bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor genomic landscape of locally advanced or metastatic urothelial carcinoma with squamous differentiation (UCS) compared to pure urothelial carcinoma (UC).
Authors: Tripathi Nishita , Jo Yeonjung , Sayegh Nicolas , Li Haoran , Nussenzveig Roberto , Haaland Benjamin , Thomas Vinay Mathew , Gupta Sumati , Maughan Benjamin L. , Swami Umang , Pal Sumanta K. , Grivas Petros , Agarwal Neeraj , Sirohi Deepika 
Published: February 2022

553 Background: UCS is a common entity and usually managed similarly to pure UC but requires focused study. Limited data are available on the genomic profile of UCS. We hypothesized that UCS would have a distinct genomic landscape compared to UC. Methods: In this IRB-approved retrospective study, pts) with advanced UCS and UC undergoing tumor based comprehensive genomic profiling from a CLIA-certified laboratory were included. An independent genitourinary pathologist reviewed all cases. Pts were determined to have UCS based on presence of any component of squamous differentiation. Pts with UC having any other secondary histology variant were excluded. Genes with alterations (GA) in less than 5% of pts and variants of unknown significance were excluded from the analysis. test was used to compare gene aberration frequency and the p-values were adjusted for false using Benjamini-Hochberg (BH) correction. Results: 87 pts were eligible and included. UCS (n=31) vs UC (n=56): median age, 66 vs 68 years; male vs female: 21/10 vs 48/8Genomic aberrations in both groups are listed in the. GA in KMT2D was found to be significantly enriched in UCS vs UC (15/31 vs 0/56, FDR <0.001, p value = <0.001). GA in CUL4A was numerically higher in UCS vs UC (4/31 vs 1/56, FDR= 0.444, p-value = 0.03). Tumor mutation burden the frequency of genomic aberrations per pt were not significantly different in the groups. Conclusions: While tumor GA in only KMT2D was significantly enriched in the UCS cohort, it is interesting to note that both KMT2D and CUL4A (higher frequency in UCS) are involved in epigenetic regulation. Identification of underlying molecular targets and biomarkers can guide further drug development in this population. Limitations include small sample size, selection and confounding biases. These hypothesis-generating data need external validation.[Table: see text]
Association of leucocyte levels in urine with tissue PD-L1 status and immune infiltration into basal bladder cancer subtype in the prospective real-world clinicopathological register trial Bladder BRIDGister.
Authors: Ecke Thorsten , Friedersdorff Frank , Veltrup Elke , Kilic Ergin , Hake Roland , Eidt Sebastian , Roggisch Jenny , Koch Stefan , Wirtz Ralph M. 
Published: February 2022

560 Background: The objective of the present study was to evaluate whether preoperative standard urine parameters such as leucocyte count in urine samples dominate in particular molecular subtypes of bladder cancer and reflect the immune infiltration status in the tissue in matched urine and TUR biopsy samples from patients being suspicious of bladder cancer and undergoing first TURB within the prospective Real World Experience registry trial "BRIDGister". Methods: For this pilot study paraffin fixed pretreatment tissue samples from the first TURB of 48 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits- Relative gene expression of subtyping markers (KRT5, KRT20) by standardized RT-qPCR systems for PD-1, PD-L1, CTLA4 (STRATIFYER Molecular Pathology GmbH, Cologne). In addition urine samples were analyzed for leucocyte and erythrocyte count. Spearman correlation, Kruskal-Wallis, MannWhitney and Sensitivity/Specificity tests were done by JMP 9.0.0 (SAS software). Results: The pilot cohort of the BRIDGister trial consisted of 48 patients (median age: 77, male 65% vs. female 35%) of diverse clinical stages (Benign lesions/no tumor 38%, pTa 23%, pT1 20%, pT2 19%) and WHO 1973 grade (G1 11%, G2 43%, G3 23%). Presence of leucocytes but not erythrocytes was negatively associated with KRT20 (r=-0.4249, p=0.0216) but positive with KRT5 (r=0.3704, p=0.0479). Moreover high levels of leucocytes in urine were positively associated with tumor expression of PD-L1 (r=0.5081, p=0.0041), PD-1 (r=0.5342, p=0.00024) and CTLA4 (r=0.4244, p=0.0194). In contrast there was no significant association of tumor PDL-1, PD-1 and CTLA4 expression with erythrocyte count in urine. Conclusions: Presence of leucotytes in urine is strongly associated with basal subtype and immune cell infiltration into early bladder cancer. As the presence of erythrcytes did not reveal these significant associations, the presence of leucocytes is not due to simple bleeding or tissue vulnerability. Moreover, the strong tumor subtype specificity further demonstrate the basal tumor specificity of urine leucocytes and therefore may be helpful for detecting and monitoring basal bladder cancer in a non invasive fashion. Given the prognostic value of tissue determination of PD-L1, PD-1 and CTLA4 quantitation on mRNA level, these results warrant further investigation to conclude on its impact on outcome prediction (BCG responsiveness, recurrence, progression, etc.), which will be prospectively analyzed in the framework of the ongoing multicenter BRIDGister Real World Experience trial.
Cost effectiveness of newly approved second/third-line agents in metastatic urothelial carcinoma (mUC).
Authors: Benjamin David Joseph , Lythgoe Mark , Raymakers Adam J N , Rezazadeh Arash 
Published: February 2022

