bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline modified Glasgow prognostic score (mGPS) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI).
Authors: Brown Jacqueline T , Liu Yuan , Martini Dylan J. , Shabto Julie M. , Russler Greta , Caulfield Sarah , Yantorni Lauren Beth , Joshi Shreyas S. , Kissick Haydn , Ogan Kenneth , Nazha Bassel , Carthon Bradley Curtis , Kucuk Omer , Harris Wayne , Master Viraj A. , Bilen Mehmet Asim 
Published: June 2021

e16546 Background: The IMDC and MSKCC risk models for mRCC were validated before the era of ICI. The mGPS incorporates albumin and C-reactive protein and reflects systemic inflammation. mGPS may be a useful prognostic biomarker of particular relevance in mRCC given the current, largely ICI-based treatment paradigm and hypothesis that systemic inflammation may contribute to ICI resistance. Methods: We retrospectively assessed mRCC patients treated with ICI (including anti-PD-1 and anti-PD-L1 agents) in any line of therapy at Winship Cancer Institute of Emory University from 2015-2018. Primary outcomes assessed included overall survival (OS) and progression-free survival (PFS). mGPS was calculated by giving 1 point for CRP > 10 mg/L and/or albumin < 3.5 g/dL with 0 points awarded for solitary low albumin. The relationship between mGPS and survival outcomes was assessed in UVA and MVA using Cox proportional hazard model and in Kaplan-Meier analysis. Results: We assessed 156 eligible patients. Median follow up was 24.2 months. Median age was 64 years, 69% were male, 20% were Black, and 78% had clear cell histology. 57.1% received anti-PD-1 monotherapy whereas all others received dual ICI or ICI combined with an antiangiogenic agent or experimental therapy in trial. Higher baseline mGPS was significantly associated with worse OS and PFS (Table). The median OS of patients with baseline mGPS of 0, 1 and 2 was 44.5 (CI 27.3, NA), 15.3 (CI 11, 24.2) and 10 (CI 4.6, 17.5) months, respectively (p<0.0001), while the median PFS of these three cohorts was 6.7 (CI 3.6, 13.1), 4.2 (CI 2.9, 6.2) and 2.6 (CI 2, 5.6) months, respectively (p=0.0216). Conclusions: A higher mGPS at the start of therapy was negatively prognostic in patients with mRCC receiving ICI. These results should be validated in a larger, prospective study. [Table: see text]
TIVO-3: Age-related tolerability outcomes of tivozanib versus sorafenib in metastatic relapsed or refractory renal cell carcinoma, a subgroup analysis of the TIVO-3 clinical trial.
Authors: Escudier Bernard , Rini Brian I. , Pal Sumanta K. , McDermott David F. , Porta Camillo , Verzoni Elena , Atkins Michael B. , Needle Michael N. , Hutson Thomas E. 
Published: June 2021

e16553 Background: Tivozanib (TIVO) is a potent and selective VEGF receptor (R) tyrosine kinase inhibitor with a long half-life designed to optimize the VEGF blockade while minimizing off-target toxicities. The TIVO-3 trial demonstrated improved progression-free survival (PFS) when compared to sorafenib (SOR; 5.6 mo. vs 3.9 mo., respectively) with a hazard ratio (HR) of 0.73. TIVO showed better tolerability with reduced need for dose interruptions (p = 0.0164) and dose reductions (p = 0.0147) as compared to SOR. Methods: Data was analyzed to identify relationships between and age or prior use of immune checkpoint inhibitors (CPI). Results: Of the 343 patients treated on study, 120 (35%) were between age 65 and 75 and 34 (10%) were over 75. Adverse events were less frequent for TIVO compared to SOR in all age groups and drug exposure was consistently greater in the TIVO arm. Of particular interest, the tolerability advantages noted in the total population are also observed in the patients 75 and over with almost half the rate of the adverse drug reactions leading to dose reduction or discontinuation compared to SOR. Patients treated with prior CPI had an increased need for dose adjustment, but dose adjustments were less common with TIVO than SOR in CPI exposed and naïve patients. Conclusions: Tivozanib was better tolerated than sorafenib regardless of age or prior CPI treatment. Dose adjustments and interruptions are more common after prior CPI. Clinical trial information: NCT02627963. [Table: see text]
Clinicopathologic features of Xp11.2 translocation renal cell carcinoma and its response to target therapy.
Authors: Yan Xieqiao , Chi Zhihong , Si Lu , Cui Chuanliang , Kong Yan , Tang Bixia , Mao Lili , Wang Xuan , Lian Bin , Li Siming , Bai Xue , Zhou Li , Dai Jie , Sheng Xinan , Guo Jun 
Published: June 2021

