bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of real-world treatment patterns and adherence to bacillus Calmette-Guerin (BCG) in the context of guideline recommendations for patients with high-risk non-muscle invasive bladder cancer (NMIBC).
Authors: Gaylis Franklin D , Emond Bruno , Manceur Ameur M , Tardif-Samson Anabelle , Morrison Laura , Pilon Dominic , Lefebvre Patrick , Ellis Lorie , Balaji Hiremagalur parthasarathy , Ireland Andrea 
Published: March 2023

470 Background: Intravesical BCG is considered a first-line (1L) treatment for high-risk NMIBC patients. Since the presence of carcinoma in situ (CIS) in NMIBC is associated with increased disease progression rates and poor clinical outcomes, BCG is prioritized in clinical guidelines for NMIBC patients with CIS. However, BCG’s US shortage may negatively affect clinical outcomes in patients. This study evaluated the adequacy of BCG treatment patterns among NMIBC patients, including a subgroup with CIS. Methods: Adults with NMIBC treated with BCG were selected from de-identified IBM MarketScan Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Treatment patterns were assessed from the first BCG claim (triggering the start of 1L treatment) until the end of the patient’s observation. Consistent with real-world literature, adequate BCG induction was defined as ≥5 BCG claims within 70 days of the first BCG claim whereas adequate BCG induction and maintenance was defined as ≥7 BCG claims within 274 days of the first BCG claim. Proportions of patients with adequate BCG induction and maintenance were compared between CIS subgroup and overall NMIBC cohorts using chi square tests. Results: Of 5,803 NMIBC patients treated with 1L BCG, 1,182 (20.4%) had documentation of CIS. Overall and CIS cohorts had similar mean age (67 years; range 18-101 years). After 1L BCG, 56.6% and 71.8% of the overall and CIS cohorts had another treatment (P<.001; table). While 86.9% and 90.0% of the overall and CIS cohorts had adequate BCG induction (P=0.003), only 41.5% and 50.8% had adequate BCG maintenance (P<.001). More patients in the CIS versus overall cohort had a cystectomy (13.9% vs 9.7%; P<.001). Conclusions: In this study, most NMIBC patients treated with BCG received adequate induction; however, BCG maintenance was inadequate and most patients had another treatment following 1L BCG. Patients with CIS were more likely to have cystectomy after BCG, suggesting higher risk of progression in this subgroup. Results of this study further emphasize a need for additional available treatment options that are safe, efficacious, and tolerable. [Table: see text]
Cost savings associated with palliative care among patients with genitourinary malignancies.
Authors: Chansriwong Phichai , Thokanit Nintita Sripaibookij , Semsarn Siriporn , Utthiya Pinyo , Kasemsup Vijj 
Published: March 2023

474 Background: The cost of cancer treatment has increased significantly in recent decades, and highest costs incurred in the last 6-months of life. Patients’ health insurance status is a factor influencing to cost of care in different from individuals’ ability to access hospital care. 80% of Thai people use the Thailand’s Universal Coverage Scheme (UCS), about 15% use the Civil Servants Medical Benefit Scheme (CSMBS). Only CSMBS can reimburse all costs of in-patient care, but UCS had to co-pay at some cost. All health scheme is equality accessibility to palliative care. Early integrated palliative care services improve the GU malignancy patients care experience, decreases healthcare utilization, and improved quality of life. Study aim was to examine Hospital-based palliative care interventions in GU malignancy patients may reduce costs. Methods: A retrospective claims database in Ramathibodi Hospital was analyzed, that included cancer patients had a medical claim for death between Jan 1, 2016 - Dec 31, 2020. Our study compared cost in patients receiving palliative care (PC) and patients receiving usual care. Costs were determined by summing paid amounts on all hospital services used within the last 6, 3 and 1 months before death, including cancer-related inpatient service, emergency room visits, cancer-related outpatient services and other hospital services with cancer diagnosis. Results: Of the 1,772 cancer patients who died, 289 (16.3%) integrated treated with PC matched to 1,483 (83.7%) were usual care patients. 107 Genitourinary Malignancies patients including 44 TCC, 36 Prostate, 22 RCC and 2 Testicular cancer, that 22 (20.6%) integrated treated with PC. Median age was 72.4 years. Patients categorized as CSMBS 48% and UCS 44.4%. The PC group had $10,244.1 (+/- 8,705.6) in last 3 months hospital costs that significantly less than in usual care $(17,174.3 +/-14,262.5) (P= 0.032) that PC group had significant reductions in medications, laboratory, and intensive care unit costs compared with usual care patients. Direct costs of inpatient care in the last 3 months of life for patients were lower in patient who received earlier PC that patients who received PC consults < 90 days was $9,728.8 (+/- 1,044.5) and patients received PC consults < 30 days cost was $12,517.7 +/- 1,476. Patients in SSS and UCS had a significantly saving cost when they received PC consultation, P=0.032. However, there was no difference in CSMBS. Conclusions: Integrated palliative care in caring GU malignant patients associates with significant hospital cost savings. Insurance status not limited in access to palliative care consultation, but influences in cost of end-of-life care.
