tbuckley/cabot-search huggingface dataset:
Adiponectin and cardiometabolic trait and mortality: where do we go?
Authors: Albert Youngwoo Jang, Philipp E Scherer, Jang Young Kim, Soo Lim, Kwang Kon Koh
Journal: Cardiovascular Research (2021)

Abstract Adiponectin is an adipocyte-derived cytokine known for its cardioprotective effects in preclinical studies. Early epidemiologic studies replicated these findings and drew great interest. Subsequent large-scale prospective cohorts, however, showed that adiponectin levels seemed not to relate to incident coronary artery disease (CAD). Even more surprisingly, a paradoxical increase of all-cause and cardiovascular (CV) mortality with increased adiponectin levels was reported. The adiponectin-mortality paradox has been explained by some groups asserting that adiponectin secretion is promoted by elevated natriuretic peptides (NP). Other groups have proposed that adiponectin is elevated due to adiponectin resistance in subjects with metabolic syndrome or heart failure (HF). However, there is no unifying theory that can clearly explain this paradox. In patients with HF with reduced ejection fraction (HFrEF), stretched cardiomyocytes secrete NPs, which further promote release of adiponectin from adipose tissue, leading to adiponectin resistance. On the other hand, adiponectin biology may differ in patients with heart failure with preserved ejection fraction (HFpEF), which constitutes 50% of all of HF. Most HFpEF patients are obese, which exerts inflammation and myocardial stiffness, i.e. likely to prevent myocardial stretch and subsequent NP release. This segment of the patient population may display different adiponectin biology from its HFrEF counterpart. Dissecting the adiponectin-mortality relationship in terms of different HF subtypes may help to comprehensively understand this paradox. Mendelian randomization (MR) analyses claimed that adiponectin levels are not causally related to CAD or metabolic syndrome. Results from MR studies, however, should be interpreted with great caution because the underlying history of CAD or CHF was not taken into account in these analyses, an issue that may substantially confound the results. Here, we discuss many aspects of adiponectin; cardiometabolic traits, therapeutic interventions, and the ongoing debate about the adiponectin paradox, which were recently described in basic, epidemiologic, and clinical studies.
Characteristics, outcomes, and risk factors of ICANS after axicabtagene ciloleucel: Does age matter?
Authors: Kitsada Wudhikarn, Radhika Bansal, Arushi Khurana, Matthew Hathcock, Michael Ruff, Ivan D. Carabenciov, Sherri A. Braksick, N. Nora Bennani, Jonas Paludo, Jose Caetano Villasboas, Yucai Wang, Patrick B. Johnston, Stephen M. Ansell, Yi Lin
Journal: Journal of Clinical Oncology (2021)

e19556 Background: CD19 chimeric antigen receptor T cell therapy possesses unique side effects including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Age is a major risk factor for ICANS. However, whether ICANS in older patients is different compared to younger patients is unknown. Herein, we report clinical course, outcomes and risk factors for ICANS in older patients with large B cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel). Methods: We comprehensively reviewed detailed clinical courses of ICANS in 78 adult patients with LBCL treated with axi-cel between June 2016 and October 2020. Incidence, manifestation, risk factors, treatment, and outcomes of ICANS were compared between patients age ≥60 (n=32) and &lt;60 (n=46) years old. Results: Baseline characteristics were comparable between older and younger patients except higher proportion of high international prognostic index and underlying cerebral microvascular disease in older patients. ICANS was observed in 16 patients in the older and 24 patients in the younger age group, with a 30-day incidence of 52% and 50%, respectively. Median time to CRS and ICANS were similar between 2 age groups. The most common initial neurological findings included aphasia, dysgraphia and encephalopathy in both age groups. Table summarizes the characteristics, clinical course and interventions of ICANS in older and younger patients. In Cox regression model, the presence of CRS was the only factor associated with ICANS in both age groups. Age, history of central nervous system involvement and cerebral microvascular disease were not associated with ICANS. Importantly, all patients had complete resolution of ICANS. No elderly patients in our cohort experienced seizure as a manifestation of ICANS. Conclusions: In our study, older age was not a risk factor for ICANS. CRS was the only factor associated with ICANS in both younger and older patients. Incidence, clinical course and neurological outcomes of ICANS in older patients treated with axi-cel were comparable to younger patients. [Table: see text]
Naxitamab and GM-CSF for consolidation of high-risk neuroblastoma (HR-NB) patients in complete remission.
Authors: Jaume Mora, Alicia Castañeda, Sara Perez-Jaume, Maite Gorostegui, Vicente Santa-María, Juan Pablo Muñoz, Amalia Varo, Salvador Mañe
Journal: Journal of Clinical Oncology (2021)

