bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of nonseminomatous testicular germ cell tumors with teratoma-free primaries with disease relapse and overall survival.
Authors: Paffenholz Pia , Landwehr Georg , Seidel Christoph Alexander , Poch Annika , Cathomas Richard , Pfister David , Heidenreich Axel 
Published: February 2022

422 Background: As the characteristics and outcome of non-seminomatous testicular germ cell tumours (NSGCT) with teratoma-containing primaries are still under debate, this study aims at evaluating recurrence-free and tumor-specific survival in this cohort of patients. Methods: We performed a retrospective analysis including 218 patients with metastatic NSGCT as a registry study within the "German Testicular Cancer Study Group". We analysed patient characteristics as well as follow-up of all included patients, being treated from 2000 to 2021. Results: Of the eligible 218 patients with NSGCT, 92 (42%) of all orchiectomy specimens had teratoma-containing primaries, while 126 (58%) were teratoma-free. Kaplan-Meier estimates revealed that 28% of all patients relapsed during a median follow-up of 58 months [35-112] with a median time to relapse of 10 months. Teratoma-containing and teratoma-free NSGCT did not show a significant difference regarding the occurrence of relapse, however, teratoma-containing NSGCT had a significantly lower rate of early relapses ( < 24 months) compared to teratoma-free NSGCT (57% vs. 82%, p = 0.035). 14% (30/218) of all patients died due to their disease with a median time to death of 15 months, however median overall survival was not reached. There was no difference regarding the tumour-specific survival between teratoma-containing NSGCT and teratoma-free NSGCT when looking at the entire cohort of patients (11% vs. 16%, p = 0.299). However, in the group of intermediate or poor IGCCCG prognosis patients, tumour-specific survival was significantly worse in patients teratoma-free NSGCT compared to teratoma-containing specimens (16% vs. 35%, p = 0.040). Furthermore, patients with intermediate or poor IGCCCG prognosis showed a higher tumour-related mortality in pure teratoma-free primaries compared to patients with pure teratoma in the orchiectomy specimens (28% vs. 14%, p = 0.070). Here, pure embryonal carcinoma showed the highest relative mortality (80%). Conclusions: In our study, NSGCT patients with teratoma-containing primaries showed a significantly lower number of early relapses as well as a reduced tumour specific survival in intermediate and poor prognosis patients compared to teratoma-free NSGCT. Especially pure embryonal carcinoma patients revealed the highest rate of mortality. Consequently, treating physicians should be aware of these patients portending a dismal prognosis.
Optimization of serum miR-371a-3p for the detection of chemotherapy-naïve minimal residual germ cell tumor.
Authors: Lafin John T. , Amini Armon , Konneh Bendu , Savelyeva Anna , Piao Jin , Nuno Michelle , Scarpini Cinzia , Howard Jeffrey , Gerald Thomas , Jia Liwei , Coleman Nicholas , Murray Matthew , Frazier Lindsay Lindsay , Amatruda James F. , Bagrodia Aditya 
Published: February 2022

423 Background: Currently used serum tumor markers exhibit middling sensitivity and specificity for the detection of germ cell tumors (GCTs). Circulating miRNAs, particularly miR-371a-3p, have exhibited strong performance characteristics in the pre-orchiectomy setting. However, the ability of miR-371a-3p to detect chemotherapy-naïve occult disease is less clear. We previously reported in a small cohort of patients that miR-371a-3p outperforms conventional markers in the context of chemotherapy-naïve minimal residual disease. Here, we expand upon that experience and further refine the assay, including the recommendation of an indeterminate range. Methods: We examined over 250 assays to compare performance between classification based on raw Cq, Cq normalized to miR-30b-5p (∆Cq), or relative quantification to normal serum (RQ). We prospectively collected pre-surgical serum samples and clinical information from GCT patients undergoing primary retroperitoneal lymph node dissection (RPLND) at our institution. Patients were classified based on histology as “Control” (pure teratoma or no GCT) or “GCT”. RNA was extracted from these samples, and miR-371a-3p (target) and miR-30b-5p (reference gene) were detected by qPCR. Performance was assessed by calculation of sensitivity, specificity, and area under the ROC curve (AUC). Results: Sensitivity, specificity, and AUC did not significantly change based on thresholding metric (Cq, ∆Cq, or RQ). We found a 25% chance that any given control sample would return a false positive result, and to combat this, estimated an indeterminate range of Cq 28-35. Repeating any indeterminate sample once improved performance. We then compared the performance of this updated process to a simple binary threshold in a cohort of patients with occult disease. 