bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying optimized YOLOv8 for heritage conservation: enhanced object detection in Jiangnan traditional private gardens
Authors: Gao Chan , Zhang Qingzhu , Tan Zheyu , Zhao Genfeng , Gao Sen , Kim Eunyoung , Shen Tao
Published: January 2024

This study aims to promote the protection and inheritance of cultural heritage in private gardens in the Jiangnan area of China. By establishing a precise visual labeling system and accelerating the construction of a database for private garden features, we deepen the understanding of garden design philosophy. To this end, we propose an improved Jiangnan private garden recognition model based on You Only Look Once (YOLO) v8. This model is particularly suitable for processing garden environments with characteristics such as single or complex structures, rich depth of field, and cluttered targets, effectively enhancing the accuracy and efficiency of object recognition. This design integrates the Diverse Branch Block (DBB), Bidirectional Feature Pyramid Network (BiFPN), and Dynamic Head modules (DyHead) to optimize model accuracy, feature fusion, and object detection representational capability, respectively. The enhancements elevated the model's accuracy by 8.7%, achieving a mean average precision (mAP@0.5) value of 57.1%. A specialized dataset, comprising 4890 images and encapsulating various angles and lighting conditions of Jiangnan private gardens, was constructed to realize this. Following manual annotation and the application of diverse data augmentation strategies, the dataset bolsters the generalization and robustness of the model. Experimental outcomes reveal that, compared to its predecessor, the improved model has witnessed increments of 15.16%, 3.25%, and 11.88% in precision, mAP0.5, and mAP0.5:0.95 metrics, respectively, demonstrating exemplary performance in the accuracy and real-time recognition of garden target elements. This research not only furnishes robust technical support for the digitization and intelligent research of Jiangnan private gardens but also provides a potent methodological reference for object detection and classification research in analogous domains.
The onset of motor learning impairments in Parkinson’s disease: a computational investigation
Authors: Gigi Ilaria , Senatore Rosa , Marcelli Angelo
Published: January 2024

The basal ganglia (BG) is part of a basic feedback circuit regulating cortical function, such as voluntary movements control, via their influence on thalamocortical projections. BG disorders, namely Parkinson’s disease (PD), characterized by the loss of neurons in the substantia nigra, involve the progressive loss of motor functions. At the present, PD is incurable. Converging evidences suggest the onset of PD-specific pathology prior to the appearance of classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in developing more effective therapies by intervening at the earliest stages of the disease. Therefore, a key challenge in PD research is to identify and validate markers for the preclinical and prodromal stages of the illness. We propose a mechanistic neurocomputational model of the BG at a mesoscopic scale to investigate the behavior of the simulated neural system after several degrees of lesion of the substantia nigra, with the aim of possibly evaluating which is the smallest lesion compromising motor learning. In other words, we developed a working framework for the analysis of theoretical early-stage PD. While simulations in healthy conditions confirm the key role of dopamine in learning, in pathological conditions the network predicts that there may exist abnormalities of the motor learning process, for physiological alterations in the BG, that do not yet involve the presence of symptoms typical of the clinical diagnosis.
Can the FIB-4 score predict the severity of acute pancreatitis in NAFLD?
Authors: Kirdok Kutay , Yogurtcu Özge , Buran Tahir , Kasap Elmas
Published: January 2024

Background

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology. NAFLD’s prevalence is increasing in the world and because of the increase non-invasive methods are gaining importance in diagnosis. The Fibrosis 4 (FIB-4) score is one of the most commonly used non-invasive scoring methods for diagnosing NAFLD today. Acute pancreatitis is a disease with inflammation and high morbidity. There are studies indicating that acute pancreatitis progresses more severely in patients with NAFLD. In our study, it was aimed to define the possible relationship between the FIB-4 score and the severity of acute pancreatitis, which has not been investigated before and contribute to the literature.

Methods

Our study was conducted by retrospectively scanning 124 patients diagnosed with acute pancreatitis between 2018 and 2020. The patients were compared with the presence of NAFLD and the FIB-4 score results in those with NAFLD.

Results

The 48th-hour Ranson score was found to be statistically significantly higher in patients with NAFLD compared to those without NAFLD. In patients with NAFLD, the total billurbin, direct billurbin, AST, ALT, ALP, GGT, and Ranson scores were found to be statistically significantly higher in those with FIB-4 score ≥ 2.67.

Conclusıon

As liver fibrosis increases in patients with NAFLD, it is suggested that liver damage accompanying acute pancreatitis increases, and the prognosis of acute pancreatitis worsens. There is a need for further studies to be conducted while centering more on this subject, which has not been investigated before in the literature.
Hyperkalemia in the tropics: multiple causes and a not so common presentation—a case report
Authors: Ittyachen Abraham M. , Sukumaran Anjely , Peter Ancy , Baby Binitha , Anthony Dawn
Published: January 2024

Background

Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. But all cases of hyperkalemia need not be symptomatic either. The feared consequence of hyperkalemia is that on the heart, it can induce fatal arrhythmias; rarely, it can present with neuromuscular signs. Most cases of hyperkalemia can be attributed to a single cause. Rarely, it can be multifactorial.

Case presentation

From the province of Kerala in India, we describe an elderly gentleman with severe hyperkalemia, who presented with quadriparesis. He had ECG changes consistent with hyperkalemia. Diverse causes were involved at the same time for the hyperkalemia. An uncommon cause observed was a diet rich in tropical fruits. As he did not respond to conservative (medications) measures, he had to be dialyzed. With dialysis, there was a rapid neurological recovery, and the potassium levels had improved.

