bluuebunny/crossref_metadata_2025_split huggingface dataset:
An internal review of chemotherapy toxicities in patients with pancreatic cancer.
Authors: Shankar Karthik , Huffman Deanna , Peterson Chelsea , Alhamad Khaled , Jayakrishnan Thejus Thayyil , Attah Abraham Attah , Alrifai Nada , Onokwai Nkechi , Cherico Adriani , Asawa Palash , Kancharla Pragnan , Srinivasamaharaj Srividya , Samhouri Yazan , Rizwan Saleha , Monga Dulabh K. 
Published: June 2021

e16258 Background: Cytotoxic chemotherapy remains the standard of care in the treatment of pancreatic ductal adenocarcinoma (PDAC). There is more excitement in the last few years regarding the use of neoadjuvant chemotherapy even when the disease is resectable. In this analysis, we sought to study the different regimens used in our institutions, in regards to setting and toxicity. Methods: We retrospectively reviewed all patients diagnosed with pancreatic adenocarcinoma at Allegheny General Hospital between 2009-2020. Data was extracted from electronic medical records and de-identified. Institutional Review Board approval was obtained. Descriptive analysis was undertaken and multivariate analysis was performed to compare differences in the prevalence of toxicity across the regimens and demographics using Stata version 16. The primary outcome was the rate of toxicity that prompted dose adjustment, stratified by the setting chemotherapy was administered (neoadjuvant, adjuvant, or palliative). Results: Of the 121 patients studied, 88 patients received chemotherapy. Median age was 69 years. 66 patients (55%) were females. 40 patients suffered from adverse effects requiring a dose adjustment. 85% of the adverse effects occurred in Caucasians. 15 out of 37 patients (42.9%) who received Folfirinox, 15 out of 31 patients (48.4%) who received gemcitabine and nab-paclitaxel, 6 out of 10 patients (60.0%) who received gemcitabine and capecitabine, 3 out of 4 patients (75.0%) who received gemcitabine monotherapy required dose adjustment (table). Folfirinox and gemcitabine with nab-paclitaxel were statistically compared and found to be not significant (p-value=0.12). No significant impacts of race, gender, or age were noted in a multivariate model. Conclusions: Approximately 42% of patients receiving chemotherapy suffered from toxicities that required dose adjustments. We found a trend toward more use of neoadjuvant chemotherapy in resectable PDAC with a similar toxicity rate compared with other settings.[Table: see text]
Clinical features and outcomes of colloid carcinoma of pancreas compared to pancreatic ductal adenocarcinoma.
Authors: Khalil Lana , Zakka Katerina Mary , Jiang Renjian , Penely Mckenna , Alese Olatunji B. , Shaib Walid Labib , Wu Christina , Diab Maria , Behera Madhusmita , Reid Michelle D. , El-Rayes Bassel F. , Akce Mehmet 
Published: June 2021

e16259 Background: Colloid carcinoma (CC) of the pancreas is a rare histopathological subtype of ductal adenocarcinoma (PDAC), with poorly defined prognostic factors and therapeutic outcomes. The aim of this study is to characterize the clinicopathological features and evaluate the overall survival (OS) and prognostic factors of patients with pancreatic CC using National Cancer Database (NCDB). Methods: Patients diagnosed with CC of the pancreas and PDAC between 2004 and 2016 were identified from the NCDB using ICD-O-3 morphology (8480/3 for CC and 8140/3 for PDAC) and topography codes (C25). Univariate and multivariable analyses were conducted and Kaplan-Meier analysis and Cox proportional hazards models were used to perform OS analysis. Results: A total of 56,846 patients met the inclusion criteria for the final analysis. Of the total population included, 2,430 patients (4.3%) had CC and 54,416 patients (95.7%) had PDAC. For both, CC and PDAC, there was a male preponderance (52.0%, 52.5%), Caucasians (85.1%, 84%), occurrence above the age of 70 (39.2%, 38.2%), and the most common primary site was the head of the pancreas (50.5%, 53%). For CC, the percentage of pathologic stage III colloid pancreas cancer appeared the lowest (3.5%, 85 patients), compared to stage I (16.7%), stage II (37.8%), and stage IV (42.1%). While in PDAC, the percentage of pathologic stage I (5.94%) and stage III (4.44%) patients was lower than stage II (37.21%) and IV (52.41%). CC and PDAC more frequently presented with < 5cm tumor, at academic or research cancer centers, and diagnosed between 2009 and 2013 compared to 2004–2008 ( p< 0.001). For both CC and PDAC, the majority underwent surgical resection (58%, 53%), systemic chemotherapy (57.8%, 63%) and did not receive radiotherapy (78.8%, 77.6%). A positive surgical margin on pathologic evaluation was associated with worse outcomes for CC and PDAC in both univariate and multivariate analysis (HR 1.61; 1.56–1.66; p< 0.001 and HR 1.43; 1.38–1.48, p< 0.001). CC had a better 1-year overall survival (OS) in all stages compared to PDAC (p < 0.001). In multivariate analysis, mucinous carcinoma histology, female sex, diagnosis between 2004 and 2009, well/moderately differentiated histology, chemotherapy, age at diagnosis less than 60, radiation therapy after surgery, and local surgical procedure of primary site and pancreatectomy (p < 0.001) were associated with better OS compared to PDAC. Colloid histology was associated with better 1-year overall survival (OS) in all stages compared to PDAC (p < 0.001). Conclusions: Colloid carcinoma of pancreas is associated with a better overall survival as compared to pancreatic ductal adenocarcinoma. This is the largest study to address the clinical features and outcomes of colloid carcinoma of pancreas.
Efficacy and safety of MUC1 targeted CIK cells for the treatment of advanced liver cancer.
Authors: Lu Yin Ying , Yu Haoyang , Tang Yunxia 
Published: June 2021