574 Background: Over the past years, the treatment landscape of platinum-refractory mUC has drastically changed with the advent of immunotherapy. More recently, several new agents including enfortumab, erdafitinib, and sacituzumab have received F.D.A. approval for the treatment of platinum-refractory mUC. It is unclear if these newly approved therapies may be cost prohibitive for patients and/or hospitals/clinics compared to the recommended NCCN category 1 second-line agent, pembrolizumab. Methods: Using acquisition costs from our home institution’s cancer center pharmacy department, we calculated the total cost of treatment for each agent. We used phase II clinical trial data to determine the median duration of treatment for each therapy. For weight-based therapies, we used 70 kg as the weight for an average human adult. Results: The three newly approved therapies for mUC have total acquisition costs in descending order as follows: enfortumab vedotin ($153,697.50), edafitinib ($131,642.62), and sacituzumab govitecan ($63,198.07). Enfortumab and sacituzumab likely have higher total costs given both therapies require infusion center use for administration, and are associated with infusion center administration fees. In comparison, pembrolizumab (standard of care per NCCN guidelines) has a total acquisition cost of $51,343.60. Conclusions: Based off median duration of treatment, pembrolizumab has the lowest total acquisition cost compared to the three newly approved therapies for mUC. Further statistical analysis of this data set is ongoing. In particular, analysis will include out-of-pocket costs for patients as well as quality-adjusted life years (QALY).[Table: see text]
Five-year survival comparison of different treatment modalities for muscle invasive urothelial carcinoma, squamous cell carcinoma and adenocarcinoma of the bladder: An analysis of the National Cancer Database.
Authors: Rivera Carlos , Jabbal Iktej Singh , Yaghi Marita , Landau Kevin Scott , Muruve Nicolas , Saravia Diana , George Tiffany L. , Nahleh Zeina A. , Arteta-Bulos Rafael 
Published: February 2022

575 Background: Localized muscle invasive bladder cancer carries a significant recurrence and mortality rate. The purpose of this study was to compare 5-year overall survival (OS) of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), RC alone, bladder preserving chemoradiotherapy (BPCRT) and radiation alone (RT) on selected histologies. Methods: We sampled the National Cancer Database (NCDB) for bladder cancer patients diagnosed with AJCC 7th Stage 2 and 3 for urothelial carcinoma (UC) including variant histologies, squamous cell carcinoma (SCC) and adenocarcinoma (AC) from 2004-2018 with definitive intent treatment. 5-year Kaplan-Meier survival plots were utilized to assess survival differences amongst treatment modalities and stratified by selected histologies. Multivariate cox regression models were used to compare hazard ratios and logistic regression analysis was performed for covariate analysis. A p-value <0.05 was considered statistically significant. Results: A total of 20,629 patients met inclusion criteria. The average age was 69.51 + 11.02 years, 68% were male. UC represented 94.1% of selected histologies, followed by 4.6% SCC and 1.3% AC. For all combined histologies, 5-year OS for patients with NAC followed by RC was 58%, 48% for RC alone, 33% for BPCRT and 10% for RT alone. RC alone provided a longer OS in the SCC and AC groups, 48% and 47% respectively (p<0.001). NAC followed by RC showed superior OS in the UC group (58%, p<0.001), with OS decreasing to 43% in SCC and 44% in AC. BPCRT showed lower 5-year OS in all selected histologies when compared to NAC followed by RC and RC alone (33% in UC, 27% in SCC and 24% in AC group). In all selected histologies, RT showed the lowest 5-year OS (10% in UC, 8% in SCC and 17% in AC group; p<0.001). Furthermore, covariables associated with lower 5-year survival were male sex (p<0.001) and TNM Stage 3 (p<0.001). Conclusions: NAC followed by RC showed improved 5-year OS for UC. The benefit of NAC was marginal for SCC and AC histology. RC is better than BPCRT for all histologies. RT alone showed inferior 5-year OS for all histologies.[Table: see text]
68ga-PSMA-11 patients with newly diagnosed and recurrent prostate cancer (Firefly).
Authors: Manogue Charlotte , Rauterkus Grant , Light Malcolm , Sussman Isabelle P. , Lieberman Alex , Huang Minqi , Davis Gaynelle , Barata Pedro C. , Layton Jodi Lyn , Lewis Brian E. , Harris Kendra Marie , Manning Hailey , Sartor A. Oliver 
Published: February 2022

