bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.
Authors: Sridharan Vishwajith , Mino-Kenudson Mari , Cleary James M. , Rahma Osama E. , Perez Kimberly , Clark Jeffrey William , Rubinson Douglas Adam , Goyal Lipika , Bazerbachi Fateh , Qadan Motaz , Parikh Aparna Raj , Ferrone Cristina R. , Casey Brenna , Fernandez Del-Castillo Carlos , Ryan David P. , Lillemoe Keith , Warshaw Andrew Louis , Krishnan Kumar , Hernandez-Barco Yasmin 
Published: June 2021

e16253 Background: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. Methods: This is a retrospective study conducted at a large healthcare system from 1996-2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. Results: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery conferred OS benefit in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy provided OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). Conclusions: Pancreatic ACC patients often present with advanced disease. Surgery confers survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.
Impact of time to treatment initiation on real-world (RW) outcomes in metastatic pancreatic cancer (mPC) in the United States.
Authors: Gbolahan Olumide B. , Outlaw Darryl Alan , Hashemi Neda , Paluri Ravi Kumar , Williams Grant Richard 
Published: June 2021

e16254 Background: The COVID-19 pandemic caused disruptions in cancer care delivery and forced oncologists to make recommendations about safely delaying initiation of cancer therapy. Compared to the adjuvant, curative setting, there is a scarcity of information about the impact of time to treatment initiation on outcomes in the palliative setting for gastrointestinal malignancies. We sought to determine the median time to initiation of systemic therapy (TIT) in mPC in the US pre-pandemic, and to assess the impact of TIT on survival outcomes. Methods: We retrospectively analyzed de-identified data of patients with mPC in the Flatiron Health nationwide EHR-derived database. Metastatic diagnosis dates between 01/2014 and 04/2020 were included. Demographics, treatments, and outcomes were collected. TIT was defined as period between diagnosis and initiation of first-line systemic therapy and was split into 3 categories (I: < 2 weeks, II: 2- <4 weeks, and III: 4-8 weeks). Overall survival (OS) was defined from time of diagnosis to time of death. Post-chemotherapy survival (PCS) was time from initiation of first-line therapy to death. Adjusted and unadjusted multinomial logistic regression were used to evaluate the association of demographics and clinical factors with TIT. PCS and OS were estimated with Kaplan-Meier curves. Adjusted (demographics and clinical factors) Cox proportional hazard models were used to estimate the effect of TIT groups on PCS and OS. Category II served as control group. Results: 3231 patients with mPC who received at least one line of treatment were identified. 29% (N= 947), 43% (N=1375), and 28% (N= 909) were in TIT categories I-III respectively. The mean age at diagnosis was 67.4 years, with no significant difference in age (P=0.14) among categories. Median TIT was 20 days. Multinomial logistic regression showed that compared to TIT II, Black patients were less likely than White patients to receive chemotherapy in less than 2 weeks (P=0.02), and those who had recurrent disease were more likely to receive therapy in less than 2 weeks (P< 0.0001). There was no significant difference in median RW OS among the groups (I: 8.13, II: 8.07, III: 9.02 months, P=0.0532). RW PCS was also similar across categories (I: 7.8, II: 7.5, III: 7.8 months, P=0.88). Adjusted cox regression analysis suggests that compared to TIT of 2-4 weeks, TIT 4-8 weeks was associated with higher RW OS (HR, 0.88, 95% CI 0.8-0.97, P=0.009), but not RW PCS (HR, 0.95, 95% CI 0.87-1.05, P=0.32). Conclusions: This real-world analysis suggests that pre-pandemic, most patients with mPC who receive 1st line therapy were treated within 4 weeks of diagnosis. Compared to TIT of 2-4 weeks, TIT 4-8 weeks was associated with higher RW OS in mPC, although the clinical significance is minimal. In crisis situations, efforts to clinically optimize patients with mPC before systemic therapy should continue to be pursued.
Is first-line immune checkpoint inhibitors (ICI) beneficial to platinum-eligible patients (pts) with advanced urothelial carcinoma (aUC)? a meta-analysis.
Authors: Cheng Ce , Chineke Iloabueke Gabriel , McBride Ali , Chipollini Juan , Gelmann Edward Paul , Recio-Boiles Alejandro 
Published: June 2021

e16506 Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I2= 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I2= 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I2= 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I2= 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I2= 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I2= 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I2= 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I2= 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I2= 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I2= 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I2= 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.
Patient outcomes following disease progression with enfortumab-vedotin (EV) in metastatic urothelial carcinoma (mUC).
Authors: Khan Mohammed Ateeb , Szabados Bernadett , Choy Julia , Jackson-Spence Francesca , Powles Thomas , Castellano Daniel , Valderrama Begoña P. 
Published: June 2021

