tbuckley/cabot-search huggingface dataset:
LincRNA-p21 as predictive response marker for preoperative chemoradiotherapy in rectal cancer.
Authors: Jose Carlos Benitez, Tania Diaz, Carme Ferrer, Melissa Acosta, Mariano Monzo, Luis Cirera, Benjamin Besse, Alfons Navarro, Marc Campayo
Journal: Journal of Clinical Oncology (2021)

e15534 Background: Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients (pts). Despite the benefits of CRT, its use in non-responder pts can be associated with increased toxicities and resection delay. The identification of CRT response biomarkers, such as long non-coding RNAs (lncRNA), could improve the management of these pts. LincRNA-p21 is a lncRNA involved in the p53 pathway and angiogenesis regulation that acts as prognostic marker in several tumors. We aim to study lincRNA-p21 expression in pretreatment samples from RC pts treated with CRT to evaluate whether lincRNA-p21 can act as a predictive biomarker for CRT response. Methods: RNA from pretreatment endoscopy biopsies from 58 RC pts treated with preoperative CRT at Mutua Terrassa University Hospital were analyzed. Pathological response was classified according to the tumor regression grade (TRG) Dworak classification. LincRNA-p21 expression was determined by RTqPCR and was correlated with CRT response and, time to relapse (TTR), disease-free survival (DFS) and overall survival (OS). Results: Samples from 58 pts were analyzed. Most of them males (n = 40, 69%). Median age at diagnosis of 67 (44-82) years. Fifty (86.2%) pts reported stage III and, 42 (72.4%) pts assessed TRG 0-3 with a 70.7% of downstaging reported. LincRNA-p21 was upregulated in stage III tumors (p &lt; 0.0001) and also in tumors with worst response to CRT regarding TRG, TGR0-3 (TRG0-3, n = 42 vs TRG4, n = 16, p = 0.019). In this line, the ROC curve analysis showed that lincRNA-p21 expression had capacity to distinguish pts with maximum response (TRG4) from others (AUC:0.7; p = 0.02). The binary logistic regression analysis validated its independence as response biomarker. LincRNA-p21 levels correlated with pts relapse after surgery. When the pts were classified in 3 groups, high, medium and low, according to lincRNA-p21 levels, RC pts with highest lincRNA-p21 expression had the shortest TTR. TTR for pts with high levels was 74.5 months (m) (95% CI:31-117), while it was 114 m (95% CI:95-133) for those with Medium levels and 123 m (95% CI:111-134) for those with low levels (p = 0.047). Conclusions: LincRNA-p21 is a marker of advanced disease and worse response to CRT. LincRNA-p21 may add valuable information for individualizing pre-operative CRT in locally advanced RC pts.
Meta-Analysis of Reversal Agents for Severe Bleeding Associated With Direct Oral Anticoagulants
Authors: Antonio Gómez-Outes, Pau Alcubilla, Gonzalo Calvo-Rojas, Ana Isabel Terleira-Fernández, Ma Luisa Suárez-Gea, Ramón Lecumberri, Emilio Vargas-Castrillón
Journal: Journal of the American College of Cardiology (2021)
The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES.