TPS189 Background: A primary challenge facing oncologists is the accurate identification of the source of the rising PSA in the recurrent disease setting and the failure of proper staging at the time of initial therapy. Current imaging modalities perform poorly in this regard. PSMA imaging is FDA approved but reimbursement remains a considerable issue for most patients. Methods: This is a phase II expanded access intermediate sized clinical trial using 68Ga-PSMA-11 (Telix Pharma cold kit) under our own Investigational New Drug (IND) with the FDA. Two cohorts are utilized, recurrent disease with a PSA > 0.2 or > 2.0 post-radiation, and newly diagnosed high risk localized disease and/or oligo-metastatic patients as assessed by conventional imaging. 300 patients will be allowed to enroll and 63 are enrolled to date. Patients will be injected with 1.8–2.2 MBq/kg body weight with 68Ga-PSMA-11 (per EANM guidelines). The lower and upper limits of the dose are set to 3 to 7 mCi respectively. Primary Objective(s): Utilize 68Ga-PSMA-11 PET images to define uptake location for localization of prostate cancer metastatic sites in patients prior to initial therapy and to utilize 68Ga-PSMA-11 PET images to define uptake location for localization of prostate cancer including both local recurrences and metastatic sites in patients with recurrent disease after initial therapy. Secondary Objectives: To assess the therapeutic consequences of 68Ga-PSMA-11 PET/CT imaging in prostate cancer patients with and without prior treatment. As such the planned therapies after the PSMA scan will be annotated and recorded. In addition, we aim to determine the number of patients with metastatic disease prior to initial therapy that was not diagnosed with conventional imaging and we aim to determine the locations of recurrent disease for those patients who have demonstrated PSA recurrence after curative therapy. Percentage of positive scans will be assessed for PSA values 0.2-0.5 ng/mL, > 0.5-1.0 ng/mL, > 1.0- > 2.0 ng/mL, and > 2 ng/mL. Results will be summarized descriptively with 95% confidence intervals. Localization of all lesions will be performed with regard to lymph nodes (pelvic versus non-pelvis), bones (by location), and other (by site). Treatment planning will be captured and quantified by radiation, surgery, hormonal therapy (type and duration), and/or observation at the time of the initial clinical visit after the PSMA scan and 6 months later. This trial is open and recruiting patients. Data analysis has not been performed. Clinical trial information: NCT04854369.
Part 1 results from NOVA-II, a randomized, double-blind, vehicle-controlled phase II study evaluating the safety and efficacy of OQL011 on VEGFR inhibitor associated hand-foot skin reaction in cancer patients.
Authors: Lacouture Mario E. , Patel Anisha B , LeBoeuf Nicole R. , Marathe Omkar Subhash , Leventhal Jonathan , Choi Jennifer N. , Lam Elaine Tat , Kaffenberger Benjamin S. , Voss Martin H , Webb Mark L , Tyler Robert Claude , Ju Juegang , Tang Hong , Luo Jie , Anadkat Milan J. , Vogelzang Nicholas J. 
Published: February 2022

