tbuckley/cabot-search huggingface dataset:
Abstract 17129: Trends of Inpatient Malignancy Admissions Among Patients With a History of Heart Transplant: Analysis of National Inpatient Sample Database
Authors: Setri Fugar, Mbachi C Uchenna, Alexis K Okoh, Olagoke Olakanmi, Alfred Solomon, Tauseef Akthar, Jorge O Gomez, Atefeh Vafah, Jayakumar Sreenivasan, Juliet A Yirerong, Ahmed Al-Ogaili, Harry Fuentes
Journal: Circulation (2018)

Introduction: Heart transplantation is associated with prolonged survival and improved quality of life in patients with advanced cardiac disease albeit with an increased risk of malignancies due to the use of immunosuppressant medications. Our study aimed to determine the types and trends of in patients’ hospitalization for malignancies among heart transplant patients. Methods: We queried the 2005 to 2014 National Inpatient Sample(NIS) database to identify all patients with a history of heart transplant (ICD-9 codes V412, 99683) who were hospitalized with a diagnosis of cancer. The main outcome was the trend in cancer admissions. Secondary outcome were inpatient mortality, total charge and length of stay. Cochran’s and Mantel-Haenszel test was used to assess trends of cancer admissions. Adjusted OR were used to compare the incidence of death between the two groups. Results: A total of 36543(weighted national estimate of 177,604) patients were admitted with a history of heart transplantation over the study period, out of which 2347(6.4%) had a diagnosis of a malignancy. Cancer patients were older (Mean age 66±12 Vs. 61.1±18 P-Value &lt;0.001) and were more likely to be male. There was an increasing trend in the rate of cancer admissions over the study period from 60 per 1000 patients in 2005 to 70 per 1000patients in 2014(P-Vale &lt;0.0001). Overall the most prevalent cancer was Non-Hodgkin’s 20.9% followed by lung Cancer 19.1%. ninety-seven patients(4.1%) had a 2 or more cancers. Patients with a diagnosis of cancer were more likely to die while inpatients as compared those without a diagnosis of cancer (6.6% vs. 3.1%, adjusted OR 2.42 95%CI 1.53-3.38 P-value &lt;0.001). Lastly, patients with cancer had an increased total median coast and a longer length of stay(Total charge(39735 vs, 32,035, P value =&lt;0.001 and 5 vs. 4. P-value &lt;0.001). Conclusion: Development of cancer among patients with a history of transplant adds significant morbidity and mortality. Further studies are needed to determine effective ways to reduce morbidity in this patient cohort.
Long-term follow-up results of a phase II study of dose-adjusted (DA)-EPOCH-R with high-dose methotrexate (HD-MTX) for newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL).
Authors: Kana Miyazaki, Rika Sakai, Noriko Iwaki, Go Yamamoto, Tomomi Yamada, Yuki Nishimura, Satoshi Tamaru, Naoko Asano, Kohta Miyawaki, Koji Izutsu, Tomohiro Kinoshita, Ritsuro Suzuki, Koichi Ohshima, Koji Kato, Naoyuki Katayama, Motoko Yamaguchi
Journal: Journal of Clinical Oncology (2021)

