bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation of renal function in patients with urothelial carcinoma treated by tislelizumab-based immunochemotherapy.
Authors: Wu Zhouliang , Hu Hailong , Shen Chong , Chen Houyuan , Zhao Gangjian , Huang Shiwang , Jia Kaipeng , Bai Yiduo , Guo Shizheng , Zhang Zhe , Li Zhi , Da La , Lin Yuda 
Published: March 2023

494 Background: Treatment based on PD-1 ICIs brings advances to the treatment of urothelial carcinoma (UC). Although acute renal insufficiency is not common in iRAEs, the safety of immunotherapy in patients with renal impairment is still unknown. Consequently, we intend to investigate the effect of immunochemotherapy on nephritic function in the short term. Methods: Between July 2019 and September 2022, data of patients (pts) with UC that underwent tislelizumab based immunochemotherapy, including demographic information (age, gender), and creatinine level in baseline, after the first, second and third cycle (C1, C2 and C3) of immunotherapy in the Second Hospital of Tianjin medical University was collected and analyzed retrospectively. Estimated glomerular filtration rate (eGFR) is calculated according to CKD-EPI formula 2009, while pts were subdivided into different groups according to baseline eGFR, referencing to CKD categories in the K-DIGO 2012 guidelines for CKD classes. Data analyses were conducted using paired samples Wilcoxon Signed Rank Test and Kruskal-Wallis H test. Results: 163 pts have been included in our analyse totally. The median age was 67 years (IQR 61-74) and 128 (78.5%) were male. 135 (82%) pts received ICIs as perioperative treatment, while 19 (12%) pts were treated after radical operation. Metastasis is found in 9 (6%) pts before firstly received immunotherapy. Median creatinine (Cr) in baseline was 80.2umol/L (IQR 68.3-95.8), while median EGFR was 82.6 (IQR 64.3-93.8) mL/min/1. 73m2 in all pts. According to CKD categories in the K-DIGO 2012 guidelines, at baseline, 57 pts are classified as G1 (eGFR≥90 mL/min/1.73m2), 74 pts as G2(eGFR <90 mL/min/1.73 m2 and≥60 mL/min/1.73 m2), 30 as G3 (eGFR <60 mL/min/1.73 m2 and≥30 mL/min/1.73 m2), and 2 as G4 (eGFR <30 mL/min/1.73 m2 and≥15 mL/min/1.73 m2). No significant difference in eGFR between pts with CKD G1-2 in comparison to baseline and after the first (C1), second (C2) or third cycle(C3) of tislelizumab based immunotherapy (All p >0.05). Notably, we found that eGFR improved in pts with CKD G3-4 when the first, second and third cycle completed, in comparison to the baseline.(p<0.001, <0.001, =0.002). Conclusions: Despite renal impairment is common in pts with UC, no evidence suggests that it is contraindicated for tislelizumab based treatment. More importantly, PD-1 immunotherapy may provide better nephritic benefits in patients with renal insufficiency. [Table: see text]
Safety, tolerability, and preliminary efficacy of TAR-200 in patients with intermediate risk non–muscle-invasive bladder cancer: A phase 1 study.