32 patients were enrolled in the study (15 Control, 17 GCT). 12 samples were indeterminate on first run (6 Control, 6 GCT). 8 remained indeterminate on a second run, all of which harbored teratoma or viable GCT. Inclusion of a second run prevented 3 false positives, improving specificity from 86% to 100% and yielding a sensitivity of 92% and AUC of 0.96 (95% CI: 0.89-1). Conclusions: The use of Cq instead of RQ to classify results for the miR-371a-3p test would eliminate the need for a normal sample in each run without injuring assay performance. In the context of chemotherapy-naïve minimal residual germ cell tumor, consideration of an indeterminate range may improve the performance of the miR-371a-3p test.
Association of household net worth with healthcare utilization in 90-day window after radical cystectomy using real-world data.
Authors: Washington Samuel L. , Lonergan Peter Eoin , Odisho Anobel Y. , Meng Maxwell , Porten Sima P. 
Published: February 2022

444 Background: Radical cystectomy (RC) remains the gold standard for muscle invasive bladder cancer yet confers significant healthcare costs. Prior work on the impact of costs commonly relied on comparisons by insurance status (yes/no) and income, a partial proxy for net worth, ie one’s net economic standing or value of financial assets minus liabilities. Few have examined the relationship between net worth and encounter type. Methods: We identified commercially insured Black, White, Asian, and Hispanic patients who underwent radical cystectomy between January 1, 2007 to April 10, 2021 in The OptumLabs Data Warehouse, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data. Demographics and costs included household net worth, health plan costs, out of pocket costs, and total healthcare costs accrued from index admission to 90 days after. Multivariable logistic regression models were generated for each encounter type [acute inpatient, emergency department (ED), outpatient, and office visit]. Odds ratios (OR) are presented with 95% confidence intervals (CI) and p-values. A p value of <0.05 was deemed statistically significant. Results: The study cohort was comprised of 141,903 patients (2.4% were Black, 11.4% Hispanic, and 8.1% Asian). Household net worth categories were near evenly distributed amongst the study cohort. Acute inpatient encounters harbored the greatest health plan (mean $24,642.80, SD $57,218.41) and out of pocket costs (mean $1,428.24, SD $2108). Office visits conferred the lowest health plan costs (mean $1,126.78, SD $4,119.12) while ED visits had the lowest out of pocket costs (mean $181.88; SD $399.65). Black patients harbored increased odds of an acute inpatient encounter (HR 1.22, 95% CI 1.16-1.29) and ED encounter (HR 1.20, 95% CI 1.14-1.27) while Asian (HR 0.76, 95% CI 0.69-0.85, p<0.001) and Hispanic (HR 0.74, 95% CI 0.69-0.78, p<0.001) patients had lower odds of an outpatient encounter. Increasing household net worth was associated with decreasing odds of acute inpatient or ED encounters, and greater odds of an office visit. Conclusions: Our study is the largest cohort of commercially insured patients to examine variations in healthcare utilization by net worth in the 90 days after radical cystectomy. Those with lower net worth harbored greater risk of an acute inpatient encounter (and higher medical costs) while those with the greater net worth had greater odds of office visits (and lower costs). Greater financial flexibility (i.e., net worth) continues to confer differences in healthcare utilization (and lower healthcare costs), even within a commercially insured population. Household net worth provides a more comprehensive assessment of patients’ financial flexibility than income alone and functions as proxy for healthcare access and privilege that could not be directly measured.
Longitudinal analysis of bladder cancer-specific mortality trends in the United States.
