bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient reported outcomes on treatment related side effects with combination therapy in metastatic renal cell carcinoma (RCC).
Authors: Battle Dena , Vaishampayan Ulka N. , Griffith Meghan , Pal Sumanta Kumar , Zhang Tian , Msaouel Pavlos , Staehler Michael D. 
Published: June 2024

e16540 Background: Combination treatments have transformed the landscape for metastatic renal cell carcinoma (mRCC). In the context of life-long therapy, effective management of treatment related toxicities is crucial to maximizing outcomes. Outside of trials, little is known about patient experiences with side-effects. We sought to assess patient experiences with combination therapy in the real-world setting. Methods: The survey was developed by the Kidney Cancer Research Alliance (KCCure) and was broadcast between 07/2022 and 09/2022 to pts via website, mailing lists and social media platforms. Those who agreed to participate were surveyed for demographics (age, gender, race, income, country) and clinical characteristics (date of the diagnosis, disease stage, treatment history). Results: 399 out of 1,062 pts responding had metastatic disease with a median age of 57 years. 245 patients had received treatment with combination therapy, 51% (126) were treated with combination IO/IO and 49% (119) were treated with combination IO/TKI. The IO/TKI breakdown were as follows: 44% (52) pembro/axi, 35% (42) cabo/nivo, 16% (19) len/pembro, and 5% (6) cabo/ipi/nivo. Among patients being treated with combination IO/IO, the most poorly managed side-effect was loss of appetite (16%), fatigue (15%) and taste alteration (11%). Patients treated with combination IO/TKI reported higher rates of daily, poorly managed side-effects, with the most bothersome being fatigue (26%), loss of appetite (15%), taste alteration (16%) and pain (11%). 63% of patients being treated with IO/TKI combinations reported dose reductions for their oral treatment. 42% of pts expressed worry that their dose reduction would reduce efficacy. Only 16% of patients proactively asked for a dose reduction. When asked if they had been prescribed additional drugs to manage their side effects, among patients being treated on IO/IO, only 10% said no. 56% of pts received steroids, 45% were prescribed anti-nausea drugs, 32% needed hormone substitute treatment, and 28% got anti-diarrheal drugs. Among pts being treated with IO/TKI, only 7% of pts reported they did not need additional drugs to manage side-effects. Most prescribed drugs were anti-nausea (56%), anti-diarrheal (45%), steroids (44%), and hormone substitute (34%). Conclusions: 90% of pts require additional medications to manage AEs. Patients being treated with combination IO/TKI regimens report higher rates of bothersome, daily side effects compared to patients being treated on IO/IO. Loss of appetite and taste alteration are side-effects that are rarely reported or discussed in the context of clinical trials. This survey indicates these toxicities may warrant closer attention. With prolonged duration of therapies in RCC and the majority of patients being affected by toxicities, judicious management is likely to make a meaningful impact on patients daily lives.
Clinical outcome differences based on gender in patients with advanced renal cell carcinoma (aRCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Choi Yujin , Goswamy Rohit Vivek , Wei Mengting , Liu Yuan , Yildirim Ahmet , 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

e16542 Background: Current first-line therapy for aRCC involves ICIs, often administered with another ICI or tyrosine-kinase inhibitors (TKIs). While there has been some literature on the association between gender and clinical outcomes in patients with aRCC, some results are contradictory and thus the true association remains unknown. We explored the role of gender in the difference in clinical outcomes of patients undergoing therapies involving ICIs. Methods: We conducted a retrospective analysis on adult patients with advanced RCC 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. CB, OS, and PFS were used to identify the association between gender and clinical outcome through univariate (UVA) and multivariate (MVA) analyses. Results: Analysis was conducted on a total of 401 patients, consisting of 283 (70.6%) males and 118 (29.4%) females. Their 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 therapy, 6 (1.5%) patients for ICI/ICI/TKI therapy, and 17 (4.23%) patients for therapy with ICI plus an experimental drug. CB, OS, and PFS all confirmed no difference in clinical outcomes of the patients based on gender in UVA and MVA. Female patients had hazard ratios (HR) close to 1 for both OS and PFS and odds ratios (OR) close to 1 for CB. Results from Kaplan-Meier (KM) plots also support the lack of difference in clinical outcomes between genders. The KM plot indicated similar OS and PFS for female and male patients, with the median OS for female and male patients being 36 and 28.2 months and the median PFS for female and male patients being 7.4 and 7.1 months, respectively. Conclusions: Patients treated with ICIs had similar clinical outcomes based on gender as indicated by insignificant differences in CB, OS, and PFS. However, prospective studies are still needed to validate such findings. [Table: see text]
Integrative genomic analysis examines molecular and clinical disparities between bladder urothelial carcinoma and upper tract urothelial carcinoma.