e16559 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 translocation RCC was found in 41 cases. The median PFS and Median OS was 6.3 months (4.4 - 8.8) and 17.3 months (12.4 - 21.8) for the whole cohort, respectively. First-line treatment mainly included sunitinib (n = 12), sorafenib (n = 13), axitinib (n = 6), and pazopanib (n = 4), and the median PFS of these regimens was 5.4 months, 5.1 months, 9.4 months, 8.3 months, respectively. Twenty-three patients received subsequent therapies, the median PFS and the median OS was 4.3 months and 12 months for the second-line therapy(n = 21), 4.3 months and 14.1 months for the third-line therapy(n = 11), 2.4 months and 9.6 months for the fourth-line therapy(n = 6). Conclusions: Metastatic Xp11.2 translocation RCC is an aggressive disease. Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) agents appeared to demonstrate some efficacy, the combination of VEGFR-TKI and immune checkpoint inhibitor (ICI) might be a useful tool for the treatment of metastatic Xp11.2 translocation RCC.
Prostate-specific antigen testing in the disabled population: A cross-sectional analysis of the Health Information National Trends Survey (HINTS).
Authors: Leong Joon Yau , Pinkhasov Ruben , Chandrasekar Thenappan , Shapiro Oleg , Daneshvar Michael , Sanford Thomas , Bratslavsky Gennady , Goldberg Hanan 
Published: June 2021

e17000 Background: Disabled patients are a unique minority population that may have lower literacy levels and difficulty communicating with physicians. Furthermore, their knowledge for cancer prevention recommendations is unknown. Herein, we aim to compare prostate-specific antigen (PSA) testing rates and associated predictors among disabled men and non-disabled men in the USA. Methods: We performed a cross-sectional study utilizing the Health Information National Trends Survey (HINTS) to analyze factors predicting PSA testing rates in men with disabilities (disabled, deaf, blind). Multivariable logistic regression models were used to determine clinically significant predictors of PSA testing in men with disabilities compared to that of the healthy cohort. Results: A total of 782 (14.6%) disabled men were compared to 4,569 (85.4%) non-disabled men. Disabled men were older with a mean age of 65.0 ± 14.2 vs. 55.0 ± 15.9 years (p < 0.001). On multivariable analysis, after adjusting for all available confounders including race, age, geographical region, survey year, marital status, health insurance, healthcare provider, amongst others, men with any disability were less likely to undergo PSA screening (OR 0.772, 95% CI 0.623-0.956, p = 0.018). Variables associated with increased PSA screening rates included age, having a healthcare provider or health insurance, and living with a partner. Although prostate cancer detection rates were shown to be higher among disabled men, this did not reach statistical significance. Conclusions: Our data suggests that significant inequalities in PSA screening exist among men with disabilities in the USA, with disabled men, especially the deaf and the blind, being less likely to be offered PSA screening. There is a clear need to implement strategies to reduce existing gaps in the care of disabled men and strive to reach equality in PSA screening in this unique population.
Sub-centimeter lymphadenopathy in germ cell testicular cancer: An ongoing surveillance challenge.
Authors: Kieran Ruth , Browne Iseult , McCaffrey John 
Published: June 2021

e17011 Background: Correct identification of retroperitoneal disease is essential for proper staging and management in germ cell tumors. A size threshold of a 10mm diameter has high specificity in assessing nodal metastases, but sensitivity can be poor at this level and many patients have sub-centimeter lymphadenopathy on post-orchidectomy staging. As many staging scans are done soon after surgery, these may represent reactive lymph nodes. We aimed to assess the prevalence of sub-centimeter lymphadenopathy on baseline imaging in our patients, and its association with recurrence. Methods: Records of patients diagnosed with testicular germ cell cancer in a tertiary cancer center (n = 55, 2015-2020) were reviewed (median followup of 26 months, range 1-59). Lymphadenopathy size measurements were taken from the scan report, which had been authorized by a radiology consultant. Results: Patients had a median age of 34 (range 19-63). 37 (67%) had pure seminomas, 2 (4%) pure embryonal tumors, 12 (22%) mixed tumors with a primarily (> 50%) embryonal component, and 4 (7%) other mixed types. 48 (87%) had stage 1 disease, 3 (6%) stage 2 and 4 (7%) stage 3 disease. 26 (47%) had CT staging preoperatively, of the remainder 69% (n = 20) were staged in the first 48 postoperative hours. 28 (51%) had no lymphadenopathy, 15 (27%) had sub-centimeter lymphadenopathy within the landing zone, 8 (15%) had lymphadenopathy measuring > 1 cm within the landing zone, 4 (7%) had lymphadenopathy elsewhere. 7 had immediate chemotherapy, 48 entered surveillance. For the 14 with sub-centimeter lymphadenopathy within the landing zone who did not have immediate chemotherapy, 3 regressed, 8 were stable. 2 underwent a PET for further assessment, 1 a biopsy. 3 increased in size. 6 patients on surveillance had a recurrence – of these 2 had seminomas with no baseline lymphadenopathy, 4 had mixed primarily embryonal tumors (3 with sub-centimeter lymphadenopathy (0.6, 0.7 and 0.9 cm each), one with a 1.3cm para-aortic lymph node). Of those 4, only 1 had significantly elevated HCG pre-operatively, all recurred in the sites of previously noted lymphadenopathy. Those with mixed, primarily embryonal disease with lymphadenopathy (representing 50% of such patients on surveillance) had a higher recurrence risk than other patients on surveillance (OR: 153, 95% CI 6-3709, p= 0.002) Those undergoing preoperative/delayed postoperative imaging (n = 28) were equally likely to have lymphadenopathy to those having imaging in the first 7 postoperative days ( X2 (3, N= 27) = 2.9, p= 0.4). 1 patient had died (unrelated causes), all others were disease-free at most recent followup. Conclusions: Sub-centimeter lymphadenopathy is more likely to be benign in those with seminomas, but even small volume lymphadenopathy in those with mixed tumors with a primarily embryonal component may represent metastatic disease, and should be monitored closely.
PTEN loss as a potential biomarker in patients with castration resistant prostate cancer M0.
Authors: Puente Javier , Castro Elena , Sánchez García María , Vidal Natalia , Moreno Jesús , Hernández David , Senovilla Jose Luis , Herrera Bernardo , Montesa Alvaro , Carles Joan , Planas Jacques , Alonso Gordoa Teresa , Vazquez-Estevez Sergio , Álvarez Sara , Casas Francisco Javier , Paz Cabezas Mateo , de Torres Ines , Olmos David 
Published: June 2021

