bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pelvic ultrasound-based deep learning models for accurate diagnosis of ovarian cancer: Retrospective multicenter study.
Authors: Cho Hyun-Woong , Lee Sanghoon , Hong Jin Hwa , Kim Seonkyung , Song Jaeyun , Lee Jae Kwan 
Published: June 2024

5543 Background: Although pelvic ultrasound is useful modality to diagnose ovarian cancer, there is few studies to evaluate the performance of deep learning model. Development of deep learning based on aggregating ultrasound images and clinical information such as age and CA-125 data might be beneficial to differentiated malignancy from benign ovarian cyst. The objective of this study is to build a deep learning model with advanced accuracy of differential diagnosis between malignant and benign lesions of ovary. Methods: Pelvic ultrasound images, information of age and ca-125 level at diagnosis from patients diagnosed with ovarian cancer or benign cyst during 2015-2022 were retrieved. The images were segmented into cystic and solid component and processed data for feature extraction. For convolutional neural network model development, patients were assigned to training dataset (565 patients), validation dataset (76 patients), and test dataset (163 patients). After feature extraction using this convolutional neural network, we also used age and tumor marker to classify these images as either malignant or benign. Using these datasets, we assessed the diagnostic value of the deep learning model. A new AI model to utilize image feature and clinical information together was developed. This model separates feature extractor and classifier from the architecture of conventional AI models, and the classifier receives clinical information data in addition to image information. ResNet50 and DenseNet121 were used in the conventional AI model. Results: In total, 804 patients who had ovarian tumors were included; 446 benign and 358 malignant. When pelvic ultrasound image of ovary was only used, ResNet50 showed AUC of 0.84 and DenseNet121 had AUC of 0.82 for this model to detect ovarian cancer. However, when segmented solid portion image and clinical data was combined with the ovary image, ResNet50 showed AUC of 0.95 and DenseNet121 had AUC of 0.96 for this model to detect ovarian cancer. Using the test data set, ResNet50 and DenseNet121 had sensitivities of 90% and 81%, specificity of 93% and 97%, positive predictive value of 92% and 95%, and negative predictive value of 92% and 86% to detect ovarian cancer, respectively. Conclusions: Binary classification model based on deep learning algorithms using pelvic ultrasound images can distinguish between benign and malignant ovarian tumors accurately. Segmentation of solid portion and clinical information of age and CA-125 at diagnosis combined with the pelvic ultrasound images increased the accuracy of the classification model.
Efficacy, safety, and biomarkers of neoadjuvant niraparib monotherapy in homologous recombination deficiency (HRD) advanced ovarian cancer: A prospective, multicenter, phase II, single-arm NANT study.
Authors: Gao Qing-lei , Liu Dan , Li Huayi , Zhang Wei , Wang Ping , Li Jundong , Shan Wanying , Liu Ronghua , Chen Gang , Wu Mingfu , Li Xiao , Liu Cheng , Yin Rutie , Zhou Shengtao , Li MaoMao , He Shanyang , Zhao Guangnian , Song Kun , Hong Li , Ma Ding 
Published: June 2024

5549 Background: The efficacy of PARP inhibitors as neoadjuvant therapy and its clear association with tumor microenvironment (TME) status remain enigmatic. Here, for the first time, we reported the efficacy and safety of niraparib monotherapy, an oral low-toxicity PARP inhibitor, as the neoadjuvant therapy in patients (pts) with HRD high-grade serous ovarian cancer (HGSOC), and directly linked pre-treatment TME components with response using cutting-edge technologies. Methods: Treatment-naïve pts with newly diagnosed advanced unresectable HGSOC and those who could not endure primary debulking surgery were enrolled to receive laparoscopic biopsies. TME landscape was profiled by single-cell RNA sequencing and multiplex immunohistochemistry. Pts with HRD ( BRCA1/2 mutations and/or genomic instability score ≥ 42) HGSOC received daily oral niraparib for two 28-day cycles. Pts with complete response, partial response (PR), or stable disease (SD) received interval debulking surgery (IDS). The co-primary endpoints were objective response rate (ORR) and R0 resection rate. Results: Between January 18, 2021 and July 18, 2023, 127 pts from six centers were screened for eligibility. Totally, 67 HRD pts received neoadjuvant niraparib monotherapy, 48 pts completed response evaluations, and 40 pts underwent IDS. Thirty pts achieved PR and 12 pts reached SD, resulting in an ORR of 62.5% and a disease control rate (DCR) of 87.5%. BRCAm pts exhibited improved responses with increased ORR (77.3%) and DCR (100.0%). For surgical outcomes, 80.0% of pts achieved R0 resection and 95.0% of pts accomplished optimal debulking. Treatment-related adverse events (TRAEs) of grade ≥3 were observed in 61.2% of pts and hematological toxicities were the most common. No fatal TRAEs were reported. Co-enrichment of MRC1+ macrophages, effector regulatory T cells, and myofibroblastic cancer-associated fibroblasts were associated with lack of response. Conclusions: Neoadjuvant niraparib monotherapy regimen achieved encouraging ORR and R0 resection rate with tolerable toxicities in pts with HRD unresectable HGSOC, offering an alternative option for those pts unwilling to receive or unable to tolerate neoadjuvant chemotherapy. Pre-treatment TME factors were correlated with clinical response to PARP inhibitors. Clinical trial information: NCT04507841 . [Table: see text]
Outcomes of reduced dosing of lenvatinib with pembrolizumab for advanced endometrial cancer.
