tbuckley/cabot-search huggingface dataset:
A phase II study of anlotinib in treating patients with relapsed or metastatic primary malignant bone tumor.
Authors: Lina Tang, Xiaohui Niu, Zhen Wang, Qiqing Cai, Chongqi Tu, Zhengfu Fan, Yang Yao
Journal: Journal of Clinical Oncology (2020)

11525 Background: Primary malignant bone tumors are rare forms of cancer and include mainly bone sarcomas, which are categorized into 3 common types based on tissue origin: osteosarcoma, chondrosarcoma and Ewing sarcoma. A phase II trial was designed to explore the anlotinib activity in patients with relapsed or metastatic primary malignant bone tumor. Methods: Eligible pts were received 12mg of anlotinib once daily, 2 weeks on and 1 week off until progression or unacceptable toxicity. Key-eligibility criteria were aged 14-70 years, histologically confirmed diagnosis of osteosarcoma, chondrosarcoma, bone derived malignant fibrous histiocytoma, giant cell tumor, Ewing sarcoma and PNET, confirmed previous chemotherapy failure, ECOG 0-1(0-2 for amputation pts), required at least one measurable lesion. We observed PFS, OS, ORR, DCR and AE in this study. Results: From August 2018 to April 2019, 42 pts were included. Of 42 efficacy-evaluable pts, 25 were man, median age was 28 (14-68) years. There were 29 pts of osteosarcoma, 9 pts of chondrosarcoma, 3pts of Ewing sarcoma and 1 pt of bone derived malignant fibrous histiocytoma. The progression-free rate at 12 weeks (PFR 12weeks ), ORR and DCR were 71.3%, 9.52% and 78.57%. Median PFS was 5.26 months (95%CI = 3.48-8.44). Median OS was 11.40 months (95%CI = 10.09, [ ). Median PFS of osteosarcoma and chondrosarcoma was 4.83 months (95%CI = 3.48, 7.13 ) and 2.76 months (95%CI = 1.31, [ ) respectively. The most common Gr 3-5 anlotinib-related AEs were hypertension (19.05%), hypertriglyceridemia (9.52%), hand-foot syndrome (7.14%), and proteinuria (4.76%). Conclusions: The phase II study shows a promising activity of anlotinib in patients with relapsed or metastatic primary malignant bone tumor and an acceptable toxicity. Clinical trial information: NCT03527888 .
Awareness of immune-related adverse events among medical residents in a community hospital.
Authors: Ajinkya Kulkarni, Mrunal Kulkarni, Vinay Edlukudige Keshava, Rithikaa Ellangovan, Rajesh Thirumaran
Journal: Journal of Clinical Oncology (2020)

e15154 Background: Immunotherapy has paved the way for new frontiers in the management of certain advanced cancers. Immune checkpoint inhibitors (ICI) have substantially improved prognosis in patients with advanced malignancy. Primary targets for ICIs include programmed cell death receptor 1 (PD-1), programmed cell death ligand 1 (PD-L1) and Cytotoxic T-lymphocyte-associated antigen 4(CTLA-4). These treatments have a wide range of adverse effects distinct from traditional chemotherapy regimens. We conducted a survey to assess the awareness of immune-related adverse events (IRAE) among medical residents in a community hospital. Methods: Internal medicine residents in a community hospital were given a survey of 10 questions related to IRAEs. A total of 40 responses were collected and analyzed. Results: 22.50% respondents were aware that nephrotoxicity is not a common side effect of immunotherapy. 35% were aware that cutaneous toxicities are the most common IRAEs. 42.50% were aware that hair loss is not a common side effect of ICIs. 42.50% were aware that patients do not need pretreatment with anti-emetics before immunotherapy. 45% were aware that the onset of hepatotoxicity is usually not seen within the first week of starting immunotherapy. 50% were aware that immunotherapy is associated with the development of pneumonitis. 62.5% were aware that steroids formed mainstay of treatment in IRAEs. 65% were aware that immunotherapy is associated with thyroid-related side effects. 67.5% were aware that patients with pre-existing autoimmune conditions are at greater risk for immune-related adverse effects. 70% were aware that immune related colitis was not treated with antibiotics. Conclusions: With the rapid advancement and use of immunotherapy the incidence of IRAEs is increasing. Involvement of single or multiple organ systems as well as flare of previously well controlled autoimmune disease can add to the challenge. As we gain more experience, long term data will emerge to help predict at-risk patients. This is a dynamic area of research and new treatments are under development. 6/10 questions were answered correctly by less than 50% respondents and 4/10 were answered correctly by 50-70% respondents. At present no data is available to gauge awareness regarding IRAEs among internists. Our survey suggests a lack of awareness among medical residents on many fronts. Lack of awareness leads to inappropriate treatment and prolonged hospital stay. Active efforts need to be taken to educate residents regarding immunotherapy and IRAEs to achieve better patient outcomes.
Factors influencing clinical efficacy and outcomes of adult primary immune thrombocytopenia
Authors: Yu Chen, Meifang Wang, Jianfang Chen, Yaofang Zhang, Gang Wang, Zefeng An, Shuting Chang
Journal: BMJ (2018)

