tbuckley/cabot-search huggingface dataset:
A phase II study of apatinib treatment for advanced biliary tract carcinoma after failure of the standard chemotherapy.
Authors: Chenchen Wang, Weijian Guo, Mingzhu Huang
Journal: Journal of Clinical Oncology (2020)

e16684 Background: There is no standard second-line therapy for advanced biliary tract carcinoma (BTC). Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an inhibitary effect on tumor formation in BTC tumorgraft mouse model in previous study, with tolerable toxicity in clinical trials for other types of advanced cancer such as gastric cancer. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with advanced BTC. Methods: This is a single-center, single-arm phase II study (NCT03427242). The key inclusion criteria were:(1) histologically confirmed advanced or metastatic BTC; (2) Prior lack of response or intolerance to at least one chemotherapeutic regimens; (3) At least one measurable lesion as defined by RECIST 1.1; (4) No prior use of anti-angiogenic targeted drugs. Eligible patients received oral apatinib 500mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment safety. Results: From Dec 1, 2017 to Jan 31, 2020, a total of 18 patients (12 males and 6 females) had been recruited, and 16 patients who had received the medication of apatinib were included in this analysis. Among these patients, 10 were previously treated with only first-line chemotherapy and 6 were treated with two or more lines of therapy. The median age was 65 (range 45-76) years old. Fourteen patients had received the efficacy evaluation after treatment. Two patients achieved partial response (PR, 14.3%), 6 patients with stable disease (SD, 42.9%),and 6 patients with progressive disease(PD). The ORR and DCR were 14.3% and 57.1%, respectively. At the last follow-up date on Jan 30, 2020, 4 patients are still on apatinib medication. The median PFS was 2.70 months (95% CI, 1.94 - 3.46), and the median OS was 7.03 months (95% CI, 3.16 - 10.9). Grade 3 or 4 adverse events were reported in 7 patients (43.8%). The detailed grade 3 or 4 adverse events were proteinuria in 5 patients, hand-foot syndrome in 2 patients, platelet count decrease in 1 patients, diarrhea in 1 patients and urine bilirubin in 1 patients (Table). Conclusions: For the patients with advanced biliary tract carcinoma, apatinib showed an anti-tumor activity with acceptable safety. Clinical trial information: NCT03427242 . [Table: see text]
Intestinal and tumor microbiome analysis combined with metabolomics of the anti-PD-L1 phase II PERFECT trial for resectable esophageal adenocarcinoma.
Authors: Nicolien C. de Clercq, Tom van den Ende, Andrei Prodan, Mark I. van Berge Henegouwen, Suzanne S. Gisbertz, Sybren L. Meijer, Sandor Schokker, Jacques J.G.H.M. Bergman, Nadia Haj Mohammad, Jelle P. Ruurda, Richard van Hillegersberg, Stella Mook, Nicole C.T. van Grieken, Tanja D. de Gruijl, Mark Davids, Maarten F. Bijlsma, Maarten C.C.M. Hulshof, Hanneke W.M. Van Laarhoven, Max Nieuwdorp
Journal: Journal of Clinical Oncology (2020)

