bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of healthcare provider treatment of advanced endometrial cancer and concordance with expert recommendations in 2023 vs 2022.
Authors: Rosenthal Kristen M. , Cartwright Megan , Constanzo Jerfiz D. , Chon Hye Sook , Duska Linda R. , Hoskins Ebony R. , Salani Ritu 
Published: June 2024

5613 Background: Practice patterns are rapidly evolving for first-line (1L) treatment (tx) of advanced endometrial cancer (aEC). In 2022, we created an online interactive decision support tool [clinicaloptions.com/Endometrialtool] for healthcare professionals (HCPs) with case-specific recommendations from 5 gynecologic oncology experts for treating 1L and second-line (2L) aEC. In 2023, NCCN guidelines included a recommendation of carboplatin/paclitaxel plus an immune checkpoint inhibitor (ICI) for 1L tx of aEC. Working with the experts, we updated the tool to its current 2023 version. Here, we compare planned tx reported by HCPs using the 2023 tool vs expert recommendations and compare practice patterns for the 2023 vs 2022 tools. Methods: To use the 2023 tool, HCPs entered key characteristics, including the tx setting; tumor histology (1L only); actionable biomarker status (dMMR/MSI-H, HER2, ER/PgR); prior tx, response, and response duration (2L only); and planned tx. After HCPs reported their planned tx, the tool showed expert recommendations for that scenario and asked if the recommendations changed the planned tx. Results: From September 2023 to January 2024, 123 HCPs entered 181 cases into the tool, of which 45% were in the 1L setting. HCPs reported a biomarker status of "unknown” in 30% of 1L cases. In 2022, all experts recommended platinum-based chemotherapy (plt CT) ± bevacizumab for 1L HER2-negative cases, whereas all experts in 2023 recommended plt CT + ICI for 1L cases with dMMR/MSI-H (Table). There was less consensus on adding ICI to plt CT when 1L cases had no actionable biomarker. In 2023, the tx planned by HCPs matched ≥1 expert in 29/54 (54%) of 1L cases—a modest improvement from 2022, when matches occurred in 19/42 (45%) of 1L cases. In 2023, match rates were highest for dMMR/MSI-H cases (50%-86%), followed by cases without actionable biomarker (36%-50%) or HER2+ (33%-67%). Overall, 88% of HCPs indicated that the tool recommendations either changed or confirmed their tx plan. Conclusions: HCPs are challenged to optimally manage 1L aEC in concordance with expert recommendations and/or NCCN guidelines. Detailed analyses of HCP tx vs expert recommendations in the 1L and 2L settings and 2023 vs 2022 practice patterns will be presented. [Table: see text]
Understanding patient and provider preferences in management of metastatic renal cell carcinoma (mRCC).
Authors: Yazdanpanah Omid , Benjamin David Joseph , Vosoughi Elham , Raad Ali , Popal Medina , Kongtim Piyanuch , Mar Nataliya , Rezazadeh Arash 
Published: June 2024

e16530 Background: First-line clear cell mRCC management has evolved to include doublet therapies containing either a tyrosine kinase inhibitor (TKI) with an immuno-oncology (IO) agent or two IO agents. Oncologists typically prescribe therapies based on guideline recommendations or their personal experience with various therapies. However, patient preferences may not be a major factor in this decision-making process. Previously published data on this topic is scarce. This study aimed to assess patient preferences in the treatment of mRCC and compare it with providers' perspectives. Methods: A single-arm, prospective study surveyed mRCC patients with a questionnaire containing descriptions of 5 possible treatment options in simple language: 1) single-agent TKI; 2) IO/IO; 3) IO/TKI; 4) phase 3 clinical trial (CT); and 5) phase 1/2 CT. Patients rated their preference for each option on a 1 (least preferred) to 10 (most preferred) scale. The same questionnaire plus de-identified patient characteristics were provided to 2 academic and 1 community oncologists. Ordinal logistic regression was used to analyze the impact of patient characteristics on each treatment ranking. Pearson’s correlation was used to calculate correlation coefficients of patients' and providers' responses. Results: A total of 48 patients were surveyed with an average age of 62. Patients' responses most frequently fell in the 7-10 category for all treatment options. Among patients, the most preferred treatment option was single-agent TKI (average score of 7.9), while the least popular one was IO/IO and early phase CTs (average score of 6.0 for both) ( p<0.01). Patient variables, including sex, race, language, insurance, employment and marital status, household income, and de novo versus recurrent mRCC, were not significantly associated with a greater likelihood of picking a particular treatment option. Among oncologists, the most preferred treatment option was early and late phase CTs (average score of 7.9 and 7.4, respectively), while single-agent TKI was the least preferred choice (average score of 5.7) ( p<0.01). Age and prior treatment history were independently correlated with oncologist therapy choices. Conclusions: This study highlights the differences between patient and oncologist mRCC treatment preferences. Patients appear to prefer single-agent TKIs, while clinical trial participation is the least favored. Socioeconomic factors had no impact on patient preferences, highlighting individuality. In contrast, oncologists prefer CTs and are influenced by patients’ age and prior therapies. Ultimately, this study underscores the importance of an individualized discussion with each patient, devoid of any assumptions, to evaluate their therapeutic objectives and make shared decisions. Patient education on clinical trials is also paramount.