Conclusions

In patients presenting with ascending paralysis, especially old people with morbidities, one differential diagnosis to be considered is hyperkalemia. Once hyperkalemia is confirmed, in addition to medications and illnesses, the preceding diet should also be enquired, especially the intake of fruits. In all, a good history in such a case is without a doubt imperative.
The lack of agency becoming part of the self
Authors: Szalai Judit
Published: January 2024

This brief commentary on Greenberg's article ‘When the illness speaks’ addresses the problem of agency in mental disorder. Complementing the perspective of the article, it advocates an approach that does not see the causal mechanism of disorder-related behaviour in terms of an exclusive disjunction between the effects of the individual patient's own agency or manifestations of the illness. When reduced agency becomes part of the person's self-conception, passivity no longer means behaviour that is alien to their ‘genuine self’. Relatedly, the requirement that the patient's self-conception be validated raises some questions regarding its therapeutic constraints.
Neo-adjuvant tislelizumab combined with lenvatinib treatment for resectable, recurrent hepatocellular carcinoma.
Authors: Ming Kuang , Xie Wenxuan , Chen Jingying , Chen Shuling , Wang Yuanqi , Shen Shunli , Peng Sui
Published: January 2024

517

Background:
The persistent challenge of elevated re-recurrence rates following secondary hepatectomy complicates the prospects for improving survival in recurrent hepatocellular carcinoma (rHCC) patients. Immunotherapy combined with targeted drugs have been the first-line therapy for advanced HCC and shown good response rate in neoadjuvant situation. However, the effectiveness and safety of the combination treatment has not been reported in rHCC patients. To address this, we conducted the present phase 2 clinical trial of neoadjuvant treatments using tislelizumab in combination with lenvatinib for rHCC patients.
Methods:
Patients with resectable rHCC patients who had previously undergone curative treatment were enrolled. Enrolled patients were treated with 2 neoadjuvant cycles of a combination of tislelizumab 200mg intravenously every 3 weeks and lenvatinib 8mg every day (12mg for patients over 60kg) for 4 weeks. Hepatectomy was conducted in six weeks after enrollment. One month after surgery, adjuvant combination of tislelizumab and lenvatinib was started for at least one year or until disease progression or intolerance of adverse reactions. The primary objective of the trial is to evaluate one-year disease-free survival (DFS) rate, and secondary endpoints include objective response rate (ORR) as assessed by RECIST 1.1, major pathologic response (defined as over 90% tumor necrosis), and safety considerations.
Results:
Until Sep 30
th
, 2023, a total of 14 patients have been enrolled. All participants underwent the complete neoadjuvant therapy with a combination of tislelizumab and lenvatinib before proceeding to hepatectomy. Throughout the neoadjuvant phase, 14.3% (2/14) of patients occurred adverse events below grade 3, with no severe adverse events occurring. The most common adverse events were fatigue (in 2 patients), hypertension (in 1 patient) and reduced appetite (in 1 patient). In 14 patients, 12 patients underwent R0 resection and 2 were waiting for hepatectomy. The average time from the initiation of the neoadjuvant therapy to hepatectomy was approximately 40.42 days. On the radiological front, one patient (8.3%) exhibited a partial response, while 11/12 (91.7%) displayed stable disease with 8 patients had tumor shrinkage. In terms of pathological outcomes, 25% of patients (3/12) achieved a complete response, whereas the remaining patients showed varying degrees of pathologic response, ranging from 5% to 85%.
Conclusions:
In summary, the dual therapy of tislelizumab and lenvatinib demonstrates encouraging safety and effectiveness as a neoadjuvant intervention for patients with rHCC. The long-term results of this combined treatment approach are eagerly anticipated. Clinical trial information: NCT04615143.
A study of the association between enzalutamide blood concentrations and adverse events in patients with castration-resistant prostate cancer.
Authors: Iguchi Taro , Kato MInoru , Hirayama Yukiyoshi , Yamasaki Takeshi , Yasuda Sayaka , Morita Nobuyo , Chikazawa Ippei , Fukushima Wakaba , Tamada Satoshi , Miyazawa Katsuhito
Published: January 2024

102

Background: Enzalutamide (ENZA) is effective in castration-resistant prostate cancer (CRPC), but subjective adverse events (AEs) such as fatigue and decreased appetite may make it difficult to continue ENZA due to AEs despite its effectiveness. Owing to AEs, half of the patients required a dose reduction to 120 mg, thereby eliminating the AEs and enabling patients to continue taking ENZA. We hypothesized that a dose reduction to 120 mg of ENZA would reduce AEs in patients while keeping serum concentrations in the therapeutic range. Methods: Patients with CRPC were treated with ENZA from 2015 to 2020 at Osaka City University Hospital and their serum was stored at least twice with written consent. All patients were treated with an initial dose of 160 mg of ENZA, and the dose was reduced to 120 mg if they complained of AEs. In the full dose group (no AEs with 160 mg of ENZA), serum concentrations of ENZA and its active metabolite (N-desmethyl enzalutamide: M2) were measured at 1, 3, and 6 months. In the reduced dose group, serum concentrations were measured before and after dose reduction. To clarify the relationship between AEs and the serum ENZA and M2 concentrations, the serum ENZA and M2 concentrations in patients with/without AEs and before/after dose reduction were compared. To examine whether dose reductions affect the efficacy of ENZA, PSA progression free survival, and the overall survival were compared between the full dose group and the reduced dose group. Results: Serum ENZA and M2 concentrations were measured in 246 samples from 84 patients and mean effective serum concentrations of ENZA + M2 were 28.0, 30.4, and 29.2 μg/mL in the full dose group at 1, 3, and 6 months, respectively; and 29.1 and 24.1 μg/mL at a dose of 160 mg and 120 mg, respectively, in the reduced dose group. Most of AEs were resolved by dose reduction and there was no statistically significant difference in PSA progression free survival (HR: 0.86, 95% CI: 0.44-1.68) or overall survival (HR: 0.60, 95% CI: 0.26-1.40) between the full dose group and the reduced dose group. Conclusions: A correlation between the ENZA dose and serum ENZA + M2 concentration was observed, but no association between AE and serum ENZA or M2 concentration was observed. Dose reduction to 120 mg reduced serum ENZA and M2 concentrations of the patients with AEs and resolved the AEs but did not affect the efficacy of ENZA. These results suggest that patients with AEs at 160 mg of ENZA can have their AEs resolved by reducing the dose to 120 mg without loss of efficacy.
Toxicity-benefit analysis of advanced prostate cancer trials using weighted toxicity scoring.
Authors: Gill Jaspreet Kaur , Sperandio Rubens Copia , Nguyen Tuan Hoang , Emmenegger Urban
Published: January 2024

