tbuckley/cabot-search huggingface dataset:
Outcomes of transarterial chemoembolization (TACE) of the liver in patients with metastatic triple-negative breast cancer (TNBC).
Authors: Anna E. Storozhakova, Liubov Yu Vladimirova, Oleg I. Kit, Evgeniy N. Kolesnikov, Aleksandr V. Snezhko, Maksim N. Chernyak, Tatiana A. Snezhko, Natalia Yu. Samaneva, Yana V. Svetitskaya, Elena A. Kalabanova, Sergey N. Kabanov, Anna V. Tishina, Maria A. Teplyakova, Aleksandr E. Lisutin
Journal: Journal of Clinical Oncology (2020)

e13107 Background: TACE is widely used in oncology in patients with metastasis in liver from GI tumors, meanwhile its opportunities in management pts with TNBC are unknown. The purpose of the study was to analyze the results of TACE of the liver metastases from TNBC. Methods: The study included 60 TNBC pts with unresectable liver metastases. 34 pts of the main group underwent chemotherapy including taxanes in standard regimens. After 6-12 chemotherapy cycles, the main group received 1-2 TACE procedures (doxorubicin 30 mg/m², 5-fluorouracil 600 mg/m², 10 ml of lipiodol and 1-2 ml of 300-500 µm HepaSphere microspheres). The control group (n = 32) received only 6-12 cycles of taxane-containing chemotherapy. Pts were aged 32-66 years, mean age in the main group 49.4, in controls 55 years. Primarily advanced breast cancer with unresectable liver metastases was diagnosed in 6 (17.6%) pts of the main group and in 5 (15.6%) controls. Progression after previous treatment was observed in 91.2% (31) main group and 90.6% (29) controls. Sizes of metastatic foci were 2.7-7.3 cm, average number 7.5. Bilobar metastases were most common. Liver metastases were own accompanied by metastases to the bones, intrathoracic lymph nodes, lungs and pleura. Obtained data were processed with software package “Statistica 7.0”. Results: Main group received a total of 46 TACE procedures performed for a maximal number of metastatic lesions, especially for those progressing after systemic therapy and the largest ones, when possible. Post-embolization syndrome after performing TACE, was observed in 60.86% (28) of cases, managed with conservative therapy for 2-7 days. Icterus was not observed. The tumor response rate was 94.1% in the main group vs. 80.6% in controls, with significant differences in PR (44.1% and 15.3% respectively, p &lt; 0.05). Median of duration treatment response was 13.4 months in the main group and 9.3 months in control group (p &lt; 0.05). CR was not achieved. Median follow-up was 17 months. 3-year disease-free survival was 63.2% in the main group and 43.8% in controls (p = 0.039). Conclusions: TACE resulted in better response to the therapy as well as improved disease-free survival in pts with TNBC. TACE is possible to be used to consolidate the achieved effect of the chemotherapy.
Survival differences by race after minimally invasive versus open radical hysterectomy.
Authors: Rebekah Summey, Jordyn Pike, Marian Yvette Williams-Brown
Journal: Journal of Clinical Oncology (2020)

6029 Background: Black patients with cervical cancer have historically experienced worse survival compared with white women, as well as decreased rates of minimally invasive surgery (MIS) including radical hysterectomy. The goal of our study is to evaluate if this disparity in survival outcomes reverses in light of new findings favoring an open approach for patients with stage IA2 and IB1 cervical cancer compared to MIS. Methods: The National Cancer Database was queried, and all black and white women with stages IA2 and IB1 cervical cancer who underwent radical hysterectomy from 2010 to 2015 were included. Patients without survival data or documented surgical approach were excluded. Demographic factors were compared using student t-tests and Z-test of proportions as appropriate. Hazard ratios (HR) for the event of mortality were calculated by race and by route of surgery. Kaplan-Meier plots were created to compare survival between groups, and the Cox proportional hazards model was used to adjust for covariates. Results: 4915 patients were identified for inclusion, 12.1% black and 87.9% white. 43.0% of patients underwent open surgery (84.9% white and 15.1% black) and 57.0% underwent MIS (90.1% white and 9.9% black). Average follow up time between groups was 39.5 months for black patients and 40.6 months for white patients. Black patients who underwent open surgery had a hazard ratio (HR) for mortality of 1.44 (95% CI: 1.03-2.00), and those who underwent MIS had a HR of 1.48 (95% CI: 1.03-2.12), when compared to white patients. Mortality rates for black patients undergoing open radical hysterectomy remained higher than those for white patients who underwent MIS. When adjusted for age, insurance status, neighborhood income and educational level, tumor type, Hispanic ethnicity, node positivity and tumor size, these hazard ratios were no longer significant. Conclusions: Following discoveries of improved outcomes following abdominal radical hysterectomy as compared with MIS, we have identified that the discrepancy in ability to undergo MIS did not resolve previously identified disparities in the outcome of death for black women.
Prospective investigation of immunotherapy-induced fatigue by rest and stress echocardiography.
Authors: Roman Zingarelli, Mandar A Aras, Dwight Bibby, Qizhi Fang, Adil Daud, Nelson B Schiller, Katy K. Tsai
Journal: Journal of Clinical Oncology (2020)

