bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood-based molecular profiling of Chinese patients with advanced renal cell carcinoma.
Authors: Fan Xiaodong , Li Mingwei , Ma Xiaoxue , Qin Jiayue , Cao Shanbo 
Published: June 2023

e16550 Background: The therapeutic landscape of renal cell carcinoma (RCC) has rapidly expanded, and there is an urgent need to develop noninvasive biomarkers that can select an optimal therapy in real time. Next-generation sequencing (NGS)-based profiling of circulating tumor DNA (ctDNA) shows promise for noninvasive detection. To evaluate the clinical utility of ctDNA analysis in RCC, we aimed to analyze the molecular characteristics of RCC using ctDNA by NGS. Methods: A total of 189 plasma samples and 26 matched tumor tissues from Chinese patients with advanced renal cell carcinoma (n = 189) were analyzed by Acornmed panel with 808 cancer-related genes, and matched white blood cell as germline comparators. Results: Overall, 29 germline mutations were detected in 14.3% (27/189) patients, such as TSC2 (5/189, 2.65%), FH (3/189, 1.6%) and VHL (2/189, 1.1%), of which 10 germline aberrations in DNA damage repair (DDR) genes were detected in 5.3% patients (10/18). In addition, a total of 1590 somatic variations were identified in 96.8% (183/189) ctDNA, including 1278 nonsynonymous single nucleotide variants, 126 small insertions or deletions, 75 copy number variations. And the median blood tumor mutation burden (bTMB) was 4.36 mut/Mb. Mutations in VHL (36/189, 19.4%) were the most prominent variation, followed by those in TP53 (19/189, 10.0%), BAP1 (12/189, 6.3%), PBRM1 (10/189, 5.3%) and SETD2 (7/189, 3.7%). Moreover, totals of 154 clinically actionable mutations from 92 patients (48.7%) were identified. In 26 patients with both tumor tissues and plasma samples, sequencing detected alterations in 100% (26/26) tumor tissue DNA (tDNA) and 96.2% (25/26) ctDNA, respectively. Furthermore, 29.6% of mutations of tissues were founded in ctDNA, and 21.6% of mutations of ctDNA were detected in tissues. Among them, 73.1% (19/26) patients had at least one overlapping variant called by tDNA and ctDNA. The most common shared mutation was VHL (5/26, 19.2%). Meanwhile, four shared copy number variants were detected in two patients (15.4%). Conclusions: Our study contributes to understand the molecular characteristics of RCC using ctDNA, which is a viable option for tissue when tissue is difficult to obtain. Furthermore, ctDNA testing by NGS is helpful for drug selection and provides more effective treatment options for RCC, particularly for hereditary RCC.
The evolution of treatment patterns in patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) and clinical outcomes: Results of a longitudinal observational cohort study in England.
Authors: Mahmoudpour Seyed Hamidreza , Knott Craig , Kearney Mairead , Boutmy Emmanuelle , Verpillat Patrice 
Published: June 2023

e16559 Background: Treatment (tx) guidelines for pts with la/mUC in England have evolved over the last decade following the approval of successive immune checkpoint inhibitors (ICIs). However, the impact of this evolution on routine clinical practice (RCP) remains unclear. We aimed to describe shifts in tx patterns and associated clinical outcomes in RCP in England. Methods: This retrospective cohort study included pts aged ≥18 years, with primary stage III/IV UC diagnosis (dx) between Jan 1, 2013 and Dec 31, 2020, in the National Cancer Registration Dataset with follow-up to May 31, 2022. Pts’ dx were stratified at Dec 31, 2017, to split the cohort into pre- and post-ICI eras. Lines of systemic therapy were derived via an algorithm using data from the Systemic Anti-Cancer Therapy dataset. Summary statistics and overall survival (OS) were calculated and compared using χ2 and log-rank tests, respectively. The Kaplan-Meier method was used to estimate median OS from dx and from systemic tx initiation. Results: In the pre- and post-ICI groups, the majority of pts were male (65.7% and 65.5%) and mean modified Charlson-Deyo Comorbidity Index was 3.4 and 3.5, respectively. Mean age was 73.2 years in both groups, while a higher percentage of pts in pre-ICI era had stage IV disease at dx (68.3% and 50.0%; p<0.001). The rate of first line (1L) tx increased from 30.4% to 35.3% (p<0.001) and second line (2L) from 31.2% to 37.3% (p<0.001). The proportion of pts who received ICI in any line increased from 13.7% to 31.6% (p<0.001). Median OS from 1L tx improved from 13.8 to 15.5 mo. Conclusions: While pt demographics did not change considerably between the two groups, 1L and 2L tx rates moderately increased over time, although remained below 40%. In both groups, >85% of treated pts received 1L platinum chemotherapy, consistent with guidelines. In the post-ICI era, approximately one-third of treated pts received ICI therapy in any line. Improved OS from 1L tx could be partially attributable to the increased availability and uptake of ICIs. [Table: see text]
Homologous recombination-related (HRR) gene mutation profiling and the association with TMB in Chinese patients with urological cancer.
Authors: Yu Bin , Yi Huan , Yu Yangyang , Xiao Mingzhe , Qi Chuang 
Published: June 2023