110

Background: The weighted toxicity score (WTS) is a metric suitable for comparing the toxicity burden in experimental versus control arms of randomized controlled trials (RCTs). When compared against clinical endpoints, the WTS can be used to evaluate the cost versus benefit of anti-cancer agents. This study sought to apply the WTS to prostate cancer (PC) clinical trials. Methods: Select phase 3 PC RCTs with reported adverse event (AE) data were compiled. The WTS was computed for each trial arm and compared to reported hazard ratios (HRs) of primary and/or secondary endpoints (i.e., overall survival (OS) and progression-free survival (PFS)). Average WTSs for the experimental versus control arms were used to calculate the toxicity differential between treatment arms. Average HRs for OS and PFS were used to compare efficacy. Results: Sixteen RCTs were analyzed (investigational agents: androgen-receptor signaling inhibitors (ARSi) [n = 4], poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy [n = 3], ARSi + PARPi as well as ARSi + ARSi combination therapies [n = 3 each], and triple therapy [n=3]). The median number of distinct reported AEs across all studies was 18 (range, 9-61). Overall, toxicity and efficacy were greater among experimental than control arms (6.62 versus 4.00 median WTS; median HR for OS 0.71, median HR for PFS 0.61). The triple therapy studies observed the lowest increase in toxicity by adding an ARSi to control therapy (10.4%), associated with 52% lower risk of progression, and 29% lower risk of death. Comparably, the ARSi + PARPi trials noted the highest increase in toxicity (79.7%), with 32% lower risk of progression and 12% lower risk of death. The PARPi monotherapy, ARSi monotherapy, and ARSi + ARSi combination therapy studies reported increased toxicity due to experimental therapy in descending order (Table). Conclusions: The WTS enables toxicity versus benefit assessment for anti-cancer regimens. Clinical application of this metric may facilitate individualized treatment planning in advanced PC management. [Table: see text]
Comparative health-related quality of life (QoL) in metastatic castration-sensitive prostate cancer (mCSPC): A living systematic review.
Authors: Garza Morales Rodolfo , Naqvi Syed Arsalan Ahmed , Ayaz Ahsan , Khakwani Kaneez Zahra Rubab , Riaz Zaryab Bin , Raina Ammad , Ravi Praful , Childs Daniel S , Andrews Jack R. , Orme Jacob , Cobran Ewan Kemar , Singh Parminder , Riaz Irbaz Bin , Bryce Alan Haruo
Published: January 2024

111

Background: Comparative evidence of quality of life (QoL) outcomes regarding life-prolonging treatments for the management of first-line treatment of metastatic castration sensitive prostate cancer (mCSPC) is not known. Methods: This systematic review uses the living interactive evidence synthesis framework (PMID: 36862387). Phase III randomized controlled trials assessing contemporary systemic treatments in mCSPC were included. Small sample size adjusted standardized mean differences (SMD; Hedges’ g) with 95% confidence intervals (CI) were computed for global QoL at 3, 6, 12, and 24 mo. Positive SMD indicated better health-related QoL, with zero indicating a null effect. Mixed treatment comparisons were made using a network meta-analysis. P-scores were computed; a higher score indicated better QoL. Results: Of 10 clinical trials initially included, eight trials (15 references) reported QoL. At 3mo global QoL was improved with abiraterone (AAP)+ADT compared to D+ADT (SMD: 0.26; 95% CI: 0.13-0.39), enzalutamide (E)+ADT (0.18; 0.03-0.33), and ADT (0.14; 0.02-0.27). At 6mo, AAP+ADT significantly improved global QoL compared to D+ADT (0.74; 0.62-0.87), E+ADT (1.74; 1.56-1.92), and ADT (1.79; 1.65-1.93). D+ADT also improved global QoL at 6mo compared to ADT (1.05; 0.93-1.16) but not when compared to E+ADT. At 12mo, AAP+ADT improved global QoL compared to E+ADT (0.20; 0.05-0.34) and ADT (0.19; 0.07-0.31) but not compared to D+ADT (0.05; -0.07-0.17). D+ADT also improved global QoL at 12mo compared to ADT (0.14; 0.03-0.24) (Table). Global QoL has not been reported for ARASENS trial at this time. These results are available on the Living interactive website. Conclusions: The totality of evidence suggests improved global QoL with androgen-pathway inhibitors (API) doublet therapy. D+ADT may offer better QoL at longer 6 and 12 months of follow-up. QoL data for triplet therapy is still emerging and will be incorporated in the living review as soon as it becomes available. [Table: see text]
Adverse outcomes (AOs) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) treated with intensified androgen deprivation therapy (ADT+).
Authors: Mir Nabiel Ali , Akmal Waqaas , Imam Maaz , Giurcanu Mihai , Szmulewitz Russell Zelig , Stadler Walter Michael
Published: January 2024