Authors: Choi Yoon Ji , Kim Jwa Hoon , Lee Jae-Lyun , Bae Woo Kyun , Kim Miso , Park Ji Hyun , Choi Jonggwon , Park Inkeun , Shin Sang Joon , Jo Jungmin , Park Se Hoon , Park Kwonoh , Kim Jiwon , Sa Jason 
Published: June 2024

e16553 Background: The clinical outcome of urothelial carcinoma presents significant variability, reflecting its intricate molecular composition, epidemiologic attributes, and primary site of origin. Despite histological similarities, upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BLCA) represent two distinct disease entities with disparate treatment responses and mutational patterns. Methods: To assess the impact of molecular heterogeneity on treatment outcomes, we conducted a comprehensive genomic analysis of 231 Korean BLCA and UTUC patients from the K-MASTER cohort. Results: Our investigation unveiled dynamic molecular properties and mutational patterns in key molecules, including TP53, FGFR3, CREBBP, and SPEN. BLCA patients demonstrated enrichment of APOBEC mutational signature activities, whereas UTUC patients were characterized by activation of the cell cycle pathway. Transcriptome analysis uncovered unique biological signatures, highlighting increased cell migration and WNT signaling in BLCA, while FGFR3 and stem-cell-like pathways predominated in UTUC. Moreover, our study identified increased treatment resistance to both platinum-based chemotherapy and immunotherapy in UTUC patients. Notably, tumor mutational burden (TMB) and microsatellite instability score independently demonstrated robust predictive capabilities for immunotherapy response in BLCA and UTUC, respectively. Lastly, a machine learning-based multivariable model identified FGFR3 mutation as a molecular determinant associated with favorable clinical outcomes, contrasting with mutations in FGFR2 linked to increased resistance to chemotherapy. Conclusions: Collectively, our findings provide important insights into the significance of molecular and clinical disparities in urothelial carcinoma, facilitating disease-specific treatment interventions.
Estimated impact of novel immune checkpoint inhibitors on reducing cancer mortality in patients with locally advanced or metastatic urothelial carcinoma in Russia.
Authors: Alekseev Boris , Alekseev Boris , Avxentyev Nikolay , Makarova Yuliya , Andreiashkina Irina 
Published: June 2024

e16560 Background: The standard first-line treatment for patients with locally advanced or metastatic urothelial carcinoma (UC) is platinum-based chemotherapy. Other available therapeutic option are immune checkpoint inhibitors (ICIs) such as pembrolizumab, nivolumab, atezolizumab, and avelumab. However, unlike other drugs in this class, avelumab can be used as maintenance therapy in patients without disease progression after first-line platinum-based chemotherapy. Objective: In this study we sought to evaluate the effects of using ICIs in treating adult patients with locally advanced or metastatic urothelial UC on reducing overall and one-year cancer mortality in Russia. Methods: A mathematical model based on overall survival and progression-free survival data from clinical trials has been proposed. This model describes duration of therapy and treatment outcomes for treatment without ICIs (historical approach), with pembrolizumab and atezolizumab in first-line in cisplatin-ineligible PDL1-positive patients; nivolumab and pembrolizumab, atezolizumab in second-line therapy according to real-life clinical practice (current approach), and with avelumab as maintenance therapy after platinum-based chemotherapy (suggested approach). The model was applied to assess the healthcare expenses and the increase in saved lives when shifting from historical to current approaches and from current to suggested methods over a three-year timeframe. This analysis considered the annual population of patients in Russia with locally advanced or metastatic UC who might initiate platinum-based therapy. Results: Annually, up to 4,182 patients with locally advanced or metastatic UC in Russia can initiate platinum-based chemotherapy. Compared with historical approach, the use of pembrolizumab, nivolumab, and atezolizumab in the first and second lines of therapy according to real-life clinical practice, allows reducing mortality from malignant neoplasms by 553 cases over a 3-year horizon. Over the same period, avelumab-based treatment would additionally save 2,506 lives. Shifting to suggested practice with avelumab maintenance therapy may lead to decrease in one-year cancer mortality from 20.3% to 20.25% and one-year bladder cancer mortality from 13.8% to 12.12%. Furthermore, the cost of saving one life with avelumab amounts to 6.0 million rubles, which is 9% lower compared to the cost of saving one life with other ICIs (6.6 million rubles). Conclusions: The use of avelumab maintenance in advanced or metastatic UC patients without progression after platinum-based chemotherapy has a significant and quantifiable impact on reducing cancer-related mortality in Russia.