Objective
To examine the influencing factors related to clinical efficacy and outcomes of adult primary immune thrombocytopenia (ITP).


Methods
The clinical data of 161 cases of ITP admitted in the Second Hospital of Shanxi Medical University from June 2013 to March 2017 were collected. The influencing factors related to clinical efficacy and prognosis of adult ITP patients were analyzed.


Results
There were 60 males and 101 females with a M/F ratio of 0.59∶1 and a median age of 45 years (18-84 years). There were 109 newly diagnosed ITP cases, 14 persistent ITP cases and 38 chronic ITP cases in this series. Seventy nine patients received intravenous immunoglobulin g (IVIg) treatment and 82 patients received high dose-dexamethasone treatment.There were no significant differences in clinical efficacy [91.13%(72/79) vs. 87.80%(72/82), χ2=0.181, P=0.914] and relapse rate [36.11%(26/72) vs. 30.55%(22/72), χ2=0.189, P= 0.910] between IVIg and high dose-dexamethosone groups. Multivariate regression analysis showed that bleeding score ≥2 was the independent risk factor for the lower clinical efficacy (RR=1.415, 95%CI:1.008-1.986, P<0.05) . Patients were followed up for a median of 9.0 months (0.5-55.0 months), 48 patients relapsed with a relapse rate of 33.33% and a median relapse time of 1.8 months (0.5-24.0 months).


Conclusions
IVIg and high dose-dexamethasone have the similar clinical efficacy and relapse rate for treatment of adult ITP. The patients with the bleeding score ≥2 are more likely to get lower remission rate.


Key words: 
Thrombocytopenia; Treatment outcome; Prognosis
Abstract 15524: Can a Home-based Cardiac Rehabilitation Program Improve the Physical Function Quality of Life in Children With Fontan Circulation?
Authors: Roni M Jacobsen, Michael Danduran, Kathleen Mussatto, Jennifer Neubauer, Salil Ginde
Journal: Circulation (2015)

Introduction: Patients after Fontan operation for complex congenital heart disease (CHD) have reduced exercise capacity and health-related quality of life (HRQOL). Studies suggest hospital-based cardiac rehabilitation programs can improve exercise capacity and HRQOL in patients with CHD; however, these programs have variable adherence rates. The impact of a home-based cardiac rehabilitation program in Fontan survivors is unclear. This pilot study evaluated the safety, feasibility, and benefits of an innovative home-based physical activity program on HRQOL in Fontan patients. Methods: A total of 14 children, 8-12 yr, with Fontan circulation enrolled in a 12-week moderate/high intensity home-based cardiac physical activity program, which included a home exercise routine and 3 formal in-person assessments at 0, 6, and 12 weeks. Subjects and parents completed validated questionnaires to assess HRQOL. The Shuttle Test Run was used to measure exercise capacity. A Fitbit® Flex Activity Monitor was used to assess adherence to the home activity program. Results: Of the 14 subjects, 57% were male and 36% had a dominant left ventricle. Overall, 93% completed the program. There were no adverse events. Parents reported improvement in their child’s overall HRQOL (p&lt;0.01), physical function (p&lt;0.01), school function (p=0.01), and psychosocial function (p&lt;0.01). Exercise capacity, measured by Shuttle Run time, improved progressively from baseline to the 6 and 12 week follow up sessions (Figure). Monthly Fitbit® data suggested good adherence to the program. Conclusion: This 12-week home-based cardiac physical activity program is safe and feasible in Fontan patients. Parent proxy-reported HRQOL and objective measures of exercise capacity significantly improved. A 6 month follow up session is scheduled to assess sustainability. A larger study is anticipated to determine applicability and reproducibility of these findings in other age groups and forms of complex CHD.
Further evidence that chilblains are a cutaneous manifestation of <scp>COVID</scp> ‐19 infection
Authors: M. Hughes, S. Rogers, G. Lepri, C. Bruni, M. Matucci‐Cerinic
Journal: British Journal of Dermatology (2020)