113

Background: mCSPC pts experience adverse outcomes (AOs) with intensified androgen deprivation, resulting in treatment discontinuation; however, there is limited data to identify those at risk. The IRONMAN registry is a global initiative to enroll advanced prostate cancer patients worldwide, and survey data on AOs, patient-reported outcomes (PROs), and clinico-epidemiologic (demographic, cancer, and treatment) details. We report the prevalence and predictors of AOs from baseline demographic, clinical, and PRO information with the onset of AOs and present a risk prediction model for clinical use. Methods: We analyzed data from 553 mCSPC patients in the IRONMAN registry from inception to March 2023 who received ADT+ alone (Abiraterone 47.6%, Enzalutamide 26.9%, Apalutamide 22.6%, Darolutamide 2.9%) and had completed baseline PROs. We defined AOs, reported by 60 global sites, as non-progression-related clinically significant serious adverse events (csSAE), treatment discontinuation, and dose reductions (DR/DC), delineated as a composite outcome based on first event. We processed baseline variable groups: Demographics (race, ethnicity, marital status, study site), Clinical Factors (age, ECOG score, metastatic sites, ADT+, concurrent medications, labs [ALP, Hb, LDH, and PSA]), Concurrent therapies (steroid use within 30 days [d] & steroid dose, radiation/surgery prior or planned in 6months) and PROs (EORTC QLQ-C30 and EPIC-23). We developed a multifactorial logistic regression model to predict adverse outcomes (AOs) within two years of initiating ADT+ therapy. All variables with less than 25-30% missing data were included. Variable selection was conducted in two layers: intra-group stepwise selection followed by an inter-group selection of variables retained from the first layer. The model's discriminatory ability was evaluated using the area under curve (AUC). Results: 553 pts met inclusion (51.6% North America, 72% White, mean age: 71 years [range, 40 to 96 years], and 62.9% confirmed bone-metastatic mCSPC). 119 pts (21.5%) developed AOs (61 csSAEs [18 dead; Median: 140 d; IQR 81-360 d], 58 DR/DC [Median: 122 d; IQR 43-262 d]). <5% went off study. The multifactorial model (n=314 pts) performed well at predicting AOs (AUC 0.77 [0.70-0.84]), with significant factors being more self-reported pain, greater urinary frequency, prednisone>5mg within 30d, more self-reported weakness and poor sexual function within 3 months of ADT+ initiation. Conclusions: 1 in 5 mCSPC patients on ADT+ experienced non-progression-related AOs at 2 years. Significant, easily assessed predictive factors are identified and may be utilized in their clinical management. A novel multifactorial model is presented to predict AOs at 2 years. Further validation, assessment of missingness bias, and imputation are planned.
Trop-2: A promising new therapeutic target in penile squamous cell carcinoma.
Authors: Weiten Richard , Kessler Carolina , Spohn Hanna Elisa , Storz Enno , Pfister David A. , Nestler Tim , Tolkach Yuri , Wirtz Ralph M. , von Brandenstein Melanie , Krausewitz Philipp , Heidenreich Axel
Published: January 2024

12

Background: Penile squamous cell carcinoma (PSCC) is an infrequent yet progressively prevalent malignancy. Despite ongoing advancements in personalized and immunotherapeutic approaches, patients grappling with the diagnosis of locally advanced or metastasized PSCC still confront a limited therapeutic arsenal, leading to an unfavorable prognosis. Consequently, an imperative mandate arises to explore alternative therapeutic modalities, particularly antibody-drug-conjugates (ADCs), which have demonstrated significant clinical efficacy in the context of metastatic solid tumor pathologies. Our aim was to ascertain the potential utility of ADCs targeting Trop-2 in both localized PSCC (PRIM) and patient-matched distant metastases (MET). Methods: Immunohistochemical analysis of Trop-2 expression was conducted in PRIM ( N=40) and their corresponding METs ( N=9, including lymph node and lung metastases). We assessed overall survival (OS) by stratifying patients into subgroups based on Trop-2 expression: weak (H-score 15-99) versus moderate/strong (H-score 100-300). Additionally, we explored the relationship between Trop-2 and HPV-dependency. Furthermore, Trop-2 mRNA expression levels were quantified via qRT-PCR, and an enzyme-linked immunosorbent assay was employed to measure Trop-2 in serum samples derived from PRIM ( N=40) and a healthy control group ( N=10). Results: We found a statistically significant increase in Trop-2 mRNA expression levels in individuals afflicted with PSCC compared to healthy controls ( p<0.0001). Moreover, a notable elevation in Trop-2 protein expression was observed in the serum specimens obtained from PSCC patients ( p<0.01). The majority of patients exhibited moderate to strong Trop-2 expression, indicative of a robust median H-score of 280 (interquartile range: 210-300). Subgroup analysis revealed a correlation between Trop-2 expression and HPV status ( p<0.01), demonstrating discernible associations with more favorable clinical outcomes, as evidenced by the log-rank (Mantel-Cox) test ( p<0.05). Conclusions: Trop-2 protein expression in PSCC holds prognostic significance. Furthermore, the elevated Trop-2 levels in both PRIM and PSCC metastases suggest that the Trop-2-targeted ADC, Sacituzumab govitecan, may emerge as a promising novel therapeutic intervention for these patients.
Post hoc analysis of rPFS and OS from the TALAPRO-2 (TP-2) study: Genomic subgroups based on likelihood of BRCA or HRR gene alteration status.
Authors: Shore Neal D. , Agarwal Neeraj , Azad Arun , Carles Joan , Fay Andre P. , Matsubara Nobuaki , De Giorgi Ugo , Joung Jae Young , Fong Peter C.C. , Voog Eric , Jones Robert J , Dunshee Curtis , Zschaebitz Stefanie , Oldenburg Jan , Lin Xun , Healy Cynthia G. , Di Santo Nicola , Laird Douglas , Zohren Fabian , Fizazi Karim
Published: January 2024