e24060 Background: Immune checkpoint inhibitors (ICI) effect durable responses in cancer patients (pts). Myocarditis is rare but fatigue is commonly reported, and whether ICI-induced fatigue is due to subclinical cardiac toxicity is unknown. We hypothesized that pts on ICI develop changes on rest and stress echocardiogram (echo) that correlate with fatigue. Methods: A prospective observational study was performed to monitor cardiac function in pts receiving ICI. Our cohort consisted of pts (n = 10) with stage III/IV melanoma, ECOG 0-1, deemed safe to exercise, without unstable cardiac symptoms. ICI-naïve pts received anti-PD1 alone or in combination with anti-CTLA-4, in adjuvant or metastatic setting. Rest transthoracic echo and dynamic staged exercise stress echo testing was conducted at baseline (prior to ICI) and at 3 and 6 months (mo) following ICI. Various echo parameters at rest and stress were compared. irAEs were detailed and surveys administered at baseline and post-follow up. Results: 10 pts (9 men, mean age 56 yrs) completed baseline cardiac testing of whom 7 completed follow up testing at 6 mo (6 anti-PD1 monotherapy, 1 metastatic combination therapy). Of these 7 pts, 5 (71%) reported increased fatigue per CTCAE at 3 or 6 mo follow up and all 7 had irAEs (3 rash, 1 colitis, 1 diarrhea, 1 hypophysitis, 1 arthralgia, 1 xerostomia). Among resting echo parameters, left ventricular outflow tract velocity time integral (LVOT VTI) was significantly reduced at 6 mo compared to baseline (22.6 ± 3.4 vs 20.0 ± 2.5, p = 0.0047), albeit still within normal range. No other resting echo parameters changed. Among exercise echo parameters, there was no difference in METs achieved, time of exercise, blood pressure or heart rate between time points. Of note, of 7 subjects who completed 6 mo testing, 2 (29%) were unable to achieve previous peak stage of exercise during testing. Conclusions: Though no echo parameter significantly correlating with fatigue was reported, nearly one-third of a small cohort of pts were unable to achieve peak exercise 6 mo after starting ICI. This combined with the statistical reduction in LVOT VTI suggests functional limitation and warrants further study. Post-follow up surveys are pending and may further inform issues important in ICI survivorship. [Table: see text]
Blockade of VLA4 sensitizes leukemic and myeloma tumor cells to CD3 redirection in the bone marrow microenvironment
Authors: Priyanka Nair-Gupta, Stephen I. Rudnick, Leopoldo Luistro, Melissa Smith, Ronan McDaid, Yingzhe Li, Kodandaram Pillarisetti, Jocelin Joseph, Bradley Heidrich, Kathryn Packman, Ricardo Attar, François Gaudet
Journal: Blood Cancer Journal (2020)