Association of race with clinical outcomes in patients with advanced renal cell carcinoma (aRCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Choi Yujin , Yildirim Ahmet , Wei Mengting , Liu Yuan , Goswamy Rohit Vivek , Brown Jacqueline T. , Nazha Bassel , Martini Dylan J. , Hartman Caitlin , McClintock Greta Russler , Zhuang Tony , Kissick Haydn , Harris Wayne B. , Carthon Bradley Curtis , Kucuk Omer , Master Viraj A. , Bilen Mehmet Asim 
Published: June 2024

e16539 Background: Race has been regarded to be associated with clinical outcome of aRCC patients undergoing therapy with ICIs, but larger data is still limited. Here, we evaluated race and clinical outcome in aRCC patients treated with ICI. Methods: A retrospective analysis was conducted on adult patients with aRCC treated with ICIs at Emory Winship Cancer Institute between 1/1/2018 and 8/31/23. Overall survival (OS) and progression-free survival (PFS) was calculated from the date of treatment initiation to death and progression, respectively. Progression was determined by RECIST v1.1 or clinical progression. Clinical benefit (CB), including stable disease, partial response, and complete response, was determined by RECIST v.1.1. Univariate (UVA) and multivariate (MVA) analyses were conducted for CB, OS, and PFS in patients to assess the association with race. Results: There was a total of 401 patients, consisted of 71.1% White patients, 21.2% African American patients, and 7.7% patients with other racial profiles. Median age was 66 (range = 18-95). Treatment plan involved 139 (34.6%) patients for single ICI therapy, 131 (32.6%) patients for ICI/ICI therapy, 108 (26.9%) patients for ICI/TKI (tyrosine kinase inhibitor) therapy, 6 (1.5%) patients for ICI/ICI/TKI therapy, and 17 (4.23%) patients for therapy with ICI plus an experimental drug. Race was significantly associated with the CB, OS, and PFS of the patients in the UVA. African American patients demonstrated worse clinical outcomes with hazard ratios (HR) significantly less than 1 for both OS and PFS and odds ratios (OR) significantly greater than 1 for CB. According to the Kaplan-Meier plots, the median OS for African American and White patients were 17.1 and 34.8 months, respectively. Similarly, median PFS for African American, White, and patients of other races were 3.6, 7.7, and 13.9, respectively. MVA also suggested greater clinical benefit for patients of White and other racial backgrounds when compared to African American patients. Conclusions: The significant difference in clinical outcomes between the racial profile of patients suggest that African American patients may have worse clinical outcomes in treatment involving ICIs. A more in-depth analysis of race’s association with clinical outcomes can be conducted to assist with treatment plan decisions in the future. [Table: see text]
Dietary interventions selectively target dysregulated metabolism and reveal metabolic vulnerabilities in preclinical models of advanced renal cell carcinoma.