136

Background: Prior to randomization in TP-2, patients (pts) (N=805; all-comers) were prospectively assessed for HRR gene alterations in tumor tissue and/or ctDNA using FoundationOne CDx and/or FoundationOne Liquid CDx. In the all-comers cohort, talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment for pts with mCRPC significantly improved rPFS vs ENZA (HR 0.63; 95% CI 0.51–0.78). To investigate if ITT results for TP-2 all-comers were driven by unidentified biomarker-positive pts, we assessed the correlation between rPFS/OS outcomes and pt BRCA or HRR alteration status. Methods: Within each analysis by BRCA or HRR alteration status, three exploratory subgroups based on the likelihood of BRCA/HRR alterations were defined using all available FoundationOne records from prospective and retrospective exploratory testing. BRCA1/2 mutated ( BRCAm; 10% ITT) or HRR mutated (HRRm; 33% ITT): pts were identified via a positive test result in either ctDNA and/or tumor tissue testing. Undetermined BRCAm (38% ITT) or undetermined HRRm (28% ITT): pts with one negative BRCAm/HRRm test result not confirmed by the other test, or for whom the results of both tests were indeterminate. Non- BRCAm (51% ITT) or non-HRRm (39% ITT): pts with negative BRCAm or HRRm status confirmed by both ctDNA and tumor tissue testing. Results: A benefit in rPFS was demonstrated in the non- BRCAm and non-HRRm subgroups (Table) with a non- BRCAm median rPFS of 33.1 vs 22.1 months favoring TALA + ENZA (HR 0.71; 95% CI 0.52–0.96). A trend towards improved OS was also observed in the non- BRCAm and non-HRRm subgroups. OS data in the undetermined HRRm (36%) and undetermined BRCAm (39%) groups were least mature. For both rPFS and OS for undetermined BRCAm and undetermined HRRm, HRs were higher than those for BRCAm, non- BRCAm, HRRm, or non-HRRm; the reasons for this are unclear. Conclusions: The statistically significant rPFS improvement in the TP-2 all-comer ITT population did not seem to be attributable to pts with undetected BRCA/HRR alterations. There was evidence of rPFS benefit in the non- BRCAm and non-HRRm subgroups in favor of TALA + ENZA. While the OS data are still maturing, there is a clear benefit for pts with BRCAm and no detrimental impact for pts negative for BRCAm or HRRm by both tumor and ctDNA. Clinical trial information: NCT03395197 . [Table: see text]
Survival outcomes of metastatic prostate adenocarcinoma by primary metastatic site: A Surveillance, Epidemiology, and End Results (SEER) database study.
Authors: Bagot Shannon , Rasmusen Veronica , Kim Sarah , Rahnemai-Azar Amir A.
Published: January 2024

200

Background: Prostatic adenocarcinoma (PAC) is the second leading cause of cancer-related death in men in the United States. The aim of this study is to investigate the effect of different sites of primary metastasis on overall survival (OS) of patients with metastatic PAC as well as identify risk factors that may impact prognosis. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 26,085 patients diagnosed with metastatic PAC between 2010 and 2020 were analyzed to assess OS. Primary metastatic sites included in the study were bone, brain, liver, or lung and patients with multiple metastatic sites were excluded. Kaplan-Meier curves and Univariate Cox Regression analyses were used to determine the effect of various primary metastatic sites on OS. Results: Of all PAC primary metastatic sites, bone was the largest group (n=25,421, 97.5%), followed by lung (n=423, 1.6%), liver (n=194, 0.7%), and brain (n=47, 0.2%). Cox Regression analysis of PAC patients found that primary liver metastasis was associated with worst OS (Hazard Ratio (HR) 1.785, p<.001) while primary lung metastasis had better OS (HR 0.738, p<.001) when compared to patients with primary bone metastasis. Further analysis of the bone metastasis group with Univariate Cox Regression models was performed to evaluate the impact of age, treatment type, and race on OS. Factors found to significantly decrease OS included diagnosis at or after age 70 (HR 1.536, p<.001) and treatment with transurethral resection of the prostate (TURP) (HR 1.239, p<.001). Factors that significantly improved OS included treatment with radical prostatectomy (HR 0.222, p<.001) and radiation therapy (HR 0.872, p=.002). No significant improvement in OS was seen with systemic therapy. Regarding race, OS was observed to be higher among Hispanic (HR 0.911, p<.001) and Asian/Pacific Islander (API) (HR 0.773, p<.001) populations when compared to Non-Hispanic Whites (NHW). No statistically significant difference in OS was found between NHW, Black, or American Indian and Alaska Native (AIAN) populations. Conclusions: Results of this study differ from previous publications that found no improvement in OS with radiation therapy and that identified AIAN race as a protective factor in PAC. These findings may inform future treatment of patients based on the site of primary metastasis and increase consideration of risk factors that can contribute to decreased survival.
Survival outcomes for rural patients with advanced prostate cancer: A SEER investigation.
Authors: Qu Liang G , Vaselkiv J. Bailey , Perera Marlon , Mucci Lorelei A
Published: January 2024