Authors: van Valenberg F. Johannes P. , van der Heijden Toine , Cutie Christopher , Bhanvadia Sumeet Kaur , Keegan Kirk A. , Hampras Shalaka , Sweiti Hussein , Maffeo John , Jin Shu , Chau Albert , Reynolds Don , Iarossi Crysti , Kelley April , Li Xiang , Stromberg Katherine , Sedelaar Michiel , Steenbruggen Jessica , Somford Diederik Meindert , Witjes Alfred Alfred 
Published: March 2023

505 Background: TAR-200 is a novel intravesical drug delivery system designed to provide a continuous, slow release of gemcitabine within the bladder. Prolonged gemcitabine exposure over days, instead of hours, such as with current standard intravesical installations, may achieve more efficient and effective tumor response. We report on the safety and tolerability of TAR-200 in patients with non-muscle–invasive bladder cancer (NMIBC). Methods: In this phase 1b, open-label, prospective study, patients with a papillary recurrence after prior histologically proven, intermediate risk (IR)-NMIBC received two 1-week TAR-200 dosing cycles over a 4- to 6-week period. The study used a marker lesion/ablation design. Cystoscopy was performed to assess for recurrent papillary disease and for complete transurethral resection of the residual bladder tumor. The primary outcome was safety of TAR-200. Secondary outcomes were tolerability, pharmacokinetics, preliminary efficacy, and immunohistochemistry. Results: In total, 12 patients received TAR-200 treatment. Insertion and removal of TAR-200 was uneventful. No TAR-200-related serious adverse events (AEs) occurred. Four patients had no TAR-200-associated AEs; the remainder had varying degrees of AEs (all grade ≤2 [CTCAEv4.0]), mainly consisting of low-grade urinary urgency, urinary frequency, and dysuria, with no delay in the treatment schedule. Two patients refused a second dosing cycle due to urinary urgency and frequency. Plasma gemcitabine concentrations remained below the lower limit of detection. Five of 12 patients (42%) had complete response (CR); of these, 4 had a pathologic CR and 1 had CR based on visual assessment (with no biopsy available for pathologic assessment). Conclusions: In this small, phase 1 series, TAR-200 appears to be safe and well tolerated in patients with IR-NMIBC. Clinical trial information: NCT02720367 .
Oncological outcome of intraarterial chemotherapy combined with radiotherapy compared to radical cystectomy for patients with muscle invasive bladder cancer.
Authors: Higashijima Katsuyoshi , Tomisaki Ikko , Minato Akinori , Harada Kenichi , Fujimoto Naohiro 
Published: March 2023

515 Background: Although radical cystectomy (RC) has been a standard treatment for muscle invasive bladder cancer (MIBC), some patients are unfit or refuse RC. Intraarterial chemotherapy combined with radiotherapy (IAC-RT) is one of the bladder preservation techniques, but there are a few data in patients who performed IAC-RT without salvage RC. The aim of this study was to evaluate the efficacy and tolerability of IAC-RT without RC compared to RC in patients with MIBC. Methods: We retrospectively reviewed patients with MIBC (T2-4N0M0) who had received either IAC-RT or RC in our hospital between January 1999 and December 2019. Intraarterial chemotherapy consisted of cisplatin (30mg/m2) and adriamycin (20mg/m2) on day 1 of each 1st, 2nd, 5th, 6th week. Concomitant radiotherapy (2 Gy/session, total 60 Gy) to whole pelvis was performed during chemotherapy. Salvage RC was not performed in all patients. Overall survival (OS), disease-specific survival (DSS), and metastasis-free survival (MFS) were compared between patients who received IAC-RT and RC. The prognostic factors of IAC-RT associated with OS were also investigated. Results: Forty-two and 143 patients received IAC-RT and RC, respectively. Of 42 patients who received IAC-RT, 28 (67%) and 14 (33%) were elective (refused RC) and imperative (comorbidity:7 poor PS:6 unresectable:1) cases, respectively. The patients who underwent IAC-RT were older (median; 77 vs 69 years old) and had poorer PS (≥2; 43% vs 4.9%) and shorter follow-up time (median; 21.9 vs 40.0 months) than those of RC. During follow up periods, metastasis, bladder cancer death, death of any cause was observed in 20, 19, and 27 patients with IAC-RT, 59, 55, and 49 patients with RC. In survival analyses, median OS was 38.7 months (95%CI, 16.9-74.7) with IAC-RT versus 154.0 months (95%CI, 70.6- not estimable (NE)) with RC, these OS curves were significantly different (P=0.001). There were not significant differences between two groups in DSS (median 46.5 vs not reached, P=0.06) and MFS (median 38.7 vs not reached, P=0.21). In multivariate analysis, clinical stage (≥T3; HR, 1.89; 95% CI, 1.04-3.46; P=0.04) and PS (≥2; HR, 2.24; 95% CI, 1.16-4.33; P=0.02) were suggested as risk factors associated with poor OS, however, treatment procedure (IAC-RT or RC) did not associate with OS. Forty of 42 (95%) patients with IAC-RT had any adverse events (AEs). Although grade3 AEs were observed in 21 (50%) patients, most of them were hematological AEs and Grade 4/5 AEs was not observed. Conclusions: IAC-RT was a useful and tolerable treatment option for patients with MIBC who were unfit or refused RC.