Authors: Ta Quang Dang , Do Connie , Sharma Kavita , Sorooshian Hormozan , Cushing Merta , Shah Nina , Bookman Michael A. , Kavecansky Juraj , Niu Fang , Hui Rita L. 
Published: June 2024

5588 Background: The advent of immunotherapy combined with multitargeted tyrosine kinase inhibitors has significantly improved the treatment of platinum-resistant endometrial cancer (EC). The phase three 309–KEYNOTE-775 trial demonstrated a survival benefit with lenvatinib/pembrolizumab in patients with mismatch repair-proficient (pMMR) advanced EC. However, lenvatinib was discontinued in 31% of patients and dose reduced in 67% due to adverse events (AE). Retrospective reports suggest that reduced dosing for lenvatinib may result in fewer dose reductions, longer time to treatment-related toxicity, and better tolerability without compromising effectiveness. Methods: This multisite, retrospective, cohort study evaluated various dosing strategies of lenvatinib in Kaiser Permanente (KP) California patients treated with lenvatinib/pembrolizumab for pMMR advanced EC between September 1, 2019 and June 30, 2023, and followed through end of membership, December 31, 2023, or death, whichever occurred first. Patients were grouped based on their initial lenvatinib dose: 20 mg daily (Group 1), <20 mg daily (Group 2), and 20 mg daily 5 of 7 days per week (Group 3). The primary outcome was 6-month progression-free survival (PFS); secondary outcomes included incidence rate of lenvatinib dose discontinuation or dose reduction due to AE. Primary analysis of outcomes was performed between Groups 1 and 2; Group 3 was described but not compared to other groups due to small sample size. Results: A total of 369 patients were included in this study (Group 1, n=204; Group 2, n=154; Group 3, n=11). Baseline characteristics were similar between all three groups with mean age of 66.6 ± 9 years; mean body mass index of 29.6 ± 8 kg/m2; and median number of prior lines of systemic therapy of 1 (IQR 1-2). There was no difference in PFS at 6 months between Groups 1 and 2 (40.2% and 33.8%, respectively; p=0.26). There was no difference between Groups 1 and 2 in the rate of lenvatinib discontinuation due to AE (7.2 and 6.6, respectively, per 100 person-year; p=0.61). However, a significantly higher incidence in dose reduction was found in Group 1 when compared to Group 2 (28.1 vs 14.3 per 100 person-year; p<0.01). Conclusions: A lower lenvatinib starting dose (<20 mg daily) in combination with pembrolizumab was no different to the FDA-approved daily dose of 20 mg for the treatment of advanced EC with respect to 6-month PFS. In addition, those who received a lower starting dose experienced fewer dose reductions but no difference in dose discontinuation due to AE. Prospective studies of dose and schedule are needed to confirm these findings and define an optimal dosing strategy.
Germline genetic profiles of women with uterine cancer: A Myriad Collaborative Research Registry study.
