tbuckley/cabot-search huggingface dataset:
A single-arm phase Ib study of autologous cytokine-induced killer (CIK) cell immunotherapy in combination with sintilimab plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)-CCICC-002.
Authors: Xiubao Ren, Li Zhou
Journal: Journal of Clinical Oncology (2021)

2531 Background: Immune checkpoint inhibitors plus chemotherapy had showed benefits for advanced non–small-cell lung cancer (NSCLC) patients without targetable mutations. Autologous cytokine-induced killer (CIK) cells can restore the antitumor immunity to improve patient outcome. Combining CIK cells with anti-PD-1 mAb plus chemotherapy may strengthen the results in patients with advanced NSCLC. Methods: This is a single-center, open-label, phase 1b trial of combination CIK cells with sintilimab (anti-PD-1 mAb) plus chemotherapy in stage IIIB-IV NSCLC patients. Systemic therapy naïve patients received platinum-based doublet chemotherapy, sintilimab, and CIK cells every 3 weeks for 4 cycles，then sintilimab, and CIK cells for maintenance therapy until disease progression or unacceptable toxicity. Results: From May 2019 to Jan 2021, 34 patients (19 squamous， 15 non-squamous NCSLC)aged 46-73 years (median age 64 years) were enrolled. Among 32 evaluable patients, the ORR was 81.3% (73.7% in squamous and 92.3% in non-squamous NSCLC)and DCR was 100%. Among the 25 PR assessed by RECIST, CMR was demonstrated in 5 (23.1%) by PET-CT. Among 3 patients with brain metastases, 2 patients achieve intracranial CR, and 1 was PR. With a median follow-up of 7.5 months, the median DOR was not reached (range 0.5m-NA), and the median PFS and OS were not mature. Grade 3 or more TRAEs included pneumonia (n = 3); thrombocytopenia, leukopenia (n = 2 each); anemia, dysphagia, cardiomyopathy, rash (n = 1 each). Biomarkers and subgroups which correlated with efficacy and AEs are being analyzed included TMB, PDL1 expression, distribution of TILs, cytokines and so on. Conclusions: CIK cells therapy in combination with sintilimab plus chemotherapy were well tolerated and showed encouraging efficacy. Further studies are warranted to confirm these preliminary results. Research Sponsor: Tianjin Medical University Cancer Institute and Hospital. Clinical trial information: NCT03987867. [Table: see text]
Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity
Authors: BH Kushner, NK Cheung
Journal: Blood (1992)

Abstract We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CD11a ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM- CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11/CD18 molecules.
Опыт применения отечественной высокочастотной электросваривающей технологии в хирургическом лечении больных с абдоминальной патологией
Authors: A.M. Babiy, B.F. Shevchenko, V.M. Ratchik, D.D. Kunkin
Journal: GASTROENTEROLOGY (2014)

Представлен опыт применения у 176 больных технологии электросваривания биологических тканей отечественным высокочастотным электрическим генератором ЕК 300 М1 в открытой и лапароскопической хирургии при абдоминальной патологии. Анализ полученных результатов свидетельствует, что электросваривание живых тканей обеспечивает надежный гемостаз, способствует процессам репарации тканей после их разъединения.
Randomized, double-blind, placebo-controlled phase 3 study of ibrutinib plus rituximab in patients with previously untreated marginal zone lymphoma (MZL).
Authors: Ariela Noy, Stephanie Hughes, Erin Biggar, Matthew Bogdan
Journal: Journal of Clinical Oncology (2021)