Characteristics and outcomes for patients (pts) with metastatic small cell urothelial carcinoma (mSCUC).
Authors: Wilson Nathaniel R. , Khandelwal Jaanki , Xiao Lianchun , Shah Amishi Yogesh , Gao Jianjun , Goswami Sangeeta , Kovitz Craig A. , Guo Charles , Czerniak Bogdan , Logothetis Christopher , Corn Paul Gettys , Tannir Nizar M. , Siefker-Radtke Arlene O. , Alhalabi Omar 
Published: March 2023

522 Background: mSCUC is an aggressive cancer with historically poor outcomes. Methods: We performed a retrospective analysis of 216 pts with mSCUC treated at MD Anderson from 1985-2020. We captured baseline demographic and clinical characteristics, metastatic sites, systemic treatments, and survival. Median overall survival (mOS) was calculated from start of frontline (1L) therapy for metastatic disease. Results: Median age was 67 years, 84% male sex, 91% primary tumor in bladder, and 88% white race. Histology included pure SCUC (30%), predominant SCUC (44%), focal SCUC (25%) and large cell (1%). Metastatic sites were lymph nodes (54%), bone/peritoneum (39%), liver (38%), brain (31%) and lung (26%). Brain metastases frequency varied across histology (pure SCUC 48%, predominant SCUC 24.5%, focal SCUC 24%, p=0.06). Treatment regimens and mOS by frontline regimen are listed (Table). mOS was 11.91 months for treated pts with sufficient follow up (n=155). mOS by 1L treatment: EP (9.51 months), IA/EP (14.10 months), other platinum chemotherapy (13.26 months), nonplatinum chemotherapy (9.74 months), immune checkpoint inhibitor (ICI) (6.51 months), EP+ICI (undefined). Of 140 pts treated with 1L chemotherapy, 43 (31%) were able to receive second line (2L) therapy. mOS among those who received 2L chemotherapy (n=27) was 13.65 months vs those who received 2L ICI (n=16) was 22.53 months (HR=0.53, 95% CI=0.26-1.10; p=0.11). Conclusions: mSCUC is a devastating malignancy with high degree of brain involvement, and poor prognosis. 1L ICI therapy alone has suboptimal survival outcomes and a chemotherapy backbone remains necessary. A deeper understanding of SCUC’s driver biology is essential for developing better therapies. [Table: see text]
Impact of neoadjuvant chemotherapy on pathological stage and survival in sarcomatoid bladder cancer.