10021 Background: Naxitamab was recently approved in the US in combination with GM-CSF for the treatment of patients (pts) with relapse/refractory HR-NB in the bone/bone marrow who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe the use of 5 cycles of naxitamab and GM-CSF through compassionate use for consolidation of HR-NB pts in first or subsequent complete remission (CR). Methods: HR-NB pts in CR (first or subsequent) after initial multimodal induction treatment were eligible. Disease status was assessed at study entry by histology of BM biopsies/aspirates obtained from bilateral posterior and bilateral anterior iliac crests, I-MIBG SPECT scan, and whole body MRI. FDG-PET was used for MIBG non-avid cases at diagnosis. Quantitative reverse transcription-polymerase chain reaction was used to assess MRD in pooled heparinized BM aspirates. Disease response was defined according to the revised INRC. Four BM aspirates and 123 I-MIBG SPECT scan or FDG-PET scans were performed after cycles 2 and 5 and every 3 months thereafter for one year in all pts to assess response. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3.0 mg/kg/infusion (9.0 mg/kg/cycle) in combination with GM-CSF at 250 ug/m 2 /day on Days -4 to 0 and at 500 ug/m 2 /day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Survival curves were built from the time of naxitamab treatment initiation by Kaplan-Meier methods and compared using the log-rank test. Results: From June 2017 to November 30 2020, 73 pts were treated: 55 (75%) in first CR and 18 (25%) in second or more CR. Majority of pts were MYCN non-amplified (n=56, 77%), all stage 4, median age at treatment initiation 4.5 years. 61 (84%) pts had received &gt;5 cycles of induction chemotherapy; 22 (30%) high-dose chemotherapy and autologous stem cell transplant (ASCT); and 36 (49%) radiotherapy before receiving naxitamab. 58 (79.5%) pts completed naxitamab therapy, 53 (73%) in continued CR. 10 (14%) pts relapsed during treatment and 5 (7%) had grade 4 toxicities: 2 apnea related to naxitamab; and 2 non-related: 1 opioid related chest rigidity syndrome and 1 stroke. 3-y event-free-survival (EFS) for all pts is 58% [95% CI, 43.5; 78.4], 74% for first CR and 19% for second or more CR (p=0.0029). 3-y OS for the whole group is 82% [95% CI, 66.8; 100.0], 92% for first CR and 66% for second or more CR pts (p=0.18). Univariate Cox models for CR group, MYCN status, number of chemotherapies, ASCT, radiotherapy, MRD, and age showed significant p value only for prior relapse as predictor of EFS (p=0.047). Conclusions: Naxitamab for HR-NB pts in CR provided excellent 3-y OS rates regardless of previous management. The only predictor for relapse is prior history of recurrence.
Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse
Authors: Sabela Bobillo, Erel Joffe, David Sermer, Patrizia Mondello, Paola Ghione, Philip C. Caron, Audrey Hamilton, Paul A. Hamlin, Steven M. Horwitz, Anita Kumar, Matthew J. Matasar, Connie L. Batlevi, Alison Moskowitz, Ariela Noy, Collette N. Owens, M. Lia Palomba, David Straus, Gottfried von Keudell, Ahmet Dogan, Andrew D. Zelenetz, Venkatraman E. Seshan, Anas Younes
Journal: Blood Cancer Journal (2021)