e16516 Background: Enfortumab Vedotin (EV) is an antibody drug conjugate (ADC), licensed for use in metastatic urothelial carcinoma (mUC), following disease progression with platinum-based chemotherapy (ChT) and immune checkpoint inhibitors (ICIs). A patient cohort now exists with disease progression following EV with no guidance for subsequent treatment. This retrospective observational study assessed patient outcomes post EV progression. Methods: Patients were identified from 3 centres in Europe (St Bartholomew’s Hospital, University Hospital Virgen Del Rocio and Hospital Universitario 12 de Octubre). Data was collected regarding treatments prior to and post EV, length of EV treatment and overall survival (OS) post EV progression. Descriptive statistics and survival analyses comparing survival outcomes stratified by treatment post EV progression were performed in SPSS (Version 27). Results: All 24 patients had received both an ICI and ChT prior to receiving EV. 10 patients received further treatment following disease progression on EV. 8 patients received ChT (6 patients platinum based, 1 patient paclitaxel, 1 patient vinflunine), 1 patient received radical radiotherapy and 1 patient received derazantinib. No patient received further ICI therapy post EV progression. 2 patients had achieved complete radiological response with EV and had no evidence of disease progression. Point bi-serial correlation showed no significant association between length of EV treatment and receiving further treatment post disease progression on EV. There was also no significant association between pre EV survival length and further treatment post disease progression on EV. Survival analysis (Kaplain-Meier, Mantel-Cox Log Rank) revealed a statistically significant difference in mean OS. Mean OS was 1 month in patients who received no further treatment vs 7 months in patients who received treatment post progression on EV (Chi-Square 16.569, p = 0.000). Conclusions: Less than half of patients who progressed on EV received subsequent treatment. Patients who did receive treatment had significantly increased OS. There is a clear gap in literature and evidence-based guidance for treatment following EV progression and further studies are required with larger samples accounting for confounding factors to further evaluate best practise post disease progression on EV.
Meta analysis of arsenic exposed genes expression profiles to develop a bladder cancer predictor.
Authors: Singhal Sonalika , Ruprecht Nathan A. , Sens Donald , Sens Mary Ann , Singhal Sandeep K. 
Published: June 2021

e16523 Background: IARC classified arsenic (As) as “carcinogenic to humans”, but despite the health consequences, there is no molecular signature available yet to predict when exposure may lead to the disease development. First aim of this study is to investigate the genetic changes due to the exposure to carcinogenic compounds such as As. Secondly, how accurately we can predict the disease association when exposed to toxic compounds. Methods: The entire analysis was performed in-silico fashion and data was collected from the public resources such as NCBI database. Two Asian population datasets exposed As were used to find significantly differently express genes. In addition, four cancer cell lines with exposure of As compounds were used to identify the association with cancer. The human bladder cancer biopsy datasets were used to develop a risk predictive model. As per the requirements, numerous machine learning (ML) approaches such as random forest, hierarchical clustering, were used to find the classification and association between the samples and outcome. Statistical approaches such as T-Test, and ANOVA, applied to find the differentially expressed genes associated with different conditions and logistic regression models applied to develop risk prediction models. Results: We identified a set of 1183 genes which were common between both the populations and were significantly changed in humans exposed to As. A subset of 157 genes associated with As exposure and involved in cancer progression was selected for risk prediction model development. A set of four genes (NKIRAS2, AKTIP, HLA-DQA1 and TBC1D7) shows the highest prediction ability of primary bladder tumor with AUC 0.96 (95% CI: 0.82- 0.99) and reproducibility of 0.75 (0.34-0.93) when applied on different dataset. Conclusions: This study identified a list of genes and bladder cancer predictive models that would be very helpful to forecast the outcomes of As exposed in humans.
Tolerability of axitinib in advanced renal cell carcinoma: A meta-analysis.
Authors: Chaudhry Bareia , Wu Shenhong 
Published: June 2021