TPS7576 Background: First-line treatment options for patients with MZL include single-agent immunotherapy, chemotherapy, or chemoimmunotherapy. While chemoimmunotherapy has a higher toxicity profile than immunotherapy alone, it may lead to longer progression-free survival (PFS). Rituximab, an anti-CD20 antibody, is FDA approved for the first-line treatment of follicular lymphoma but not specifically for advanced MZL. Ibrutinib is a Bruton’s tyrosine kinase inhibitor approved in the United States for patients with MZL who require systemic therapy and have received ≥1 prior anti-CD20-based therapy. The combination of ibrutinib and rituximab has proven effective and is well tolerated in other B-cell lymphomas; it may serve as an effective chemotherapy-free option for the treatment of previously untreated MZL. Methods: NCT04212013 is a multicenter, double-blind, placebo-controlled, randomized, phase 3 study designed to compare the efficacy of ibrutinib + rituximab vs placebo + rituximab in patients with previously untreated MZL. Adults (≥18 y) with histologically documented MZL (splenic, nodal, and extranodal subtypes), no prior systemic treatment for MZL (prior splenectomy or other local surgical or radiation treatment allowed), measurable disease on CT scan, documented evidence of need for treatment, and Eastern Cooperative Oncology Group performance status ≤2 are eligible. Patients will be randomly assigned 1:1 to receive ibrutinib 560 mg once daily or placebo; all patients will also receive rituximab 375 mg/m 2 on days 1, 8, 15, and 22 of cycle 1. Subcutaneous dosing after dose 1 is allowed. Treatment with ibrutinib or placebo will continue for 30 mo or until disease progression, unacceptable toxicity, patient or investigator decision to withdraw, noncompliance, death, or study termination. Clinical assessments will occur every 4 weeks until week 13, at week 25, and then every 6 mo thereafter. Imaging assessments will be conducted at week 13, at week 25, and then every 6 mo thereafter. Response will be investigator assessed per the revised International Working Group for Non-Hodgkin Lymphoma (RECIL) criteria. At month 30, patients who have a complete response (CR) will discontinue treatment; patients who have a partial response (PR) or stable disease may continue treatment at investigator discretion. Safety will be assessed throughout the study and for 30 days after the last dose of study treatment. The primary endpoint is CR rate at month 30. Secondary endpoints include overall response rate (CR + PR), duration of response, PFS, overall survival, and safety. Enrollment has started and will continue until approximately 138 patients are enrolled. Clinical trial information: NCT04212013.
Association of HER2 expression with pathologic features and prognosis in stage II and III colon cancer.
Authors: Zehua Wu, Huabin Hu, Yanhong Deng
Journal: Journal of Clinical Oncology (2021)

3524 Background: We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression in stage II and III colon cancer after curative resection. Methods: Paraffin-embedded tumors from consecutive primary stage II and III colon cancer patients were analyzed for HER2 protein expression by immunohistochemistry between April, 2013 and May, 2020. HER2 determination of immunohistochemistry scores (0/1+/2+/3+) was according to HERACLES diagnostic criteria. Results: A total of 2088 stage II and III colon cancer patients were included (53.8% stage II, 46.3% stage III). HER2 scored positive (3+) was detected in 48(2.3%) tumors, and was correlated with younger age (P &lt; 0.001), well/moderate differentiation (P = 0.026), proficient mismatch repair (pMMR) (P = 0.045) and KRAS wild-type (P &lt; 0.001). HER2 scored positive (3+) was not significantly associated with disease-free survival (DFS) compared with HER2 scored negative (0/1+), neither in stage III patients (multivariable HR, 0.86; 95CI, 0.38 to 1.94; P = 0.717), nor in stage II patients (multivariable HR, 1.68; 95CI, 0.74 to 3.84; P = 0.218). In a separate analysis involving stage II patients without any high-risk factor (n = 741), those with HER2 scored positive (3+) tumors (n = 16) showed significantly reduced DFS (multivariable HR, 2.91; 95CI, 1.04 to 8.81; P = 0.041) compared with patients with HER2 scored negative (0/1+) tumors, independent of sex, age and MMR status. Conclusions: HER2 scored positive (3+) was independently associated with poor DFS in stage II colon cancer patients without high-risk factors. HER2 expression determination may help to judge the prognosis of those patients and guide adjuvant chemotherapy.
MAPK pathway alteration may be a new integrated diagnosis term.
Authors: Chuandong Cheng, Ying Ji, Tiantian Han, Xiaomin Li, Yahui Huang, Weijie Sun, Guanghua Lu, Wanglong Deng, Ran Ding, Fanfeng Bu
Journal: Journal of Clinical Oncology (2021)