Authors: Kamran Sophia C. , Ghosh Anushka , Goldberg Saveli , Chino Fumiko , Efstathiou Jason A. 
Published: February 2022

445 Background: Bladder cancer is the most common malignancy of the urinary system. Advances in diagnosis, imaging, and treatments have led to improvements in bladder cancer management. Recent data demonstrate decreasing bladder cancer-specific mortality (BCSM) rates between 2014-2018 for both males and females, however, these trends have not been further examined by race, ethnicity, or geographical location. Using a comprehensive dataset of BCSM over 2 decades, we sought to evaluate differences in BCSM rates overall and by sex, race, ethnicity, location and urbanization category in the United States (US). Methods: Age-adjusted mortality rates for bladder cancer (ICD10 code 67) were obtained for males and females of all ages in the US from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database. BCSM rates from 1999-2019 were estimated using linear regression. BSCM trends were evaluated by sex, race (White vs. Black), ethnicity (Hispanic vs. Non-Hispanic), urbanization category, and census region. BCSM rates were compared by F-test. Data analysis was performed using SAS 9.4. All p-values are based on a two-sided hypothesis test with values < 0.05 considered statistically significant. Results: From 1999-2019, age-adjusted BCSM rate overall has decreased linearly by (-)0.0073 per 100,000 population/year (p < 0.05). Evaluating by sex, both female [(-)0.131] and male [(-)0.022] BCSM rates decreased yearly (p < 0.05). By ethnicity, male Hispanic and female Non-Hispanic patients had significantly decreasing BCSM rates [(-)0.021 and (-)0.011, respectively, p < 0.05]. White patients had a slightly decreasing rate of BCSM [(-)0.0003, p = NS] while Black patients had an increasing BCSM rate [(+)0.022, p < 0.05] – the difference between the two rates was significant (p < 0.0001). BCSM rates were significantly decreasing in all census regions (Northeast, Midwest, South, Midwest, p < 0.05). BCSM rate in micropolitan (rural) regions has increased yearly [(+)0.006], and rate differences between rural vs large fringe metro (suburban) and vs small metro (population < 250,000) categories, both with significantly decreasing BCSM rates, were statistically significant (p = 0.03 and p = 0.047, respectively). Conclusions: Using comprehensive data on BCSM in the United States over two decades, we demonstrate that the overall mortality rate from bladder cancer has been decreasing. However, when disaggregating age-adjusted BCSM by sex, race, ethnicity, census regions, and urbanization categories, significant differences in mortality rates are found including worsening mortality for Black patients, demonstrating that improvements in BCSM are not equitable across variables. Further evaluation of these trends is important to understand how to target specific populations to improve BCSM and overall outcomes for all patients with bladder cancer.
Vesical Imaging-Reporting and Data System (VI-RADS).
Authors: Ikuma Shunsuke , Kimura Go , Mikami Hikaru , Yanagi Masato , Endo Yuki , Takeda Hayato , Akatsuka Jun , Toyama Yuka , Kondo Yukihiro 
Published: February 2022

453 Background: The VI-RADS has been widely used as diagnostic criteria for MRI to predict muscle-invasive of bladder cancer (MIBC). The aim of this study is to evaluate the diagnostic performance of VI-RADS in our hospital and the clinicopathological features of true positive (TP), false positive (FP), true negative (TN), and false negative (FN) cases to identify possible factors for misdiagnosis. Methods: Of the 286 patients who underwent TURBT at our hospital from January 2019 to October 2020, we selected 129 consecutive cases who had performed preoperative enhanced mpMRI and diagnosed as urothelial carcinoma pathologically. We defined VI-RADS score ≥4 as positive for MIBC. The clinicopathological features of TP, FP, TN, and FN groups were retrospectively analyzed and compared. Chi-square test and Mann–Whitney U test were used for the test between the two groups. Results: VI-RADS score in MIBC cases were 2 cases for ≤3 and 22 for ≥4, and in non-MIBC cases 91 cases for ≤3 and 14 for ≥4. The diagnostic performance of VI-RADS for MIBC was 92% for sensitivity, 87% for specificity, 61% for positive predictive value, 98% for negative predictive value, 88% for accuracy and the area under the curve (AUC) was 0.89. There were no statistical differences of age and %male cases between TP (22 cases), FP (14), TN (91) and FN (2) groups. Pathological features of the (TP, FP, TN, FN) groups were shown (table). TP had significantly larger tumor size than the other three groups, and higher %G3, %tumor necrosis and %variant+ than FP and TN. FP group had significantly larger tumor size than the TN. Conclusions: VI-RADS showed high diagnostic performance in predicting MIBC. Our study showed that larger tumor size was a significant factor for overestimation, suggesting the need for improved accuracy in cases with large tumor size.[Table: see text]
Impact of FDA label change on immunotherapy for metastatic urothelial cancer (mUC) and subsequent changes in mortality.