e17043 Background: Until 2018, there were no approved agents for high risk non-metastatic castration-resistant prostate cancer (nmCRPC). Recently, three second-generation anti-androgens (apalutamide, enzalutamide and darolutamide), in combination with ADT, have demonstrated a significant benefit in metastasis-free survival (MFS) and overall survival.According to conventional imaging, nmCRPC state is the opposite to mCRPC. Nevertheless, CRPC is a continuous in which nmCRPC may share similar biology and biomarkers such as PTEN loss, which has proven to be a useful and targetable biomarker in mCRPC. Methods: We performed a prospective and multicenter analysis of 77 patients (pts) with nmCRPC. We collected blood samples as well as prostate cancer diagnostic biopsy whenever they were available. The aim of this study is to find potential biomarkers that could identify pts at a higher risk of metastasis development. Here we report preliminary results according to PTEN status. Results: We have analyzed 32 patients for PTEN loss. We report preliminary results using an IHC assay based on the IPATENTIAL150 PTEN score. Median age was 66 years and 50% of patients had a Gleason score > 8 irrespectively of PTEN status. We identified 24 patients (75%) with PTEN loss with a median PSA at diagnosis of 13,1 ng/ml, and a PSA doubling time (PSA-DT) of 6,3 months vs. 37,35 ng/ml and 3,5 months respectively in the PTEN non-loss pts. In the PTEN loss population, 9 pts (37,5%) did not receive any local treatment vs. 2 pts in the PTEN non-loss (25%). Mediantime from diagnosis to CRPC was 11.5 vs 8.0 yrs in PTEN loss vs. non-loss pts. In the PTEN loss population 2 patients received apalutamide plus ADT and 2 darolutamide plus ADT, these patients were excluded for the MFS analysis. Median MFS was 37 months in the PTEN loss population vs. 23 months in the PTEN non-loss. However, with a median follow-up of 38 months, 54% of PTEN loss pts had developed metastasis and 50% of PTEN non-loss pts. Skeleton was by far the first site of metastasis in PTEN non-loss pts (75%), while PTEN loss pts developed metastasis in lymph nodes (38,5%) nearly as much as in the skeleton (46%). Conclusions: To our knowledge, this is the first data of PTEN loss as a biomarker in nmCRPC. In our study, PTEN loss in primary tumor is more frequent than previously documented for mCRPC. PTEN loss appears to provide a better prognosis and higher lymph node involvement. Further analysis will be performed to corroborate these results and identify other factors involved.
Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.
Authors: Kaur Anahat , Wang Shuai , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek 
Published: June 2021

e17502 Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]
Global line-1 hypomethylation as novel biomarker for cervical cancer in Nigerian women living with HIV.
Authors: Zheng Yinan , Musa Jonah , Joyce Brian Thomas , Wang Jun , Gursel Demirkan , Silas Olugbenga A. , Abdulkareem Fatimah Biade , Imade Godwin , Akanmu Alani , Wei Jian-Jun , Kocherginsky Masha , Kim Kwnag-Youn , Wehbe Firas Hazem , Achenbach Chad , Anorlu Rose , Simon Melissa A. , Sagay Atiene , Ogunsola Folasade , Murphy Robert , Hou Lifang 
Published: June 2021

