bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological features and transcriptomic profiles of MED15-TFE3-rearranged renal cell carcinoma: A retrospective study of 14 cases.
Authors: He Sike , Liu Haoyang , Hu Xu , Sun Guangxi , Liu Zhenhua , Shen Pengfei , Zeng Hao 
Published: January 2024

462 Background: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare type of RCCs with various fusion types and heterogeneous clinicopathological features. MED15-TFE3 is a fusion that usually present as an extensive cystic mass with low malignant potential. We sought to summarize the clinicopathological, transcriptomic characteristics and survival outcome in MED15-TFE3-rRCC patients. Methods: All 14 cases were collected retrospectively fromSichuan University West China Hospital from 8/2011 to now. Diagnosis of MED15-TFE3 fusion was confirmed by fluorescence in situ hybridization and RNA sequencing. The clinicopathological features and follow-up data were collected for further analysis. The tumor transcriptomic profiles were analyzed by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis via R tool. Results: The median age was 43.5 years (range, 22 to 70). Majority of the cases were female (10/14). 8 patients (57.1%) underwent radical nephrectomy, 1 patient received cytoreductive surgery, and 5 patients (35.7%) received partial nephrectomy. At initial diagnosis, most cases (10/14) were localized disease, while 2 patients had regional lymph nodes metastasis, and 1 patient had distant metastasis (bone). For the patients without distant metastasis (n=13), 2 patients developed metastasis (liver, lung, abdominal, in situ) with disease-free survival of 11.4 and 29.0 months. As for the pathological features, 10 (71.4%) of thesamples presentedcystic morphologically, and other 4 (28.6%) were papillary. 10 (71.4%) were in G2 by ISUP score. For metastatic patients, 3 received first-line therapy (1 axitinib, 1 axitinib + sintilimab, 1 sunitinib), 2 received second-line therapy (1 axitinib + sintilimab, 1 axitinib + toripalimab), 1 received third-line therapy (axitinib + toripalimab + everolimus). They are still under follow-up. GSEA analysis illustrated that compared to paraneoplastic tissue, apical surface, bile acid metabolism, KRAS signaling, Xenobiotic Metabolism, and estrogen response were upregulated in tumor. For the patients with distant metastases, the transcriptomic analysis revealed that organelle fission, nuclear division, mitotic nuclear division, and chromosome segregation were significantly upregulated, which may be associated with tumor metastasis. The overall immune cell infiltration was comparable in metastatic patients and non-metastatic patients. However, the expression level of type 17 T helper cell, B cells, plasmacytoid dendritic cell, and activated dendritic cell were significantly different. Conclusions: MED15-TFE3 rRCC mainly present low-grade cystic renal neoplasm with favorable prognosis. For metastatic MED15-TFE3 rRCC, there is no standard therapy. And the transcriptomic evidence may provide insights for future research.
Development of AB-2100, an autologous integrated circuit T (ICT) cell therapy targeting CA9 intended for the treatment of ccRCC.
Authors: Landon Mark , Scarfo Irene , Chew Marvin , Sudhakah Rakesh , Nguyen Michelle , Mohanty Suchismita , Chen Jeremy , Gomez Alma , Attanasio Nickolas , Fearon Amanda , Chan Ivan , Sail Vibhavari , Gardner Thomas , Millare Beatriz , Thomas Vince , Zhou Stanley , Smith Jenessa , Mcdevitt Jennifer , Boroughs Angela , Gray-Rupp Levi 
Published: January 2024

472 Background: Relapsed/refractory clear cell renal cell carcinoma (ccRCC) progressing after treatment with CPI and VEGF inhibitor remains an area of unmet need. We have developed AB-2100, an autologous, integrated circuit T (ICT) cell engineered to include three new features: a sequential “AND” logic gate that requires the IO presence of two antigens in the tumor microenvironment (TME) to trigger T cell killing; a shRNA-miR module to enhance resistance to suppressive TME via constitutive knockdown of FAS and TGFBR2; and a constitutive synthetic pathway activator (SPA) that increases STAT3 signaling for enhanced T cell cytotoxicity and expansion. Methods: A previous clinical study of CA9-specific CAR-T cell therapy was limited by on-target, off-tumor toxicity. To overcome this, AB-2100 includes a sequential “AND” logic gate that consists of a priming receptor (PrimeR) targeting PSMA, and a CA9-targeted CAR that is upregulated