Authors: Andrew J. Armstrong, Taro Iguchi, Arun Azad, Arnauld Villers, Boris Alekseev, Daniel P. Petrylak, Russell Zelig Szmulewitz, Antonio Alcaraz, Neal D. Shore, Jeffrey Holzbeierlein, Francisco Gomez-Veiga, Brad Rosbrook, Fabian Zohren, Gabriel P. Haas, Georgia Gourgioti, Nader N. El-Chaar, Arnulf Stenzl
Journal: Journal of Clinical Oncology (2021)

5071 Background: In ARCHES (NCT02677896), ENZA + ADT reduced the risk of radiographic progression and improved secondary clinical outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) with variable patterns of disease spread over placebo (PBO) + ADT. This post hoc analysis aimed to evaluate the efficacy of ENZA + ADT in patients with bone oligometastatic mHSPC compared to polymetastatic mHSPC in ARCHES. Methods: Patients with mHSPC (n = 1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel chemotherapy. This post hoc analysis included patients with bone metastases only, categorized as oligometastatic (1–≤5 metastases) or as polymetastatic (≥6 metastases) based on central review at screening. Efficacy outcomes were compared across treatment arms. Results: Of the ARCHES population with bone metastases (n = 512), the largest subgroup included patients with ≤5 metastases (ENZA + ADT, n = 160; PBO + ADT, n = 136). Baseline characteristics were generally comparable between treatment arms and across subgroups. When compared to PBO + ADT, ENZA + ADT improved rPFS and secondary endpoints in patients with ≤5 metastases (Table). Similar results were observed across other oligometastatic subgroups (1–≤4) as well as in polymetastatic disease (≥6). The safety profile of ENZA + ADT versus PBO + ADT was similar across subgroups and consistent with previous findings. Conclusions: This post hoc analysis demonstrates that ENZA + ADT provides clinical benefit across bone oligometastatic as well as polymetastatic mHSPC, supporting the utility of ENZA irrespective of metastatic burden in the ARCHES study. Clinical trial information: NCT02677896. [Table: see text]
Neoadjuvant chemoradiotherapy with sequential ipilimumab and nivolumab in rectal cancer (CHINOREC): A prospective randomized, open-label, multicenter, phase II clinical trial.
Authors: Johannes Laengle, Irene Kuehrer, Dietmar Pils, Julijan Kabiljo, Judith Stift, Friedrich Herbst, Bernhard Dauser, Matthias Monschein, Peter Razek, Stefanie Haegele, Wolfgang Huller, Reinhold Fuegger, Hans Geinitz, Andreas L. Petzer, Clemens Bitterman, Friedrich Laengle, Dietmar Tamandl, Joachim Widder, Rainer Schmid, Michael Bergmann
Journal: Journal of Clinical Oncology (2021)

TPS3623 Background: Immune checkpoint inhibitors (ICI), such as ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) or nivolumab (anti-programmed cell death protein 1) have been proven to be an effective strategy in solid cancers. However, ICI seem not to be effective in microsatellite stable (MSS) cancers. As they might lack an immunogenic priming, radiotherapy (RT) is capable to induce an immunogenic cell death (ICD) and subsequently an immunogenic tumor immune microenvironment (TIME). Thus, RT might restore the susceptibility of MSS tumors to ICI and consequently leading to an effective anti-tumor immune response. Methods: This is a prospective, randomized, open-label, multicenter, phase II investigator-initiated clinical trial (IIT), including patients with locally advanced rectal cancer (LARC). Patients receive either neoadjuvant chemoradiotherapy (CRT) alone (50 Gy in 2 Gy fractions over 25 working days + capecitabine 1650 mg/m 2 /d PO) or in combination with ipilimumab (1 mg/kg IV on day 7) and nivolumab (3 mg/kg IV on day 14, 28 and 42). Patients will undergo surgery within 10-12 weeks post CRT. The primary endpoint is incidence of treatment-emergent adverse events (AEs) assessed by the Clavien-Dindo classification of surgical complications and the common terminology criteria of adverse events (CTCAE). Secondary objectives are radiographic and pathological therapy response. Serial liquid (plasma, serum and peripheral blood mononuclear cells) and tissue biopsies will be taken before, during and after neoadjuvant treatment. Genomic, transcriptomic, epigenomic and proteomic pattern of liquid and tissue biopsies, as well as the immune cell infiltrate of resected specimen, will be correlated with therapy response and clinical outcome. Currently 8 of planned 80 patients have been enrolled. Registration numbers: NCT no. NCT04124601, EudraCT no. 2019-003865-17. Clinical trial information: NCT04124601.