e16561 Background: Homologous recombination deficiency (HRD) is associated with tumorigenesis and could predict the response of PARP inhibitor (PARPi) therapy and immunotherapy. Loss of function or deleterious mutations in homologous recombination-related (HRR) genes contribute to HRD phenotype. Methods: Tumor tissue samples from 484 Chinese patients with urological cancer were sequenced with 551 cancer-related genes. 957 patients with WES data from the TCGA datasets were included for analysis. Results: In the Chinese cohort, 35.88% (47/131) bladder cancer (BCa) patients, 15.47% (28/181) renal cell carcinoma (RCC) and 37.21% (64/172) prostate cancer (PCa) patients exhibited somatic HRR (sHRR) gene mutations. The most frequently mutated genes were BRCA2 (12% in BCa, 5% in RCC) and CDK12 (17% in PCa), respectively. The germline HRR (gHRR) gene mutations were identified in 62.6% (82/131) BCa, 55.33% (96/180) RCC and 60.62% (97/160) PCa patients. The most frequently mutated gene was BRCA2 (24% in BC, 18% in RCC, 26% in PCa). 7.6% (10/131) BCa patients, 1.7% (3/181) RCC patients and 2.9% (5/173) Pca patients carried both germline and somatic HRR gene mutations. In the TCGA cohort, 38.69% (159/411) BCa patients, 11.62% (43/370) RCC and 6.25% (11/176) PCa patients exhibited somatic HRR (sHRR) gene mutations. The most frequently mutated gene was ATM (14% in BCa, 4% in RCC, 5% in PCa). Interestingly, for the patients with PCa, the somatic mutant frequency of HRR genes in Chinese cohort was higher than that in TCGA cohort (37.21% vs 6.25%, p < 0.001). The sHRR-Mut patients had a higher median TMB compared to the sHRR-WT patients (Chinese cohort: BCa 13.97 vs 4.96, p < 0.001; RCC, 4.96 vs 2.84, p < 0.001; PCa, 5.64 vs 2.84, p < 0.001, TCGA cohort: BCa, 7.21 vs 3.63, p < 0.001; RCC, 1.68 vs 1.42, p = 0.003; PCa, 1.03 vs 0.71, p < 0.001). However, the median TMB was similar between the gHRR-Mut and the gHRR-WT patients (Chinese cohort, BCa 6.38 vs 7.09 p = 0.646; RCC, 3.55 vs 2.84, p = 0.229; PCa, 3.55 vs 2.84, p = 0.111). Conclusions: Our data reported the genetic landscape of HRR gene in Chinese urological cancer patients and suggested that patients with altered HRR genes may be rational candidates for precision oncology treatment and provide new opportunities to predict the tumor response to multiple treatments.
Comparison of the genomic profiles of primary and recurrent lesions in patients with advanced bladder carcinomas.
Authors: Chen Lijuan , Lin Guomin , Pang Fei 
Published: June 2023