e16536 Background: Axitinib has been used extensively as a single agent or in combination with immunotherapy in the treatment of advanced renal cell carcinoma. It can be often discontinued due to adverse events. A meta-analysis of clinical trials was performed to evaluate the overall tolerability of axitinib in this setting. Methods: PubMed (Up to November 2020) was searched to identify clinical trials of axitinib in advanced or metastatic renal cell carcinoma. Reported data was collected to include axitinib and control discontinuation due to adverse events. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals depending on the heterogeneity of included studies. Results: A total of 11 studies including 4,056 patients (axitinib alone n = 1384, axitinib combination n = 987, control n = 1685) were included for analysis. The summary discontinuation rate for axitinib due to adverse events was 13.4% (95% CI; 11.7-15.2%) with 8.9% (95% CI: 5.3-14.6%) as a single agent and 26.6% (95% CI:17.8 –37.8%) in combination with other agents. In comparison with controls based on randomized controlled studies, axitinib overall has similar discontinuation rate due to adverse events (RR: 1.18, 95% CI: 0.77-1.80). However, there was a significantly higher discontinuation rate with axitinib in combination with other agents including immunotherapeutic agents PD-L1 inhibitors than control treatment (RR: 1.52, 95% CI: 1.24-1.86). Conclusions: The tolerability of axitinib may vary significantly with its use as a single agent or in combination in the treatment of advanced renal cell carcinoma. Further studies are needed to improve its tolerability as a part of combination therapy.
Lenvatinib (LEN) + pembrolizumab (PEMBRO) treatment in patients (pts) with metastatic clear cell renal cell carcinoma (RCC): Final results of a phase 1b/2 trial.
Authors: Lee Chung-Han , Shah Amishi Yogesh , Hsieh James J , Rao Arpit , Pinto Alvaro , Bilen Mehmet Asim , Cohn Allen Lee , DiSimone Christopher , Shaffer David R. , Gironés Sarrió Regina , Gunnestad Ribe Sara , Wu Jane , Schmidt Emmett V. , Kubiak Peter , Okpara Chinyere , Smith Alan D. , Motzer Robert J. 
Published: June 2021

e16542 Background: Immune checkpoint inhibitors (ICIs) are commonly used as first-line treatment for pts with advanced RCC. In the recent phase 3 CLEAR trial, LEN + PEMBRO showed improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) vs sunitinib in first-line treatment of advanced RCC (Motzer R et al. NEJM. 2021). Additional treatment options are needed for pts with disease progression on ICIs. A phase 1b trial of LEN + PEMBRO was performed in multiple tumor types and included an expansion part into a phase 2 cohort of ICI-pretreated, treatment-naïve, or previously treated ICI-naïve pts with metastatic RCC (NCT02501096). We report the final results of the RCC cohort with an extended follow-up. Methods: Eligible pts were ≥18 years old and had measurable disease. Efficacy analyses were conducted by prior therapy grouping. The primary endpoint was ORR at week 24 (ORRwk24) per immune-related (ir) RECIST by investigator assessment. Secondary endpoints included ORR, duration of response (DOR), PFS, OS, and safety. Exploratory endpoints included tumor response assessed per RECIST v1.1 by independent review committee (IRC). Subgroup analyses of the ICI-pretreated group will be included in the poster. Results: The recommended doses determined in phase 1b were LEN 20 mg daily + PEMBRO 200 mg once every 3 weeks (Taylor M et al. JCO. 2020). The study enrolled 145 pts (efficacy analysis, n=143; safety analysis, n=145). At data cutoff (August 18, 2020), the median follow-up time was 19.8 months. The ORRwk24 was 55.8% (95% CI 45.7–65.5) for ICI-pretreated pts (n=104), 72.7% (95% CI 49.8–89.3) for treatment-naïve pts (n=22), and 41.2% (95% CI 18.4–67.1) for previously treated ICI-naïve pts (n=17). The median OS for the previously treated ICI-naïve pts was 30.3 months and was not reached in the other groups. Additional efficacy analyses are shown in the table. Treatment-related adverse events occurred in 99.3% of pts; the most common were fatigue (58.6%), diarrhea (55.2%), and hypertension (40.0%). Most pts (69%) maintained the LEN starting dose or were reduced to LEN 14 mg daily (dose level −1). Conclusions: LEN + PEMBRO demonstrated promising antitumor activity with a manageable safety profile in pts with metastatic RCC, including pts who were ICI-pretreated. Clinical trial information: NCT02501096. [Table: see text]
Clinical outcomes in metastatic renal cell carcinoma (mRCC) treated with combination of nivolumab and cabozantinib (nivo-cabo) in the salvage setting.
Authors: Ravindranathan Deepak , Liu Yuan , Martini Dylan J. , Nazha Bassel , Brown Jacqueline T , Russler Greta , Yantorni Lauren Beth , Caulfield Sarah , Master Viraj A. , Carthon Bradley Curtis , Kucuk Omer , Bilen Mehmet Asim 
Published: June 2021