Neoadjuvant immunotherapy-driven bladder preservation for muscle-invasive bladder cancer: A multicenter, propensity score-matched cohort study.
Authors: Hu Jiao , Ou ZHENYU , Chen Minfeng , Liu Jinhui , Yan Luzhe , Chen Jinbo , Liu Peihua , Zu Xiongbing 
Published: June 2024

e16598 Background: The rise of neoadjuvant immunotherapy has brought neoadjuvant immunotherapy-driven bladder preservation (Neoimmu-CMT) into the spotlight, yet its application is hampered by a scarcity of robust clinical evidence. There are no comparative studies on the effectiveness of Neoimmu-CMT versus traditional trimodal therapy (TMT) or neoadjuvant chemotherapy-driven bladder preservation (NAC-CMT). To address this gap, our study (ChiCTR2300069303) aims to assess Neoimmu-CMT's viability and identify suitable candidates through a multicenter, propensity score-matched (PSM) analysis. Methods: The study included 163 patients from 14 hospitals, categorized into Neoimmu-CMT (n=97), TMT (n=30), and NAC-CMT (n=36) subgroups. PSM was utilized to mitigate baseline variability. Primary outcomes were disease-free survival (DFS), bladder-intact DFS (BI-DFS), and overall survival (OS). Univariate and multivariate Cox analyses were used to identify potential prognostic factors. Biomarker assessment comprised immunohistochemistry and single-cell RNA sequencing. Results: Post-PSM, Neoimmu-CMT significantly outperformed NAC-CMT in DFS (HR: 2.112, 95% CI: 1.247-3.576, P=0.005) and BI-DFS (HR: 2.329, 95% CI: 1.138-4.770, P=0.021), with a 2-year BI-DFS rate of 90.28% compared to NAC-CMT's 71.59%. However, Neoimmu-CMT and TMT showed no significant difference in DFS and BI-DFS, with Neoimmu-CMT marginally surpassing TMT in 2-year BI-DFS rates (86.42% vs. 80.89%). Clinical complete response to neoadjuvant treatment and lower clinical T stage were positive prognostic factors for Neoimmu-CMT. Interestingly, regardless of being combined with ADC (HR: 1.283, 95% CI: 0.224-7.359, P=0.780) or chemotherapy (HR: 0.769, 95% CI: 0.255-2.323, P=0.642), the DFS outcomes did not surpass those received with sole immunotherapy. Furthermore, conventional clinical parameters such as tumor-associated hydronephrosis, tumor number, and histology type did not emerge as significant predictors for bladder preservation outcomes. Biomarker analysis showed the tumor microenvironment immune phenotype closely relates to bladder preservation outcomes. Conclusions: Neoimmu-CMT is a promising bladder preservation strategy, comparable to TMT and superior to NAC-CMT. Its advancement could significantly broaden bladder preservation treatment options.
Preliminary results of sexual quality of life (QOL) outcome for intermediate-high risk prostate cancers treated by stereotactic radiotherapy (SBRT) and androgen deprivation therapy (ADT): Clinical and dosimetric factors.