e16575 Background: Bladder carcinomas (BCs) is featured by high incidence of recurrence which remains to be a big clinical challenge. This study aimed to compare the genomic profiles of primary and recurrent BCs in advanced stage. Methods: Primary and recurrent tissues (and control blood) were collected and somatic variants including short variants, copy number variations, gene rearrangements and TMB (Tumor Mutation Burden) were analyzed following the CAP/CLIA-certificated workflows. Chi-Square Test/Fisher Test was applied to compare the difference between two variables. Results: To eliminate the impact of stage, only patients in advanced stages were included (stage III-IV) in this study. 53 patients were investigated, including 43 primary and 10 recurrent (evidence of tumor observed after radical treatment). It should be noted that matched primary and recurrent samples were not obtained from the same patient. Median age of the patients was 64 years old. The proportion of male patients was 86% (n = 37) in the primary cohort and 60% (n = 6) in the recurrent cohort. Among the primary cases, the most frequent alterations were detected in TP53 (58.1%), TERT (51.2%), KMT2D (27.9%), KDM6A (23.3%) and RB1 (23.3%). Among the recurrent cases, the most frequent alternations were showed in TERT (70%), KMT2D (50%), PIK3CA (50%), TP53 (50%) and KDM6A (40%). PIK3CA substitution and KRAS substitution showed significant difference when comparing between the two cohorts. PIK3CA substitution preferentially occurred in recurrent samples (50% recurrent vs 14% primary, p-value = 0.01), mostly occurred in E545K; while KRAS substitution showed 4.7% in primary and 30% in recurrent with p-value = 0.04, all presented as G12V. TMB showed no significant difference between the two cohorts (6.2 vs 6.3 muts/Mb, p-value = 0.72). Conclusions: By NGS, we observed that substitutions in PIK3CA and KRAS showed significant difference between primary and recurrent samples from advanced BCs patients. PIK3CA and KRAS mutations were reported to be associated with local recurrence in CRC, but no association was observed in early stage non-muscle-invasive BCs. Our findings may provide a different insight into the treatment selections for advanced BCs, although the sample size is small.
Monoamine oxidase as a potential target for the development of new therapeutic strategies for bladder cancer.
Authors: Camargo Gabriela Cardoso de Arruda , Oliveira Gabriela , Alonso João Carlos Cardoso , Ribeiro de Souza Bianca , Silva Santos Bruna Nayara Nayara Silva , Ávila Monaliza , Roberto Isadora Manzato , Duran Nelson , Fávaro Wagner José 
Published: June 2023

e16611 Background: Bladder cancer (BC) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. As the overall prognosis of BC has not changed over the past 30 years, there is a pressing medical need to develop new diagnostic and therapeutic approaches. At present, efforts to deeply understand the pathogenic mechanisms that support urothelial carcinogenesis could help in identifying new therapeutic targets. Monoamine oxidases (MAOs) A and B are oxidative isoenzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Recently, MAOs expression have been associated with metastasis and decreased overall survival in various types of cancer. However, the role of MAOs in BC is still poorly explored. This study characterized and compared the molecular profiles of MAO-A and MAO-B isoenzymes in the different histological stages of non-muscle (NMIBC) and muscle (MIBC) invasive bladder cancer, aiming the adaptation of these biomarkers as a criterion of clinical response, risk stratification and outcome prognosis. Methods: Sixty formalin-fixed paraffin-embedded samples of bladder were obtained from 34 to 96-year-old patients (mean 65 years) with BC diagnosis in University of Campinas and Paulinia Municipal Hospital/ Brazil. Subsequently, the samples were divided into 6 groups: pTis group, low-grade pTa group, high-grade pTa group, pT1 group and pT2 group; and submitted to immunohistochemistry analysis for MAO-A and MAO-B. The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: All stages and grades of NMIBC and pT2 (MIBC) showed positive immunoreactivity for both MAO-A and MAO-B. MAO-A immunoreactivities were significantly higher (p < 0.01) in the high-grade pTa, pTis and pT2 groups in relation to low-grade pTa and pT1. Likewise, MAO-B immunoreactivities were remarkably higher (p < 0.01) in the high-grade pTa and pT2 groups. No statistical differences were found between pTis and low-grade pTa for MAO-B. Interestingly, pT1 group showed the lowest (p < 0.01) MAO-A and MAO-B immunoreactivities in relation to other stages and grades of BC, probably due to disruption of the extracellular matrix, with consequent reduction in O2 delivery (hypoxia). Conclusions: These findings collectively characterize the contribution of MAOs in BC pathogenesis and suggest that MAOs have potential as a therapeutic target in BC.
Circulating chromatin conformation signatures to enhance PSA positive predictive value and overall accuracy for prostate cancer detection.
Authors: Akoulitchev Alexandre , Hunter Ewan , Salter Matthew , Powell Ryan , Naithani Tarun , Green Jayne , Fiorentino Francesca , Ahmed Hashim Uddin , Pchejetski Dmitri , Winkler Mathias 
Published: June 2023