Abstract Redirecting T cells to specifically kill malignant cells has been validated as an effective anti-cancer strategy in the clinic with the approval of blinatumomab for acute lymphoblastic leukemia. However, the immunosuppressive nature of the tumor microenvironment potentially poses a significant hurdle to T cell therapies. In hematological malignancies, the bone marrow (BM) niche is protective to leukemic stem cells and has minimized the efficacy of several anti-cancer drugs. In this study, we investigated the impact of the BM microenvironment on T cell redirection. Using bispecific antibodies targeting specific tumor antigens (CD123 and BCMA) and CD3, we observed that co-culture of acute myeloid leukemia or multiple myeloma cells with BM stromal cells protected tumor cells from bispecific antibody-T cell-mediated lysis in vitro and in vivo. Impaired CD3 redirection cytotoxicity was correlated with reduced T cell effector responses and cell–cell contact with stromal cells was implicated in reducing T cell activation and conferring protection of cancer cells. Finally, blocking the VLA4 adhesion pathway in combination with CD3 redirection reduced the stromal-mediated inhibition of cytotoxicity and T cell activation. Our results lend support to inhibiting VLA4 interactions along with administering CD3 redirection therapeutics as a novel combinatorial regimen for robust anti-cancer responses.
NCI protocol 10250: A phase II study of temozolomide and olaparib for the treatment of advanced uterine leiomyosarcoma.
Authors: Matthew Ingham, Jacob B Allred, Katherine Gano, Suzanne George, Steven Attia, Melissa Amber Burgess, Sosipatros Alexandros Boikos, Nam Bui, James Lin Chen, Julia Lee Close, Mahesh Seetharam, Premal H. Thaker, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2020)

TPS11570 Background: Soft tissue sarcoma (STS) is a heterogenous malignancy of mesenchymal origin and includes more than 50 biologically distinct subtypes. Leiomyosarcoma (LMS), a neoplasm of smooth muscle origin, represents up to 20% of STS. The uterus is the most common site of origin in women. Advanced uterine LMS (uLMS) is initially treated with gemcitabine + docetaxel or anthracycline-based chemotherapy but overall survival remains &lt; 24 mos. Besides recurrent alterations in RB1, TP53 and ATRX, insight into cancer biology of uLMS remains limited. Recently, whole exome and transcriptomic sequencing studies suggest uLMS harbors characteristic defects in the homologous recombination (HR) DNA repair pathway and thus features of BRCAness. HR-deficient cancers are unable to efficiently repair double-stranded DNA breaks and appear sensitive to treatment with poly ADP-ribose polymerase (PARP) inhibitors. In preclinical studies, the combination of temozolomide (T), an alkylating agent, and olaparib (O), a PARP inhibitor, was synergistic and markedly suppressed proliferation of uLMS models. A recent phase II study in small cell lung cancer defined the RP2D for T + O where the chief toxicity was myelosuppression. Methods: NCI Protocol #10250 is a single-arm, open-label, multi-center phase II clinical trial of T + O in patients with advanced uLMS. Eligible pts have ECOG PS ≤ 2, progression on ≥ 1 prior line of therapy and disease measurable by RECIST v1.1 and amenable to image-guided biopsy. Pts receive T 75 mg/m2 PO daily + O 200 mg PO BID on days 1-7 in 21-day cycles. The 1° endpoint is objective response rate (ORR). A one-stage binomial design is used to evaluate for an ORR ≤ 10% (null hypothesis) versus ≥ 35% (alternative hypothesis). The design calls for 22 patients. If 5/22 respond, the treatment is promising. This design yields 93% power and 1-sided type I error of 6%. 2° endpoints include progression free survival and safety. All pts undergo tumor biopsies pre-treatment and during cycle 2. Tissue is used for correlative analysis interrogating uLMS for features of BRCAness through (a) whole exome sequencing/RNAseq to evaluate for alterations in HR pathway component genes, (b) RAD51 foci formation by immunohistochemistry as a functional marker of HR pathway activity and (c) protein expression of Schlafen family member number 11 (SLFN11), an emerging biomarker for PARPi. Tumors are also evaluated for MGMT protein expression, a known determinant of sensitivity to T. The study opened to accrual 10/2019. Clinical trial information: NCT03880019.
Debridement and primary suturing combined with specific electromagnetic irradiation for incision fat liquefaction after orthopedic surgery
Authors: Xiaoyun Yan, Yuwei Li, Yan Wen
Journal: BMJ (2016)

Forty six patients with incision fat liquefaction after orthopedic surgery were randomly divided into two groups from January 2008 to January 2014. Patients in treatment group (n=23) received debridement and primary suturing combined with specific electromagnetic irradiation and those in control group (n=23) received moist dressing healing only. The average healing time of treatment group and control group was (14.3± 2.0) and (22.1±3.9) d, respectively (P<0.05); the average number of dressing change in treatment group and control group was 2.3 ± 1.1 and 14.8±7.2, respectively (P<0.05). There was no case of complicated infection in treatment group, while there were 4 cases of infection in control group. The results indicate that debridement and primary suturing combined with specific electromagnetic irradiation can reduce the number of dressing change, shorten the wound healing time in treatment of incision fat liquefaction after orthopedic surgery.