Authors: Roy Arya Mariam , Jatwani Karan , Muthusamy Kumarasamy Vasanthan , Perimbeti Stuthi , Jiang Changchuan , Gupta Kush , Guru Khurshid , Chatta Gurkamal S. , Gopalakrishnan Dharmesh 
Published: March 2023

530 Background: Sarcomatoid bladder cancer is an extremely rare and aggressive histological variant with poor prognosis and limited consensus regarding its management given rarity and lack of high-quality data. Radical cystectomy (RC) is the mainstay of treatment in muscle-invasive disease and adjuvant therapy is often offered to eligible patients with high-risk features. Data regarding the role of neoadjuvant chemotherapy (NAC) for this variant is limited. Methods: The National Cancer Database was queried to identify patients diagnosed with sarcomatoid bladder cancer from 2004 to 2018. Patients older than 18 years with cT2-4aN0-1M0 sarcomatoid bladder cancer who received curative-intent surgery were included in the analyses. Clinical T4b/N2-3/M1 disease and receipt of adjuvant chemotherapy were employed as exclusion criteria. The population was divided into two cohorts based on the receipt of NAC. Chi-Square and Mann Whitney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed to adjust for confounding factors associated with overall survival. Models were adjusted for age, race, sex, income, stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 573 patients were identified - 70% were males and 93% were White; 139 (25%) received NAC (NAC+) while 434 (75%) did not (NAC-). NAC+ patients were younger (65 vs 71 years, p < 0.001). Downstaging to pT0-1N0 at the time of RC was significantly more frequent in the NAC+ group compared to the NAC- group (32 (24.5%) vs. 28 (6.8%), p = 0.001). Overall survival (OS) was also significantly longer in the NAC+ group (median of 40.8 vs. 19.4 months, log-rank p = 0.003). On multivariable analysis, NAC+ (Hazard Ratio (HR) = 0.73, 95% CI 0.56-0.91, p = 0.02), pathological downstaging to pT0-1N0 (HR = 0.5, 95% CI 0.31- 0.8, p < 0.001), and any pathological upstaging (HR 4.1, 95% CI 1.5-6.6, p < 0.001) were independently associated with all-cause mortality, while other factors were not (Table). Conclusions: In this large retrospective analysis, administration of NAC in muscle-invasive sarcomatoid bladder cancer was associated with higher rates of downstaging to non-muscle-invasive disease at the time of RC and reduced all-cause mortality. [Table: see text]
Association of biomarkers and outcomes in patients (pts) with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs).
Authors: Reyes Kevin R , Zhang Li , Zhu Xiaolin , Jindal Tanya , Deshmukh Prianka , de Kouchkovsky Ivan , Kumar Vipul , Maldonado Edward , Kwon Daniel H , Chan Emily , Porten Sima P. , Borno Hala , Bose Rohit , Desai Arpita , Aggarwal Rahul Raj , Small Eric Jay , Fong Lawrence , Chou Jonathan , Friedlander Terence W. , Koshkin Vadim S 
Published: March 2023

532 Background: ICIs form the backbone of treatment for mUC. However, only a minority of pts benefit and additional biomarkers of ICI response are needed. Methods: In our institution, we identified mUC pts treated with ICI monotherapy who had next generation sequencing (NGS). Somatic alterations present in ≥10% of pts ( ARID1A, CCND1, CDKN2A, CDKN2B, ERBB2, FGF3, FGF4, FGF19, FGFR3, KDM6A, MDM2, MLL2, PIK3CA, RB1, TERTp, TP53, TSC1), as well as DNA-damage response (DDR) alterations and tumor mutational burden (TMB) were analyzed as biomarkers. These biomarkers were individually evaluated in separate multivariate models while accounting for clinical factors including age, BMI, ECOG PS, primary tumor location, histology, hemoglobin, neutrophil to lymphocyte ratio and albumin. Multivariate cox regression and logistic regression models were used to measure hazard ratios (HR) and odds ratios (OR) for overall survival (OS), progression-free survival (PFS) and observed response rate (ORR). Results: Among 152 mUC ICI-treated pts, 107 had NGS data (FoundationOne, UCSF500, Strata), including 85 with TMB data. For the 107 pts with NGS, median age was 70 yrs, majority were male (69, 64%), Caucasian (70, 65%), had pure urothelial histology (57, 53%), and had first-line ICI (55, 51%). ORR was 35%, median PFS was 3.9 mos (95% CI: 2.6-7.5 mos), and median OS was 17.4 mos (95% CI: 14.1-30.6 mos). Biomarkers associated with improved outcomes to ICI, independent of relevant clinical factors, included alterations in ARID1A and DDR, as well as high TMB (>10 Mut/Mb). Inferior outcomes were seen in pts with CDKN2B, KDM6A, FGF3, FGF4, and FGF19 alterations (Table). Conclusions: In this large retrospective multivariate analysis controlling for clinical factors in ICI-treated mUC pts, we found multiple biomarkers associated with improved or inferior outcomes. These hypothesis-generating findings can inform clinical decision making and trial design for mUC pts treated with ICIs, and should be validated in larger cohorts. [Table: see text]
Germline mutational profile in metastatic urothelial malignancy.