Authors: Vader Daniel , Parikh Ravi Bharat , Li Haojie , Imai Kentaro , Hubbard Rebecca A. , Mamtani Ronac 
Published: February 2022

459 Background: In May 2017, atezolizumab and pembrolizumab (IO) received accelerated approval for first-line treatment of cisplatin-ineligible patients with mUC, irrespective of PDL1 test status. In June 2018, the FDA and EMA restricted IO to cisplatin-ineligible patients with PDL1 positive tumors based on early review of data from confirmatory trials which suggested decreased overall survival in patients with PDL1 negative tumors treated with IO. We assessed the impact of the FDA label change on clinical outcomes of mUC patients in routine care. Methods: We conducted a controlled interrupted time series analysis using the US Flatiron Health electronic health record-derived de-identified database. The study sample included patients from 280 cancer clinics nationwide diagnosed with mUC and compared patients potentially impacted by the label change (cisplatin ineligible patients initiating first-line IO or carboplatin-based chemotherapy) to a comparator group who would have been unaffected by the label change (patients initiating first-line cisplatin-based chemotherapy) from 01 April 2017 to 17 May 2018 (pre-label change) and 20 June 2018 to 01 March 2020 (post-label change), excluding a 30-day wash out period encompassing the time-period between the initial FDA safety alert (18 May 2018) and the official FDA label change (19 June 2018). We used Cox regression to estimate adjusted pre-/post-label change related mortality differences in patients receiving carboplatin-chemotherapy or IO, accounting for secular changes in survival through comparison with the cisplatin comparator group. Results: The study included 829 patients with mUC initiating treatment in the pre-label change period (582 IO or carboplatin, 247 cisplatin) and 1,184 patients in the post-label change period (849 IO or carboplatin, 336 cisplatin), respectively. The use of IO, carboplatin, and cisplatin was similar across time-periods (pre-label change: 44.4%, 25.8%, and 29.8%; post-label change: 48%, 23.6%, 28.4%); while PD-L1 testing increased (6.6% to 28.1%). In adjusted models, there were no differences in survival in any of the groups following the FDA label change policy (table). Conclusions: The U.S. FDA label restriction on first-line immunotherapy was associated with increased PD-L1 testing but was not associated with changes in treatment patterns or improved mortality among patients with mUC.[Table: see text]
Use of perioperative treatment (tx) among patients (pts) undergoing radical resection (RR) for muscle-invasive urothelial cancer (MIUC) in France, Germany, Italy, Spain, the United Kingdom, the United States, Canada, China, and Japan.