Key words: 
Surgical wound infection; Physical therapy modalities
AMBLor: A prognostic and stratifying biomarker for adjuvant immunotherapy of AJCC stage II melanomas.
Authors: Marie Labus, Robert Ellis, Tom Ewen, Sebastian Podlipnik, Alison Greenwood, Ashleigh McConnell, Anna Long, Tom Ness, Claire Jones, Niki Stefanos, Philip Sloan, Akhtar Husain, Paul Barrett, Susana Puig, Grant A. McArthur, Penny Lovat
Journal: Journal of Clinical Oncology (2020)

e22094 Background: The success of adjuvant therapy for patients with AJCC stage III melanomas coupled with the increased risk of mortality for patients with AJCC stage IIB compared to IIIA tumours has paved the way to adjuvant immunotherapy trials for patients with sentinel lymph node (SLNB) –ve AJCC stage II disease. However, the lack of biomarkers able to appropriately stratify high-risk tumour subsets limits patient recruitment. We have recently identified the combined immunohistochemical (IHC) expression of AMBRA1 and Loricrin (AMBLor) in the epidermis overlying non-ulcerated AJCC stage I melanomas as a robust prognostic biomarker and valuable pre SLNB test. Methods: Retrospective analysis of AMBLor was performed in three geographically distinct cohorts of AJCC stage II melanomas using a clinically validated automated IHC assay and semi quantitative binary scoring analysis to define high vs low risk subgroups. Results: Data revealed loss of AMBLor overlying non-ulcerated high risk AJCC stage IIA or B tumours correlated with a significant reduction in disease free survival (DFS) at 12 years to 55% compared to 89% for patients with AMBLor low risk tumours (P = 0.015; HR 4.83, 95% CI: 2.29-10.14). Sub-cohort multivariate analysis of 80 non ulcerated stage IIB tumours also revealed reduced DFS at 12 years to 68% in AMBLor high-risk compared to 83% in AMBLor low-risk tumour subsets, with an assay sensitivity of 97% and a negative predictive value of 90%. Furthermore, sub-cohort analysis of SLNB –ve AJCC stage IIA or B tumours additionally identified 5 genuinely low risk cases in which DFS at 10 years was 100% compared to only 36% in 37 patients in which AMBLor was lost. Conclusions: Collectively these data indicate AMBLor as a novel prognostic biomarker for patients with non-ulcerated AJCC stage II melanomas as well as companion/stratifying biomarker for adjuvant immunotherapy, the use of which will increase clinician confidence for patient recruitment as well as reduce patient morbidity.
Effect of Aspirin vs Placebo on the Prevention of Depression in Older People
Authors: Michael Berk, Robyn L. Woods, Mark R. Nelson, Raj C. Shah, Christopher M. Reid, Elsdon Storey, Sharyn Fitzgerald, Jessica E. Lockery, Rory Wolfe, Mohammadreza Mohebbi, Seetal Dodd, Anne M. Murray, Nigel Stocks, Paul B. Fitzgerald, Catherine Mazza, Bruno Agustini, John J. McNeil
Journal: JAMA Psychiatry (2020)

Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression.To determine whether low-dose aspirin (100 mg) reduces the risk of depression in healthy older adults.This double-blinded, placebo-controlled randomized clinical trial was a substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined if aspirin increased healthy life span, defined as survival free of dementia and disability. The prespecified secondary outcome was depression. Individuals of all races/ethnicities older than 70 years in Australia, as well as white individuals older than 70 years and black and Hispanic individuals older than 65 years in the United States, were included.Participants were randomized to aspirin (100 mg daily) or placebo, with a median (interquartile range) follow-up of 4.7 (3.5-5.6) years.The primary outcome was a proxy measure of major depressive disorder defined as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale.Of the 19 114 participants enrolled in the trial, 9525 received aspirin and 9589 received a placebo. The mean (SD) age was 75.2 (4.0) years in the aspirin group and 75.1 (4.5) years in the placebo group; 9531 (56.4%) were women. Participants' demographics and clinical characteristics at baseline were similar between groups. A total of 79 886 annual CES-D-10 measurements were taken, with a mean of 4.2 measurements per participant. There were no significant differences at annual visits in the proportions of CES-D-10 scores of 8 or more between the aspirin and placebo groups. The incidence rate of new CES-D-10 scores of 8 or more was 70.4 events per 1000 person-years in the aspirin group and 69.1 in the placebo group (hazard ratio, 1.02 [95% CI, 0.96-1.08]; P = .54).Low-dose aspirin did not prevent depression in this large-scale study of otherwise healthy older adults.ClinicalTrials.gov Identifier: NCT01038583.
Effects of an e-home based symptom management and mindfulness training program on quality of life in breast cancer survivors.
Authors: Karis Kin-Fong Cheng, Rosalind Siah, Melvyn Zhang, Shian-Ling Keng, Wan-Hua Wong, Roger Ho, Hsuen Elaine Lim
Journal: Journal of Clinical Oncology (2020)