A range of cutaneous conditions including chilblain‐like lesions have been reported in patients with Coronavirus 2019 (COVID‐19) due to severe acute respiratory Syndrome coronavirus 2 (SARS‐Cov‐2). Using clinical data and images, the authors of a recent nationwide Spanish survey identified 5 clinical patterns which were associated with different patient demographics, onset (timing), and prognosis.
Pharmacodynamic effects in blood and tumor tissue of eftozanermin alfa, a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist.
Authors: Monica Motwani, Dimple Modi, Sudhir Penugonda, Chun Zhang, Joann Palma, Alexis Cunningham, Emiliano Calvo, Maja J.A. de Jonge, Patricia LoRusso
Journal: Journal of Clinical Oncology (2020)

e15668 Background: Eftozanermin alfa (eftoza; formerly known as ABBV-621), a 2nd-generation tumor necrosis factor-related apoptosis-inducing ligand receptor agonist, is being evaluated in previously treated solid and hematologic malignancies (NCT03082209). In a dose-expansion cohort, patients (pts) with KRAS-mutant colorectal cancer (n = 24) and pancreatic cancer (n = 24) were evaluated at 3 dose levels with 12 mandatory paired biopsies per tumor type (pretreatment [Tx] and on-Tx collection). Following eftoza dosing, RNA and protein expression including posttranslational modifications were assessed in tumor biopsies to understand the target engagement and downstream pathway activation. Plasma was evaluated for changes in somatic mutant allele frequency and M30, M65 (circulating apoptotic markers). Methods: Biopsies were collected anytime during the screening period (pre-Tx) and 24±4 h following 2nd or 3rd infusion (on-Tx). Of the requested 4–6 fresh biopsy cores, 1–2 cores were collected as formalin fixed paraffin embedded (FFPE) and the rest were frozen tissue. FFPE tissue was analyzed by multiplex immunohistochemistry (IHC) and RNAseq; reverse phase protein array was used for frozen cores. Plasma was collected at cycle 1 predose and 2, 8, 24, 48, and 168 h postdose and analyzed for M30, M65 (by ELISA) and circulating tumor DNA (64-gene PlasmaSELECT assay). Results: Twenty-five pts consented to biopsies; paired biopsies were obtained from 16 pts at a 64% success rate: FFPE (n = 15) and frozen cores (n = 12). Tumor cells were detected in 11/15 (73%) FFPE and 4/12 (33%) frozen cores. Increase in M30, activated caspases, and cleaved PARP levels was observed in on-Tx biopsy samples compared with pre-Tx, thus serving as evidence for apoptosis induction in tumors following eftoza dosing. Changes in the tumor microenvironment were observed post-Tx by RNAseq and multiplex IHC (eg, CD68 level). Downregulation of prosurvival signaling pathways (eg, AKT/MEK) was also observed following eftoza dosing. Thirteen out of 16 pts showed transient increase in mutant allele fractions post eftoza Tx that correlated with increased plasma circulating tumor markers M30 and M65 at similar time points, suggesting activation of apoptosis pathway. Increase in M30, M65 levels also preceded increase in liver enzymes (ALT/AST) at 2, 48 hr post-Tx. Conclusions: Pharmacodynamic effect of eftoza was successfully demonstrated in blood and tumor tissue, including induction of apoptosis and modulation of PI3K and MEK signaling pathways. Clinical trial information: NCT03082209.
Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial
Authors: Elise van Mulligen, Angelique E Weel, J M Hazes, Annette van der Helm-van Mil, Pascal Hendrik Pieter de Jong
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To evaluate the 2-year clinical effectiveness of two gradual tapering strategies. The first strategy consisted of tapering the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) first (i.e., methotrexate in ~90%), followed by the tumour necrosis factor inhibitor (TNF-inhibitor), the second strategy consisted of tapering the TNF-inhibitor first, followed by the csDMARD. Methods This multicentre single-blinded randomised controlled trial included patients with rheumatoid arthritis (RA) with well-controlled disease for ≥3 consecutive months, defined as a Disease Activity Score (DAS) measured in 44 joints ≤2.4 and a swollen joint count ≤1, which was achieved with a csDMARD and a TNF-inhibitor. Eligible patients were randomised into gradual tapering the csDMARD followed by the TNF-inhibitor, or vice versa. The primary outcome was the number of disease flares. Secondary outcomes were DMARD-free remission (DFR), DAS, functional ability (Health Assessment Questionnaire Disability Index (HAQ-DI)) and radiographic progression. Results 189 patients were randomly assigned to tapering their csDMARD (n=94) or TNF-inhibitor (n=95) first. The cumulative flare rate after 24 months was, respectively, 61% (95% CI 50% to 71%) and 62% (95% CI 52% to 72%). The patients who tapered their csDMARD first were more often able to go through the entire tapering protocol and reached DFR more often than the group that tapered the TNF-inhibitor first (32% vs 20% (p=0.12) and 21% vs 10% (p=0.07), respectively). Mean DAS and HAQ-DI over time, and radiographic progression did not differ between groups (p=0.45, p=0.17, p=0.8, respectively). Conclusion The order of tapering did not affect flare rates, DAS or HAQ-DI. DFR was achievable in 15% of patients with established RA, slightly more frequent in patients that first tapered csDMARDs. Because of similar effects from a clinical viewpoint, financial arguments may influence the decision to taper TNF-inhibitors first.
A survey of cancer testis antigen (CTA) expression across T-cell lymphoma subtypes.
Authors: Helen Ma, Craig R. Soderquist, Enrica Marchi, Luigi Scotto, Govind Bhagat, Owen A. O'Connor
Journal: Journal of Clinical Oncology (2020)