e14022 Background: The 2016 CNS WHO classification is the first to include molecular factors to classify in glioma. We are in the age of glioma subgroups, in which the category depended on the histological and molecular composition, providing more clinical behavior, prognosis, and therapeutic targets hints. The most well-known molecular modifications are IDH1/2 mutation, ATRX variant, TP53 variant, BRAF mutation or fusion, 1p/19q co-deletions. However, there is a diagnostic term“NOS” in the 2016 CNS WHO classification，which indicates that a tumor could not be placed into a more specific WHO category. Here, our analysis of the MAPK pathway may suggest a new subtype. Methods: Targeted next-generation DNA sequence of the 131-genes panel was performed on gliomas in 119 patients. We measured the somatic variations in the MAPK pathway after filtering known driver mutations. The analysis of genomic alterations was performed using a two-sided Fisher exact test. Results: 90/119（75.6%）were excluded due to known driver mutations. 29/119(24.4%) were classified in NOS with a typical “single MAPK pathway alteration” and different histological characteristics and WHO grade. The median age at diagnosis was 35 years (4-79) in our gliomas. The most frequent mutations were NF1(10/29), FGFR1(7/29), KRAS (6/29), BRAF (3/29), PTPN11(2/29), although there are other gene mutations like FGFR2, FGFR3, AKT1, MAP2K1. According to cIMPACT-NOW update 4, our pediatric gliomas ( &lt; 30 years, n = 14) could be identified as “diffuse glioma, other MAPK pathway alteration.” Our adult gliomas have a higher frequency of NF1 mutations（8/15 vs. 2/14, p = 0.05), a lower KRAS (1/15 vs. 5/14) and FGFR1 (2/15 vs. 5/14) mutations than children. Conclusions: Our result suggests that MAPK pathway alteration may be a new integrated diagnosis term in all ages of glioma. Moreover, KRAS and FGFR1 may be associated with pediatric gliomas. NF1 is more common in adult gliomas.
Single-arm, phase 2 study of regorafenib plus nivolumab in patients with mismatch repair-proficient (pMMR)/microsatellite stable (MSS) colorectal cancer (CRC).
Authors: Marwan Fakih, Kanwal Pratap Singh Raghav, David Z. Chang, Johanna C. Bendell, Timothy Larson, Allen Lee Cohn, Timothy K. Huyck, David Cosgrove, Joseph A. Fiorillo, Lawrence E. Garbo, Shruthi Ravimohan, Von Potter, David D'Adamo, Neelesh Sharma, Ying A. Wang, Sabine Coppieters, Matthias Herpers, Carolina Soares Viana de Oliveira, Andrew Scott Paulson
Journal: Journal of Clinical Oncology (2021)