upon PrimeR engagement with PSMA expressed on the tumor neovasculature. A series of assays were performed to assess the specificity and potency of AB-2100: dual-antigen specificity of the logic gate was assessed in vitro and in vivo against CA9+ and PSMA+CA9+ tumors; vascular priming was modeled by co-culturing AB-2100 cells with PSMA-expressing endothelial cells and CA9+ tumor cells; a FAS cross-linking assay was conducted to assess the impact of FAS knockdown; the enhanced anti-tumor activity conferred by TGFBR2 shRNA and SPA modules were assessed in a 786-O xenograft model; and AB-2100 potency was measured in a subcutaneous renal A498 xenograft. Results: AB-2100 selectively kills tumors that express both CA9 and PSMA, and not tumors that express CA9 alone, as assessed by in vitro cytotoxicity against single or dual antigen expressing tumor cell lines and by a dual flank xenograft model. Furthermore, we confirmed that co-culture with PSMA-expressing endothelial cells was sufficient to upregulate CA9 CAR expression and enable tumor cell killing. Finally, AB-2100 containing both shRNA-miR and SPA modules demonstrated enhanced anti-tumor activity in xenograft RCC models. Conclusions: These data demonstrate that AB-2100 selectively targets tumors co-expressing PSMA and CA9, and can overcome multiple suppressive mechanisms in the TME. These results support the evaluation of AB-2100 in the clinic for the treatment of advanced or metastatic ccRCC.
Cellular and molecular determinants of limited anti-tumor immunity in chromophobe renal carcinoma (ChRCC).
Authors: Labaki Chris , Alchoueiry Michel , Bi Kevin , Zhang Long , Hobeika Charbel , Bakouny Ziad , El Ahmar Nourhan , Matar Sayed , Priolo Carmen , Khabibullin Damir , Schindler Nicholas R. , Camp Sabrina Yvonne , Saliby Renee Maria , Saad Eddy , Signoretti Sabina , Van Allen Eliezer Mendel , Shukla Sachet A , Henske Elizabeth , Choueiri Toni K. , Braun David A. 
Published: January 2024

476 Background: ChRCC is a rare form of kidney cancer with a poor prognosis in the metastatic setting, in part due to very limited responses to immune checkpoint inhibitors (ICIs), as compared to clear cell RCC (ccRCC). The mechanisms underlying the poor response of ChRCC to ICIs remain largely uncharacterized. We therefore investigated at the single-cell resolution the cellular and molecular determinants of anti-tumor immunity in ChRCC. Methods: ChRCC samples with matched normal kidney specimens were evaluated using single-cell RNA (scRNA-seq) and single-cell T-cell receptor (scTCR-seq) sequencing. Similar data (scRNA-seq and scTCR-seq) was obtained for ccRCC samples (Braun DA. et al., 2021). T cell clonotypes were inferred and classified into their degree of expansion (poorly, moderately and highly expanded). Diversity metrics (normalized Shannon’s entropy) were calculated. Using a previously described methodology (Young M.D. et al., 2018), the cell of origin (COi) of ChRCC was inferred from scRNA-seq data of normal kidney samples, followed by differential gene expression (DGE) and pathway analysis (DPA) between the putative COi and ChRCC cells to identify potential mediators of diminished immune responses. Immunohistochemistry (IHC) of ChRCC and ccRCC samples was used to assess CD8+ and PD-1+ immune cell populations. Results: Analysis of the scTCR-seq data identified a higher proportion of poorly expanded clonotypes in ChRCC as compared to ccRCC (p=0.05), along with a lower proportion of highly expanded clonotypes (p=0.07). Normalized (Shannon’s) entropy was found to be higher in ChRCC versus ccRCC (p<0.05). Analysis of annotated scRNA-seq data identified a lower proportion of CD8+ and CD4+ T-cells among immune cells in ChRCC vs. ccRCC (44.6 vs. 9.6% and 12.3 vs. 3.2%, respectively). DGE between ChRCC and its putative COi (alpha-intercalated cell) showed a lower expression of HLA class I genes in ChRCC (p<0.05). DPA showed a marked downregulation of antigen presentation and protein processing pathways in ChRCC (p<0.05). IHC analysis showed a markedly low infiltration of CD8+ and PD-1+ immune populations in ChRCC, as compared to ccRCC. Conclusions: ChRCC cells have marked downregulation of HLA class I genes and antigen processing pathways related to their COi. Additionally, ChRCC tumors have poor infiltration of T-cells, which show a low degree of clonal expansion. These mechanisms may help to explain the limited anti-tumor immunity and ultimately, the poor response to ICIs seen among patients with ChRCC.