Abstract Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.
心室性頻拍(VT)発作が原因と推測された左室内血栓の一手術例
Authors: 和田朋之, 宮本伸二, 穴井博文, 田中秀幸, 竹林聡, 森田雅人, 岩田英理子, 首藤敬史, 葉玉哲生
Journal: Circulation (2006)
The expression of THOX2 in colorectal mucinous adenocarcinoma and its relationship with prognosis.
Authors: Xue Zhang, Jing Han, Zhisong Fan, Li Feng, Long Wang, Jing Zuo, Yudong Wang, Dan Li, Jiayin Liu
Journal: Journal of Clinical Oncology (2021)

e15529 Background: The role of THOX2 in the occurrence and development of tumors has gradually attracted attention, but there is no study on the expression and function of THOX2 in colorectal mucinous adenocarcinoma (MC). The purpose of this study was to investigate the expression of thyroid oxidase 2 (THOX2) in colorectal MC and its relationship with prognosis. Methods: 30 patients with colorectal adenocarcinoma (AC) and 15 patients with MC were selected from The Fourth hospital of Hebei Medical University from October 1, 2018 to July 1, 2019. They were selected to detect the mRNA and protein levels of THOX2 in the colorectal cancer tissues of the two different pathological types using qRT-PCR and immunohistochemistry (IHC) methods. A total of 109 patients with MC who received surgical treatment between January 1, 2015 and January 1, 2015 were selected. The clinicopathological parameters of the patients were collected and survival follow-up was performed. The expression of THOX2 protein in MC tissues was detected by IHC test, and the differences in the expression of THOX2 protein in different tissues were analyzed by χ 2 test. Cox univariate and multivariate analyses were used to investigate the relationship between clinicopathological characteristics, THOX2 protein expression level and DFS and OS in patients with MC. Results: The levels of THOX2 mRNA and protein in 15 cases of MC were significantly higher than those in 30 cases of AC. The high expression of THOX2 protein in MC tissues was closely correlated with tumor site, whether mixed with other pathological types, TNM stage, lymph node metastasis, M stage, and liver metastasis, peritoneal metastasis and other site metastasis occurred in patients after initial treatment. Cox regression analysis of 95 patients' survival data showed that high expression of THOX2, right colon and lymph node metastasis were influential factors for DFS in MC patients, and were independent prognostic factors for predicting DFS in MC patients. The expression of THOX2, lymph node metastasis, liver metastasis after adjuvant therapy and peritoneal metastasis are the influencing factors of OS in MC patients. Lymph node metastasis is an independent prognostic factor for OS in MC patients. Conclusions: The expression of THOX2 in MC was significantly higher than that of AC, and it was related to the malignant biological manifestations of tumor. At the same time, the high expression of THOX2 is associated with short DFS and OS in patients with MC, and may be used as a potential biomarker and efficacy predictor for MC patients.
Telehealth to increase access to transplant survivorship care for allogeneic stem cell transplant recipients regardless of distance to transplant center or neighborhood income.
Authors: Nausheen Ahmed, Sarah Fitzmaurice, Cherie Morey, Tania Torres, Darla Beckman, Siddhartha Ganguly, Rajat Bansal, Liza Rodriguez, Haitham Abdelhakim, Anurag K Singh, Sunil H. Abhyankar, Leyla Shune, Robert Kribs, Clint Devine, Jennifer Hanses, Muhammad Umair Mushtaq, Joseph McGuirk
Journal: Journal of Clinical Oncology (2021)