3560 Background: The role of immunotherapy in the treatment of pMMR/MSS metastatic CRC is not established. A Japanese phase 1b trial in this setting showed the combination of regorafenib (multikinase inhibitor with immunomodulatory activity) plus nivolumab (anti PD-1) had encouraging activity and manageable safety (Fukuoka, 2020). This study further assessed the safety and efficacy of this combination. Methods: Patients (pts) from the US aged ≥18 years who progressed on/were intolerant to standard chemotherapy were enrolled. Regorafenib was given orally, once daily in 28-day (D) cycles (21D on/7D off) plus IV nivolumab 480 mg on D1. Regorafenib starting dose was 80 mg; if well tolerated, it could be escalated to 120 mg in Cycle 2. Primary endpoint was overall response rate (ORR; RECIST 1.1); secondary aims included disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety (NCI-CTCAE v5.0 grade). Biomarker analysis was exploratory. Results: 70 pts (59% male) started treatment. At baseline, median age was 57 years (range 34–85), ECOG PS 0/1 was 51%/49%, 67% had liver metastases (mets), and the primary tumor site was right-sided colon in 36% and rectum in 17%. Median number of cycles was 3.0 (range 1–13); 41% of pts escalated regorafenib to 120 mg. Five pts (7.1%) had a partial response (PR) lasting ≥16 weeks (wks) and 22 (31.4%) had stable disease (SD); pts without liver mets had a higher ORR (21.7%). In pts with tumor samples (n = 40), higher baseline expression (IHC) of cytotoxic T cells (CD3+/CD8+/GranzymeB+), Tregs (FoxP3+), and macrophages (CD68+) trended with clinical benefit (PR/SD ≥16 wks/PFS); pts with liver mets had lower expression. Lower plasma levels of biomarkers of vascular biology (e.g. VEGF-D, Ang-2, VWF) trended with longer PFS. Grade (Gr) 3 treatment-emergent adverse events (TEAEs) occurred in 53% of pts and Gr 4 in 10%. Three pts had a Gr 5 TEAE: n = 1 related to the combination (sepsis); n = 1 related to nivolumab only by investigator (sepsis); n = 1 unrelated to treatment (respiratory failure). Most common Gr 3/4 TEAEs: maculopapular rash (14%), fatigue (7%), pneumonia (6%), increased bilirubin (6%). Conclusions: Combination treatment with regorafenib (up to 120 mg/day) and nivolumab (480 mg every 28D) has manageable safety. Efficacy of this combination in the North American population did not emulate results in the Japanese population. Absence of liver mets and expression of specific biomarkers indicate a better response and may warrant further analysis. Clinical trial information: NCT04126733. [Table: see text]
Right-censoring bias in trials shared at the Project Data Sphere platform.
Authors: Enrique Barrajon, Antonio López Jiménez, Laura Barrajon
Journal: Journal of Clinical Oncology (2021)

e13543 Background: Independent of the bias inherent to the design and execution of clinical trials, bias may be the result of patient censoring. A bias index (BI) was developed to detect right-censoring bias and tested in datasets availabe at Project Data Sphere, a data sharing research platform maintained by the CEO Roundtable on Cancer, Inc.,* a nonprofit corporation to improve outcomes for cancer patients by openly sharing deidentified data. Methods: Project Data Sphere platform was searched for clinical comparative trials with available experimental and comparator survival datasets: overall survival (OS) and event-free survival (EFS: disease-free survival, DFS, or progresssion-free survival, PFS). The R language and the integrated development environment Rstudio were used to import and manage the datasets. BI was defined in the events time domain as the adjusted proportion of censor times below the mean event time. Comparison of BI in different datasets were made with the two-sided Wilcoson unpaired test. A weighted regression model was applied to estimate the influence of bias on survival results as measured by the hazard ratio (HR). Results: Out of 184 trials, 19 trials offered both comparator and experimental arms, 3 of them not based on survival analysis and 4 of them with 2 substudies, providing 72 datasets based on OS and/or EFS, for a total of 16532 patients (90.8% of the 18198 patients in published trials). BI over the theshold was found in 24% of EFS datasets (versus 0% in OS datasets, Wilcoxon p = 0.0007), especially in PFS (35% vs 0% in DFS datasets, p = 0.00004). Nearly two thirds of the variance in the HR of EFS datasets was explained by the HR of OS datasets (adj.R2 = 0.638, p = 1.5e-5), approaching to what was found in the corresponding publications (adj.R2 = 0.751, p = 7.81e-5). Though the trials sample is small, introducing the BI of control and experimental datasets in the model decreases the residual standard error (3.831 vs 3.958) and increases the correlation (adj.R2 = 0.99, p &lt; 2.2e-16), resulting in the model: HR(EFR) = 0.985 HR(OS) + 0.36 BI(exper) – 0.42 BI(control). Conclusions: This study is a proof of concept that right-censoring bias may be detected and estimated in clinical trials, especially in PFS datasets, and opens the possibility for correcting biased estimations in survival and increasing the precision in the prediction of OS from preliminary EFS. (*) This abstract is based on research using information obtained from ProjectDataSphere.org, which is maintained by Project Data Sphere LLC. Neither Project Data Sphere nor the owners of any information from the web site have contributed to, approved or are in any way responsible for the contents of this abstract.
Time from First Symptom Onset to the Final Diagnosis of Multiple Myeloma — Possible Risks and Future Solutions: Large Retrospective and Confirmatory Prospective 'Deutsche Studiengruppe Multiples Myelom' (DSMM) Analysis
Authors: Giulia Graziani, Georg W. Herget, Gabriele Ihorst, Henning Schäfer, Jakob Neubauer, Annette M. May, Justus Duyster, Hermann Einsele, Ralph Wäsch, Monika Engelhardt
Journal: Blood (2017)
Factors associated with successful publication of abstracts in women malignancies: Are we closing the gender gap?
Authors: Ankita Kapoor, Arjun Khunger, Unnati Bhatia, Simrat Gill, Yagya Ahlawat, Maithreyi Sarma, Harshit Kapoor, Mazen Jizzini, Samar Nasir, Nikhil Agrawal, Kathleen Kokolus, Emese Zsiros, Shipra Gandhi
Journal: Journal of Clinical Oncology (2021)