Updated automated PROMISE assessment: Treatment response evaluation based on PSMA PET/CT.
Authors: Benitez Cecil Mayra , Sahlstedt Hannicka , Brynolfsson Johan , Berenji Gholam Reza , Juarez Jesus Eduardo , Kane Nathanael , Tsai Sonny , Rettig Matthew , Nickols Nicholas George , Duriseti Sai 
Published: January 2024

48 Background: PSMA PETs can track treatment response in patients with prostate cancer. Recent integration of the RECIP framework with PROMISE v2 allows quantitative assessment of PSMA PETs. While useful for assessing differentially responding lesions, manual measurement and tracking is cumbersome and PSA reliance can be misleading. We evaluated an automated AI-enabled platform, aPROMISE, for longitudinal lesion tracking to evaluate treatment response based solely upon tumor volume. Methods: Patients with castration sensitive or resistant disease undergoing 18F-DCFPyL PET/CTs during workup and at ≥3 months after treatment were included. Tracer-avid lesions were identified using the aPROMISE algorithm. Detected lesions were manually approved by an experienced nuclear medicine physician. After lesion identification and approval, the total tumor volume was calculated. The corresponding low-dose CT was auto-segmented, allowing anatomic compartment (prostate/bed, node, bone, or visceral) annotation of 18F-DCFPyL-avid lesions. Baseline and follow-up PETs were deformably co-registered to automatically match individual lesions if they were in the same anatomic compartment, and had overlap <10 mm center-to-center (<50 mm for rib lesions). Unmatched lesions on follow-up PET were noted as new. Response was assessed as CR (no avidity in follow-up), PR (volume decrease ≥30% without new lesions), SD (volume decrease ≥30% with new lesions), or PD (volume increase ≥20% plus new lesions). Volume changes at the total tumor and individual lesion levels were also assessed independent of RECIP imaging criteria. Results: The automated algorithm assigned the correct RECIP classification in 97% of the 67 cases with 14 as CR, 14 as PR, 20 as SD, and 19 as PD. 1027 of the 1686 lesions identified on baseline PET were seen on follow-up. 673 of the 1700 lesions identified on follow-up PET were new. Conclusions: For response assessment using 18F-DCFPyL PET/CT and RECIP imaging criteria, the automated algorithm and manual detection achieved the same clinical classifications. Automated approaches may allow more granular lesion analysis The precision and accuracy this automated process is being validated in prospective clinical studies.
Evaluating prognostic models for stage I seminoma within the randomised trial of imaging and surveillance in seminoma testis (TRISST).
Authors: Huddart Robert A , Cafferty Fay Helen , Murphy Laura , James Elizabeth , Schiavone Francesca , Rustin Gordon J. S. , Sohaib Syed A , Joffe Johnathan K. 