Outcomes with immune checkpoint inhibitor (ICI) therapy in patients with FGFR2/3 alterations in advanced urothelial carcinoma (aUC).
Authors: Talukder Rafee , Bakaloudi Dimitra Rafailia , Makrakis Dimitrios , Tripathi Nishita , Agarwal Neeraj , Jindal Tanya , Koshkin Vadim S , Johnson Jeffrey , Zakharia Yousef , Brown Jason , Rey-Cárdenas Macarena , Castellano Daniel , Alva Ajjai Shivaram , Zakopoulou Roubini , Korolewicz James , Drakaki Alexandra , Barata Pedro C. , Grivas Petros , Khaki Ali Raza 
Published: March 2023

478 Background: Erdafitinib is FDA-approved for patients (pts) with advanced urothelial carcinoma (aUC) with FGFR2/3 mutation or fusion and progression after platinum-based chemotherapy. It is postulated that FGFR3-altered aUC may be a “cold tumor” and associated with non-T cell-inflamed phenotype and, thus, may be less responsive to ICI. We hypothesized that pts with aUC that harbor FGFR2/3 alterations would have lower response and shorter survival on ICI. Methods: We performed a retrospective cohort study of pts with aUC treated with ICI and available genomic data in 11 institutions; pts with pure non-UC, treated with combinations or on clinical trial were excluded. Outcomes (overall response rate [ORR], progression free survival [PFS] and overall survival [OS] were compared in pts with and without FGFR2/3 alterations. PFS and OS was compared using Cox proportional hazards. All analyses were performed in the overall population and also categorized by treatment line (1st line [1L] vs salvage [2+L]). Multivariable models were adjusted for an internally developed risk score for 1L and Bellmunt risk score for 2+L; p<0.05 was significant. Results: 310 pts met inclusion criteria; 217 pts, 206 pts, and 204 pts were included in ORR, OS and PFS analyses, respectively. Median follow up time was 37 months [mo]. Overall, median age at ICI initiation was 69, 74% men, 85% White, 27% mixed histology, 24% upper tract, 15% liver metastases, 55% ECOG PS 0-1; 101 pts (33% of total population) had FGFR2 or FGFR3 mutation/fusion. ORR to ICI in pts with FGFR2/3 alteration was 25% (95% CI 15-37%) vs 46% (95% CI 38-55%) in pts without such alterations. PFS was shorter for pts with FGFR2/3 alteration (median [m] PFS 4 mo vs 7 mo without such alterations; HR=1.53 [95% CI 1.09-2.15], p=0.015). However, OS was similar in both groups (mOS 14 mo in both groups; HR=1.09 [95% CI 0.75-1.58], p=0.65). ORR, PFS and OS analyses stratified by ICI treatment line (1L vs 2+L) are shown in the Table. Conclusions: In this multisite retrospective study, the presence of FGFR2/3 alterations was associated with lower ORR and shorter PFS in pts with aUC treated with ICI. Limitations include retrospective nature, lack of randomization and central scan review, selection bias, missing data, and possible residual confounding. Findings suggest that FGFR2/3 alterations may impact response and PFS with ICI and might inform discussion on the optimal sequence of therapies in aUC but need external validation and ideally clinical trial data. [Table: see text]
Neoadjuvant chemotherapy (NAC) versus adjuvant chemotherapy (AC) in patients with clinically node-positive upper tract urothelial cancer (UTUC) who underwent radical nephroureterectomy (RNU).