TPS12130 Background: The first five years post-treatment for breast cancer are a critical phase, when the survivors may face a multitude of problems, including persistent and/or late-emerging symptoms following the cancer and its treatment, psycho-social distress associated with the risk of cancer recurrence, chronic uncertainty and social disruption. Thus, this trial will answer the research questions of 'Will the combined symptom management and mindfulness-based training programme be a promising approach to assist women with breast cancer in transition from treatment to survivorship?', and 'Since breast cancer survivors have infrequent clinical follow-up, will e-Home based system provide a feasible option for post-treatment care?' Methods: We aim to develop an e-Home based symptom management and mindfulness training programme for breast cancer survivors and to determine its effects on the endpoints including quality of life, symptom distress, psychosocial adjustment, psychological morbidity, and unplanned outpatient attendance or hospitalisation in breast cancer survivors. (ClinicalTrials.gov Identifier: NCT02931864) We employ a randomised clinical trial with four study arms (with 47 subjects, who have completed cancer treatment for stage 0 to 3 breast cancer between 6 months to 5 years previously, in each arm) together with a process evaluation; group 1 (usual care), group 2 (experimental group: five weekly sessions of online symptom management + mindfulness training programme and usual care), group 3 (comparison group 1: online symptom management programme and usual care), and group 4 (comparison group 2: online mindfulness training programme and usual care). Subjects will complete questionnaires measures of 6-item Social Support Questionnaire, Breast Cancer Survivor Self- Efficacy Scale, the Quality of Life-Cancer Survivor Scale, Memorial Symptom Assessment Scale, Psychosocial Adjustment to Illness Scale, short version of the Fear of Recurrence Scale, Hospital and anxiety Depression Scale, and Five Facet Mindfulness Questionnaire at baseline, at 8 weeks from time 1 (time 2), at 12 weeks from time 1 (time 3) and at 24 weeks from time 1 (time 4). Intention-to-treat approach will be used. Repeated measures analysis of variance will be used to examine the differences on outcome measures among the experimental, comparison, and control groups across study time points. Currently, 162 of 188 planned subjects have been enrolled and the trial continues as planned. Clinical trial information: NCT02931864 .
Monotherapy with levetiracetam for absence epilepsy in children
Authors: Yue Huang, Chun Wu, Jian-jun Wang
Journal: BMJ (2011)

Objective To assess the efficacy and safety of levetiracetam (LEV) monotherapy in children with absence epilepsy.Methods Fifty five children [ 34 males,21 females,aged (8.1 ± 4.8) y ] with typical absence seizures were treated with LEV ( n =25 ) or valproic acid ( VPA,n =30) from Jan 2009 to Jun 2010.Patients were followed up for 1y; the seizure frequency,electroencephalogram (EEG) and side effect were observed at 6th month and 12th month after the initiation of therapy.Results During the follow-up,none had aggravated symptoms of epilepsy.There were no significant differences in seizure frequency(t =0.76,P =0.450; t =0.67,P =0.504),abnormal EEG ( x2 =0.120,P =0.729 ; x2 =0.043,P =0.836 ) and seizure control ( x2 =0.051,P =0.821 ; x2 =0.078,P =0.780) after 6 and 12 months of treatment between two groups.No death or severe side effects were observed; 2 cases (8.0％) in LEV group had mild adverse effect( drowsiness and restlessness)and 2 cases (6.7％ ) in VPA group had weight gain and nausea.Conclusion The results suggest that monotherapy with LEV is effective and safe for treatment of childhood absence epilepsy.

Key words: 
Epilepsy,absence; Therapy; Child