Authors: Johnson Caitlin Ruth , Aryasomayajula Chinmayi , Francoeur Alex Andrea , Stewart Chelsea , Kapp Daniel Stuart , Chan John K 
Published: June 2024

5617 Background: To compare uterine cancer patient characteristics and genetic mutational profiles by age and self-identified ancestry. Methods: Data on uterine cancer patients who had germline, MyChoice, and/or Precise testing were collected from the Myriad Collaborative Research Registry. Mutations in genes of interest were obtained from TAPUR studies currently under enrollment. Graph Pad Prism v 10.1.1 was utilized for statistical calculations. Results: Of the 38,133 uterine cancer patients, 42.8% were diagnosed at <50 years (younger) and 57.2% at ≥50 years (older). Approximately, 77.1% identified as Non-Hispanic White (NHW), 7.0% as Non-Hispanic Black (NHB), 2.2% as Hispanic, and 3.7% as Non-Hispanic Asian/Pacific Islander (NHAPI). Approximately 29.1% patients had germline Lynch gene mutations with 16.5%, 28.8%, 36.1%, and 18.4% occurring in MLH1, MSH2, MSH6, and PMS2, respectively (p<0.001). Younger patients were more likely to have Lynch syndrome (9.6% vs 7.5%; p<0.001) and MLH1 (1.2% vs 0.8%; p<0.001) or MSH2 (3.1% vs 1.5%; p<0.0001) mutations compared to older patients. Regarding race, MLH1 mutations were found in 5.2% of NHW and NHAPI, 4.9% of Hispanics, and 2.2% of NHB (p<0.001). MSH2 mutations were most common among NHAPI (9.8%) and NHW (9.7%) followed by Hispanics (5.8%) and NHB (3.2%; p<0.001). MSH6 mutations were most common in NHW (12.8%) vs Hispanics (6.5%), NHAPI (6.3%), or NHB (4.5%; p<0.001). PMS2 mutations were highest among NHW (5.8%) followed by Hispanics (4.7%), NHAPI (4.4%), and NHB (2.9%; p=0.004). There were no differences in TMB (p=0.07), PDL1 (p=0.16), or MSI status (p=0.13) by age; however, younger patients had more HRD positivity (37.8% vs 30.9%; p<0.0001) vs the older group. Regarding race, 50.0% of NHAPI, 36.9% of NHW, 30.8% of Hispanic, and 11.6% of NHB patients had high TMB (p=0.004). There were no significant differences in tumor HRD status (p=0.3), MSI status (p=0.3), or PDL1 positivity (p=0.4) by racial group. Additionally, 6.8%, 6.6%, 6.3%, and 4.4% of Hispanics, NHW, NHAPI, and NHB were BRCA positive. BRCA2 mutations were more present among Hispanics (4.2%) vs NHW (3.7%), NHAPI (3.4%), and NHB (2.3%; p=0.02). There were no differences in BRCA1 (p=0.3) or PTEN (p=0.8) mutations by racial group. Hispanic patients had the most germline p53 mutations (2.0%) followed by NHAPI (1.5%), NHW (1.4%), and NHB patients (0.7%; p=0.01). PDL-1 inhibitors may be useful among NHB based on germline POLE mutations (4.3%) vs NHW (1.2%), Hispanic (1.1%), and NHAPI patients (0.8%; p<0.001). Conclusions: There are significant differences in germline testing results for women with uterine cancer by race/ethnicity and age, especially in Lynch genes which has implications for immunotherapy eligibility in the advanced and recurrent setting. Further work must be done to identify targetable mutations in minority populations.
Safety and efficacy profile of belzutifan, a hypoxia-inducible factor-2α inhibitor, in patients with renal cell carcinoma: Meta-analysis and systematic review.