Comparison of 18F-FDG, 68Ga-FAPI, and 68Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor
Authors: Zhaoting Cheng, Sijuan Zou, Siyuan Cheng, Shuang Song, Xiaohua Zhu
Journal: Clinical Nuclear Medicine (2021)

Abstract We present image findings of 18 F-FDG, 68 Ga-FAPI, and 68 Ga-DOTATATE PET/CT in a 35-year-old woman with multiple metastases of pancreatic neuroendocrine tumor. The images of PET/CTs using 3 different tracers all showed multiple foci of increased activities in the liver and pancreas body, in which 68 Ga-FAPI PET/CT displayed the highest tumor-to-liver ratios. However, 68 Ga-DOTATATE PET/CT detected more small metastatic lymph node and bone metastases, which were missed by both FDG and FAPI PET/CT.
Molecular characteristics of H3 K27M mutation gliomas in Chinese adults.
Authors: Peng Zhang, Tiantian Han, Yi Lu, Weijie Sun, Wanglong Deng, Guanghua Lu, Didi Guo, Xiaomin Li, Fanfeng Bu
Journal: Journal of Clinical Oncology (2021)

e14018 Background: Diffuse midline glioma H3 K27M–mutant is a specific entity added to the 2016 update of the WHO classification of CNS tumors. H3K27M-mutant gliomas are diagnosed primarily in children and adolescents with TP53 and/or ATRX mutations. However, the characteristics of H3 K27M-mutant gliomas in adults have not been explicitly described. Methods: We performed the 131-gene panel targeted sequencing on tumor samples from 33 adults H3 K27M-mutant gliomas( &gt; 18 years) and 13 children and adolescents H3 K27M-mutant gliomas(≤18 years) in a CAP certified laboratory. Somatic mutations, copy number variations, and fusion genes were detected following the standard operating procedure (SOP). The MS-based assay measured MGMT promoter methylation. We calculated the tumor location and the median age in different cohorts. Results: In our adult cohort, 22/33（66.7%）had a midline location（spinal cord n = 2, thalamus n = 7, brainstem n = 6, cerebellum n = 3, pineal region n = 1, Basal ganglia region n = 3）, 6/33（18.1%）had a non-midline location (Lateral ventricle n = 2, Cerebral hemispheres n = 4). In the children and adolescents cohort, 11/13（84.6%）occurred in midline location, 1/13(7.7%) occurred in the Lateral ventricle. MGMT promoter methylation did not differ in adult and pediatric H3 K27M-mutant gliomas (12.1% vs. 0). H3 K27M-mutant adult gliomas significantly co-occurred with the NF1 mutation(P = 0.008937). The median age of H3 K27M-mutant adult gliomas with NF1 modification (13/33, 39.4%) is higher than the NF1 wild type (49 years vs. 38 years, P = 0.107), although the difference has no statistical significance. Conclusions: In Chinese adults, as in children, H3 K27M mutation gliomas are characterized by a constant midline location, low rate of MGMT promoter methylation. Inconsistently, H3 K27M mutant adult gliomas are featured by a higher rate of NF1 mutations. Our molecular profiling analysis revealed the H3 K27M mutation in adult gliomas. Our research suggests potential molecular pathogenesis of H3K27M mutant adult gliomas and identifies more therapeutic targets for precision medicine.
Plasma hPG<sub>80</sub> circulating prograstin levels in cancer patients in Nigeria: Prolevcan study.