e17016 Background: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. Methods: n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. Results: PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.93 and NPV of 0.95 when tested on the independent prospective cohort. Conclusions: Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing, with further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence as the next step for PSE adoption in PCa screening.
Do we need to redefine the phoenix criteria after the arrival of the new generation imaging techniques?
Authors: Muelas Rodrigo , Puerto Francés Clara , Morillo Virginia , Sanchez Angel L. , Piquer Teresa , Fernández Camacho Encarnación , Aznar-Tortonda Vanessa , Plaza Patricia , Mingarro de leon Maria , Ferrer-Albiach Carlos 
Published: June 2023

e17018 Background: The biochemical recurrence (BCR) criteria are different depending on the primary tumour treatment: PSA ≥0.2 ng/mL after radical prostatectomy (RP) and PSA ≥ 2 ng/mL above the nadir after radiotherapy (RT)[Phoenix criteria]. The latter was established based on the detection of metastasis by conventional imaging tests (CT and bone scanning). Next generation imaging (NGI) techniques (18F-choline PET/CT and specially 18F-PSMA PET/CT), allow detection of metastasis with PSA values much lower than the Phoenix criteria. The purpose of this study is to compare the profile of patients diagnosed with metastatic hormone sensitive prostate cancer (mHSPC) by NGI techniques after BCR according to the primary tumour treatment performed. Methods: Patients diagnosed with mHSPC in our Radiation Oncology Department after BCR between February 2021 and December 2022 were reviewed. All of them underwent NGI: 18F-choline PET/CT if there was BCR following RT or a PSA level > 2 ng/ml after PTR; 18F-PSMA PET/CT if there was BCR after PTR or if 18F-choline PET/CT offered diagnostic uncertainties. Then, were stratified according to primary treatment: PTR (+/- salvage RT to the prostatic bed) vs RT (external or brachytherapy). PSA levels prior to NGI, number of metastases (≤5: oligometastatic vs > 5: polymetastatic) and their location (M1a: exclusive lymph node metastasis, M1b: presence of bone metastasis and M1c: presence of visceral metastasis) were compared. Results: A total of 38 patients were idiagnosed with mHSPC: 42.1% after PTR and 57.9% after RT. PTR group had PSA levels prior to NGI of 1.08 ng/ml, of which 75% were 18F-PSMA PET/CT. Twenty-five per cent of patients in this group were classified as polymetastatic. In RT group the median PSA levels prior to NGI was 3.5 ng/ml, of which 68.2% were 18F-choline PET/CT. The proportion of polymetastatic patients was 50%. The location of metastases in PTR and RT group was: M1a (68.8% vs 59.1%), M1b (31.3% vs 36.4%) and M1c (0% vs 4.5%). Conclusions: The percentage of polymetastatic patients in RT group is double that of PTR group, which is a worse prognostic factor. (4). This difference in the number of metastases is due to the higher PSA levels prior to NGI in RT group, which is directly related to the definition established by the Phoenix criteria(3). Given that NGI techniques can detect metastases with PSA values below the Phoenix criteria, it would be reasonable to redefine it in order to reduce the percentage of polymetastatic patients through earlier detection and thus improve their prognosis.
Longitudinal variability in symptom burden for patients with prostate cancer (PC).
Authors: Wong Risa Liang , Cheng Heather H. , Fann Jesse R. , Hnida James , Chakoian Marty , Jannat Samia , Schenker Yael , Yu Evan Y. , Gore John L. 
Published: June 2023