7551 Background: CD5+ DLBCL is characterized by a poor prognosis and frequent central nervous system (CNS) relapse after standard immunochemotherapy. In the primary analysis of our multicenter phase II study of DA-EPOCH-R/HD-MTX for newly diagnosed stage II-IV CD5+ DLBCL, the 2-year (yr) progression-free survival (PFS) was 79% and the 2-yr CNS relapse rate was 9% at a median follow-up of 3.1 yrs (Miyazaki, et al. 2020). The aim of this preplanned 5-yr follow-up was to assess PFS, overall survival (OS), the CNS relapse rate, and late toxicity. Methods: A total of 47 patients (pts) with newly diagnosed stage II-IV CD5+ DLBCL between 20-75 yrs old and ECOG PS of 0-3 were enrolled. The treatment included 4 cycles of DA-EPOCH-R followed by 2 cycles of HD-MTX (3.5 g/m 2 ) and 4 additional cycles of DA-EPOCH-R. Intrathecal administration of MTX and/or cytarabine was not allowed. 45 (96%) pts completed the protocol treatment. The data were updated as of December 1, 2020. Results: The median follow-up of alive pts was 6.0 yrs (range, 5.0-7.7). The pts’ characteristics were as follows: age, 37-74 yrs (median, 62); male, 38%; ECOG PS &gt; 1, 4%; stage III/IV, 57%; IPI HI/H, 47%; CNS-IPI high, 21%; and ABC/GCB/unclassified (n = 46), 85%/9%/7%. The 5-yr PFS and OS were 72% (95% CI, 57-83%) and 79% (95% CI, 64-88%), respectively. The 5-yr PFS and OS of pts with CD5+ ABC DLBCL (n = 39) were 72% and 74%, respectively. The 5-yr CNS relapse rate in all 47 pts was 9% (95% CI, 3-22%). There were no CNS relapse events after the primary analysis. Neither grade 3/4 late adverse events nor cardiac events of any grade were observed. Possible second malignancies were recorded in 6 (13%) pts. Among them, one pt who received R-ICE as salvage therapy experienced acute myeloid leukemia. The other 2 pts had colon cancers treated with endoscopic polypectomy/mucosal resection. Conclusions: Both the survival benefit and safety of DA-EPOCH-R/HD-MTX were maintained during a 5-yr follow-up, indicating the excellent efficacy, and safety of this approach as a first-line therapy for CD5+ DLBCL. Clinical trial information: UMIN000008507.
A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations
Authors: Bin Wang, Wei Liu, Jiao Jiao Li, Senlin Chai, Dan Xing, Hongsheng Yu, Yuanyuan Zhang, Wenjin Yan, Zhihong Xu, Bin Zhao, Yanan Du, Qing Jiang
Journal: Bioactive Materials (2021)

Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament (ACL) transection model of OA achieved similar reparative effects as repeated high doses of MSCs, as evaluated through imaging and histological analyses. Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer, together with MSCs grown either within 3D constructs or as a monolayer. Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group. RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group, as well as phenotypic maintenance in the co-cultured chondrocytes. The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.
Antitumor activity of dostarlimab in patients with mismatch repair-deficient/microsatellite instability–high tumors: A combined analysis of two cohorts in the GARNET study.
Authors: Dominique Berton, Susana N. Banerjee, Giuseppe Curigliano, Sara Cresta, Hendrik-Tobias Arkenau, Cyril Abdeddaim, Rebecca Sophie Kristeleit, Andrés Redondo, Charles A. Leath, Antonio Antón Torres, Wei Guo, Ellie Im, Thierry Andre
Journal: Journal of Clinical Oncology (2021)

2564 Background: Dostarlimab is an investigational, humanized programmed death 1 (PD-1) receptor monoclonal antibody that blocks interaction with the PD-1 ligands, PD-L1 and PD-L2. GARNET (NCT02715284) is a phase 1 study assessing the antitumor activity and safety of dostarlimab monotherapy in patients with solid tumors. Methods: This multicenter, open-label, single-arm study is being conducted in 2 parts: dose escalation and expansion. Here we report on the 2 expansion cohorts that enrolled mismatch repairdeficient/microsatellite instabilityhigh (dMMR/MSI-H) patients. Cohort A1 enrolled patients with advanced or recurrent dMMR/MSI-H endometrial cancer (EC), and cohort F enrolled patients with advanced or recurrent dMMR/MSI-H or POLε-hypermutated non-EC solid tumors, mainly gastrointestinal (GI) tumors (99 [93.4%] had GI tumors, including 69 [65.1%] with colorectal cancer). Patients received 500 mg IV of dostarlimab every 3 weeks for 4 cycles, then 1000 mg IV every 6 weeks until disease progression or discontinuation. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by RECIST v1.1. Here we report ORR and DOR, by individual cohort and as an overall population, in patients with dMMR tumors identified by immunohistochemistry testing. Results: For this interim analysis, an efficacy analysis was performed for the patients who had baseline measurable disease and ≥6 months of follow-up in the study (N = 209). The ORR was 41.6% (95% CI, 34.9%48.6%) for the combined A1+F dMMR cohorts (Table). Responses were durable, and median DOR has not been reached in either cohort (median follow-up: cohort A1, 16.3 months; cohort F, 12.4 months). A total of 267 patients were included in the safety population (all patients who received ≥1 dose; cohort A1, N = 126; cohort F, N = 141). Treatment-related adverse events (TRAEs) were consistent across tumor types. Overall, the most frequently reported any-grade TRAEs were asthenia (13.9%), diarrhea (13.5%), and fatigue (11.2%). The most common grade ≥3 TRAEs were anemia (2.2%), lipase increased (1.9%), alanine aminotransferase increased (1.1%), and diarrhea (1.1%). No deaths were attributed to dostarlimab. Conclusions: Dostarlimab demonstrated durable antitumor activity in patients with dMMR solid tumors, with consistent antitumor activity seen across endometrial and nonendometrial tumor types. The safety profile was manageable, with no new safety signals detected. Most TRAEs were low grade and were similar across cohorts. Clinical trial information: NCT02715284. [Table: see text]
A phase Ⅰ open-label dose-escalation study of AL2846 in combination with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Rui Liu, Ting Deng, Ming Bai, Le Zhang, Tao Ning, Xia Wang, Zhi Ji, Yuchong Yang, Shaohua Ge, Hongli Li, Jingjing Duan, Yi Ba
Journal: Journal of Clinical Oncology (2021)