Authors: Omolara A. Fatiregun, Dominique Joubert, Berengere Vire, Abigail Anni Frances Simon-Hart, Olaniyi Andrew Adekeye, Younes Mahi, Alexandre Prieur
Journal: Journal of Clinical Oncology (2021)

3029 Background: Progastrin is a tumor-promoting peptide which is detectable in the blood of patients with different cancers. hPG 80 (circulating progastrin) is produced by cancer cells. Recently it was reported that hPG 80 is detected in the blood of cancer patients, suggesting its potential utility for cancer detection. In this Nigerian study, we assessed the performance of hPG80 in diagnosed cancer patients versus healthy volunteers. Methods: Plasma samples of 50 patients with breast (n = 41) and colorectal (n = 9) cancer, aged from 26 to 70 years, were assayed for hPG 80 levels with the DxPG80 kit from ECS-Progastrin. The diagnostic performance (ROC AUC) of hPG 80 was assessed compared to 50 healthy volunteers aged from 21 to 38 years. Results: Plasma hPG 80 levels were significantly higher in cancer patients compared to controls (median values: 4.59 pM (IQR: 2.02-8.27 pM) vs 1.37 pM (IQR: 0-3.11 pM), p &lt; 0.0001). The median value of hPG 80 level was 3.96 pM (IQR: 1.61-7.89 pM) for breast cancers and 6.43 pM (IQR: 2.80-15.86 pM) for colorectal cancer patients. ROC AUC for all cancers, breast cancer and colorectal cancer were 0.75, 0.74 and 0.82 respectively. There was no correlation between hPG 80 blood levels with age or CA15.3 levels. Conclusions: Plasma hPG 80 is a simple and relatively affordable blood test, it shows potential utility as a biomarker for cancer detection, monitoring and treatment assessment. Further prospective studies are needed to explore and confirm its potential.
Abstract 16158: Effectiveness of Hybrid Nano-Coating for the Next-Generation Drug-Eluting Stents Technology
Authors: Terumitsu Hasebe, Shunto Maegawa, Tomohiro Matsumoto, Nami Nishimura, Masao Nishimura
Journal: Circulation (2019)

Introduction: Recently, the U.S. Food & Drug Administration (FDA) has approved the Biotronik’s Orsiro drug-eluting stents (DES) system. This is the first ultrathin, bioabsorbable polymer-coated DES...
Prospective cohort study of Kaposi sarcoma treated under real-world conditions in Malawi.
Authors: Edwards Kasonkanji, Yolanda Gondwe, Morgan Dewey, Joe Gumulira, Matthew Painschab, Mina Hosseinipour, Dirk Dittmer
Journal: Journal of Clinical Oncology (2021)

11569 Background: Kaposi sarcoma (KS) is the leading cancer in Malawi (34% of cancers). Outside of clinical trials, prospective KS studies from sub-Saharan Africa (SSA) are few and limited by loss to follow up. We conducted a prospective KS cohort study of standard of care bleomycin/vincristine (BV) at Lighthouse HIV clinic, in Lilongwe, Malawi. Methods: We enrolled pathologically confirmed, newly diagnosed, HIV+ KS patients from Feb 2017 to Jun 2019. We collected clinical and treatment characteristics, toxicity, and outcomes of KS with follow-up censored Jun 2020. Patients were treated with bleomycin (25 mg/m 2 ) and vincristine (0.4 mg/m 2 ) every 14 days for a planned maximum of 16 cycles. STATA v13.0 was used to calculate descriptive statistics and Kaplan Meier survival analysis. Toxicity was graded using NCI CTCAE v5.0. Results: We enrolled 138 participants, median age 36 (IQR 32-44) and 110 (80%) male. By ACTG staging, 107 (78%) were T1 (tumour severity), 46 (33%) were S1 (illness severity) and 46 (33%) had Karnofsky performance status ≤70. Presenting symptoms included edema in 69 (53%), visceral disease in 9 (7%), and oral involvement in 43 (33%). Prior to KS diagnosis, 70 (51%) participants were aware of being HIV+ for median 17 months (IQR 6-60) and had been on ART for median 16 months (IQR 6-60). Median CD4 count was 197 (IQR 99-339), median HIV-viral load was 2.6 log copies/mL (IQR 1.6 – 4.8) and 57% were HIV-suppressed ( &lt; 1000 HIV copies/ml). The median number of cycles was 16 (IQR 7-16). 