Authors: Basu Trinanjan , Sahu Jay Prakash , Gnair Ratheesh , Kamat Shounak Jairam 
Published: June 2024

e17085 Background: There has been numerous evidence about ADT and radiotherapy on sexual QOL among prostate cancer (Pca) patients. This study analyzed the impact of SBRT on sexual health of Pca treated by SBRT and ADT. This also monitored dosimetry related to penile bulb (PB) and neurovascular bundles (NVB). Methods: Consecutive series of 40 Pca patients of intermediate and high-risk group (NCCN) were included. Baseline sexual function was assessed using Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC‐CP) questionnaire for sexual symptoms score. Patients received ADT as per risk groups. Radical SBRT was 36.25Gy in 5 fractions (Pelvic nodal 25 Gy in 5 fractions for high risk) on alternate days or weekly. Mean Dose to penile bulb and dose received by bilateral NVB were documented. Sexual function by EPIC-CP monitored at baseline and then 6 monthly till last follow up. Results: With median age of 61 years and median follow up of 20 months, 20% (8) patients belong to NCCN intermediate favourable risk category,15% (6) Intermediate unfavourable risk category and 65% (26) High risk category. All high risk Pca received elective pelvic nodal radiotherapy. Mean dose to penile bulb was in range of 9.5-29.4Gy. NVB Dose ranged from V34.4 (83.3% - 91.8%), V32 (94.5-99.16%) V28(99.76-100%). The EPIC‐CP for sexual symptoms score reported (out of 12) median score at baseline of 3 (range2-4), at 6 months 4.5 (range3-6)), at 12 months 5 (range 3-7), at 24 months 5.5 (range 4-7) and at 30 months 7 (range 6-8). The higher score represented worsening sexual function QOL. Till last follow up 38/40 patients were biochemically controlled with acceptable gastro-intestinal and genito-urinary late effects. Both the median and mean score of EPIC-CP sexual domain declined over follow up period representing clinical effect of ADT and dose received to PB and NVB. Sexual function scores declined gradually in both risk groups (High risk > intermediate risk) and vitality/hormonal scores were unchanged from baseline in both groups at 3 and 6 months. Few patients beyond 3 years of follow up reported some degree of recovery in EPIC-CP score in sexual function domain. Conclusions: A substantial group of patients in our study had mild or no erectile dysfunction at base-line but compromised sexual health after ADT and SBRT. The technical challenge of sparing NVB for high risk Pca patients combined with effect of ADT remains a concern. However, PB dosage were in the acceptable range signifying multitude of factors besides only dosimetric features. Late recovery of sexual function to some extent probably a possibility. There are limitations in documentation of sexual QOL by EPIC-CP in our cohort and future prospective documentation and pragmatic sparing of NVB can highlight specific issues related to sexual QOL.
Performance characteristics of ExoDx urinary biomarker: A single-institution analysis.
Authors: Murdock Andeulazia , Xu Vincent Eric , Antar Ryan Michael , Pio Faozia , Bowler Nicholas , Whalen Michael Joseph 
Published: June 2024

e17090 Background: Prostate cancer screening relies on prostate-specific antigen, which may lead to unnecessary prostate biopsies. The ExoDx Prostate (EPI) test, a urinary exosome assay, has been developed for the detection of clinically significant (Gleason Grade Group ≥2) prostate cancer (csPCa) to improve specificity. This study analyzes the performance characteristics of EPI compared to/in concert with a multiparametric MRI (mpMRI)-based pathway at a single academic institution. Methods: Patients who underwent EPI testing between 10/2019 to 5/2023 were reviewed for EPI score, demographics, MRI characteristics, and biopsy results. Patients were categorized by EPI score (high risk ≥ 15.6 vs. low risk < 15.6). Outcome variables of biopsy and MRI were compared between EPI risk groups using Chi square and Mann Whitney-U test. Spearman correlation was used to estimate the correlation between EPI score and PI-RADS and Gleason score. Receiver operator curve (ROC) analysis assessed the performance of EPI and PI-RADS score for prediction of csPCa. An optimal cutoff value was determined for EPI using ROC, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed. Statistical comparisons were two-sided with a p-value <0.05 being statistically significant. Results: Of n=173 patients with EPI scores, 28.9% were low risk and 71.1% were high risk. EPI had weak correlation with PI-RADS score on prostate MRI (r = 0.30, p <0.001). An optimal EPI score cutoff for the detection of csPCa of 26.43 was determined (sensitivity 0.720, specificity 0.537, PPV 0.367, NPV 0.800). On ROC analysis, PI-RADS with score of ≥4 had better predictive performance for detecting csPCa with an Area Under the Curve (AUC) of 74.6% (sensitivity: 0.696, specificity: 0.721, PPV: 0.485, NPV: 0.862), versus an AUC of 63.1% with EPI testing. By utilizing a criteria of PI-RADS score ≥4 and EPI ≥ 26.43, we found improved PPV and specificity over either alone (PPV: 0.556 vs 0.485 vs 0.367, respectively) (specificity: 0.873 vs 0.721 vs 0.537, respectively). In addition, we found that with utilization of either PI-RADS score ≥4 or EPI ≥ 26.43, there was improved NPV and sensitivity (NPV: 0.962 vs 0.862 vs 0.800, respectively) (sensitivity: 0.957 vs 0.696 vs 0.720, respectively). Conclusions: Our study supports EPI testing as a way to assess risk for csPCa, ideally in combination with mpMRI, and also prompts reevaluation of 15.6 as an optimal cutoff EPI score.