e15246 Background: T-cell lymphomas (TCL) are a rare and heterogeneous group of non-Hodgkin lymphomas (NHL) that originate from T- and NK-cells and portends a poor prognosis. One promising therapeutic strategy involves generation of tumor associated antigen directed T-cells (TAA-T) against specific CTA. RNAseq have established that combinations of histone deacetylase inhibitors and hypomethylating agents uniquely induce genes characterized as cancer testes antigens (CTA), which may increase immunogenicity. There is a lack of data on the baseline expression of CTA across the TCL, limiting application of TAA-T. We sought to establish the baseline expression of CTA in PTCL using immunohistochemistry to better understand treatment effects. Methods: A tissue microarray was created using formalin-fixed paraffin embedded tissue from 40 patients with diverse T-cell neoplasms. Expression of WT1, SCP1, survivin, PLAC1, SSX2, and PRAME was evaluated by immunohistochemistry. The percentage of positive tumor cells (divided into quartiles), staining intensity (weak, moderate, strong), and subcellular localization (nuclear, cytoplasmic) was assessed. Results: Forty patients with T-cell lymphomas were included in the analysis. The median age of diagnosis and median number of treatments was 60.2 years and 2 (0-9), respectively. Thirty-nine (98%) patients expressed at least one CTA. A high frequency of survivin, which is associated with cell proliferation and is expressed on normal lymphoid tissue, was expressed in 98% of TCL, 5% expressed WT1, and 12.5% expressed SCP1, and expression of other CTA was not observed. Of five patients with anaplastic large cell lymphoma, 3 samples were positive for SCP1 and one was also positive for WT1. One of 9 angioimmunoblastic T-cell lymphoma samples was positive for SCP1. Of 4 T-lymphoblastic lymphoma patients, 1 was positive for WT1, and of 3 transformed mycosis fungoides specimens, 1 demonstrated SCP1 expression. In this sample set, we did not find a correlation with expression and response to chemotherapy. There were no patients with CTA expression who were treated with epigenetic treatments. Conclusions: We described low expression of CTA on T-cell lymphomas, which is consistent with the literature on expression by RT-PCR. By establishing this baseline expression of CTA, we have the foundation on which to measure changes in CTA expression pre- and post-treatment by immunohistochemistry.
Rectal cancer in young patients: Clinicoepidemiologic profile and treatment outcomes.
Authors: Pankaj. Goyal, Udip Maheshwari, Parveen Jain, Chaturbhuj Agrawal, Krushna A. Chaudhari, Sumit Goyal, Ullas Batra, Sneha J Bothra, Varun Goel, Vineet Talwar, DC Doval
Journal: Journal of Clinical Oncology (2020)