22

Background: It is unknown if the impact of rural versus urban settings may impact outcomes in men with metastatic prostate cancer, and in particular survival. This study aimed to examine differences in survival for patients in the United States with de novo metastatic prostate cancer, according to urban-rural status. Methods: This retrospective cohort study utilised data from the publicly available Surveillance, Epidemiology, and End Results database. Data on demographics, urban-rural status, histopathology, and survival were extracted for men aged 18-75 diagnosed with metastatic prostate cancer between 2009-2018. Rurality was re-classified from the rural-urban continuum code which ranged from 1 (most urban) to 9 (most rural). Individuals missing rurality status or survival-related data were excluded. Overall and cancer-specific survival between individuals living in urban and rural settings were analysed using multivariable Cox regression and adjusted restricted mean survival time modelling. Subgroup analyses were performed for histological subtypes of prostate cancer. Sensitivity analyses were performed using varying definitions of rurality. Results: Altogether, 21,291 individuals were included, with 2,510 living in rural settings, defined as rural-urban continuum code ≥ 4. The rural and urban participants differed in age, race, U.S. region, and marital status. There was no association between urban-rural status and overall survival (adjusted hazard ratio [HR] = 1.03, 95% confidence interval [CI]: 0.97-1.09, 11,333 events) or cancer-specific survival (1.03, 0.97-1.10, 9,380 events) using Cox regression models. Adjusted restricted mean survival time modelling demonstrated that urban patients lived 2.29 months longer than rural patients (95% CI: 0.61-3.97). Sub-analyses of neuroendocrine, intraductal, and other histological subtypes did not show an association between urban-rural status and overall survival. A more selective definition of rurality (rural-urban continuum code ≥ 5) resulted in a persisting difference in overall mean survival time (2.12 months, 0.24-4.01) using restricted mean survival time modelling. Similarly, a broader definition of rurality (rural-urban continuum code ≥ 3) also resulted in a difference in overall mean survival time (1.98 months, 0.59-3.36). Conclusions: This retrospective analysis demonstrated that a U.S. individual with metastatic prostate cancer who resided rurally died sooner compared to those from urban areas, suggesting greater disease impact in rural settings.
Risk of early non-cancer deaths in adults diagnosed with metastatic genitourinary (mGU) cancers: A retrospective cohort study.
Authors: Ayaz Ahsan , Naqvi Syed Arsalan Ahmed , Riaz Zaryab Bin , Bibi Arifa , Khakwani Kaneez Zahra Rubab , Cobran Ewan Kemar , Singh Parminder , Bryce Alan Haruo , Riaz Irbaz Bin , Mir Sajid Ahmad
Published: January 2024

229

Background: We aim to investigate non-cancer cause of death in adults within 2 years after initial diagnosis of mGU cancers including bladder cancer (BC), kidney cancer (KC), and prostate cancer (PC). Methods: Surveillance, Epidemiology, and End Results (SEER) database (2004-2020) was searched to obtain data on death caused by cardiovascular diseases (CVD), kidney diseases (KD), respiratory diseases (RD), liver diseases (LD), diabetes mellitus (DM), and sepsis in adults (>20y of age) diagnosed with mGU cancers. Standardized mortality ratios (SMRs) with 95% confidence interval (CI) were calculated within 2y of initial diagnosis. SMR was defined as the observed deaths from each category divided by the expected number of deaths in the age-matched US population for the same period. SMR >1 indicated increased while <1 indicated decreased mortality. Stratification factors included age (<50y, 50-70y, >70y), race (White, Black, Asian/Pacific Islander), ethnicity (Hispanic, non-Hispanic), chemotherapy, and radiotherapy. Results: This study including 77,246 mGU cancer patients showed that the greatest risk of early death was observed to be caused by sepsis (SMR: 4.21, 95% CI: 3.64-4.84) followed by CVD (1.70, 1.62-1.80), KD (1.58, 1.31-1.90), LD (1.58, 1.16-2.09), DM (1.56, 1.32-1.82), and RD (1.38, 1.22-1.56). Patients aged <50y observed the highest risk of mortality caused by sepsis (61.76, 30.83-110.5) followed by KD (28.06, 9.11-65.48) and CVD (5.63, 3.60- 8.84). However, patients aged 50-70y were more likely to die by RD (2.47, 1.94-3.09) and LD (2.01, 1.38-2.82). The results were consistent for Black patients; sepsis (6.59, 5.04-8.46) followed by RD (2.01, 1.41-2.78) and KD (1.64, 1.04-2.46). Asian/Pacific Islanders were more likely to die from CVD (2.52, 2.13- 3.00) and DM (2.21, 1.21-3.71). Hispanics were more likely to die from LD (3.11, 1.66-5.32) and non-Hispanics from sepsis (4.28, 3.68-4.96). This risk of death due to sepsis was increased with chemotherapy (7.06, 5.22-9.33) and radiotherapy (4.92, 3.58-6.61). Detailed results are available in Table. Conclusions: Sepsis remained the leading cause of early non-cancer-deaths in mGU cancers consistently across all subgroups. Younger adults were more likely to die from CVD and KD, Black patients from RD, and Hispanics from LD. [Table: see text]
Impact of race on outcomes to 177Lu-PSMA-617 (LuPSMA) for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Rami Avina , Ng Thomas SC , Rothmann Emily , Stoltenberg Hailey , Wolanski Andrew , Ritzer Jolivette , Choudhury Atish Dipankar , Gao Xin , Haberman Veronica , Kako Bashar , Kilbridge Kerry L. , Morgans Alicia K. , O'Shea Aileen , Taplin Mary-Ellen , Jacene Heather , Ravi Praful
Published: January 2024