e16278 Background: To assess the efficacy and safety of CIK treatment with MUC1/CD3 bis-Ab for patients with advanced liver cancer. Methods: A total of 11 patients were enroll from when in which hospitals, including 5 male and 6 female patients with a median age of 59 years old. Trial Design and Treatment: All participants provided written informed consent before enrollment. The study protocol was approved by the institutional review board at each participating center. All methods and procedures associated with this study were conducted in accordance with the Good Clinical Practice guidelines and accorded ethically with the principles of the Declaration of Helsinki and local laws. This phase I clinical study was a single-armed open-labeled trial. All patients received targeted activated CIK cell treatment of 6x109 cells/month until the disease progressed, the patient could not tolerate the treatment, or the study endpoint had reached. PBMC were collected from each patient on D0. After PBMC collection, patients received 10 mg/day decitabine for 5 consecutive days (D0–D4). On D14 the first batch of CIK cells were harvested and the infusion of cells was performed in two consecutive days (total cells ≥ 6x109). The bispecific antibody was infused together with CIK cells. After cell infusion, the bispecific antibody was infused alone for another 3 days. Each treatment course lasted for 4 weeks, with a total of 4 courses. Results: Efficacy: 9 patients completed 4 or fewer courses of CIK bispecific antibody treatment, and 2 patients completed 9 courses of treatment. Till the data cut-off date of Dec. 31, 2020, 9 patients died, of whom 5 patients achieved SD and 4 patients had PD. Two patients (case 1 & 2) are still alive, of whom one achieved PR and one achieved SD during CIK treatment, and both achieved CR after subsequent PD-1 inhibitor treatment when the disease progressed. The PFS ranged from 1-16.7 months with a median PFS of 4 months, and the OS ranged from 3.9-32.7 months with a median OS of 13.2 months. The DCR of CIK treatment reached 63.6%. Safety: All 11 patients developed fever after cell infusion, which subsided after a few hours by oral administration of Xinhuangpian. 2 patients developed anorexia. Other AEs included debilitation, drowsiness, nausea, hepatotoxicity and dizziness. Five patients discontinued treatment due to serious AEs. Conclusions: This study showed that adjuvant CIK cell immunotherapy prolongs the survival time of patients with advanced liver cancer, which is mainly due to the local tumor chemotaxis of CIK cells via the MUC1/CD3 bispecific antibody and the decitabine pretreatment. Clinical trial information: NCT03146637.
Exploring the synergistic effects of cabozantinib (cabo) and a programmed cell death protein 1 (PD1) inhibitor in metastatic renal cell carcinoma (mRCC) with artificial intelligence (AI).
Authors: Duran Ignacio , Costa Luis , Puente Javier , Anido Urbano , Martin Lidia , Gómez Jessica , Castellano Daniel 
Published: June 2021