11034 Background: We aimed to determine abstract characteristics associated with successful peer-reviewed publication after presentation at ASCO annual meeting in the women’s malignancy category (breast &amp; gynecologic cancer). Awareness of this could help meeting organizers &amp; attendees understand factors associated with impactful abstracts. Methods: All oral &amp; poster abstracts (OA: n = 53 &amp; PA: n = 527) in Breast (Loco/Regional/Adjuvant &amp; Metastatic) &amp; Gynecologic cancers category (2017 &amp; 2018 meeting) were included. Subsequent publication was confirmed by searching PubMed by title, names of first &amp; last authors for abstracts published by January 2021. Time to online publication, US or foreign journal publication &amp; impact factor (IF) were recorded. We also recorded number of authors, single/ multi-institution studies &amp; gender of first/ last author, which was confirmed by viewing biography details on their institutional websites. Descriptive analysis was performed &amp; association between above factors &amp; publication matrix was analyzed using multiple logistic regression model, Chi-square and t-test. Results: 45/53 OA (85%) &amp; 269/527 PA (51%) were published in peer-reviewed journals. Median number of authors for published PA was 12 vs 11 for unpublished (p = 0.24). Females (F) presented 34% (18/53) OA &amp; 49.3% (260/527) PA. 55% (143/260) PA presented by female authors &amp; 47.1% (126/267) presented by male (M) authors (p = 0.073) were published. No difference in publication between single vs multi-institution studies (p = 0.76) for PA was noted. Average time to journal publication for OA &amp; PA was 15.45 (SD +/- 3.37) &amp; 17.73 (SD +/- 1.27) months (mo) respectively. Mean IF for OA was 27.95 (SD+/- 6.18) while for PA was 10.96 (SD+/- 1.75). For published OA, 33% (15/45) had female first &amp; 29% (13/45) had female last authors. For published PA, 50.2% (135/269) had female first while only 37.5% (101/269) had female last authors. There was no association between gender of last author to IF (p = 0.39), single vs multi-institution study (p = 0.48) or time to publication (p = 0.44) for PA. Conclusions: More than 75% of OA &amp; 50% of PA were successfully published regardless of gender, number of authors or institutions involved. We observe a slight disparity in senior authorship for females and although this was not statistically significant, we are encouraged that the gap is closing in first authorship.[Table: see text]