TPS396 Background: Hand-foot skin reaction (HFSR) is associated with the use of multi-targeted tyrosine kinase inhibitors sharing vascular endothelial growth factor receptor inhibitory (VEGFRi) activity (e.g., cabozantinib, regorafenib, sorafenib, sunitinib). HFSR affects the palms and soles with edema, erythema, hyperkeratosis, pain, and bullae/blisters impacting quality-of-life, activities of daily living, and consistent VEGFRi dosing. HFSR incidence differs among VEGFRi, ranging from 5-69% (all grades) and 1-19% (grade 3). Topical urea has marginal benefit, and to date, there are no regulatory authority approved HFSR treatments. The pathogenesis of HFSR has been partially associated with impaired vascular repair mechanisms resulting from inhibition of VEGF signaling. Nitric oxide (NO) has been reported to induce VEGF upregulation at a moderate concentration. We hypothesized that topical stimulation of VEGF signaling through OQL011, an NO donor, will safely and effectively mitigate HFSR. Methods: NOVA-II is a phase 2, double-blind, randomized vehicle-controlled trial evaluating the safety and efficacy of OQL011 for the treatment of moderate to severe HFSR. Subjects receiving a VEGFRi (either mono- or combination therapy) and have Grade ≥2 HFSR per NCI CTCAE v5.0 for palmar plantar erythrodysesthesia (PPE) were eligible. For Part 1, 31 subjects were randomized (2:1) and received 0.2% OQL011 topical ointment or vehicle TID for 6 weeks. The primary endpoint is the proportion of patients who achieve an NCI CTCAE v5.0 for PPE Grade 0 or 1 by Week 3. An investigator global assessment (IGA) scale is being developed to assess HFSR recovery, and a secondary endpoint will measure the proportion of patients who have improvement in HFSR severity and achieve an IGA score of clear (0) or almost clear (1) by Week 3 and/or Week 6. A Chi-square test will be used to detect a difference between the treatment arm and the vehicle-control arm. Additionally, the IGA score will be validated by assessing the inter- & intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient outcomes including Visual Analog Scale of Pain, HFSR Quality of Life questionnaire will also be reported. This study began enrolling patients in December 2019 and completed the last patient Visit in August 2021. Data lock, unblinding and data analysis will be completed by mid-November. Clinical trial information: NCT04088318.
Sacituzumab govitecan (SG) plus enfortumab vedotin (EV) for metastatic urothelial carcinoma (UC) progressing on platinum-based chemotherapy and PD1/L1 inhibitors (ICB): Double antibody drug conjugate (DAD) phase I trial.
Authors: McGregor Bradley Alexander , Kwak Lucia , Mantia Charlene , Ravi Arvind , Berchuck Jacob E , Ravi Praful , Xu Wenxin , Tuff Martha , Bellmunt Joaquim , Gao Xin , Sunkara Rajitha , Sonpavde Guru P. 
Published: February 2022

TPS588 Background: There have been multiple advances in therapy of advanced urothelial carcinoma following platinum and ICB; SG and EV are both FDA approved in this space though durations of response are short and overall survival limited at < 13 months. Given different mechanisms of action, non-overlapping toxicities and potential for synergy, EV and SG is hypothesized to have manageable toxicities and demonstrate additive anti-tumor activity. Methods: NCT04724018 is a single-center (Dana-Farber/Harvard Cancer Center), open-label, non-randomized phase I trial using a Bayesian Optimal Interval design. SG and EV agents are administered intravenously (IV) on days 1 and 8 every 3 weeks (1 cycle) until progression or intolerable toxicities. Laboratory evaluation is performed on days 1 and 8 every cycle with additional blood collected throughout treatment for pharmacokinetic and antidrug antibody studies. Imaging is performed at baseline and every 6 weeks for the first 4 cycles followed by every 9 weeks thereafter. Up to 4 dose levels of the combination of SG and EV are studied with a starting dose of SG of 8 mg/kg and EV of 1 mg/kg (dose level 1) with additional dose escalations outlined in table. Dose de-escalation of SG to 6 mg/kg with the starting dose of EV 1 mg/kg (dose level -1) is permitted. A total of 3 to 18 patients are expected to be enrolled in current dose level depending on dose limiting toxicities (DLTs). DLT is assessed during cycle 1 of therapy and toxicities are captured up to 4 weeks after the last dose of therapy and being defined by ≥1 of the following: neutropenic fever, thrombocytopenic bleeding, grade 3 neuropathy, of any duration and any other grade ≥3 non-hematologic toxicity to include hyperglycemia (except alopecia) lasting >1 week or requiring >3 weeks interruption of therapy or dose reduction. The first patient per 3-patient cohort is required to complete 1 full cycle (3 weeks) before additional patients can be enrolled in that cohort. Therefore, up to 24 patients may be accrued. Trial continues to enroll at dose level one. Clinical trial information: NCT04724018. [Table: see text]
Acid Dissociation Constant of Bis(2-Ethylhexyl) Hydrogen Phosphate Impregnated in a Polymer Layer Coated on Silica Microparticles
Authors: Miyagawa Akihisa , Takeuchi Masayuki , Arai Tsuyoshi , Watanabe Sou , Sano Yuichi , Nakatani Kiyoharu 
Published: February 2022