e13615 Background: Transplant Survivorship Clinic at our institution serves to improve outcomes and overall health of allogeneic transplant survivors. The COVID19 pandemic allowed for growth of telemedicine in our program. We examine the patterns of use of telehealth and hypothesize that the use of telemedicine allowed continued access to care compared to the era prior to availability. We compared our transplant survivorship clinic data from July- December 2020, when telehealth was well established and compared to July-December 2019. Methods: All patients seen by the survivorship team for end of treatment visits, graft versus host disease assessments and survivorship visits annually between July-December 2019 and July-December 2020 were included. Their zip codes were used to get direct distance to survivorship clinic, average drive time, driving distance and average household income as in zip-codes.com database. Results: Total number of office visits in July-Dec 2019 was 163 visits (0% via telehealth) and in July-Dec 2020 was 228 (66.2% via telehealth). All encounters (telehealth and office visits) were lower in July and August 2020 compared to July and August 2019 but higher in months of September -December 2020 compared to 2019. Comparing all encounters during 7/2019-12/2019 to 7/2020-12/2020, there was no statistically significant difference in median age (58yr vs 60 yr), gender (males: 58% vs 59%), race (non-white: 11% vs 8.7%), median years from transplant (4yr vs 3 yrs), median income of patient neighborhood ($63,735 vs $60,465) and average drive time to center from zip code (40 min vs 51min). Comparison of patients who chose telehealth vs. office visit is summarized in table. While there was no statistically significant difference in age when comparing all encounters in 2019 and 2020, those who chose telehealth were younger (55yrs vs 60yrs, p=0.003). Conclusions: There were higher patient encounters in the 2020 period compared to 2019. Most of these 2020 encounters were via were telehealth, demonstrating the role of telehealth in increasing access. Younger patients appeared to choose telehealth, but telehealth served patients up to the age of 77 yrs. Utilization of telehealth appeared to be irrespective of demographics such as gender, neighborhood income and driving distance to the center. Comparison of telehealth vs office visit for July-December 2019 and 2020.[Table: see text]
Overall survival (OS) with encorafenib (enco) + cetuximab (cetux) in BEACON CRC: Effect of prior therapy for <i>BRAF</i> V600E-mutant metastatic colorectal cancer (mCRC).
Authors: Scott Kopetz, Dan Aderka, Axel Grothey, Eric Van Cutsem, Rona Yaeger, Harpreet Singh Wasan, Takayuki Yoshino, Jayesh Desai, Fortunato Ciardiello, Ashwin Gollerkeri, Adele Golden, Michelle L. Edwards, Josep Tabernero
Journal: Journal of Clinical Oncology (2021)

3583 Background: Enco + cetux (doublet) has been approved in the US, EU, and Japan for the treatment of BRAF V600E-mutant mCRC after progression on 1–2 prior regimens. In the BEACON CRC study (NCT02928224), median OS (95% CI) with the doublet was 9.3 months (8.0–11.3) compared with 5.9 months (5.1–7.1) with cetux + irinotecan or FOLFIRI (control) in patients (pts) with BRAF V600E-mutant mCRC (HR 0.61 [95% CI: 0.5–0.8]). This post-hoc analysis investigates OS by prior therapies to the doublet treatment in pts with BRAF V600E-mutant mCRC from the BEACON CRC study. Methods: OS of pts treated with the doublet or control were compared according to prior treatment with bevacizumab, oxaliplatin, or FOLFOXIRI and duration of prior anticancer therapy (ACT). Results: The proportion of pts in the doublet and control arms who received prior bevacizumab were 64% and 55%, respectively. Of pts who had one prior therapy, 95% and 88% received prior oxaliplatin and 20% and 14% received prior FOLFOXIRI, respectively. OS by prior treatment in the doublet and control arms is shown in the table. In the doublet arm, pts who had bevacizumab &lt; 4 months before start of study treatment had a median OS of 8.3 months (95% CI: 6.2–11.2); those who had bevacizumab ≥4 months prior had a median OS of 10.7 (95% CI: 7.5–17.7). Within each treatment arm, OS was similar regardless of prior treatment with oxaliplatin or FOLFOXIRI. The duration of prior ACT was similar across study arms, ranging from 5.6–5.8 months for the first line of ACT. Conclusions: In the BEACON CRC study, pts treated with the doublet for BRAF V600E-mutant mCRC demonstrated similar OS regardless of prior therapies or duration of prior therapy use. This exploratory post-hoc analysis provides data that reflect the prior treatment landscape clinicians may face when deciding subsequent treatment regimens for pts with BRAF V600E-mutant mCRC. Clinical trial information: NCT02928224. [Table: see text]
Abstract I23: Identifying metabolic dependencies in pancreatic cancer
Authors: Alec Kimmelman
Journal: Cancer Research (2019)