62 (45%) participants missed at least one dose due to stock out. Amongst patients with missed doses, the median number was 3 (IQR 2-4) for bleomycin and 2 (IQR 1-3) for vincristine. 14 (10%) participants experienced at least one reduced dose due to toxicity. 5 (4%) participants suffered grade ≥3 anaemia, 13 (9%) grade ≥3 neutropenia, and one participant had grade 4 bleomycin-induced dermatitis. There was no reported grade ≥3 bleomycin lung toxicity or vincristine-induced neuropathy. Of 115 evaluable participants, responses at the end of therapy were: complete response in 52 (45%), partial response in 27 (23%) stable disease in 5 (4%), and progressive disease in 31 (28%). Median duration of follow-up was 20 months. At censoring, 69 (50%) were alive, 36 (26%) dead, and 33 (24%) lost to follow-up. Overall survival is shown Table as crude and worst-case scenario; worst-case assumes all participants lost to follow up died. Conclusions: Here, we present one of the most complete characterizations of KS presentation and treatment from SSA. As in other studies from the region, the majority of patients presented with advanced disease, chemotherapy stock-outs and loss to follow up were common, and mortality was high. Studies are planned to understand the virologic characteristics, improve therapies, and better implement existing therapies.[Table: see text]
Novel non-terminal tumor sampling procedure using fine needle aspiration supports immuno-oncology biomarker discovery in preclinical mouse models
Authors: Suzanne Isabelle Sitnikova, Sophie Munnings-Tomes, Elena Galvani, Stacy Kentner, Kathy Mulgrew, Chris Rands, Judit España Agustí, Tianhui Zhang, Kristina M Ilieva, Guglielmo Rosignoli, Hormas Ghadially, Matthew J Robinson, Tim Slidel, Robert W Wilkinson, Simon J Dovedi
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immuno-oncology therapies are now part of the standard of care for cancer in many indications. However, durable objective responses remain limited to a subset of patients. As such, there is a critical need to identify biomarkers that can predict or enrich for treatment response. So far, the majority of putative biomarkers consist of features of the tumor microenvironment (TME). However, in preclinical mouse models, the collection of tumor tissue for this type of analysis is a terminal procedure, obviating the ability to directly link potential biomarkers to long-term treatment outcomes. Methods To address this, we developed and validated a novel non-terminal tumor sampling method to enable biopsy of the TME in mouse models based on fine needle aspiration. Results We show that this technique enables repeated in-life sampling of subcutaneous flank tumors and yields sufficient material to support downstream analyses of tumor-infiltrating immune cells using methods such as flow cytometry and single-cell transcriptomics. Moreover, using this technique we demonstrate that we can link TME biomarkers to treatment response outcomes, which is not possible using the current method of terminal tumor sampling. Conclusion Thus, this minimally invasive technique is an important refinement for the pharmacodynamic analysis of the TME facilitating paired evaluation of treatment response biomarkers with outcomes and reducing the number of animals used in preclinical research.
A randomized phase III, two-arm trial of paclitaxel, carboplatin, and maintenance letrozole versus letrozole monotherapy in patients with stage II-IV, primary low-grade serous carcinoma of the ovary or peritoneum.