e17019 Background: Patients with PC often live for many years and can experience burdensome symptoms associated with PC and its treatment. The longitudinal fluctuations in symptom burden for a given individual with PC, or for groups with different PC disease states, are not well-described. We assessed self-rated performance status (PS), pain interference with daily activities, bother from sexual dysfunction, depression, and anxiety symptoms longitudinally for a cohort of patients with PC. Methods: For one year, patients with PC and ≥1 Urology or Medical Oncology clinic visit in the prior 6 months were emailed surveys every 60 days containing the ECOG PS instrument (range 0-4, higher scores = worse PS), PROMIS Pain Interference Short Form 4a (normalized range 1-5, higher scores = greater pain interference), PROMIS Sexual Bother (Male) items SFBOT 204, 205, and 206 (normalized range 1-5, higher scores = greater bother), PHQ-9 depression scale (range 0-27, score ≥10 considered positive for moderate symptoms), and GAD-7 anxiety scale (range 0-21, score ≥10 considered positive for moderate symptoms). We used chart review to obtain baseline characteristics and one-way ANOVA for comparisons. Results: For 201 enrolled patients, mean (SD) number of surveys completed was 5.8 (1.8) over a mean (SD) of 10.6 (3.1) months. At baseline, 50.7% had localized PC (LPC), 18.9% biochemically recurrent PC (BCR-PC), and 30.3% metastatic PC (MPC). 40.8% of patients were on androgen deprivation therapy, which was not associated with greater sexual bother (p = 0.17). Mean (SD) values for ECOG PS, pain interference, sexual bother, the PHQ-9, and the GAD-7 are shown by PC disease state (Table). For patients who completed ≥2 surveys (N = 192), mean (SD) ranges for these scales were 0.4 (0.6), 0.8 (0.9), 1.2 (0.8), 3.7 (3.3), and 2.6 (2.6), respectively. Mean range differed by PC disease state for ECOG PS (0.31 LPC vs 0.63 BCR-PC vs 0.59 MPC, p = 0.003) and pain interference (0.63 LPC vs 1.02 BCR-PC vs 0.95 MPC, p = 0.03). For patients with ≥1 positive PHQ-9 (N = 36) or GAD-7 (N = 11) screen over ≥2 surveys, a mean (SD) of 41% (30%) and 39% (33%), respectively, of their total screens were positive. Mean (SD) ranges for these patients were 8.4 (3.6) for the PHQ-9 and 8.5 (3.4) for the GAD-7 (both p < 0.001 compared with those who never screened positive). Conclusions: Patients with more advanced PC had worse PS, pain, and depression, but those with BCR-PC reported greater longitudinal fluctuations in PS and pain. Patients who screened positive for depression or anxiety only did so in ~40% of their surveys, and had greater longitudinal variability in their PHQ-9/GAD-7 scores than those who never screened positive. [Table: see text]
Testicular GERM cell tumors treatment outcome in a national cancer institution in Peru.
Authors: Rioja Patricia , Valencia Guillermo , Morante Zaida , Fuentes Hugo , Mantilla Raul , Salinas Agramonte Luis André , Sanchez Alarcon Jorge Luis , Vidaurre Tatiana , Neciosup Silvia P. 
Published: June 2023

e17031 Background: Testicular germ cell tumor (TGCT) is the most common neoplasm in young men and the incidence has been increasing over the last few decades, especially among Hispanic men. Multidisciplinary management is associated with excellent oncological outcomes. Here, we describe the treatment outcome of TGCT patients treated in single institution in Peru. Methods: We conducted a retrospective study of TGCT treated at Instituto Nacional de Enfermedades Neoplasicas from 2016 to 2019. Clinical and pathological data were collected from medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and compared with long-rank test. A level of p < 0.05 was considered significant. The statistical package SPSS v19 was used for the data analysis. Results: 221 patients were identified, 56% were non-seminomatous (NS) and 44% were seminomatous (S). Orchiectomy was performed in 94% of patients, only 6% underwent orchiectomy after chemotherapy. In both groups, the treatment regimens were: BEP (Bleomycin/Etoposide/cisplatin) 90%, Carboplatin 8.1% and EP (Etoposide/Cisplatin) 1.8%. 42 (21%) of patients receive rescue therapy, being the most frequent TIP (paclitaxel/ifosfamide/cisplatin). In NS patients, 5-year PFS was superior in good risk compared with poor risk (100% vs. 86%, p = 0.028) and for tumor markers level, S0 was superior to S3 (100% vs. 82%, p = 0.008). In S, 5-year PFS was no significant in any of groups of analysis. With a median follow-up of 57 months, OS in NS was 91%, 83% and 81% in 12, 36 and 60 months, respectively and OS in S was 96%, 87% and 87% in 12, 36 and 60 months, respectively. The analysis of 5-year OS according to clinical stage and risk stratification are shown in the Table 1. Only 2 patients received high-dose chemotherapy and still in complete response. Conclusions: Despite the high incidence of advanced TGCT, our patients had excellent survival results; being lower in those with CS III (both NS and S groups), poor risk and S3 for NS, and intermediate risk for S. Multidisciplinary management in a high volume institution is important for better outcomes in our patients. [Table: see text]