry proportion, p=0.0007). NHB men were also less likely to have actionable OncoKB somatic mutations in the PIK3CA gene when compared to NHW men (OR=0.48, p=0.03). Increased AFR ancestry was associated with the presence of nonsynonymous predicted driver mutations in SPOP (OR=1.04, p=0.04), while both EAS and SAS ancestries were associated with fewer such mutations in TP53 (OR=0.95 in both cases, p=0.02 and 0.003). Conclusions: Analysis of a large real-world cohort leveraging genetic ancestry inferred from NGS data confirms previously known associations between the presence of somatic alterations in prostate cancer genes and race/ethnicity, and identifies novel associations of potential precision therapeutic relevance.
Association of plant-based diet index with quality of life in patients with prostate cancer.
Authors: Loeb Stacy , Hua Qi , Bauer Scott , Kenfield Stacey A. , Morgans Alicia K. , Mucci Lorelei A 
Published: June 2023

5037 Background: Plant-based diets have many health benefits including a lower risk of fatal prostate cancer. Less is known about the relationship between diet and functional outcomes among prostate cancer survivors. We hypothesized that greater consumption of plant-based food after prostate cancer diagnosis is associated with improved quality of life (QOL). Methods: This prospective cohort study included 3,505 participants in the Health Professionals Follow-up Study with non-metastatic prostate cancer (1986-2016). Overall and healthful Plant-based Diet Indices were calculated from food frequency questionnaires with cumulative updating. QOL scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations between Plant-based Diet Indices and 5 QOL domains, adjusted for clinical and demographic factors. Results: Higher Plant-Based Diet Index was associated with improved scores for sexual function, urinary irritation/obstruction, and urinary incontinence among men with prostate cancer. Consuming more healthful plant-based foods was also associated with better scores for bowel function and hormonal/vitality in the age-adjusted models. Results were similar in sensitivity analyses excluding patients with pre-existing erectile dysfunction or lower urinary tract symptoms, and adjusting for use of sexual or urinary medications. A limitation is that no participants followed a strict vegan diet. Conclusions: This prospective study suggests that greater consumption of healthful plant-based foods is associated with modest improvements in QOL domains among patients with prostate cancer. [Table: see text]
64Cu-SAR-bisPSMA (PROPELLER) positron emission tomography (PET) imaging in patients with confirmed prostate cancer.
Authors: Lengyelova Eva , Wong Veronica , Lenzo Nat , Parker Michelle , Emmett Louise 
Published: June 2023

5039 Background: Prostate cancer (PC) is the second most frequent malignancy in men globally. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is overexpressed in PC. Recently, several new 68Ga- and 18F-based PSMA-targeted PET agents have been approved by the FDA to detect PC, which offer improved sensitivity and specificity compared to traditional imaging. Methods: PROPELLER (NCT04839367) investigated 64Cu-SAR-bisPSMA in 30 men with untreated, histopathologically proven, primary PC with intermediate- to high-risk features. At screening, patients completed 68Ga-PSMA-11 PET/CT at 1h post dose. Following enrollment, patients received either 100MBq, 150MBq or 200MBq of 64Cu-SAR-bisPSMA, followed by PET/CT at 2-4h post dose. Safety was evaluated before and after 64Cu-SAR-bisPSMA dosing. The 68Ga-PSMA-11 and 64Cu-SAR-bisPSMA PET/CT scans were evaluated by 2 independent, blinded central readers for image quality, PC detection, and intensity of tracer uptake in lesions (SUVmax and Tumor-to-Background Ratio [TBR]). Results: A single, Grade 1 64Cu-SAR-bisPSMA-related AE was reported in the 200MBq cohort. Both readers scored 200MBq of 64Cu-SAR-bisPSMA as the dose providing the highest image quality. In this cohort, 64Cu-SAR-bisPSMA and 68Ga-PSMA-11 was able to detect primary PC in 100% and 77.8% of patients for Reader 1 and 85.7% and 83.3% of patients for Reader 2, respectively. In the 200MBq cohort, Reader 1 identified 41 lesions with 64Cu-SAR-bisPSMA vs 36 lesions with 68Ga-PSMA-11, while Reader 2 identified 31 lesions with 64Cu-SAR-bisPSMA vs 22 lesions with 68Ga-PSMA-11. In the 200MBq cohort, 64Cu-SAR-bisPSMA consistently showed higher uptake compared to 68Ga-PSMA-11 (SUVmax: Reader 1 median [IQR]: 31.40 [27.45] vs 10.08 [13.92], p < 0.001, Reader 2 median [IQR]: 41.00 [46.09] vs 14.58 [14.98], p < 0.001); TBR: Reader 1 median [IQR]: 49.07 [67.69] vs 21.91 [35.71], P = 0.0015), Reader 2 median [IQR]: 76.34 [66.37] vs 23.90 [33.05], p < 0.001). Conclusions: 64Cu-SAR-bisPSMA was safe and effective for detecting PSMA-expressing lesions. 200 MBq of 64Cu-SAR-bisPSMA was determined as the optimal dose for future trials. 64Cu-SAR-bisPSMA PET/CT showed a greater number of lesions and lesions exhibited significantly higher uptake when compared to 68Ga-PSMA-11 in men being with intermediate- to high-risk PC. Further studies to evaluate 64Cu-SAR-bisPSMA as an imaging agent in patients with biochemical recurrence of PC are underway. Clinical trial information: NCT04839367 .
Prognostic factors for relapse in patients with clinical stage I testicular seminoma: A nationwide, population-based cohort study.
Authors: Wagner Thomas , Toft Birgitte Grønkær , Lauritsen Jakob , Bandak Mikkel , Christensen Ib Jarle , Engvad Birte , Jessen Michael Kreiberg , Agerbaek Mads , Dysager Lars , Rosenvilde Josephine , Berney Daniel , Daugaard Gedske 
Published: June 2023