Authors: Barry Emily , De Souza Andre Luiz , Holder Sheldon L. , Lagos Galina , Mega Anthony E. , Carneiro Benedito A. , Amin Ali 
Published: March 2023

550 Background: 24% of patients with high-risk urothelial carcinoma have pathogenic germline mutations (Nassar, Genetics in Medicine 2020). In that study, demographics, metachronous/synchronous tumors, and family history did not differ between germline and sporadic cases of bladder cancer. We report herein the prevalence of actionable mutations and de novo metastatic disease in patients with germline mutations who developed metastatic urothelial carcinoma. Methods: We retrospectively analyzed a database of 90 patients with metastatic urothelial carcinoma (urethral, bladder, and upper tract disease) at our institution who had genetic testing performed on tumor specimens. T-student test was performed to calculate statistical significance for the distribution of age, while Chi-square test evaluated the frequency distribution of gender, actionable mutations, and de novo metastatic disease. Patients’ tumors were sequenced by a 700 gene panel for both somatic and germline mutations. Comprehensive chart review was performed to extract clinical data. Results: Out of the 90 patients reviewed, 11 (11.1%) had germline mutations. Of these patients, 5 had upper tract urothelial carcinoma, 5 had bladder cancer, and 1 had urethral cancer. Nine patients had pathogenic germline mutations: MUTYH, BRCA2 (each representing 1.8% of patients); APC, BRCA1, CDKN2A, FH, MSH2 (each representing 0.9% of patients). Two patients had germline mutations of unknown significance ( APC, CHEK2). Age (T-value 1.62053, p=1.08453), gender (Chi-square 0.0024, p=0.961037) or de novo metastatic presentation (Chi-square 0.5, p=0.4795) were not statistically significant between patients with germline and sporadic mutations. Somatic actionable mutations included ATR, BRCA2, BRAF, CDK12, ERBB2, FBXW7, FGFR3, HRAS, MTAP, and PIK3CA. Microsatellite instability high (MSI-H) status was only present in the patient with germline MSH2 mutation. PD-L1 expression was high (CPS ≥10) in 4 patients with germline mutations. Tumor mutational burden ranged from 1.1 to 28.4 mutations per Megabase. Conclusions: Our findings further define the clinical and genomic characteristics of patients with metastatic urothelial carcinoma and germline mutations in a tertiary center. Further investigation is warranted to validate these findings in national sequencing databases.
The genomic landscape of TERT alterations in bladder cancer.
Authors: Jalkanen Aimee , Basu Gargi D. , Hall David W. , Hoag Jess R , LoBello Janine R. , Baehner Frederick L. , Thakkar Snehal Govind , Dorff Tanya B. 