Abstract
We demonstrate that apparent pKa of extractant impregnated in a polymer phase varies with the cross-linking degree and the coexistence of other extractants, which induces a change in the hydrophobicity of the polymer phase. The results presented herein will be beneficial for the development of novel solid-extraction adsorbents.
Direct versus indirect restorations in the treatment of tooth wear: a report of two cases
Authors: Mehrabi Farima , Romeed Shihab 
Published: February 2022

The process of tooth wear is multifactorial in aetiology, and when the progression has been considered excessive enough to be associated with aesthetic and functional concerns, appropriate assessment of each case and its treatment selection must be made, using evidence-based practice to treat such patients. Composite and ceramics are dental materials that have long been used for the restoration of patients with tooth wear. This article will explore the comparisons and rationale between direct and indirect methods and materials, using two rehabilitation cases as examples to show the impact of management of such patients. Although some cases may require a removable treatment option, this article will focus on non-removable options only. CPD/Clinical Relevance: This article provides readers with an understanding of the selection criteria and utility values when deciding whether to restore a patient's dentition with indirect or direct materials.
Dentigerous cyst: a rapidly expanding swelling in a young patient
Authors: Cant Aisling , Sanghvi Risha , Patel Vinod , Siddik Dania 
Published: February 2022

We present a case of a dentigerous cyst associated with an unerupted premolar tooth, and its surgical management in a 4-year-old child. Of note, 8 months prior to presentation, the patient was seen for extraction of multiple primary teeth under general anaesthesia. At the time of extraction, there were no signs of extra- or intra-oral mandibular swellings. Dentigerous cysts are one of the most common paediatric intra-osseous lesions. This case highlights the importance of taking a thorough dental history and the benefit of a multidisciplinary approach. This report also demonstrates the surgical management of this lesion, which included surgical excisional biopsy under general anaesthesia. CPD/Clinical Relevance: The reader should consider dentigerous cysts as a differential diagnosis in paediatric patients who present with dental swellings.
Mechanical effects of surgical variations in the femoral neck system on Pauwels type III femoral neck fracture
Authors: Jung Chang-Ho , Cha Yonghan , Yoon Ha Seung , Park Chan Ho , Yoo Jun-Il , Kim Jung-Taek , Jeon Yongho 
Published: February 2022

Aims In this study, we aimed to explore surgical variations in the Femoral Neck System (FNS) used for stable fixation of Pauwels type III femoral neck fractures. Methods Finite element models were established with surgical variations in the distance between the implant tip and subchondral bone, the gap between the plate and lateral femoral cortex, and inferior implant positioning. The models were subjected to physiological load. Results Under a load of single-leg stance, Pauwels type III femoral neck fractures fixed with 10 mm shorter bolts revealed a 7% increase of the interfragmentary gap. The interfragmentary sliding, compressive, and shear stress remained similar to models with bolt tips positioned close to the subchondral bone. Inferior positioning of FNS provided a similar interfragmentary distance, but with 6% increase of the interfragmentary sliding distance compared to central positioning of bolts. Inferior positioning resulted in a one-third increase in interfragmentary compressive and shear stress. A 5 mm gap placed between the diaphysis and plate provided stability comparable to standard fixation, with a 7% decrease of interfragmentary gap and sliding distance, but similar compressive and shear stress. Conclusion Finite element analysis with FNS on Pauwels type III femoral neck fractures revealed that placement of the bolt tip close to subchondral bone provides increased stability. Inferior positioning of FNS bolt increased interfragmentary sliding distance, compressive, and shear stress. The comparable stability of the fixation model with the standard model suggests that a 5 mm gap placed between the plate and diaphysis could viably adjust the depth of the bolt. Cite this article: Bone Joint Res 2022;11(2):102–111.