5041 Background: Approximately 20% of patients with clinical stage I testicular seminoma will relapse after orchiectomy. No robust prognostic factors for relapse exist which challenges risk assessment and counselling for patients. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We therefore assessed prognostic factors for relapse in a large unselected nationwide population-based setting with centralized pathology review. Methods: Patients with clinical stage I seminoma diagnosed in Denmark between 2013 and 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, microscopic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified clinical and histopathological prognostic factors and relapse were assessed by use of Cox regression analysis. Potential prognostic factors included age, pre-orchiectomy values of β-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH), tumor size, tumor multifocality, tumor necrosis, lymphovascular invasion, pagetoid rete involvement, and invasion of rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea, and tunica vaginalis. Results: In total, 924 patients were included. During a median follow-up of 6.3 years, 148 (16%) patients relapsed. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated pre-orchiectomy levels of β-hCG and LDH were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors, to 64% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the model had an overall concordance statistic of 0.70. Conclusions: The provided prognostic factors allow a long-awaited opportunity to make more informed treatment decisions about post-orchiectomy management in patients with clinical stage I seminoma. These should replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies. [Table: see text]
Hospital Anxiety and Depression Scale (HADS) score trends among testicular cancer survivors: A longitudinal study.
Authors: Alkhatib Khalid Y. , Roberson Daniel , Talwar Ruchika , Jia Hanna , Nathanson Katherine , Malkowicz S. Bruce , Guzzo Thomas J. , Pierorazio Phillip , Jacobs Linda A. , Vaughn David J. 
Published: June 2023

5042 Background: The rarity of testicular germ cell tumors, in conjunction with the young age of its patients, makes it challenging to study its long-term adverse effects. We sought to investigate the changes in Hospital Anxiety and Depression Scale (HADS) scores over time in our institutional cohort of testicular cancer (TC) survivors, hypothesizing that anxiety and depression indices will improve over time, and specifically after treatment completion. Methods: A longitudinal analysis of TC survivors at the University of Pennsylvania between 2013 and 2020, quality of life metrics were measured annually during routine clinic visits. A validated HADS score was utilized to calculate indices of anxiety and depression. Multivariable linear mixed-effects regression models adjusted for pathology type, stage, treatment type, age, marital status, education, income, insurance, employment status, living situation, and time from diagnosis to first survey administration were used to calculate the mean predicted HADS, HADS-Anxiety, and HADS-Depression scores. ANOVA was used to test for parallelism and changes between survey scores. Each item is rated on a 4-point scale (ranging from 0 = no not at all, to 3 = yes definitely), for a total score ranging from 0-21 for each sub-scale with a cut-off point of 8/21 for anxiety or depression. Results: A total of 353 patients were included in the study. Baseline mean scores were 7.3, 4.9, and 2.4 for HADS overall, HADS-Anxiety, and HADS-Depression, respectively. Mean scores did not change over time, ANOVA testing of p=0.84, p=0.78, and p=0.0.65 for overall HADS, HADS-Anxiety, and HADS-Depression, respectively. Stratification by pathology, stage, or treatment did not show any significant interaction. Conclusions: Our data demonstrates that there was no significant change over time in HADS scores, thus considering the risks associated with depression and anxiety, such as suicide, it is essential to consider early referrals to psychiatric services. Our results are from a single institution, limited by a small sample size, and data lacks granularity, including mental health history. Nonetheless, our findings serve as a framework for future prospective studies of TC survivors.
Penile squamous cell carcinoma (PSCC) with elevated tumor mutational burden (TMB): A genomic landscape study.
Authors: Sager Rebecca A , Spiess Philippe E. , Li Roger , Grivas Petros , Kamat Ashish M. , Necchi Andrea , Pavlick Dean C. , Huang Richard S.P. , Lin Douglas I. , Ross Jeffrey S. , Danziger Natalie , Jacob Joseph M , Bratslavsky Gennady 
Published: June 2023