Published: January 2024

501 Background: Prognosis in stage I seminoma is excellent. Most patients are cured by orchiectomy and, for the 15%-20% that relapse, salvage treatment is generally successful (survival approaching 100%). Relapse risk is reduced with adjuvant carboplatin but may unnecessarily expose young patients to long-term health risks. Effective and reliable risk stratification could guide use of adjuvant treatment and potentially reduce intensity of surveillance for the lowest risk patients. We used data from a UK multicentre, phase III trial to evaluate prognostic factors for relapse in stage I seminoma, including validation of a recently proposed model from the European Association of Urology (EAU)(1). Methods: TRISST used a randomised, factorial design to evaluate imaging schedules (3 vs 7 scans) and modality (MRI vs CT) in surveillance for men who had undergone orchidectomy for stage I seminoma (n=669). In this secondary analysis, model selection was used to fit a multivariable Cox regression to TRISST data to investigate factors predicting time to relapse, including: age, tumour mass size, rete testis invasion (RTI), T stage, lymphovascular invasion (LVI), side of tumour, and tumour markers (LDH, β-HCG). The final model was used to divide the cohort into risk groups. Relapse risk was also estimated according to EAU prognostic groups. Harrell’s C-index was used to measure model fit. Results: Based on TRISST data, tumour size ≥4cm and pT3 disease were associated with the highest risk (multivariable hazard ratio for ≥4cm vs <2cm: HR=4.00, 95% confidence interval 2.00-8.01; pT3 vs pT1: HR=3.89, 1.77-8.57). Patients with one or both of these features (24% of the cohort) had 5-year relapse rate of 22.0%. Medium risk (age<30 years and/or 2-4cm and/or pT2) and low risk (age≥30 years, <2cm and pT1) groups had 5-year relapse rates 12.0% and 2.3% respectively. The EAU model was a good fit to the TRISST data (C-index=0.62); 66%, 33% and 2% fell into the very low, low and high-risk EAU groups respectively with 5-year relapse rates of 10.1%, 16.1% and 45.5%. Conclusions: In stage I seminoma, relapse risk in patients managed with surveillance following orchiectomy is low for the majority of patients. Tumour size is consistently shown to be the best predictor of relapse. The EAU prognostic model, validated here, identifies a small group (>5cm, with RTI and LVI) with particularly high risk who may benefit from adjuvant therapy. Reference: 1. Boormans J, et al. Journal of Clinical Oncology 2023; 41 (6_suppl): 410. Clinical trial information: ISRCTN65987321 .
Excess intermediate risk nonseminoma and regional lymph node metastases at presentation in patients with Hispanic germ cell tumor.
Authors: Kolawa Adam , Iyengar Siddharth , Tiu-lim Justin Wayne Wong , Arizpe Angel , Pan Elizabeth , Chen Irene , Frost Stefani , Daneshmand Siamak , Schuckman Anne K. , Djaladat Hooman , Quinn David I. , Tulpule Varsha , Hu James S. , Cortessis Victoria K. , D'souza Anishka 
Published: January 2024

502 Background: Testicular germ cell tumors (TGCTs) is the leading solid-organ malignancy of adolescent/young adult males. Incidence is rising in all racial/ethnic groups, and most rapidly in Hispanics, who tend to be younger than non-Hispanic white (NHW) patients at diagnosis yet have poorer survival. Understanding these disparities is an urgent research priority, but granular prognostic information is inadequate in large population-based registries. We therefore initiated an investigation of a largely Hispanic clinical cohort. Methods: We identified consecutive patients with pathologically confirmed TGCT treated from 2015 to 2020 at two major referral centers in the US, with a large Hispanic population (the Los Angeles General Medical and USC/Norris Comprehensive Cancer Centers) and collected detailed features of demography, clinical presentation, treatment, and outcome into a structured RedCAP database. We used chi-square, Fisher exact, and Mann-Whitney U tests to compare established prognostic features between Hispanic and NHW patients. Results: Among 27 NHW and 75 Hispanic patients, Hispanics were younger at diagnosis (median 27 vs 30 years, p=0.5), diagnosed less frequently with pure seminoma (12% vs 23%, p=0.19), and experienced shorter time to first progression (median 8.5 vs 19 months, p=0.6). Among non-seminoma patients, Hispanics had higher probability of IGCCCG intermediate risk (26% vs 0%, p=0.03) but similar frequency of poor risk disease (Table). Accordingly, Hispanics had more regional lymph node involvement at presentation (48% vs 19%, p=0.03) but comparable frequency of visceral metastasis. Conclusions: Hispanic patients had adverse features already evident in population-based data, and novel findings of higher risk stratification and greater lymph node involvement than NHWs. Expansion of clinical series will be vital to identifying factors and processes that underlie adverse presentation and outcomes of Hispanics with TGCT, and to refining guidelines for care of the growing population of Hispanic patients with TGCT. [Table: see text]
Racial differences and predictors of outcomes in testicular cancer based on the National Cancer Database (NCDB).
Authors: Yu Eun-mi , Wang Hongkun , Aragon-Ching Jeanny B. 