Authors: Broughton Edward I , Gschwend Jürgen E. , Witjes J. Alfred , Berry Mia , Kostikas Michael , Montgomery Rachel , Lambert Annabel , Teitsson Siguroli , Milloy Neil 
Published: February 2022

467 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by RR is the standard of care in cisplatin-eligible pts with MIUC. Adjuvant chemotherapy (AC) with cisplatin-based tx may be offered to those not given NAC. The unmet need this survey tried to evaluate is the post-RR burden of disease, quality of life (QoL) and perioperative tx patterns among MIUC pts. Methods: Real-world descriptive data were drawn from Adelphi’s MIUC Disease-Specific Programme: A point-in-time survey conducted with clinical/medical oncologists/urologists and their pts in 9 countries between January and June 2021. Physicians completed a survey on their pts’ clinical characteristics and tx patterns, while pts voluntarily completed a series of patient-reported outcome measures. Results: Of 2178 pts (data provided by 320 physicians), 30% received NAC only, 26% received AC only, 38% received no NAC or AC tx, and 6% received both. 1744 pts had initial tumour in the bladder; 35% received NAC only, 24% AC only, 35% no NAC or AC tx, and 6% received both. Of 387 pts with upper-tract urothelial carcinoma (UTUC), 51% received no NAC/AC tx, 35% received AC only, and 12% NAC only. More pts with T3 disease received no NAC/AC tx (36%) or NAC (35%) than AC (24%). Of 734 pts with nodal disease, 36% received NAC only. Of all pts, 60% experienced symptoms at data abstraction: 50% in pts who received NAC only, 71% in pts who received AC only and 82% in pts of those who received both. Pts reported similar EQ-5D-5L utility index scores (mean = 0.86; range: 0.84 [AC only] to 0.89 [NAC only]). Overall, feeling pain (40%) and stress (39%) were the EQ-5D domains with the worst scores. Pts who received AC only reported nominally lower EQ-5D visual analogue scale scores (71.11) compared with pts who received no NAC/AC (73.17) or pts who received NAC only (75.05). EORTC QLQ-C30 Global Health Status scores were 60.0 in pts who received AC only, 64.1 in pts who received NAC only or no NAC/AC, and 66.7 for pts who received both NAC and AC. Conclusions: Nearly 40% of pts remain untreated in either NAC or AC setting in 9 countries. A higher proportion of pts with UTUC go untreated. AC was more frequently used in UTUC vs BC pts; and in pts with Tis. NAC was implemented more frequently in pts T3 disease and in those with N+ disease. Pts who received AC appear to have nominally worse QOL and more symptoms, further demonstrating the need for efficacious adjuvant tx that does not decrease post-RR QoL.[Table: see text]
Association of Medicaid expansion with racial disparities in timely neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC).
Authors: Jiang Changchuan , Perimbeti Stuthi , Deng Lei , Jatwani Karan , Roy Arya , Chatta Gurkamal S. , George Saby , Gopalakrishnan Dharmesh 
Published: February 2022

472 Background: Timely initiation of NAC is critical to improve outcomes in MIBC. Medicaid expansion through the Affordable Care Act improved racial disparities in healthcare access for patients with advanced cancers. This study aimed to assess the association of Medicaid expansion with racial disparities in time-to-NAC in MIBC. Methods: This case-control study queried the National Cancer Database for 18-64 years old Black and White adults who were diagnosed with stage II&III bladder cancer and treated with NAC from Jan 1, 2008 to Dec 31, 2018. The primary endpoint was the timely receipt of NAC, defined as initiation within 45 days from the diagnosis of resectable MIBC. Racial disparity was defined as percentage-point (PP) difference for Black vs. White patients, adjusted for age, sex, income level, clinical stage, and year of diagnosis. Results: The study included 5053 patients (7.2% Black, n = 391). In states without Medicaid expansion, Black patients became less likely to receive timely NAC than their White counterparts (2008-2013: Black 59.6% vs White 63.8%, p = 0.53; 2014-2018: Black 47.9% vs White 61.2%, p < 0.01). In contrast, the racial disparity was narrowed in states with Medicaid expansion (2008-2013: Black 35.7% vs White 62.9%, p < 0.01; 2014-2018: Black 53.4% vs White 59.5%, adjusted PP difference -2.4; p = 0.20). The adjusted difference-in-differences estimate revealed a 26.0 PP reduction in racial disparity (95% CI, 8.1%-44.0%; p < 0.01). Conclusions: Medicaid expansion was associated with significant reduction in racial disparity between Black and White patients in the timely receipt of NAC for MIBC.