Authors: Amanda Nickles Fader, Lilian Tran Gien, Austin Miller, Al Covens, David Marc Gershenson
Journal: Journal of Clinical Oncology (2021)

TPS5601 Background: Low-grade serous carcinoma of the ovary or peritoneum (LGSOC) is a rare subtype of epithelial carcinoma. Differences in epidemiology, pathogenesis, disease presentation, and clinical outcomes have been characterized between women diagnosed with LGSOC and those with the p53-driven high-grade serous carcinoma (HGSOC). Ultimately, patients with LGSOC should be treated differently than those with HGSOC. Several studies suggest that LGSOC is relatively chemoresistant and that most tumors robustly express estrogen and progesterone receptors. Recently, retrospective reports suggest that utilization of the aromatase inhibitor, letrozole, as monotherapy or in addition to platinum/taxane-based chemotherapy in those with primary advanced-stage LGSOC results in preliminarily promising survival outcomes. Methods: This study is a two-arm, randomized, open-label, Phase III clinical trial. The primary objective is to assess whether letrozole monotherapy (2.5 mg po daily) is non-inferior to carboplatin (AUC 5-6) and paclitaxel (175 mg/m 2 ) followed by letrozole maintenance therapy with respect to progression free survival in women with primary, Stage II-IV LGSOC who have undergone an attempt at maximal surgical cytoreduction. Secondary endpoints include incidence of adverse events, objective response rate in those with measurable disease after surgery, response duration, overall survival, and adherence to letrozole maintenance therapy. Study subjects must have undergone a bilateral salpingo-oophorectomy, and p53 IHC testing of tumors is required to rule out those with aberrant p53 expression commonly observed in HGSOC tumors. Study strata include residual disease status and country of enrollment. Four hundred and fifty patients will be enrolled in the United States, Canada and South Korea through the NRG Oncology trials network. Correlative aims include analyzing the association of ER/PR tumoral expression with aromatase inhibitor therapy response and determining ESR1 mutational status in those who develop letrozole resistance. The study includes two interim analyses; at 20% information time, a futility analysis will be conducted, and at 40% information time, both efficacy and futility will be assessed. This is one of the first randomized trials performed in women with primary, advanced LGSOC, and the study is open with 71 patients enrolled at the time of abstract submission. Clinical trial information: NCT04095364.
EMBR-14. INFLUENCE OF MRI FEATURES ON THE SURVIVAL AND IMPACT ON INDIVIDUAL MOLECULAR SUBGROUPS: RESULT FROM 171 PATIENTS WITH MEDULLOBLASTOMA
Authors: Archya Dasgupta, Madan Maitre, Babusha Kalra, Abhishek Chatterjee, Rahul Krishnatry, Jayant Goda, Neelam Shirsat, Sridhar Epari, Ayusi Sahay, Amit Janu, Sona Pungavkar, Girish Chinnaswamy, Aliasgar Moiyadi, Prakash Shetty, Tejpal Gupta, Rakesh Jalali
Journal: Neuro-Oncology (2021)

Abstract Background To investigate the influence of different MRI features on survival in patients with medulloblastoma. Methods A total of 171 patients were included in the study, including 131 pediatric and 40 adults (&amp;gt; 18 years). A set of 16 pre-defined semantic MRI features was analyzed using T1W (pre and post-contrast), T2W, and diffusion-weighted imaging (additional sequences as available). Patients with a definitive event (recurrence) or a minimum follow up of 12 months (in case of no recurrence) were included in the current analysis. All patients were treated and followed up according to standard institutional practice. Log-rank test was used for univariate analysis (UVA) and Cox regression for multivariate analysis (MVA). Results The molecular subgroups were as follows: WNT-27 children, 7 adults; SHH-31 children, 29 adults; group 3–32 children, 3 adults; and group 4–41 children, 1 adult. The median follow up was 45 months (range 1 to 137 months). For all the patients, on UVA the recurrence-free survival (RFS) was significantly (p&amp;lt;0.05) influenced by location-vertical, brainstem involvement, contrast uptake area, contrast heterogeneity, necrosis, and calcification. Similar factors (T2W homogeneity instead of area of contrast) impacted overall survival (OS). On MVA, location-vertical, brainstem involvement, and calcification were significant features for both RFS and OS. Tumor location-vertical was the only feature influencing RFS and OS within the SHH subgroup. For group 3 tumors, contrast uptake area (RFS and OS) and calcification (RFS alone) had a significant influence (MVA). Within group 4, contrast pattern (RFS) and T2W homogeneity (RFS and OS) were significant factors on UVA, none on MVA. Conclusion Several MRI features can be linked with survival in patients with medulloblastoma, with a specific impact on individual molecular subgroups. Considering the entire population, non-central location on the vertical aspect, tumors away from brainstem, calcification are risk factors associated with inferior outcomes.