5044 Background: TMB has emerged as a novel biomarker of immune checkpoint inhibitor (ICPI) response in a wide variety of malignancies, but not yet in PSCC. Methods: 397 clinically advanced PSCC underwent hybrid capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). TMB was determined on up to 1.1 Mb of sequenced DNA and categorized into three groups: <10 mutations/Megabase [muts/Mb] (low), 10-19 muts/Mb (high), and >20 muts/Mb (very high). MSI was determined on 114 loci. Genome-wide loss of heterozygosity (gLOH) was determined using validated pipelines and PD-L1 expression by IHC (TPS and Dako 22C3). Statistical comparisons utilized the Bonferonni correction method. Results: There were 339 (85.4%) TMB low, 40 (10.1%) TMB 10-19 and 18 (4.5%) TMB very high PSCC cases. The mean age of PSCC with very high TMB at 70.1 yrs was older than TMB low at 63.4 yrs (p=.08). The GA per tumor frequencies ranged from 5.4 to 5.5 in the 3 groups. There were no significant differences in genomic ancestry among the 3 groups. The TMB 10-19 and TMB very high tended to feature an APOBEC genomic mutational signature more than the TMB low PSCC cases (74 and 76% vs 44%). MSI high status was absent in the TMB low PSCC, but was present in 7.5% in the TMB 10-19 and 11.8% in the TMB very high cases. gLOH levels above 16% were similar in all 3 groups and ranged from 6.2 to 9.4%. GA associated with differences in TMB status in the PSCC cases included higher PIK3CA GA in TMB 10-19 (40.0%) vs TMB low (18.3%; p=.035) and TMB very high (66.7%) vs low (p=.0002). CDKN2A GA were higher in TMB low (45.7%) than the combined TMB 10-19 + very high (25.9%; p=.049). GA in KMT2D were higher in the combined TMB 10-19 + very high (29.3%) than TMB low (7.7%; p=0002). FGFR3 GA were similar in all 3 groups. In total, 6.5% of all GA were predicted to be of germline nature. The highest proportions of germline GA were seen for HRR genes ATM and CHEK2 (both 40%) and BRCA2 (37.5%) and PMS2 (40%) linked to Lynch syndrome. PD-L1 expression was not significantly different among the 3 groups with TMB low (78.3%), TMB 10-19 (64.2%) and TMB very high (54.5%). HPV identification was more frequent as TMB increased: 28.3% for TMB low, 50.0% for TMB high and 58.8% for TMB very high groups. Conclusions: The evaluation of PSCC by CGP based on TMB levels reveals significant differences in biomarkers for the near 15% of cases that have TMB ≥10 muts/Mb. TMB and MSI status can also serve as biomarkers of response to SOC anti-PD1 based on the current FDA indications. These data may be useful to provide rationale for inclusion of PSCC in basket or umbrella trials testing novel monotherapies or combination therapies. [Table: see text]
Effects of [177Lu] Lu-PSMA-617 on overall survival in TheraP versus VISION randomized trials: An exploratory analysis.
Authors: Soon Yu Yang , Marschner Ian , Hofman Michael S , Emmett Louise , Davis Ian D. , Stockler Martin R. , Martin Andrew James 
Published: June 2023

5045 Background: Observed effects on overall survival (OS) differed in the first two randomized trials (RCTs) of [177Lu] Lu-PSMA-617 (LuPSMA) in metastatic, castration-resistant prostate cancer. TheraP randomized participants to LuPSMA or Cabazitaxel (CBZ). In TheraP, the CBZ group (n = 101) included 20 participants who crossed over to LuPSMA, and the LuPSMA group (n = 99) included 32 who crossed over to CBZ. VISION randomized participants to treatment with or without LuPSMA, plus physicians’ choice among protocol-defined treatments, excluding CBZ. Thirty-eight percent of control group participants in VISION had received CBZ prior to randomization. This study investigated explanations for differences in these RCTs in the observed effects of LuPSMA on OS. Methods: Individual participant data (IPD) on survival time from VISION was extracted from published survival curves for comparison with IPD from TheraP. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighting (IPCW) were used in TheraP to estimate treatment effects on OS in counterfactual analyses assuming crossover had not occurred in either group, or in both groups. Results: OS was longer in the comparator group of TheraP than the comparator group of VISION (HR: 0.57, 95% CI 0.43 - 0.75) while OS was similar in the LuPSMA groups of VISION and TheraP (HR: 0.92, 95% CI 0.70 - 1.19). No significant differences in OS between the LuPSMA and CBZ groups of TheraP were apparent using counterfactual analyses assuming crossovers had not occurred (No crossover from CBZ: RPSFT HR 0.97, 95% CI 0.62 –1.52, IPCW HR 0.92, 95% CI 0.65-1.32; No crossover from LuPSMA: RPSFT HR 0.97, 95% CI 0.60–1.58, IPCW HR 0.82, 95% CI 0.55–1.24; No crossover from LuPSMA or CBZ: RPSFT HR 0.97, 95% CI 0.53-1.74, IPCW HR 0.82, 95% CI 0.53–1.27). Conclusions: The difference in observed effects of LuPSMA on overall survival in TheraP and VISION are better explained by the use of different comparator treatments in their control groups than by crossovers in TheraP from Cabazitaxel to LuPSMA, or LuPMSA to Cabazitaxel. Clinical trial information: NCT03392428 , NCT03511664 .