e16210 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 10%. Overexpression of c-Met is associated with the poor prognosis in patients with PDAC and it was noted that phosphorylation of c-Met is increased in gemcitabine-resistant PDAC. AL2846 is an oral c-Met inhibitor, which targets multiple receptor tyrosine kinases (RTK’s) primarily including c-Met, VEGFR1, KIT, Axl and RET. The combination of AL2846 with chemotherapy may improve the clinical efficacy of PDAC. Based on these consideration, a phase Ⅰ clinical trial was initiated to determine the maximum tolerated dose (MTD) of AL2846 in combination with gemcitabine in patients with advanced PDAC and to clarify the potential anti-tumor activity. Methods: Patients with untreated locally advanced or metastatic PDAC were enrolled to receive oral AL2846 once daily in a fasted state in combination with gemcitabine intravenous infusion over 30 min on days 1, 8, and 15 every 28 days. The starting dose level is AL2846 40 mg and gemcitabine 1000 mg/m 2 . Primary endpoint was the maximum tolerated dose (MTD), defined as the highest dose level at which ≤33 % of patients incurred a dose-limiting toxicity (DLT), and RP2D. Secondary endpoints included response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: As of January 1, 2021, a total of 15 patients with PDAC were enrolled and received 4 dose-levels of AL2846 (40 mg: n = 1; 60 mg: n = 6; 90 mg: n = 3; 120 mg: n = 5) treatment. DLTs occurred in 1 patient who experienced grade 3 abnormal liver function. The most common grade 3 or above drug-related adverse events were neutropenia (n = 7, 46.7%), thrombocytopenia (n = 5, 33.3%), leukopenia (n = 4, 26.7%), GGT increased (n = 4, 26.7%), hyperbilirubinemia (n = 3, 20.0%) and alkaline phosphatase increased (n = 3, 20.0%). Among the 15 patients available for efficacy evaluation, 1 patient (6.6%) achieved partial response who was at the dose levels of 90mg. There were 4 patients whose PFS was more than 5 months. Although there were no more than 2 DLT events, we chose 90 and 120 mg as the target dose for RP2D according to the dose reduction and proportion of gemcitabine. Conclusions: The RP2D of AL2846 in combination with standard dose of gemcitabine were 90 and 120 mg QD continuously. The results demonstrated that AL2846 in combination with gemcitabine was well tolerated at doses up to 120 mg. Further clinical studies about the efficacy of AL2846 in pancreatic cancer are in progress. Clinical trial information: CTR20201021.
Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy
Authors: Udo F.H. Engelke, Rianne E. van Outersterp, Jona Merx, Fred A.M.G. van Geenen, Arno van Rooij, Giel Berden, Marleen C.D.G. Huigen, Leo A.J. Kluijtmans, Tessa M.A. Peters, Hilal H. Al-Shekaili, Blair R. Leavitt, Erik de Vrieze, Sanne Broekman, Erwin van Wijk, Laura A. Tseng, Purva Kulkarni, Floris P.J.T. Rutjes, Jasmin Mecinović, Eduard A. Struys, Laura A. Jansen, Sidney M. Gospe, Saadet Mercimek-Andrews, Keith Hyland, Michèl A.A.P. Willemsen, Levinus A. Bok, Clara D.M. van Karnebeek, Ron A. Wevers, Thomas J. Boltje, Jos Oomens, Jonathan Martens, Karlien L.M. Coene
Journal: Journal of Clinical Investigation (2021)