27

Background: Prior work suggests that African American (AA) and other minority patients (pts) derive equal benefit from taxane chemotherapy and androgen receptor pathway inhibitors (ARPIs) for mCRPC as white pts. LuPSMA showed an overall survival (OS) benefit in mCRPC pts after prior taxane and ARPI. However, there are no data on racial differences in outcomes to LuPSMA. Methods: We queried an IRB-approved registry of all pts treated with at least 2 cycles of LuPSMA between June 2022 and August 2023 at two academic medical centers in Boston, MA. Clinical data, including self-reported race, was abstracted from the electronic medical record. Pts of AA, Hispanic/Latino and Asian race were categorized as minorities. Outcomes of interest were the proportion of patients with ≥50% decrease in PSA levels during LuPSMA therapy (PSA50) and OS, defined from the date of the first cycle of LuPSMA. PSA50 and OS between races were compared with the Chi-Square and log-rank tests, respectively. Results: A total of 156 pts were included. Median age at LuPSMA initiation was 73 years (range 53-92) and the median number of prior lines of therapy was 5 (range 2-12); all pts had received ≥1 taxane and ≥1 ARPI. 136 (87%), 10 (6%), 6 (4%) and 4 (3%) pts were White, AA, Hispanic/Latino and Asian, respectively. The median number of LuPSMA cycles received in the entire cohort was 4 (range 2-7), and median follow-up was 7.1 months. A numerically higher proportion of minority pts had visceral disease at baseline compared to White pts (50% vs. 31%, (X2 = 2.87, p=0.090). Overall, 86 pts (55%) had a PSA50, with PSA50 of 55% (n=75), 60% (n=6), 67% (n=4) and 25% (n=1) amongst White, AA, Hispanic/Latino and Asian pts, respectively. There was no significant difference in PSA50 between White and minority pts (X2 = 0.00, p=0.990). Median OS in the entire cohort was 12.9 months and was not significantly different between White and minority pts (12.9 months vs. 8.5 months, p=0.533). The Table summarizes outcomes by race. Conclusions: PSA50 and OS were comparable between minority and White pts receiving LuPSMA for mCRPC, despite minority pts tending to present with more visceral disease, a known adverse prognostic factor. Validation of these findings and efforts to widen access to LuPSMA amongst minorities are required, given that pts of all racial backgrounds appear to benefit equally from LuPSMA. [Table: see text]
Racial disparities in genitourinary cancer mortality trends in the United States, 2000-2020: A CDC database study.
Authors: Al Armashi Abdul Rahman , Thierheimer Marisa , Garcia Jorge A. , Brown Jason R
Published: January 2024

28

Background: Prostate, bladder, and kidney cancers account for substantial burden of cancer incidence and mortality in the United States. In 2020, an estimated 168,000 new cases and 32,000 deaths were attributed to these cancers. Studies examining racial disparities of mortality trends are needed. Methods: We utilized the CDC WONDER database to obtain mortality data for kidney, bladder, and prostate cancers between 2000-2020. Age-adjusted mortality rates per 100,000 persons were calculated and standardized to the Year 2000 US standard population. Rates were stratified by race, including White, Black, Asian/Pacific Islander (API), and American Indian/Alaska Native (AIAN). The National Cancer Institute Joinpoint Regression Program was utilized to calculate average annual percent changes (AAPCs). AAPCs were considered significant if the 95% confidence interval (CI) excluded zero. Results: Over the study period, 318,919 kidney cancer deaths, 150,613 bladder cancer deaths, and 516,508 prostate cancer deaths were identified. Between 2000-2020, amongst all races, mortality from prostate cancer (-1.8%; CI -2.0, -1.6), bladder cancer (-0.3%; CI -0.5, -0.2), and kidney cancer (-1.1%; CI -1.2, -0.9) all significantly declined. Considering racial disparities, prostate cancer mortality fell considerably in all race groups, most significantly among Black (-2.8%, CI -3.2%, -2.4%) and AIAN (-2.4%, CI -2.9%, -1.8%) populations, outpacing reductions in API (-1.7%, CI -2.6%, -0.8%) and White (-1.6%, CI -1.9%, -1.4%) populations. In bladder cancer, the decline in mortality was statistically significant for Black (AAPC: -0.8%, CI -1.1%, -0.6%) and for White, (-0.4%, CI -0.6%, -0.1%), but not for API individuals (-0.3%, CI -0.9%, 0.3%). For kidney cancer, mortality dropped substantially across all examined races, with the steepest decline seen in Black (-1.4%, CI -1.7%, -1.2%) and AIAN (-1.7%, CI -2.5%, -1.0%) compared to White (-1.0%, CI -1.2%, -0.9%) and API (-1.4%, CI -4.2%, 1.6%, non-significant) population. Conclusions: This study represents the most comprehensive population database analysis assessing GU cancer mortality trends. While an overall decline in GU cancer mortality was observed, which was comparatively greater for Black Americans over the past two decades, significant racial disparities continue to persist. Focused and targeted efforts are essential to address these disparities. [Table: see text]
Performance of the F-PSMA 1007 PET/CT for high-risk prostate cancer staging: Experience from a Latin American reference center.
Authors: Peña Rodriguez Sebastian , Diaz Ritter Cesar Alejandro , Caicedo Juan Ignacio , Ramirez Natalia , Rojas Julian , Gutierrez Andres Felipe , Mogollón Maria Paula , Medina Camilo
Published: January 2024