e16555 Background: Nonclinical and clinical data suggest that cabo with a PD1 inhibitor provides synergistic antitumor activity in patients with mRCC, possibly by a cabo-induced switch to an immunopermissive tumor microenvironment. We used a complementary, unbiased, AI approach to gain a holistic view of the complex interplay between multiple pathways, cells and molecules and identify the mechanisms that may underpin this synergism. Methods: Biological targets associated with mRCC pathophysiology or drug actions were identified from proteomic, genomic and transcriptomic databases and literature. Using systems- and AI-based technology, the data were integrated using machine learning into mathematical models of the human mRCC protein network topology. The combined effects of cabo and a PD1 inhibitor on biological targets were simulated assuming target receptors were fully activated or fully inhibited. Relevant effects on known cancer processes (e.g. angiogenesis, metastasis, cell proliferation, immune evasion) were identified using artificial neural networks. Biologically plausible synergistic mechanisms were described with sampling methods. Results: Inhibition of VEGF/VEGFR and GAS6/TAMR axes by cabo enhanced the known effects of PD1 inhibitors on immune evasion mechanisms by modulating multiple humoral and cellular components of the innate and adaptive immune responses (Table). PD1 inhibitors further enhanced the anti-angiogenic and tumor pro-apoptotic effects of cabo by modulating pro- and anti-angiogenic factors and T cell cytotoxicity. Conclusions: These data provide a mechanistic rationale and further support for the beneficial combination of cabo and a PD1 inhibitor and may guide future nonclinical and clinical research.[Table: see text]
Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).
Authors: Parikh Anish B. , Psutka Sarah P. , Yang Yuanquan , Collier Katharine , Miah Abdul , Li Mingjia , Mori-Vogt Sherry , Hinkley Megan , Orcutt Delaney , Trott Elliott , Gross Evan , Hussey Duncan , Kramer Joel , Oliva Kaylee , Mortazavi Amir , Monk Paul , Folefac Edmund , Clinton Steven K. , Yin Ming 
Published: June 2021

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]
Association of elevated serum CEA with visceral metastasis and distinctive circulating tumor DNA alterations in castrate-resistant prostate cancer.
Authors: Bray Alexander , Malalur Pannaga G. , Drusbosky Leylah , Gourdin Theodore Stewart , Lilly Michael B. 
Published: June 2021

e17023 Background: Serum carcinoembryonic antigen (CEA) is elevated in certain subtypes of castrate resistant prostate cancer (CRPC) such as aggressive variant prostate cancer (AVPC). Independent association of CEA expression with clinical stage and specific tumor gene variants could enable its use as a prognostic indicator and non-invasive biomarker of therapeutic response. Methods: Circulating tumor DNA (ctDNA) alterations in a commercially available panel of genes (Guardant Health) and serum CEA from 178 CRPC patients were retrospectively analyzed. These patients were defined as AVPC or non-AVPC based on the presence of 1 or more of the published Aparicio criteria (Aparicio et al, 2013). Clinical characteristics and ctDNA alterations were compared in patients with elevated and normal CEA. AVPC and non-AVPC patients were then compared to evaluate the uniqueness of CEA associated findings. Results: Patients with CRPC and elevated serum CEA were more likely to have liver (36.1% vs 12.0%, p = 0.002) and lung metastasis (19.4% vs 6.4%, p = 0.0441) compared to patients with normal CEA. When ctDNA profiles were analyzed there were no significant differences in rates of single nucleotide variants (SNVs) between patients with elevated and normal CEA. In contrast, patients with elevated CEA were significantly more likely to harbor copy number amplifications (CNAs) in BRAF, CDK6, FGR1, MET, CCNE1, MYC, KIT, CCND2, PIK3CA, RAF1, and KRAS. Of these, only PIK3CA and KRAS were significantly elevated in AVPC patients compared to non-AVPC patients. Relative to non-AVPC CRPC, patients with AVPC were significantly more likely to have clonal SNVs in TP53, PTEN, or RB (p = 0.0131). They were also more likely to have clonal SNVs in TP53 (p = 0.06). Conclusions: 1.) Elevated serum CEA is independently associated with visceral metastases in patients with CRPC. 2.) Elevated serum CEA in CRPC is associated with specific gene amplifications which are detectable by ctDNA analysis and not associated with AVPC as a whole. 3.) The ctDNA findings in patients with AVPC mirror previous tissue-based studies which documented recurrent genetic variations in TP53, PTEN, and RB (Aparicio et al, 2016). Together these findings outline a potential role for ctDNA profiling and serum CEA as non-invasive biomarkers in CRPC. They also suggest that elevated serum CEA may be associated with a genetically distinct subtype of AVPC.
Comparative efficacy of docetaxel versus novel hormonal agent in de novo metastatic hormone-sensitive prostate cancer: Real-world data curated by deidentified chart abstraction.
Authors: Liaw Bobby Chi-Hung , Guin Sunny , Jun Tomi , Ayers Kristin , Patel Bonny , O'Connell Timmy , Dietz Matthew , Klein Michael , Prentice Tony , Newman Scott , Fink Marc , Zhou Xiang , Schadt Eric , Chen Rong , Oh William K. 
Published: June 2021