e16570 Background: The CheckMate 9ER trial showed that the combination of nivolumab and cabozantinib (nivo-cabo) in first line setting for treatment of mRCC was superior to sunitinib in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) and led to its FDA approval. We report outcomes of cohort of patients with mRCC treated with nivo-cabo in the salvage setting. Methods: We retrospectively reviewed 17 patients with mRCC treated at Winship Cancer Institute who progressed through at least one line of prior therapy. These patients were then treated with either sequences: [1] cabozantinib and then add nivolumab upon progression (n = 8) and [2] nivolumab/ipilimumab or nivolumab and then add cabozantinib upon progression (n = 9) with two with nivolumab and ipilimumab. Median PFS and OS rates, and clinical benefit (defined as complete response or partial response, or stable disease) were described. Results: Thirteen patients had clear cell histology and four patients had non-clear cell histology. For sequence [1], the mPFS for cabozantinib alone was 9.9 months and combination of nivolumab added to cabozantinib was 8.9 months. For sequence [2], the mPFS for nivolumab with or without ipilimumab was 5.9 months and combination of cabozantinib added to nivolumab was 10.4 months. The 12-month OS rate was 88% for sequence [1] and 89% for sequence [2]. The 24-month, OS rate was 50% for sequence [1] and 89% for sequence [2]. 5/8 (63%) patients in sequence [1] and 7/9 (78%) patients in sequence [2] had clinical benefit. 3/8 (37.5%) patients in sequence [1] and 2/9 (22%) patients in sequence [2] experienced immune-related adverse effects such as hypothyroidism (grade II for two patients), pneumonitis (grade II), hepatic transaminase elevations (grade II), and pancreatitis (grade III). No patients in sequence [1] needed dose reduction in cabozantinib once nivolumab was added. 3/9 (33%) patients had dose reduction in cabozantinib in sequence [2] due to diarrhea. Conclusions: Nivo-cabo demonstrates activity in the salvage setting but there is still need to understand the optimal sequencing of both agents in the treatment of mRCC. Outcomes from this combination treatment are to be further validated from ongoing phase III trial, PDIGREE (NCT03793166).
Comparative analyses of survival differences in patients with urothelial versus non-urothelial upper tract carcinomas: Results from the National Cancer Database (NCDB).
Authors: Aragon-Ching Jeanny B. , Wang Hongkun 
Published: June 2021

e16582 Background: The true incidence of upper tract cancers in the United States is not well defined, with cancers combined with kidney cancer and ureteral cancers grouped with rare urinary organ cancer. It is estimated to occur at 5% of urothelial carcinomas with a rough estimate of 3750 cases annually. Little data exists for non-urothelial variants of upper tract cancers. Methods: The primary objective of this retrospective review is to evaluate trends and differences between urothelial (UC) versus non-urothelial (nUC) histologies (squamous, sarcomatoid, small cell or neuroendocrine, adenocarcinoma) for upper tract cancers and compare the demographics, disease characteristics, treatment, incidence of stage and survival according to NCDB. Results: Data from diagnosis in year 2004 – 2017 were extracted from the NCDB. A total of 29743 urothelial and 561 non-urothelial cases for upper tract cancers were identified. More men were diagnosed with urothelial carcinoma, UC (62%) and non-urothelial carcinoma, nUC (58%) for non-urothelial carcinoma. The median age was similar for both groups, 73 years (UC) and 72 years (nUC). Majority were Caucasian at 92% (UC) and 91% (nUC) with incidence of 4% in the UC and 6% in the nUC cohorts for African-American patients. Primary surgery with nephroureterectomy occurred more frequently in the UC cohort (85%) compared to the nUC (58%). More patients were diagnosed with stage IV cancer based on the AJCC Clinicopathologic stage grouping in the nUC group (29%) compared to UC at 8.1%, but overall survival was not different for stage IV cancers with median OS of 8.57 mos (CI, 8.05-9.10) for UC vs 7 mos (CI, 5.62 – 9.26) nUC; logrank p = 0.283 although survival was significantly different for earlier stages of Stage 0 & 1 at 80.53 mos UC (CI, 78.13, 83.25) vs 28.98 mos nUC (CI, 20.3, 46.78), p < 0.001; and for stage II & III at median OS of 35.65 mos UC (CI, 33.38, 38.05) vs 15.75 mos nUC (CI, (11.17, 26.87) that is also significantly different though with lesser significance with longer follow-up. Conclusions: Upper tract urothelial cancers compared to non-urothelial cancers have similar poor outcomes upon diagnosis of metastatic disease though outcomes are with urothelial upper tract is better with earlier stage upon diagnosis compared to non-urothelial cancers, highlighting the importance of early diagnosis with perhaps curative intent treatment.