4042 Background: Colorectal cancers are 3 rd most common cause of cancer globally however studies of rectal cancers alone in younger patients are scarce. Rectal cancers in Asian patients present at a younger age and has an aggressive tumor biology. This study looks at rectal cancer in young patients, ≤30 years old, with the aim to report clinico-epidemiologic profile and treatment outcomes in this subgroup. Methods: Retrospective analysis was conducted at a tertiary care centre. Of total 845 rectal cancer patients between 2012-2017, 103 patients of young rectal cancers were enrolled. Kaplan Meier method was used for survival analysis and cox regression analysis was done to identify factors affecting survival. Results: Young rectal cancer patients constituted 12.2% of the total rectal cancer patients. Male: Female ratio was 2.3:1 and the mean age was 24.7 ± 3.9 years. Around 73.8 % patients had locoregional disease (stage I/II/III) at presentation.CEA levels were elevated in 36.9% of patients, while most common histology was signet ring cell histology which was present in 51.5% of patients. Of 76 patients with locoregional disease, 75% received neoadjuvant chemoradiotherapy, 7.9% received neoadjuvant chemotherapy alone while 3.9% received neoadjuvant radiotherapy alone. Of 76 patients with locoregional disease, 55 patients underwent surgery of which 53.9% underwent low anterior resection while 18.4% underwent abdomino-perineal resection. Pathologic CR rates were seen in 13.3%, while recurrences were seen in 55.4% of non-metastatic patients. Overall 5-year survival for the whole study group was 19.5%, while 1-year PFS and 3-year DFS for metastatic and non-metastatic disease were 5% and 43.8% respectively. On regression analysis elevated CEA levels and not achieving a pathologic CR (pCR) with neoadjuvant therapy had a trend towards worse overall survival (HR 2, 95% CI 1-4, p = 0.063), (HR 4.7, 95% CI 0.64-35.1, p = 0.125) respectively. Conclusions: Rectal cancers in Asia present at younger age and this younger population is associated with advanced stage, increased CEA at presentation, aggressive histology and poor survival. CEA raise and not achieving pCR were associated with trend towards worse survival.
Relationship between nystagmus and effectiveness in Semont maneuver for patients with benign paroxysmal positional vertigo
Authors: Shuxia Qian, Xiaoling Zhang
Journal: BMJ (2016)

Semont maneuver was performed in 97 patients with benign paroxysmal positional vertigo involving the posterior semicircular canal. Among 97 patients the Semont maneuver was successful in 69 cases and failed in 28 cases. There were three nystagmus patterns during the third position of the Semont maneuver: orthotropic nystagmus (n=45), no nystagmus (n=42) and reversed nystagmus (n=10); and the effective rates in three groups were 93%, 64% and 0%, respectively (P 0.05).


Key words: 
Vertigo, benign paroxysmal positional; Nystagmus, pathologic
Effects of combined model with contract signing, team cooperation and telehealth care on social support and quality of life for empty nest elders at home
Authors: Fenfen Wang, Li Tang, Xueping Chen, Hualing Wang, Pei Jiang
Journal: BMJ (2015)

Objective
To evaluate the effects of combined model of contract signing, team cooperation and telehealth care on social support and quality of life for empty nest elders at home.


Methods
A total of 320 empty nest elders at home were randomly divided into experimental group and control group. The elders in experimental group received contract signing, team cooperation and telehealth care for 1 year; For control group, routine nursing model was implemented. The elders were examined with social support (SSRS) and quality of life (SF-36) before and after intervention.


Results
After intervention, the scores of SSRS for experiment and control groups in subjective support 21.4±4.2 and 18.4±3.7, objective support 7.0±1.6 and 6.0±2.3, social support availability 7.6±2.2 and 6.1±2.5; the scores of SF-36 between experiment and control groups in physical functioning 74.8±14.9 and 66.3±15.6, role-physical 72.3±15.8 and 65.9±14.7, bodily pain 71.3±19.8 and 62.4±15.0, general health 54.2±13.0 and 47.8±13.1, vitality 58.4±17.4 and 50.2±13.9, social functioning 58.0±17.9 and 48.8±21.3, role-emotional 74.0±18.9 and 64.8±18.0, mental health 59.5±12.8 and 50.1±11.3; the rate of standard management of hypertension between experiment and control groups were 97.0% and 86.1%, the control rate of hypertension between experiment and control groups 72.3% and 61.7%, the control rate of diabetes between experiment and control groups 85.4% and 64.7, there were significant inter-group differences in all the above indicators (P<0.05).


Conclusion
The combined model of contract signing, team cooperation and telehealth care can significantly improve social support and quality of life for elders.


Key words: 
Community health services; Aged; Quality of life