Authors: Orsi Sabrina , Chang Musea , Delle Fontane Ilaria , Jawadwala Abbas , Colligan Sean , De Nigris Filomena , Pili Roberto 
Published: June 2024

e16545 Background: Long-term toxicities and acquired resistance to targeted therapies represent a critical clinical challenge for the treatment of advanced clear cell and non-clear cell renal cell carcinoma (RCC), thus highlighting the need for novel therapeutic strategies. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of RCC. As diet has been reported to alter the availability of circulating metabolites available to tumors, dietary interventions represent an innovative strategy to selectively target metabolically dysregulated tumors. Unfortunately, tumor cell plasticity, intratumor heterogeneity, and a lack of understanding regarding metabolic vulnerabilities in tumors are a critical roadblock in the use of dietary restrictions in patients. Therefore, the overall goals of the present study were to better understand nutrient utilization and metabolic dysfunction in RCC to provide biologic rationale for incorporating dietary interventions with standard cancer care. Methods: Using Seahorse, immunohistochemistry, immunofluorescence, metabolomics, and transcriptomics in patient-derived cell lines and murine xenograft models, we investigated the impact protein restriction and alternate day fasting have on energy dynamics in preclinical models of clear cell and translocation RCC. Results: Interestingly, regardless of inherent metabolic phenotype, alternate day fasting was more effective than protein restriction at reducing tumor growth in vivo. Integrated multi-omics analyses of these tumors revealed increased bile acid metabolism with alternate day fasting, indicating a potential tumor suppressive role for these metabolites. Surprisingly, alternate day fasting induced a strong reduction of circulating amino acids that was not observed with protein restriction. Similarly, protein restriction significantly reduced serum triglyceride levels which were not observed in the alternate day fasting group to the same extent. Furthermore, analysis of non-tumor bearing animals revealed distinct metabolite signatures for each dietary restriction that can be easily detected in the blood as a marker of the metabolic state of the host during treatment. Ongoing combination studies with either protein or calorie restriction and targeted therapies, such as standard of care receptor tyrosine-kinase inhibitors, suggest the benefit of using dietary interventions as an adjunct therapy in RCC. Conclusions: Overall, these studies reveal that selective dietary interventions alter the metabolic landscape of RCC and expose vulnerabilities that can be exploited further with targeted therapy.
Efficacy of erdafitinib in FGFR2/3-altered metastatic urothelial cancer including patients with CDK2NA/B or MTAP loss: Analysis of UNITE study.
Authors: Jiang Cindy Y. , Jindal Tanya , Epstein Ilana B. , Nguyen Charles B , Nizam Amanda , Bakaloudi Dimitra Rafailia , Taylor Amy K , Milowsky Matthew I. , Shah Sumit , Hoimes Christopher J. , Bilen Mehmet Asim , Zakharia Yousef , Emamekhoo Hamid , Grivas Petros , Gupta Shilpa , Bellmunt Joaquim , Alva Ajjai Shivaram , Koshkin Vadim S , Alhalabi Omar , Campbell Matthew T 
Published: June 2024

e16571 Background: Erdafitinib (erda) is a fibroblast growth factor receptor (FGFR) inhibitor used in previously-treated FGFR2/3-altered locally advanced/metastatic urothelial cancer (LA/mUC). FGFR2/3 alterations (alts) are present in 15-20% of patients (pts) with LA/mUC. We aimed to investigate “real-world” outcomes of erda in LA/mUC. We hypothesized that efficacy of erda would be similar to clinical trial data. Methods: Pts with FGFR2/3 alts who received erda were included. Overall survival (OS) and progression-free survival (PFS) measured from erda start were assessed with KM method and group comparison by long rank test. Categorical variables and observed response rate (ORR) were compared using Fisher’s exact test with Baptista-Pike method for 95% confidence intervals. Cox regression model used to describe PFS and OS for subgroups. Results: Among 633 pts from 16 US sites, 487 (77%) had NGS data, 94 (19%) had FGFR2/3 alts and 39 (41%) received erda. In erda treated pts, median age was 70, most were male (79%), white (87%), had primary bladder tumor (68%), and pure urothelial pathology (74%). Most received prior anti-PD1/L1 (92%) with pembrolizumab as the most common (72%); 56% received prior platinum-based chemotherapy with 77% cisplatin-based. Median prior therapy lines was 2. ORR to erda was 32% (12/37; all partial responses); another 12 pts had stable disease as best response. Median PFS was 7.5 months (mos) and median OS 18 mos. CDK2NA/B or MTAP loss was seen in 15 pts (38%) and ORR in these pts was 35%. 33 pts had canonical FGFR2/3 alts (S249C, Y373C, R248C, and FGFR3-TACC3 fusion) and 6 pts had non-canonical alts (A248C, A391E, Y375C, V555L/T807L, and JAKMIP1-FGFR3 fusion) with no significant difference in PFS (HR 0.8; CI 0.29, 2.3; p = 0.66), OS (HR 0.4; CI 0.06, 2.3; p = 0.086) or ORR (OR 2.1; CI 0.27, 27.7; p = > 0.99). Subgroup PFS/OS analysis in Table. Conclusions: Erda showed efficacy similar to clinical trial data. In this retrospective study with notably underpowered analyses, non-canonical FGFR2/3 alts or CDK2NA/B or MTAP loss did not seem to effect outcomes. Larger prospective studies, including granular NGS data, are needed to further validate “real world” data and further explore predictive biomarkers for erda to inform optimal therapy sequencing. [Table: see text]
PD-1 inhibitor plus paclitaxel, pingyangmycin and platinum-based chemotherapy as bladder-sparing therapy for high-risk non-muscle-invasive bladder cancer/muscle-invasive bladder cancer: A retrospective study.