Authors: Jatwani Karan , Roy Arya Mariam , Attwood Kristopher , George Anthony , Faisal Muhammad Salman , Muthusamy Kumarasamy Vasanthan , Perimbeti Stuthi , Jiang Changchuan , Chatta Gurkamal S. , Gopalakrishnan Dharmesh 
Published: March 2023

486 Background: UTUC is less common and associated with poorer stage-for-stage prognosis compared to urothelial bladder cancer. AC is regarded as a standard-of-care in high-risk UTUC based on superior disease-free survival compared to observation in the POUT trial, though fewer than 10% of patients in this trial had lymph node involvement.1 CheckMate 274 revealed lesser magnitude of benefit with adjuvant nivolumab in UTUC compared to bladder cancer on post hoc analysis.2 The preferred sequence of perioperative systemic therapy in node positive UTUC remains unclear. Methods: We queried the National Cancer Database for adult patients with clinically node positive (cTanyN1-3M0) UTUC diagnosed between 2004 and 2018. Patients were divided into two groups based on the perioperative treatment strategy - NAC or AC. Patients who did not undergo RNU were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 862 patients were identified - 362 (42%) underwent NAC while 500 (58%) received AC. No significant differences were noted between the groups regarding age, sex, or insurance status. Patients with cT1-2 UTUC more often received NAC (27.9% vs 11.8%, P <0.001) while those with cT3-4 disease more frequently received AC (38.9% vs 57.4%, p<0.001). Rates of NAC vs AC were not significantly different based on clinical N stage (P = 0.35). Overall survival in the NAC group was significantly longer than the AC group (median of 47.1 vs. 20.2 months, log-rank P < 0.001). On multivariable analysis, only the sequence of perioperative chemotherapy was independently predictive of overall survival (Hazard Ratio of 1.38 for AC, with 95% CI 1.14-1.68, P = 0.001). Conclusions: In this large retrospective analysis of outcomes among patients with clinically node positive UTUC who underwent RNU, NAC was associated with significantly longer overall survival compared to AC. References: 1) Birtle A, Lancet 2020; 2) Bajorin DF, NEJM 2021.
Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.
Authors: Riveros Carlos , Ranganathan Sanjana , Haque Waqar , Xu Jiaqiong , Geng Michael , Anis Maryam , Muhammad Taliah , Farach Andrew M. , Teh Bin S. , Wallis Christopher J.D. , Sonpavde Guru P. , Satkunasivam Raj 
Published: March 2023

488 Background: Elective nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiotherapy (WP-CCRT) compared to bladder-only (BO)-CCRT has not been demonstrated. Currently, the National Comprehensive Cancer Network (NCCN) guidelines do not recommend whether to include pelvic nodes in the radiation field. Using real-world data from the National Cancer Database (NCDB), we sought to compare the overall survival (OS) between BO-CCRT and WP-CCRT for MIBC. Methods: Using the 2019 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2018. We selected patients with clinical T2-T4N0M0 disease receiving TMT as first-line treatment. TMT was defined as transurethral resection of bladder tumor followed by CCRT: 60–65 Gy of RT delivered to the bladder with concurrent single- or multiple-agent chemotherapy. Patients were stratified into BO-CCRT vs. WP-CCRT. Overall survival (OS) analysis was performed using Kaplan-Meier estimates and multivariable Cox proportional hazards regression analysis. The variables included in the multivariable Cox regression model were age, sex, race, comorbidity burden (as per the Charlson-Deyo comorbidity index), facility type, insurance status, median income quartile, rurality, distance from facility, and clinical T stage. Results: A total of 605 patients receiving TMT for MIBC were identified: 162 (26.8%) BO-CCRT and 443 (73.2%) WP-CCRT. The median follow-up time was 25.6 months (interquartile range [IQR]: 4.8-42.6) and 28.7 months (IQR: 3.0-51.6) for BO-CCRT and WP-CCRT, respectively. The median OS was 32.9 months (95% confidence interval [CI] 30.8 – not reached) and 48.3 months (95% CI 39.6 – not reached) for BO-CCRT and WP-CCRT, respectively. However, multivariable Cox regression analysis failed to find an association between WP-CCRT (hazard ratio [HR] 1.08, 95% CI 0.76-1.54) and improved OS, compared to BO-CCRT. Conclusions: Elective nodal-irradiation (WP-CCRT) in the setting of TMT for MIBC was not associated with a benefit in OS compared to BO-CCRT.