Published: January 2024

503 Background: The incidence of testicular cancer in the U.S. is highest in white (W) men and lower in black (B), Hispanic (H) and Asian-American men, with reports of increasing trends in Hispanic men with worse outcomes (Li et al., BMC Cancer 2020). We aim to verify the emerging ethnicity variations in a large database. Methods: Using the NCDB database with patient-level data extraction from 2004 to 2020, we sought to identify the incidence, demographics, regional differences, treatment, and outcomes in men who are Hispanic versus non-Hispanic White (NHW) and other races with testicular cancer diagnoses (non-seminoma, NS; seminoma, S) with differences in treatment patterns from different institution types, insurance across regions. Results: There were 81571 pts in all with 46979 S pts W and 34592 NS pts W vs 1754 S pts B and 1106 NS pts B with 5396 S pts H and 5609 NS pts H with other races/unknown for the rest. More S patients were treated at comprehensive community cancer programs (17%) compared to NS pts (6.1%). The majority of patients had Charlson-Deyo Score of 0 (92.7% of S pts and 93.7% of NS pts), had private insurance (74.1% S pts, 69.1% NS pts), though incidence appeared to be similar except for a slight drop in 2020 at 5.9% compared to 6.6% during years 2018 to 2019. Most were diagnosed with Stage I (29.6%) and Stage II and III (16.3%) though it was unknown/missing for 54%. Overall survival (OS) was better for S compared to NS in all pts (p<0.0001), and in stages II & III (p<0.001). OS was better for W vs B (p<0.0001), NHW vs H (p<0.0001), and with differences in Charlson-Deyo score (p <0.0001), facility type (p=0.008) and insurance status (p <0.0001). OS p-values are from Log-rank tests. Conclusions: Our analysis reveals some differences in survival trends with better survival in seminoma compared to non-seminoma, though Blacks and Hispanics have worse outcomes compared to Whites and Non-Hispanic Whites. This highlights the need for targeted efforts to bridge gaps in care.
Trends and disparities in hospice care utilization in testicular cancer in the United States of America from 2003 to 2020: Analysis of CDC WONDER database.
Authors: Jatwani Karan , Sukaina Mahnoor , Khosla Atulya Aman , Singh Rohit , Garg Tulika , Chahal Rutvi , Patel Archit , Muthusamy Kumarasamy Vasanthan , Gopalakrishnan Dharmesh 
Published: January 2024

504 Background: Testicular cancer (TC) is a malignancy with five-year survival reaching up to 95%. It is estimated that 470 deaths from this disease will occur in the United States in 2023. Even with exceptional survival rates, it is important to recognize the need of hospice in these patients. Enrollment in hospice is associated with lower healthcare costs, symptom burden, and psychological distress and improved quality of life. We used publicly available CDC WONDER (Centers for Disease Control and Prevention for Wide-ranging Online Data for Epidemiologic Research) database with the aim to explore the trends of hospice utilization in patients with testicular cancer nationwide in the US. Methods: The search and analysis were conducted using the CDC WONDER database from January 01, 2003, to December 31, 2020. The data for deaths due to TC were pooled using the International Classification of Diseases-10th Revision codes C62, C62.0, C62.1 and C62.9. The inclusion criteria included males aged >15 years. The demographic data was obtained to calculate descriptive statistics using age, census region, and utilization of hospice mortality accordingly over the past two decades. Results: The analysis demonstrated that overall mortality due to TC were 6,969 from 2003-2020. Of these deaths, 520 (7.46%) were recorded in hospice facilities. According to the US census regions, the highest number of hospice deaths were recorded in Census Region 3: South (CENS-R3) 8.99%, followed by Census Region 1: Northeast (CENS-R1) 8.03%, and Census Region 2: Midwest (CENS-R2) 7.23%. While the lowest number of deaths were observed in Census Region 4: West (CENS-R4) at 5.30%. The lowest hospice mortality was 1.9% in 2005 and increased over the years to the highest of 10.4% in 2019, with a slight decline in 2020 which is 7.9%. Moreover, when stratified by age groups, the lowest hospice mortalities are recorded in the age group 15-34 years (6.32%), 35-54 years (7.08%), 55-74 years (10.10%), 75-85+ years (8.72%). Conclusions: To our knowledge this is the first study utilizing CDC WONDER database to demonstrate hospice care utilization in TC related deaths. We observed a steady increase in hospice utilization from 2005-2019 throughout the US with a decline in 2020 possibly related to COVID pandemic. Age stratification further revealed lower utilization in 15-34 years age group compared to 55-74 highlighting the need to improve hospice discussions early in this age group. This study highlights the disparities in end-of-life care in TC and should promote policy-level changes in the states with lower utilization of hospice services to improve access of care in TC patients.