Published: March 2023

551 Background: Some of the most common mutations seen across cancers occur in TERT, where promoter mutations upregulate TERT transcription. In bladder cancer, TERT mutations are associated with poor prognosis, especially for recurrence. In this study, we identified TERT promoter mutations in bladder cancer and determined whether mutations at other genes were significantly associated. We also examined whether TERT mutation frequency is associated with age or gender. Methods: We utilized the Oncomap ExTra genomic profiling assay to identify alterations. This assay performs tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations. In addition to the exome, several noncoding regions are sequenced, including the TERT promoter. Single-nucleotide variants, indels, copy number alterations, alternative transcripts, and gene fusions are all detected. Tumor mutational burden (TMB) and microsatellite instability (MSI) are also calculated. Results: Of 194 bladder cancer patient specimens assayed between April 2018 and August 2022, 153 (78.9%) carried a TERT promotor mutation (Table). The C228T and C250T single base substitutions were the most common, at 57.7% and 15.5%, respectively. Of note, one patient had a TERT fusion caused by an inversion involving MARCHF6 as the partner gene. Many patients harbored mutations in other genes, with two possibly associated with TERT status: BRCA2 was mutated in 6 (3.9%) TERT-mutated and 7 (17.1%) TERT-wild type patients (Fisher’s Exact Test, p=0.007), and FGFR3 was mutated in 33 (21.6%) TERT-mutated and 3 (7.3%) TERT-wild type patients (p=0.042). In addition, TMB-high was in 93 (60.8%) TERT-mutated and 10 (24.4%) TERT-wild type patients (p=0.071). None of these associations were significant after correcting for the false discovery rate. There was no significant difference in median (or average) age of individuals with versus without a TERT mutation (71.0 and 70.0 yrs, respectively). In addition, there was no significant difference in frequency of TERT alterations in males (82.0%) versus females (70.9%). Conclusions: The Oncomap ExTra assay allowed identification of both commonly observed and rare TERT promoter mutations, including a fusion, in 78.9% of bladder cancer patients. Such assays are useful to identify both TERT alterations prognostic for progression and patients eligible for clinical trials evaluating TERT-directed therapies. In addition, TERT mutations may be associated with FGFR3 mutations and high TMB, which have matched therapies, though these associations need to be validated in an independent cohort. [Table: see text]
Differential treatment response of prostate and metastatic lesions in patients with newly diagnosed metastatic prostate cancer.
Authors: Esen Baris , Seymen Hulya , Falay Okan , Tarim Kayhan , Kılıç Mert , Bavbek Sevil , Kordan Yakup , Tilki Derya , Esen Tarik , Demirkol Mehmet Onur 
Published: March 2023

56 Background: We aimed to evaluate the response of primary tumor to systemic treatment in patients with newly diagnosed mPCa with serial PSMA PET/CT scans. Methods: A total of 43 patients with newly diagnosed mPCa who had significant prostatic PSMA uptake at baseline PSMA PET/CT (bPSMA) and underwent at least one follow-up PSMA PET/CT (fPSMA) after receiving systemic treatment were included in the study. Those who received any definitive treatment at localized stage and those who underwent radiotherapy to prostate before fPSMA were excluded. Prostatic and metastatic PSMA response after systemic treatment was categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) as recommended by guidelines. Discordant behavior between prostate and metastases was defined as the condition when metastatic lesions are responding (CR or PR) to systemic treatment while prostate had progressed or vice versa. CHAARTED criteria was applied to categorize patients according to the volume of metastatic disease. Results: The mean age of patients at bPSMA was 67.7 ± 8.5 years. The median PSA at bPSMA was 31.7 ng/dL (IQR: 11.3 – 106.0). Patient characteristics and treatments are summarized. The median time interval between bPSMA and the first fPSMA was 5.7 months (IQR: 4.6 – 7.5). Nine patients (20.9%) had CR, 25 (58.1%) had PR, 5 (11.6%) had SD and 4 (9.3%) had PD at prostate following systemic treatment. Patients with low-volume disease had prostatic CR twice more commonly than those with high-volume disease (27.3% vs 14.3%). In 6 (13%) cases, a significant PSMA uptake at prostate was detected despite a complete response of all metastatic sites. Discordant treatment responses at the prostate and metastatic sites were observed in 6 out of 43 (16%) patients. Conclusions: Discordant behavior between prostate and metastases are not rare in mPCa. Almost one-fourth of patients with low-volume mPCa achieved a complete prostatic response with systemic treatment only. Prostatic response on PSMA PET/CT following systemic treatment can be used to select ideal patients for the treatment of the primary tumor in patients with mPCa. [Table: see text]