Authors: Li Jun , Wang Ziyong , Li Zheng , Li Ruiqian , Jiang Haiyang , Hu Chen , Bi Ying , Zhu Yong , Wu Wenzhao 
Published: June 2024

e16601 Background: Radical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy is the standard approach for muscle-invasive bladder carcinoma (MIBC), and also a treatment option for high-risk non-muscle-invasive bladder cancer (HR-NMIBC), but removal of the bladder has a significant impact on pts quality of life. Bladder-sparing treatment have emerged to be an alternative choice for patients who are concerning about the life quality after surgery. we aim to investigate the efficacy and safety of neoadjuvant PD-1 inhibitor plus paclitaxel, pingyangmycin and platinum-based chemotherapy as a bladder-sparing therapy for high-risk NMIBC/MIBC patients. Methods: This retrospective study enrolled HR-NMIBC/MIBC patients who received at least one cycle of PD-1 inhibitor plus paclitaxel、pingyangmycin (bleomycin A5 hydrochloride) and platinum-based chemotherapy ["4P" therapy] and underwent imaging evaluation from Feb 2022 to Nov 2023. The objective response rate (ORR), pathological complete response rate (pCR), bladder-intact event-free survival (BI-EFS), Recurrence free survival (RFS), overall survive (OS) and adverse events (AEs) were observed. Results: Twenty-three pts (4 pts HR-NMIBC,19 pts MIBC) were included, with median age of 70 and 87.5% male, of which 5 pts (21.7%) received 1 cycle and 18 pts (78.2%) received 2 cycles of treatment. In all pts, the ORR was 87.0% (20/23), with 34.8% (8/23) had a complete response, 52.2% (12/23) had a partial response, 13.0% (3/23) had a stable disease. In different PD-1 therapy group, toripalimab group has 100% (15/15) of ORR, 40.0% (6/15) had a complete response; tislelizumab group has 62.5% (5/8) of ORR, 25.0% (2/8) had a complete response. 18 of the 23 pts underwent TURBT and 5 pts declined TURBT. Among 18 evaluable pts, pCR was achieved in 7 pts (38.9%). The cut-off date of data collection was Feb 1 2024, median follow-up time was 6.5 months[range:2.1-23.3 months], 2 patients relapsed and underwent TURBT without RC. None of the 23 patients have underwent RC. Survival data are not yet mature, 1 patient died of pneumonia (unrelated to chemotherapy or PD-1 inhibitor). Any grade of adverse event occurred in 23 pts (100%), grade 3 or higher toxicity rate was 30.4% (7/23). 18 pts (78.3%) experienced immune-related AEs, and 1 patient (4.3%) had grade 3 immune-related AEs. No discontinuations due to immune-related AEs. Conclusions: These data support neoadjuvant PD-1 inhibitor plus paclitaxel, pingyangmycin and platinum-based chemotherapy as a potential bladder-sparing option for patients with HR-NMIBC/MIBC.
Bladder preservation in muscle invasive bladder cancer (MIBC): A population based analysis.