Authors: Shafique Nouman , Javeed Zainab , Bajwa Shammas , Ghaffar Umar , Muhibullah - , Ahmed Jawad , Zain Sarmad , Kaur Navneet , Ghaffar Ali , Kunwar Digbijay , Farooqui Sabeeh , Iqbal Abdul Ghani , Naqvi Syed Mujtaba Ali , Qadeer Abdul , Ehsan Amna , Shafiq Iqra , Shafique Adeena , Rizwan Umer , Hussain Rida , Lohana Abhi 
Published: June 2024

e16531 Background: Hypoxia-inducible Factor-2α (HIF-2α) is a transcription factor that accumulates in clear cell renal cell carcinoma (ccRCC) and is responsible for genes involved in oncogenesis. Belzutifan is a HIF-2α inhibitor that has shown promising anti-tumor effects in patients with ccRCC. Our objective is to summarize the available literature on the safety and efficacy profile of the drug. Methods: An electronic search was conducted on PubMed, Embase, and Cochrane from inception till January 31st, 2024. We identified patients aged ≥ 18 years with ccRCC who received Belzutifan. We extracted data on objective response rate, complete response rate, any grade adverse effect (AE) and grade ≥3 AE. Data was analyzed using R (v.4.3) and reported as proportions with respective 95% confidence intervals (CI) on forest plots. Results: Three studies (n=168 patients) were identified that reported the use of Belzutifan in ccRCC. Our analysis showed that pooled proportion of objective response rate and complete response rate was 35% (95% CI: 24% – 47%) and 1% (95% CI: 0% – 5%) respectively. Pooled proportion of patients experiencing any grade AE and grade ≥3 AE was 98% (95% CI: 95% – 99%) and 49% (95% CI: 29% – 69%) respectively. Conclusions: Belzutifan is a novel drug that inhibits HIF-2α which in turn results in anti-tumor effects of the drug against ccRCC. The drug has an acceptable safety and efficacy profile from limited data but more studies are needed to establish a complete picture of drug’s adverse effects and clinical benefits. Pooled proportion of patients developing (A) Objective Response, (B) Complete response (C) Any adverse effect and (D) Grade ≥3 adverse effects. [Table: see text]
Association of body mass index (BMI) with survival outcomes in patients with metastatic renal cell carcinoma (mRCC).
Authors: Goswamy Rohit Vivek , Yildirim Ahmet , Choi Yujin , Wei Mengting , Liu Yuan , Brown Jacqueline T , Nazha Bassel , Martini Dylan J. , Hartman Caitlin , McClintock Greta Russler , Zhuang Tony , Kissick Haydn , Harris Wayne Bernard , Carthon Bradley Curtis , Kucuk Omer , Master Viraj A. , Bilen Mehmet Asim 
Published: June 2024

e16535 Background: Recent data have reported on obesity as a probable protective factor in metastatic RCC (mRCC). Current knowledge and expanding data suggests a higher BMI (overweight and obese patients) have better survival outcomes. We hypothesize that mRCC patients studied at our institution, Emory’s Winship Cancer Institute, will display similar clinical outcome trends. Methods: We conducted a retrospective analysis of patients with mRCC treated at Winship Cancer Institute between 1/1/2018 and 8/31/23. Overall survival (OS) and progression-free survival (PFS) were defined as months from treatment initiation to death or clinical/radiographic progression, respectively. The correlation between BMI and OS/PFS was studied in 399 patients diagnosed with metastatic RCC under systemic therapy. The groups were divided into overweight and obesity (BMI > 25 kg/m2) and underweight or normal (BMI < 25 kg/m2). Univariate (UVA) and multivariate (MVA) analyses were carried out for OS and PFS using Cox proportional hazard model. Results: A total of 401 eligible patients were included with a median follow up of 60 months. Median age was 66 years (range = 18-95), 71% were male, 29% were female, and 81% had clear cell histology. 36% received checkpoint inhibitor (CPI) monotherapy, 28% received combination CPI, and 26% received CPI in combination with tyrosine kinase inhibitor (TKI). 4% received other therapies. Lower BMI (<25) at initiation of systemic therapy was significantly associated with worse OS and PFS (table). Conclusions: Lower BMI at baseline and during therapy was associated with worse clinical outcomes. This helps validate the association between obesity and improved survival, a potential "obesity paradox." Results should be validated in a larger, prospective study to further understand the complex relationship between BMI, lipid metabolism, and clinical outcomes in mRCC. [Table: see text]
Incidence and outcomes of thromboembolic events in renal cancer related hospitalization in the United States: A propensity matched national study.