e17047 Background: The addition of docetaxel or a novel hormonal agent (NHA), such as abiraterone acetate or enzalutamide, has become standard of care for mHSPC, but prospective data for comparative efficacy remains limited. Clinical variables abstracted through natural language processing of free text from patient charts can provide real-world data to answer important clinical questions. Methods: Using an innovative data abstraction process, we retrospectively identified men with de novo mHSPC within deidentified charts from the Mount Sinai Health System treated with either docetaxel or a NHA between January 1, 2014 and April 30, 2019. Dates were chosen to reflect the timeline for which these therapeutic agents received regulatory approval for mHSPC, but also to allow sufficient clinical follow up after treatment initiation. Primary outcome of failure-free survival (FFS), defined as the time to next treatment, was assessed using the Kaplan-Meier method and multivariable Cox proportional hazards models. We additionally performed multivariable analysis to evaluate the prognostic significance of post-treatment PSA nadir on FFS. Results: A total of 94 de novo mHSPC patients that received either docetaxel or an NHA were identified using proprietary Sema4 data abstraction process: 52 received docetaxel, 42 received an NHA. Use of an upfront NHA in mHSPC was associated with a significantly longer FFS compared to docetaxel (20.7 vs. 10.1 months, p = 0.023). While NHAs were associated with a significantly longer FFS than docetaxel in patients with high metastatic burden of disease (25.12 vs. 9.63 months, p = 0.014), this was not observed in low-volume disease (20.71 vs. 26.5 months, p = 0.9). In multivariable model analysis adjusting for age, baseline PSA, and metastasis burden, docetaxel remains independently associated with worse FFS compared to NHA (HR 1.96, 95% CI 1.12−3.45, p = 0.019). Irrespective of docetaxel or NHA use, lower post-treatment PSA nadir levels were associated with improved FFS (58.95 vs. 11.57 vs. 9.4 months for PSA ≤0.2, 0.2-0.4, > 0.4ng/ml, respectively; p < 0.001). Conclusions: Clinical variables abstracted from deidentified clinical documentation can efficiently provide relevant and reliable data upon which clinical research can be based. Comparative analysis of real-world data demonstrates superior FFS in de novo mHSPC treated with a NHA as compared to docetaxel. The depth of PSA response holds prognostic value for mHSPC outcomes, regardless of treatment used.
Phoenix Cancer Support Network provides non-medical assistance to reduce disparities among cancer patients.
Authors: Weiss Glen J. , Thompson Adam R. , Pastuszak Kathryn M. , Torre Samantha R. , Martin Jeanette S. 
Published: June 2021

e18502 Background: Social determinants of health (SDOH) can lead to gaps in supportive care resources and services available to cancer patients. Established in 2017, Phoenix Cancer Support Network (PCSN) is a non-profit that endeavors to empower cancer patients (clients) throughout their cancer journey by providing support, guidance, and direction while promoting and protecting the unique needs, lifestyle, and abilities of each client and their caregivers. In this study, we investigate the non-medical needs of patients that engaged with PCSN for assistance and the increases in services provided over time. Methods: All patients that applied for and were eligible to receive assistance from PCSN were included. Eligibility requirements include patients primarily residing in Arizona and are receiving cancer therapy. Non-medical services offered included transportation, groceries and meals, housecleaning, other domestic services (e.g., child care or dog walking), financial support, and household goods. Summary statistics were conducted. Results: Between December 2017 and November 2020, 188 clients (117 were female) were offered assistance by PCSN. The median age was 58 (range 23-92). The number of clients assisted was 2 in 2017, 81 in 2018, 58 in 2019, and 38 in 2020. 145 clients had a solid tumor and 131 were actively undergoing cancer treatment when seeking PCSN assistance. Of 67 clients with available income data, 55 clients earned less than $25,000/year including 41 clients that were unemployed and 21 clients without insurance coverage. Most frequently requested services were transportation (49%), groceries and meals (41%), financial support (34%), housecleaning (26%), and other domestic services (10%). Of those requested services, PCSN was able to provide assistance for 76% of transportation, 62% of meal services, 79% of financial assistance, 50% of housecleaning, and 100% of other domestic services requested. Details of total expenditures for these services by year are depicted in the Table.Transportation service has been the largest expenditure overall, followed by other domestic services and groceries and meals. Conclusions: PCSN clients have needs that span multiple non-medical resources, reflecting potential sources of improvement in reducing disparities in the cancer community. At least 25% of clients requesting non-medical assistance reported annual income below $25,000/year. The amount of services provided has increased yearly, particularly transportation services. Additional study and follow-up to understand these service gaps and the impact of SDOH is warranted.[Table: see text]