Abstract Pancreatic cancers are highly resistant to currently available therapeutics, which results in a 5-year survival rate of approximately 6%. We believe that this resistance points toward altered cell metabolic pathways. In this regard we have previously shown that that oncogenic Kras promotes a rewiring of pancreatic cancer metabolism, allowing carbon sources to be utilized in a variety of biosynthetic pathways. Importantly, several of these metabolic pathways are critical for tumor growth and therefore represent potential therapeutic targets. Ongoing studies from our group are exploring targeting various aspects of metabolism as therapeutic approaches. Additional studies from our group have demonstrated pancreatic cancers have elevated basal autophagy, which is required for their continued growth. Importantly, inhibition of autophagy pharmacologically or genetically leads to decreased oxidative phosphorylation, a drop in ATP production, and ultimately growth inhibition. These findings have implicated autophagy as a key component of pancreatic cancer metabolism and have motivated the opening of multiple clinical trials assessing the efficacy of hydroxychloroquine as an autophagy inhibitor in pancreatic cancer. These trials are now showing activity of autophagy inhibition in this disease. Recently, we have identified an autophagy/lysosome-dependent metabolic crosstalk that exists between pancreatic tumor cells and the surrounding stroma. Ongoing work from our group seeks to understand the metabolic contributions that autophagy makes in pancreatic tumors as well as further define the metabolic crosstalks. These and other aspects of pancreatic cancer metabolism will be discussed. Citation Format: Alec Kimmelman. Identifying metabolic dependencies in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I23.
Integration of molecular cancer classification and next-generation sequencing to identify metastatic patients eligible for PARP inhibitors.
Authors: Lowell L. Hart, Kai Treuner, Li Ma, Jenna Wong, Catherine A. Schnabel, James Andrew Reeves
Journal: Journal of Clinical Oncology (2021)

e15080 Background: Olaparib, rucaparib, and niraparib are 3 poly-ADP-ribose polymerase inhibitors (PARPi) approved by the FDA for ovarian, breast, pancreatic, prostate, fallopian tube and peritoneal cancers with BRCA mutations. Several ongoing clinical trials aim to determine the efficacy of PARPi in various other cancer types, including specific cancer subtypes, such as clear cell renal cell carcinoma and cholangiocarcinoma either as monotherapy or combination therapy; however, eligibility for PARPi therapy requires the identification of the primary tumor type and confirmation of BRCA mutation. The 92-gene assay (CancerTYPE ID) is a validated gene expression classifier of 50 tumor types and subtypes for metastatic patients with unknown or uncertain diagnoses. Multimodal biomarker testing, including next-generation sequencing (NGS), enables identification of actionable biomarkers to guide targeted therapy selection. In the current study, a database of metastatic cases that integrates tumor type with biomarker analysis was characterized to identify those eligible for PARPi treatment. Methods: MOSAIC (Molecular Synergy to Advance Individualized Cancer Care) is an IRB-approved, de-identified database of cases submitted for CancerTYPE ID testing with tissue-guided multimodal biomarker testing by NGS, including tumor mutational burden (TMB) fluorescent in situ hybridization (FISH), and microsatellite instability (MSI), and immunohistochemistry (IHC) (NeoTYPE profiles, Neogenomics). For the current study, metastatic cancers classified as ovarian, breast, pancreatic, or prostate were identified in the database, followed by NGS analysis to detect mutations in BRCA1 or BRCA2. Results: The current analysis included 2151 CancerTYPE ID cases, from which 71 ovarian, 47 breast, 12 pancreatic and 15 prostate cancer cases were identified. Out of 46 cases of ovarian cancer with molecular biomarker results, NGS identified 7 (15.3%) cases with BRCA1 mutation and 4 (8.7%) cases with BRCA2 mutation. Additionally, 4 (10.5%) cases with BRCA1 mutation and 1 (2.6%) case with BRCA2 mutation out of 38 cases of breast cancer with BRCA results were detected. No cases of prostate cancer or pancreatic cancer with mutations in BRCA1 or BRCA2 were detected. Conclusions: These findings in metastatic patients demonstrate the clinical utility of tumor type identification combined with molecular biomarker profiling, leading to additional options for patients with advanced disease. Specifically, analysis of the MOSAIC database identified a subset of patients with metastatic cancers eligible for PARPi therapy based on tumor type and BRCA mutation status. As new and approved PARPi are evaluated for efficacy in additional tumor types, patients can be identified that may be eligible for these targeted cancer drugs.