Background. Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5′-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.
Abstract 15918: Right-Sided Subcutaneous Implantable Cardioverter-Defibrillator in Patient With Situs Inversus Totalis
Authors: Emrie Tomaiko, Meenakshi Sridhar, Sharon Kusne, Carla Lockhart, Jonathan Ko, Wilber Su
Journal: Circulation (2019)

Introduction: Patients with dextrocardia or situs inversus with cardiac structures to the right side of the chest may be considered for the placement of the S-ICD. For effective defibrillation, thi...
Clinical features and outcomes of colloid carcinoma of pancreas compared to pancreatic ductal adenocarcinoma.
Authors: Lana Khalil, Katerina Mary Zakka, Renjian Jiang, Mckenna Penely, Olatunji B. Alese, Walid Labib Shaib, Christina Wu, Maria Diab, Madhusmita Behera, Michelle D. Reid, Bassel F. El-Rayes, Mehmet Akce
Journal: Journal of Clinical Oncology (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 &lt; 5cm tumor, at academic or research cancer centers, and diagnosed between 2009 and 2013 compared to 2004–2008 ( p&lt; 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&lt; 0.001 and HR 1.43; 1.38–1.48, p&lt; 0.001). CC had a better 1-year overall survival (OS) in all stages compared to PDAC (p &lt; 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 &lt; 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 &lt; 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.
Prior tonsillectomy and subsequent risk of breast cancer in females: Systematic review and meta-analysis.
Authors: Salah Eddine Oussama Kacimi, Mounir Ould Setti, Amira Yasmine Benmelouka, Mohammad Aloulou, Hanane Zoubida Sekkal, Laila Salah Shamseldin, Jovana Vidovic, Selma Nihel Klouche-Djedid, Jaffer Shah, Farah Yasmin, Omar Riffi, Ahmed M Afifi, Sherief Ghozy
Journal: Journal of Clinical Oncology (2021)

10568 Background: Exposure to recurrent infections in childhood was linked to an increased risk of cancer in adulthood. There is also evidence that a history of tonsillectomy, a procedure often performed in children with recurrent infections, is linked to an increased risk of leukemia, and Hodgkin lymphoma. Tonsillectomy could be directly associated with cancer risk or it could be a proxy for another risk factor such as recurrent infections and chronic inflammation. Nevertheless, the role of recurrent childhood infections and tonsillectomy on the one hand, and the risk of breast cancer (BC) in adulthood remain understudied. Our study aims to verify whether a history of tonsillectomy increases the risk of BC in women. Methods: A systematic review was conducted using PubMed, Google Scholar, Scopus, Embase and Web of Science databases from inception through November 2020 to identify the studies which explored the association between history of tonsillectomy and BC in females. The Newcastle Ottawa Scale was used to assess the quality of included studies. Odds ratio (OR) was used to measure effect size. The Random/Fixed effects model was applied to synthesize the associations between tonsillectomy and BC risk based on heterogeneity. Heterogeneity was assessed using the I-squared statistic. A forest plot was generated, and publication bias was assessed. The leave-one-out sensitivity analysis was performed to check if results were driven by a single study. Results: Seven studies with a total of 7259 patients were included in our analysis; out of them, 2200 patients were diagnosed with BC. Patients with a history of tonsillectomy (n = 2843) showed higher subsequent risk of developing BC (OR = 1.252; 95% CI = 1.115 - 1.406; P &lt; 0.001; I 2 = 9%) as compared to patients without a history of tonsillectomy (n = 4416). Using the leave-one-out sensitivity analysis to iteratively remove one study at a time, we confirmed that no single study had a substantial influence on the overall effect size. Conclusions: Our study supports and confirms the evidence that a history of tonsillectomy is associated with an increased risk of breast cancer. These findings are also an argument in support of the hypothesis that recurrent childhood infections are linked with adulthood breast cancer.
Factors on survival for patients of EGFR mutation advanced lung adenocarcinoma with EGFR-TKIs combined with radiotherapy: Real-world data from single center.
Authors: Yuxiang Wang, Wenjian Yu, Jian Shi, Nan Jiang, Zhoufan Wang, Jie Yang, Zhongfei Jia, Meng Song
Journal: Journal of Clinical Oncology (2021)