Authors: Ozgun Guliz , Eigl Bernhard J. , Parimi Sunil 
Published: June 2024

e16608 Background: Although available data supports trimodal therapy (TMT) as a bladder sparing treatment for MIBC with outcomes comparable to cystectomy, uptake in Canada is low. A retrospective evaluation in British Columbia, Canada, was undertaken to evaluate real-world outcomes in MIBC patients (pts) undergoing bladder sparing radiotherapy (RT). Methods: MIBC pts were identified from the BC Cancer registry who received RT with curative intent between Jan 1, 2002, and Dec 31, 2020. Disease free survival (DFS), overall survival (OS), and disease specific survival (DSS) were calculated for those receiving RT versus combined modality treatments. Further analysis was undertaken to identify factors associated with outcomes. Results: The population was 231 pts, predominantly male (74%), median age 81 (range: 44-95). Almost all (97%) presented with high-grade MIBC, and 67.1% had an ECOG score of 0-1. The reasons for bladder preservation were frailty/comorbidities (77.1%), pt preference (16%) and inoperability (6.9%). 170 (73.6%) pts underwent RT alone; the remainder were treated with chemoRT (16.5%), neoadjuvant chemotherapy (nCT)+RT alone (5.6%), nCT+chemoRT (3%), chemoRT+adjuvantCT (0.9%), and RT+adjuvantCT (0.4%). The median OS in the RT-only group (25.2 months, 95% CI, 19.5-31) was significantly lower than for chemoRT (39.7 months, 95% CI, 13.5-65.9, p=0.013). Pts who underwent maximal transurethral resection of the bladder tumor (TURBT) in the chemoRT group exhibited significantly prolonged OS (56.5 vs. 31.9 months, p=0.006). Pts with maximal TURBT who had a second TURBT while waiting for RT demonstrated a significant improvement, compared to those with a second TURBT due to submaximal TURBT (59.3 vs. 13.3 months, p<.001). Despite these findings, DSS analysis did not show statistically significant differences between the treatment groups (p=0.38), even when stratified by maximal TURBT (p=0.207). Similarly, the median DFS did not represent a difference between the groups (26.6 vs. 22.2 months, p=0.772). Cox regression analysis revealed the absence of carcinoma in situ trended towards a decreased risk of death (HR: 0.52, p<0.001), as did the absence of hydronephrosis (HR: 0.65, p=0.009) and an increase in the total number of RT fractions (HR: 0.92, p=0.001). In the analysis of treatment modalities (RT vs. chemoRT), there was a significant difference in the distribution of recurrence sites (Chi-Square=4.15, p=0.04). Local recurrences were identified less frequently in the chemoRT group. Conclusions: This population-based study showed notable demographic and treatment-related characteristics that influenced OS, DSS, and DFS. While respecting the limitations of retrospective cohort studies, overall outcomes in this cohort are inferior to those predicted for TMT, but adherence to best practices such as maximal TURBT and combined modality chemoRT result in acceptable long term survival rates.
The tumor immune profile of bladder cancer (BC) with HER2 over-expression and the investigation into RC48-ADC versus BCG in high-risk non-muscle invasive BC with HER2 over-expression.
Authors: Liu Haoyang , Chen Junru , Liu Haolin , Zhu Qiyu , Bao Yige , Liao Banghua , Zeng Hao 
Published: June 2024

e16614 Background: Patients diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC) face a challenging prognosis, with a 5-year disease progression rate reaching up to 40%. The current standard treatment for HR-NMIBC involves transurethral resection of bladder tumor (TURBT) followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG) therapy. BCG therapy is reported to exert anti-tumor therapeutic effects by inducing both innate and adaptive immunity. Multiple studies have reported HER2 positivity in 20-44% of NMIBC cases, and HER2 overexpression is strongly associated with poor tumor immunity and an unfavorable cancer prognosis. Disitamab Vedotin (DV; RC48-ADC) is an antibody-drug conjugate (ADC) comprising a fully humanized HER2-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable mc-vc linker. This study aims to evaluate the therapeutic potential of RC48-ADC in HR-NMIBC patients and explore the association between HER2 expression and immune profile of Bladder Cancer (BC). Methods: A retrospective analysis was conducted on patients diagnosed with NMIBC exhibiting HER2 overexpression (immunohistochemistry ≥2+) who underwent adjuvant therapy with either RC48-ADC or BCG at West China Hospital of Sichuan University between 2019 and 2023. The primary study endpoint was recurrence-free survival (RFS). Utilizing molecular data on bladder cancer (BC) from The Cancer Genome Atlas (TCGA), we included 100 cases each of HER2-low and HER2-high, determined by HER2 expression levels before and after a 25% threshold, to assess differences in tumor immunity between the two cohorts. Results: The study included 27 patients diagnosed with HR-NMIBC displaying HER2 over-expression. After TURBT, 10 patients received adjuvant therapy with RC48-ADC, while 17 received adjuvant therapy with BCG. Kaplan-Meier analysis revealed that patients receiving RC48-ADC exhibited better RFS compared to those receiving BCG (p=0.027). Additionally, in the RC48-ADC-treated group, the twelve-month RFS rate was 100%, while in the BCG-treated group, it was 58.8%. According to TCGA molecular data, our results showed that HER2-low BC demonstrated higher expression levels of various immune-related cytokine, including CXCL5, CXCL8, CXCL9, CXCL11 and so on. ESTIMATE analysis revealed that HER2 expression was negatively correlated with the interstitial score, immune score, and ESTIMATE score. Moreover, ssGSEA revealed stronger immune infiltration in the HER2-low BC group, including NK cells, B cells, CD8 T cells, Th1 cells, Th2 cells, and others. Conclusions: HER2 over-expression significantly influences the tumor immunity of BC and the HER2-directed ADC RC48 has demonstrated promising efficacy as adjuvant therapy in patients with HR-NMIBC according to RFS.