68GaPSMA-11 PET/CT to monitor treatment response in patients with metastatic prostate cancer: The concordance between biochemical response and PSMA response.
Authors: Esen Baris , Seymen Hulya , Tarim Kayhan , Köseoğlu Ersin , Bolukbasi Yasemin , Falay Okan , Demirkol Mehmet Onur , Tilki Derya , Esen Tarik 
Published: March 2023

49 Background: The aim of this study was to assess whether PSMA PET is associated with flares, with discordant results in regard to biochemical response, and with positivity rates at low PSA values while monitoring metastatic prostate cancer (mPCa) receiving systemic treatment. Methods: A total of 96 patients with PSMA PET-detected mPCa who underwent at least one follow-up scan after receiving systemic treatment were included in the study. PSA levels at baseline PSMA PET-CT (bPSMA) and follow-up PSMA PET scans (fPSMA) were recorded. Any significant PSMA uptake at prostate and/or metastatic lesions were considered PSMA positivity. PSMA response were decided according to PSMA PET Progression (PPP) criteria . Biochemical progression was defined as ≥25% increase in PSA (1 ng/dL was the minimal starting value). PSMA PET and PSA response were dichotomized into progressive disease (PD) vs non-PD. Discordant responses among different metastases and prostate were defined as the condition when some metastatic lesions (or prostate) are responding (CR or PR) to systemic treatment while others had progressed. Results: A total of 346 serial PSMA PET/CT (96 bPSMA and 249 fPSMA) scans were evaluated. The median time between consecutive PSMA PET scans was 6.3 months (IQR: 4.7 – 10.6) Overall PSMA PET positivity rate of fPSMA scans was 88.4% (220/249). PSMA positivity rates according PSA levels were summarized. PPP was detected in 93 cases (37.8%) and biochemical progression was observed in 73 cases (30.2%). PSA and PSMA responses were highly concordant (Cohen’s K=0.623, p<0.001). PSA-PSMA discordant responses were detected in 39 scans (17%). The possible causes could be identified in 34 of 39 scans (87%) while no obvious reason for discordance could be shown in the remaining 5. Conclusions: PSMA PET/CT showed very high detection rates of malignant lesions even in very low PSA values when monitoring treatment response in patients receiving systemic treatment for mPCa. PSA and PSMA responses were highly concordant. In cases with discordance, the reason seems to be the discordant behaviour of intraprostatic and metastatic lesions and not necessarily PSMA flares. PSMA PET is a promising biomarker to assess treatment response in patients with mPCa. [Table: see text]
The Bristol Bladder Trial: Five year outcomes in patients treated with neoadjuvant cabazitaxel and cisplatin chemotherapy for muscle invasive transitional cell carcinoma of the urinary bladder.
Authors: Challapalli Amarnath , White Paul , Masson Susan , Foulstone Emily , Renninson Emily , Bravo Alicia , Pearson Sylvia , Dailami Narges , Persad Raj , Koupparis Anthony , Rowe Edward , Oxley Jon , Kabala Julian , Ash-Miles Janice , Bahl Amit 
Published: March 2023

493 Background: Neoadjuvant cisplatin-based combination chemotherapy (NAC) improves survival in muscle invasive bladder cancer (MIBC). However, response rates and survival remain suboptimal. We sought to evaluate the efficacy of cabazitaxel with cisplatin in this patient group. These patients have now been followed for survival status for 5 years post NAC and radical cystectomy. Methods: This was a single arm (Simon 2 stage), phase 2 study. Patients with MIBC were included if fit to receive NAC and to undergo radical cystectomy. 26 evaluable patients were required to detect an objective response rate (ORR) of >35% with 80% power. ORR was defined as pathological complete response (pCR) plus partial response (pathological downstaging, ≥T2 at diagnosis to ≤T1 at cystectomy). Treatment was with cisplatin 70mg/m2 and cabazitaxel 15mg/m2 on day 1 of a 21-day cycle, for 4 cycles prior to surgery. Toxicity was recorded using CTCAE v.4.03. QoL data was assessed during and after chemotherapy using EQ-5D-5L and EORTC-QLQ-C30, BLM30 questionnaires. Patients were followed for 5 years post cystectomy for progression free survival (PFS) and overall survival (OS). Results: ORR was seen in 15 out of 26 evaluable patients, 57.7%, with 24.6% achieving pCR. 1 out of 15 patients who achieved ORR died due to disease progression in the 5 year follow up period. The median PFS and OS were not reached by the 5 year follow up time point with a 5 year survival rate of 65.4% being seen in this patient cohort. Median OS in non-responders (11 patients) was 20.5 months and 5 year survival rate for the non-responders was 36.4% compared to 93.3% for responders. Conclusions: Neoadjuvant cabazitaxel with cisplatin chemotherapy is an effective regimen with 65.4% patients alive and progression-free at 5 years. It also indicates that ORR (and not just pCR), is a good predictor of patient survival at 5 years post radical cystectomy with only 1 out of 15 patients who achieved ORR progressing and dying in this period. However, in current clinical practice, there are no validated predictive biomarkers regarding potential response to NAC. Taken together with our previously published data, cabazitaxel with cisplatin as neoadjuvant chemotherapy is a safe, well-tolerated and effective regimen and should be compared to the regimens e.g. cisplatin/gemcitabine considered as standard in this setting. Clinical trial information: NCT01616875 .