e21126 Background: The aim was to retrospectively evaluate survival and prognostic factors for patients of advanced lung adenocarcinoma with EGFR mutation by a real world data. Methods: From Jan, 2015 to Dec, 2020, lung adenocarcinoma with EGFR positive mutation, advanced (clinical stage III-IV), without surgery, received EGFR-TKIs and radiotherapy (RT) were enrolled. OS and PFS were calculated. Results: 238 patients were included, 101 in males and 137 in females; the median ages was 61. The RT was performed at the time of no-PD in 71 and PD in 167 cases. The median dose of RT was 50 Gy. The rate of acute AE during RT was 36.1% in grade 1-2 and 4.8% in grade 3-4. The follow-up ended at 30, Dec, 2020. The 1-, 2-, 3-years OS,PFS1and PFS2 were 84.4%,59.7%, 38.7%, 52.0%,29.4%, 16.3%, 86.6%, 64.6%, 45.6%. mOS, mPFS1and mPFS2 were 30.3, 14.1, 33.6 months, respectively. Multivariate analysis showed the independent factors for OS were ages (median were 34.0 and 24.9 months for ≤65 and &gt; 65) and clinical stage (median were 22.8, 34.8 and 27.4 months for stage III (33), IVA (84) and IVB (121 cases), respectively), chemotherapy (CT) (median were 27.4, 28.1, 32.5, 44.3 months for TKIs alone(120), TKIs concurrent CT (43), TKIs sequential CT (32), CT sequential TKIs (43 cases), respectively) and total response (the medians were 32.5, 27.2, 33.3 months for CR(7)+PR(107), SD(70) and PD(54 cases), respectively); Independent factors: PFS1 was the time of RT at no-PD and PD (the median were 17.8 and13.2 months), chemotherapy, (the median were 16.1, 12.1, 11.0, 13.5 for TKIs alone, TKIs concurrent CT, TKIs sequential CT, CT sequential TKIs), and total response (the medians were 18.8, 11.7, 10.9 months for CR+PR, SD and PD); PFS2 was the total response (the medians were 58.3, 21.6, 20.9 months for CR+PR, SD and PD, respectively). Univariate analysis also showed doses of RT (the median was 12.3 months for &lt; 50 Gy and 15.5 months for ≥ 50 Gy, p = 0.018) was associated with PFS1, the first-line drugs of TKIs (the median were 39.1, 35.0, 25.6 and 38.6 months for Gefitinib (89), Icotinib (109), Erlotinib (29) and others (11 cases), respectively, p = 0.044) and chemotherapy (the medians were 45.6, 30.6, 18.7, 41.4 months for TKIs alone, TKIs concurrent CT, TKIs sequential CT, CT sequential TKIs, respectively, p = 0.007) were related with PFS2; but the type of EGFR mutation (94 in 19 exon, 118 in 21 exon and 26 cases in others) was not related with survival. Conclusions: EGFR-TKIs combined RT was tolerable and efficient for patients of advanced lung adenocarcinoma with EGFR mutation. TKIs add RT at the time of no-PD could improve PFS1. CT sequential TKIs was probably in favour of OS, even PFS. The better total response (CR+PR) was associated with longer OS, PFS1 and PFS2. But the result need to be proved furtherly.