Authors: Sultan Muhammad , Kumar Manoj , Farooq Faryal , Afzal Muhammad Sohaib , Nasir Bilal , Byreddi Laxman Yashwant , Atluri Sundeep , Devarkonda Vishal , Ali Shafaqat 
Published: June 2024

e16544 Background: Venous thromboembolic events (VTE) are a significant cause of morbidity and mortality in cancer patients. We aim to investigate the incidence and outcomes of acute DVT and PE in renal cancer compared to all other malignancies. Methods: The National Readmission Database (2016-2020) was queried to identify all-cause admissions for patients with any active malignancy. Cohorts were divided into renal cancer vs other cancers. A Propensity Score Matching (PSM) model matched both cohorts. Multivariate regression & Mahalanobis distance propensity matching were used to compare incidence rates and outcomes. Results: Among 1.2 million all-cause hospitalizations of patients with renal cancers, about 3.8% suffered an acute VTE. The majority had DVT (1.8%), followed by PE (1.4%) & DVT with PE (0.6%). On a propensity-matched & multivariate analysis, patients with renal cancers have a lower incidence of DVT (2.1% vs 2.8%, aOR: 0.76) & DVT with PE (0.7% vs 1%, aOR: 0.73) [p <0.001] as compared to other malignancies. Interestingly, rates of acute PE are similar to other malignancies (p>0.05). Among VTEs, acute PE was associated with the highest mortality (aOR: 3.17), followed by DVT with PE (aOR: 2.52) & DVT (aOR: 2.15) [p <0.001]. Resource utilization is also higher in renal cancers complicated by VTE, with patients suffering a DVT having the highest LOS (8 vs 3 days) & total cost of hospitalization ($24,403 vs $16,628) [p<0.001] followed by DVT with PE and only PE [p<0.05]. Interestingly, readmission rates are similar in patients with different VTEs (DVT, PE, or DVT with PE, p >0.05). Conclusions: Hospitalizations in renal cancers were less frequently complicated by venous thromboembolism as compared to other malignancies. Mortality was highest for PE while resource utilization was highest for the DVT group.
Kidney outcomes in patients with bladder cancer: Insights from real-world data—A National Inpatient Sample (NIS) study, 2020.
Authors: Tanariyakul Manasawee , Saowapa Sakditad , Polpichai Natchaya , Wannaphut Chalothorn , Yingchoncharoen Pitchaporn , Thongpiya Jerapas , Siladech Pharit , Olavarria Bernal Diego Alonso , Chaisrimaneepan Nattanicha , Dejthevaporn Thitiya Sirisinha , Wattanachayakul Phuuwadith 
Published: June 2024

e16622 Background: Bladder cancer constitutes a notable etiological factor in kidney disease, precipitating acute kidney injuries (AKI) through mechanisms such as post-renal obstruction, with the potential for progression to chronic kidney disease (CKD) over time. The objective of this study is to systematically evaluate the correlation between bladder cancer and the manifestation of acute or chronic kidney disease across various stages, with a focus on hospitalized patients undergoing treatment for bladder cancer. Methods: The 2020 United States National Inpatient Sample (NIS) database was subjected to analysis in this study. We focused on adult patients (≥18 years) with a primary discharge diagnosis of bladder cancer, specifically those who were hospitalized for cancer and presented with a diagnosis of acute kidney injury or diverse stages of chronic kidney disease, as identified through pertinent ICD-10 CM codes. Utilizing survey multivariable logistic and linear regression analysis, we calculated adjusted odds ratios (ORs) to assess the outcomes of interest. A p-value of <0.05 was deemed statistically significant in this analytical framework. Results: In 2020, 81,995 eligible patients were identified, with 75.62% being male. The ethnic distribution was 81% Caucasian, 8% Black, 5% Mexican American, and 2% Asian. Using a multivariable regression model adjusting for patient and hospital-level factors, bladder cancer showed a significant association with acute kidney injury (OR 1.92, 95% CI: 1.85-2.00, P < 0.001) and all stages of chronic kidney disease (OR 1.66, 95% CI: 1.58-1.74, P < 0.001). Further analysis revealed no significant association with early CKD stages 1 and 2 (P = 0.25 and 0.26), but a notable association with increased risk for CKD stages 3 and 4 (OR 1.45, 95% CI: 1.37-1.52, P < 0.001) and (OR 1.69, 95% CI: 1.56-1.83, P < 0.001), respectively. Intriguingly, bladder cancer displayed a negative association with CKD stage 5 (OR 0.76, 95% CI: 0.63-0.78, P < 0.001). Conclusions: In summary, our study reveals that bladder cancer in hospitalized cancer patients is linked to increased risks of acute kidney injury (AKI), CKD stages 3 and 4, and a decreased risk of CKD stage 5. Vigilant kidney function monitoring is crucial during cancer hospitalization, given the elevated risk of worsening function. Proactive interventions are necessary to address kidney-related complications. Further longitudinal cohort studies are warranted to enhance our understanding and devise strategies to reduce the risk of CKD in individuals with bladder cancer.