Development and validation of a prognostic nomogram for survival in testicular and non-testicular primary choriocarcinoma (CC).
Authors: Alenezy Abdalwahab , Alshwayyat Sakhr Abdulsalam , Alshwayyat Tala Abdulsalam , Alshwayyat Mustafa , Alajmi Falah 
Published: June 2024

e17112 Background: Primary CC is a rare germ cell tumor that occurs in males. The testes are the most frequent location. However, it can also develop in extragonadal sites such as the mediastinum, retroperitoneum, or lungs. A prognostic index for estimating the clinical outcomes of CC would be attractive in the current clinical practice. We aimed to develop and validate an effective nomogram for predicting survival in patients with testicular and non-testicular CC. Methods: We analyzed data from the Surveillance, Epidemiology, and End Results database of patients diagnosed with pure CC between 2000 and 2018. Patients who were not diagnosed based on histology, previous history of cancer or other concurrent malignancies, and unknown data were excluded. Patients were divided into two groups: testicular and non-testicular CC. The clinicopathological features of each group were compared using the chi-squared test. Kaplan-Meier estimation, log-rank tests, and Cox regression analyses were used to identify the prognostic factors for OS and CSS. A nomogram was developed to predict 5-year OS, and a calibration curve was plotted to evaluate the agreement between actual (observed) outcomes and expected probabilities. Results: The study included 363 patients, with 270 (74.4%) classified as having testicular CC and 93 (25.6%) as having non-testicular CC. Testicular CC patients had better OS and CSS (HR = 0.52, 95% CI: 0.38-0.71, and HR = 0.52, 95% CI: 0.37-0.71, respectively) than non-testicular CC patients. Multivariate analyses identified the following independent prognostic factors for testicular CC: localized stage, surgery, tumor size ≥ 4 cm, radiotherapy, and chemotherapy. Interestingly, the use of radiotherapy was associated with poor OS and CSS (HR = 1.8, 95% CI: 1.17-2.85 and HR = 1.7, 95% CI: 1.05-2.73, respectively). For non-testicular CC, the independent prognostic factors for OS and CSS were age ≥ 30 years, regional stage, surgery, and chemotherapy. We developed a prognostic nomogram that integrated significant variables, including age, surgery, chemotherapy, radiation therapy, stage, and tumor size. For testicular CC, the model assigned the highest weight to surgery, followed by radiation and tumor size. The AUC was 0.702 (95% CI: 0.638–0.766) and the calibration curves exhibited a mean error of 0.034. The non-testicular CC model assigned the highest weight to chemotherapy, age, and surgery. The AUC was 0.737 (95% CI, 0.631–0.843), and the calibration curves for 5-year survival demonstrated a mean error of 0.028. Conclusions: We developed and validated a novel nomogram for predicting the survival of patients with testicular and non-testicular CC. This personalized tool, incorporating key clinical factors such as age, stage, surgery, and treatment type, empowers clinicians with objective risk assessment, aiding in patient management and treatment decision-making.