e17513 Background: Nigeria faces a high health burden of cervical cancer (CC), which is worsened by high prevalence of human immunodeficiency virus (HIV) infection. Repetitive elements (RE) are DNA sequences that occur in multiple copies throughout the human genome. HIV infection can lead to RE hypomethylation that causes genome instability, an event often seen in the early phase of tumorigenesis. We aim to examine global RE hypomethylation as a novel epigenetic biomarker for CC among HIV-positive women in Nigeria. Methods: This study involved three groups of women: a) HIV-positive with CC (n=39); b) HIV-positive and cancer-free (n=52); and c) HIV-negative with CC (n=23). We estimated three types of global RE methylation in cervical tissue using genome-wide methylation data: long interspersed nuclear elements (LINE-1), Alu, and human endogenous retrovirus (HERV). We used multiple linear regression adjusting for age, education, parity, employment, cancer stage, body mass index, and sample batch to compare the biomarkers across the HIV/ICC groups and paired t-test to compare 26 pairs of tumor vs. surrounding normal tissues, stratified by HIV status. Receiver operating characteristic curve (ROC) and area under the ROC (AUC) were used to examine the diagnostic value. Results: Among HIV-positive women, all 3 global RE methylation biomarkers were hypomethylated in CC compared to cancer-free (LINE-1: mean difference [MD]=-0.049, p-value=2.9e-8; Alu: MD=-0.011, p-value=2.0e-4; HERV: MD=-0.013, p-value=1.7e-6). Paired analyses showed a larger, more significant MD in HIV-positive stratum than HIV-negative, especially LINE-1 (MD=-0.048 vs. -0.020, p-value=0.004 vs. 0.254). LINE-1 achieved the highest AUC (0.85, 95% CI: 0.76-0.95) in distinguishing tumor tissue from normal tissue among HIV-positive women, followed by HERV (0.82, 95% CI: 0.73-0.92) and Alu (0.60, 95% CI: 0.47-0.72). Conclusions: Global LINE-1 hypomethylation may serve as a novel biomarker for CC screening and early detection for women living with HIV in low- and middle-income countries.
L-MOCA: An open-label study of olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer.
Authors: Gao Qing-lei , Zhu Jianqing , Zhao Weidong , Huang Yi , An Ruifang , Zheng Hong , Qu Pengpeng , Wang Li , Zhou Qi , Wang Danbo , Lou Ge , Wang Jing , Low John , Kong Beihua , Yin Rutie , Xie Xing , Liu Jihong , Sun Wei , Zang Rongyu , Ma Ding 
Published: June 2021

e17526 Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the poly (ADP-ribose) polymerase inhibitor (PARPi) olaparib, significantly improves progression-free survival (PFS) versus placebo. This is the first study to evaluate the efficacy and tolerability of the olaparib (Lynparza), an oral PARPi, in patients with platinum-sensitive relapsed (PSR) ovarian cancer, carried out exclusively in Asia. Methods: In this open-label, single arm trial, patients with PSR high grade epithelial ovarian cancer who had received ≥2 previous lines of platinum-based chemotherapy with a response, were enrolled from 28 centres in China and Malaysia. All patients received oral olaparib (300 mg) tablet twice daily until disease progression or unacceptable toxicity. The primary endpoint was PFS assessed by investigator according to RECIST 1.1 criteria. Secondary endpoints included time to TFST, PFS2, TSST, OS, and safety endpoints included adverse events (AEs). Subgroup analysis of PFS was examined by BRCA status. Data were summarized by descriptive statistics; time-to-event endpoints were analyzed using Kaplan-Meier method. Primary analysis was performed when 60% of PFS events had been achieved. Results: Between 2018 and 2020, the 224 patients recruited into this study received oral olaparib (full analysis set). 224 patients (91.5% from China and 8.5% from Malaysia) provided BRCA mutation status by blood and tissue testing. 47.3% patients were BRCAm, 41.1% patients were gBRCAm,52.2% patients were BRCAwt and 0.4% patients were BRCA unknown. 35.7% patients had received ＞2 lines of chemotherapy. At data cut-off (Dec 25th, 2020), 139 patients had disease progression; median PFS (mPFS) was 16.1 (95% CI 13.3-18.3) m in all patients. The mPFS was 21.2m, 21.4m and 11.0m in BRCAm, gBRCA and BRCAwt subgroups, respectively. The overall incidence of any AE and SAE was 99.1% and 25.4%, respectively. There were 9.4% patients who discontinued therapy due to the treatment related AE. The most common AEs were anemia, nausea and vomiting. Conclusions: The L-MOCA study demonstrates olaparib maintenance treatment is effective and well tolerated in Asian PSR ovarian cancer patients regardless of BRCA status. Clinical trial information: NCT03534453. [Table: see text]