A pilot study of tazemetostat and pembrolizumab in advanced urothelial carcinoma (ETCTN 10183).
Authors: Hussain Maha H. A. , Kocherginsky Masha , Singh Parminder , Myint Zin , Jiang Di Maria , Wulff-Burchfield Elizabeth Marie , Sharon Elad , Piekarz Richard , Meeks Joshua J , VanderWeele David James 
Published: March 2023

506 Background: Despite response to systemic therapy, few metastatic urothelial carcinoma (mUC) patients (pts) achieve durable responses. Mutations in the COMPASS-related proteins KMT2D, KMT2C, and KDM6A are found in 66% of UC patients suggesting histone regulation may be an acquired mechanism of tumor viability. We previously found regression of UC in mice when treated with EZH2 inhibitor, tazemetostat. In vivo administration of tazemtostat enhanced the immune response with direct regulation of cytokines and antigen recognition machinery (MHCI and MHCII). We hypothesized that restoration of epigenetic imbalance, combined with immunotherapy, may improve outcomes in mUC pts. Methods: ETCTN 10183 (NCT03854474) is a pilot study evaluating the efficacy of tazemetostat 800 mg BID + pembrolizumab 200 mg every 3 weeks for cisplatin-refractory (Cohort A) or cisplatin/chemo-ineligible advanced UC (Cohort B) pts, with N=12 pts in each cohort. The primary objective is to identify the recommended phase two dose (RP2D) of tazemetostat in combination with pembrolizumab. Secondary objectives include RECIST-based response rate, safety, and progression-free survival. The maximum planned treatment duration is 2 years. Translational objectives include defining total and COMPASS-related genes tumor mutational burden, tumor subtyping, TCR clonality, T cell infiltration, and PDL-1 expression. Results: In the safety lead-in phase, 6 mUC pts were treated. There were no dose-limiting toxicities (DLTs). The RP2D for tazemetostat was established at 800 mg BID. Here we report results of fully accrued cohort A (N=12); 67% males, 33% females, 83% white, 8.3% Black, and 25% Hispanic/Latino ethnicity. The primary sites of UC were: bladder (n=9, 75%), renal pelvis (n=2, 17%), and ureter (n=1, 8.3%). The median (interquartile range, IQR) time since primary diagnosis was 1.1 years (0.7, 1.9); 11/12 patients had non-nodal metastatic disease; 10/12 had 1 or more visceral/bone metastasis. Median number of treatment cycles was 5 (IQR: 3-11; range 1-35). Median duration on protocol treatment was 12 weeks (IQR: 7-30; range 3-107 weeks). Three pts had treatment related grade 3/4 AEs: grade 4 sepsis (n=1), grade 3 lymphopenia (n=2); anemia, increased alkaline-phosphatase, and HSV oral infection (n=1 each). Best response was partial response (PR) in 3 pts (25%) and 3 (25%) had stable disease. Median PFS was 3.1 months (95%CI: 2.3-NA), and median overall survival was 8.0 months (95% CI: 4.7 – NA). Conclusions: The RP2D dose for tazemetostat is 800 mg + 200 mg Pembrolizumab q 3 weeks. The combination was feasible, well tolerated, and resulted in durable responses in poor-risk chemo-refractory UC patients. Clinical trial information: 03854474 .