286

Background: Diagnostic staging in high-risk prostate cancer patients seeks to define the local extent of the disease as well as determine the presence of lymph nodes and distant metastases. Molecular imaging, such as PET PSMA, provides higher sensitivity and specificity for the detection of nodal and distant metastases compared to conventional imaging. 18F-PSMA-1007 is radiotracer that represents a cost-effective alternative to 68Ga-PSMA-11, although evidence is limited. We aim to describe the performance of PSMA-1007 in the staging of patients with high risk for prostate cancer in a Latin America reference center. Methods: We performed a cross-sectional study that included prostate cancer patients who underwent 18F-PSMA1007 PET/CT for initial staging in our center of reference between 2020-2023. Descriptive analysis was performed with frequencies for discrete variables, and central tendency and dispersion measures for continuous variables. High risk was defined using the NCCN prostate cancer guidelines. Contingency tables were designed to evaluate associations between groups. To compare categorical variables, we use Chi-square and ANOVA for continuous variables. This analysis was performed using Jamovi 2.3.21 statistical software. Results: Two hundred and seventeen patients were included. The median age was 67 years. The median PSA distribution was 12 ng/ml. The most frequent Gleason group was group 4 (42,7%), followed by group 3 (25,5%). The most prevalent results on the PET pattern are presented in Table. 32% of the patients presented positive lymph node findings. Before the F-PSMA 1007 PET/CT, 24% of the patients had lymph node involvement identified and 33.2% had negative lymph nodes with conventional imaging. These values changed to 39% and 56% respectively, with the F-PSMA 1007 PET/CT. Bone was the most frequent metastasis site (14,3%), followed by extrapelvic lymph node metastasis (12%). A favorable correlation between higher PSA levels and stratified risk assessment by PSMA pattern was evident (p< 0.001). Conclusions: 18F-PSMA-1007 is an innovative radiotracer that can be used to evaluate the extension of prostate cancer involvement. Future studies with prospective cohorts should be carried out to establish analyses between 18F-PSMA-1007 use and its influence on the oncological management of these patients.[Table: see text]
Racial disparities in GU cancer metastasis: A comprehensive analysis from 2010-2018.
Authors: Al Armashi Abdul Rahman , Garcia Jorge A. , Brown Jason R
Published: January 2024

30

Background: Patterns of metastatic spread vary between bladder, kidney, and prostate metastasis. Of these cancers, kidney cancer often spreads to the brain, while prostate cancer is most likely to spread to bone, for example. Sites of metastasis can influence prognosis and in some instances may even direct therapy. The knowledge gap on racial disparities in metastatic patterns merits further investigation. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified bladder, kidney, and prostate cancer patients (2010-2018) in White (W) and Black (B) races. Data on metastasis to the lungs, liver, bones, and brain at diagnosis were extracted. The relative risk (RR) was calculated to compare the metastatic patterns between Black and White patients. P-value, and confidence interval were computed using SPSS 28.0. Results: 3.95% of Black and 1.65% of White patients had metastasis at diagnosis. Black patients had metastasis prevalence of 3.2% lung, 1.8% liver, 4.4% bone, and 0.3% brain. Comparatively, White patients had 1.3%, 0.8%, 3.2%, and 0.3% respectively. For bladder cancer, Black patients had a 60% higher risk for bone and lung metastasis and double the risk for liver metastasis compared to White patients. In kidney cancer, Black patients had a 90% higher brain metastasis risk but 20% lower for bone and lung than White patients. For prostate, Black patients had comparatively heightened risks of bone, lung, and liver metastases by 10%, 20%, and 30%, respectively. Conclusions: Racial disparities are evident in GU cancer metastatic patterns at time of diagnosis. Black patients especially have higher liver metastasis, often associated with poor prognosis. Further studies are vital to unravel biological, socioeconomic, and other contributing factors. [Table: see text]
Utilization of patient-reported outcomes to assess adherence to relugolix when combined with radiation therapy.
Authors: Gaudian Kelly , Koh Min Ji , Koh Min Jung , Collins Ryan , Zwart Zoya , Danner Malika , Zwart Alan , Ayoob Marilyn , Yung Thomas M. , Fallick Mark , Kumar Deepak , Carrasquilla Michael , Leger Paul Denis , Dawson Nancy Ann , Suy Simeng , Collins Sean P.
Published: January 2024

319

Background: Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy (RT). Relugolix is an oral GnRH receptor antagonist that achieves rapid testosterone suppression. Non-adherence to oral medications due to poor social support or bothersome side effects may increase the risk of cancer recurrence. This prospective study sought to evaluate early testosterone suppression and relugolix drug adherence when combined with RT. Utilization of patient-reported outcomes (PROs) to evaluate oral medication adherence and guide intervention may improve appropriate utilization of oral medications. This study focuses on the use of the Simplified Medication Adherence Questionnaire (SMAQ) as a tool to assess relugolix adherence. Methods: Relugolix was initiated at least 2 months prior to questionnaire administration. Adherence was assessed using the SMAQ. Total testosterone levels were obtained at the time of SMAQ administration. Castration was defined as serum testosterone ≤ 50 ng/dL. Poor drug adherence was delineated as failure to reach castration or non-adherence per the SMAQ (any non-adherence answer, missed >2 doses in last week or since last visit). To compare the demographic and clinical characteristics of patients who adhered to treatment versus who did not, t-test, Wilcoxon rank sum test, Chi-square test, and Fisher’s exact test were used. A p-value <0.05 determined statistical significance. Results: Between May 2021 and June 2023, 92 men were treated at Georgetown with relugolix and RT per an institutional protocol. The median age was 73 years, and 32% of patients were non-white. Patients initiated relugolix at a median of 5 months prior to the SMAQ (2-24 months). 97% of patients achieved castration (≤ 50 ng/dL) at the time of the SMAQ. 96% of men reported always taking relugolix at the appropriate time. 3% discontinued medication due to bothersome side effects, 18% reported forgetting to take the medication, and 2% reported missing a dose during the weekend. 99% and 97% did not miss a dose more than 2 times in the last week and since the last visit, respectively. Overall patient-reported drug adherence was 73%. Conclusions: Relugolix allows for high rates of castration and drug adherence when combined with RT. Monitoring drug adherence during treatment allows for prompt detection of non-adherence and timely intervention. Future studies should focus on how to optimally incorporate this questionnaire into patient management. [Table: see text]