4556 Background: Both human and rodent studies provide evidence for a role of the microbiome in patients who respond to checkpoint inhibition (CI). So far, no study has unraveled the physiological link between intestinal and tumor microbiome composition in relation to response to CI. The PERFECT trial was a single-arm phase II feasibility study investigating the addition of atezolizumab (PD-L1 inhibitor) to neoadjuvant chemoradiotherapy (nCRT) for resectable esophageal adenocarcinoma (NCT03087864). An exploratory objective of this trial was to evaluate intestinal and tumor microbiome composition including plasma metabolomics as potential biomarkers for immunological and pathological response. Methods: Using 16S rRNA gene sequencing, we analyzed fecal, duodenal and tumor samples at baseline (V0), 3 weeks after start of atezolizumab (V1), and 1 week before surgery (V2). We compared microbiome composition and metabolomics from patients with pathological complete response (pCR; ypT0N0) to patients with a pathological incomplete response. Differences in alpha diversity metrics were tested using mixed linear models. Beta-diversity associations were assessed using permutational MANOVA (adonis) and multilevel PCA (mixOmics). Biomarkers were identified using a machine learning model (XGboost) feature selection. Plasma metabolomics (Metabolon) were determined with liquid chromatography mass spectrometry (LC-MS). Results: Microbiome profiles were significantly altered after start of treatment in all sample types. None of the sample types showed a relation between alpha or beta diversity and pCR. On taxonomical level, we found that the tumor and duodenal baseline samples were weak predictors for response (AUC 0.60 and 0.62, respectively), but better compared to fecal microbiome composition (AUC = 0.49). We identified the top 20 microbes that predicted pCR best in tumor and fecal samples and found significant correlations with metabolites involved in bile acid metabolism. Conclusions: Both tumor and duodenal baseline biopsies were better predictors of pathological response compared to fecal microbiome. Microbes predictive of pCR showed significant correlations with metabolites involved in bile acid metabolism, which is known to indirectly influence immunosurveillance in cancer. Data on immune response in relation to the microbiome and metabolomics are expected Spring 2020. Clinical trial information: NCT03087864 .
鼻内镜下鼻腔泪囊造口术治疗慢性泪囊炎泪道阻塞26例
Authors: 朱丽丽, 翟丕力, 王伟, 张伟, 张卫东
Journal: BMJ (2005)

鼻内镜下鼻腔泪囊造口术是近年来治疗慢性泪囊炎、泪道阻塞的一种新方法,自2001年1月至2004年1月,我们采用该术式治疗慢性泪囊炎、泪道阻塞26例(26只眼),疗效满意,现报告如下。
Contemporary strategy of psychotherapy for anxiety and depression disorder
Authors: Feng Qiang, Zhao Xudong
Journal: BMJ (2016)

焦虑障碍和抑郁障碍在社区门诊患者中常见，心理治疗是一种重要的干预方式。通过对惊恐障碍、广泛性焦虑、恐惧症、社交焦虑障碍4种类型的焦虑障碍和抑郁障碍的心理治疗方式和循证医学证据进行阐述，以提高社区全科医师对焦虑障碍和抑郁障碍治疗的认识。
The PEGASUS trial: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients.
Authors: Sara Lonardi, Clara Montagut, Filippo Pietrantonio, Elena Elez, Andrea Sartore-Bianchi, Noelia Tarazona, Stefania Sciallero, M. Giulia Zampino, Stefania Mosconi, Susana Muñoz, Luca Lazzari, Paolo Luraghi, Salvatore Siena, Alberto F. Sobrero, Roberto Labianca, Valter Torri, Alberto Bardelli, Josep Tabernero, Silvia Marsoni
Journal: Journal of Clinical Oncology (2020)

TPS4124 Background: Moving stage III Colon Cancer (CC) into the precision medicine space is a priority in view of the lack of molecular markers driving adjuvant treatment. Retrospective studies have demonstrated the tremendous prognostic impact of circulating tumor DNA (ctDNA) analysis after curative intent surgery, and suggested that lack of conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy reflects treatment failure. With these premises, we have designed the PEGASUS trial (NCT04259944). Methods: PEGASUS is a prospective multicentric study designed to prove the feasibility of using liquid biopsy (LB) to guide the post-surgical and post-adjuvant clinical management in 140 microsatellite stable Stage-III and T4N0 Stage-II CC patients. The LUNAR1 test (Guardant Health, Redwood City, CA, USA) will be used for ctDNA determination. For the efficacy analysis, the PEGASUS cohort will be compared with a 3:1 matched cohort of 420 patients from the TOSCA trial (NCT00646607). A LB executed 2-4 weeks post-surgery will guide a “Molecular Adjuvant” treatment: i) ctDNA+ patients will receive CAPOX for 3 months and ii) ctDNA- patients will receive capecitabine (CAPE) for 6 months but will be retested after 1 cycle, and if found ctDNA+ will be switched to CAPOX treatment. At the end of the “Molecular Adjuvant” treatment a further LB will be performed and instruct subsequent treatment. Positive patients (ctDNA+/+ and ctDNA-/+) will receive an up-scaled “Molecular Metastatic” systemic treatment for 6 months or until radiological progression or toxicity: i) ctDNA+/+ patients will be treated with FOLFIRI; ii) ctDNA-/+ patients with CAPOX. These patients will be subjected to a LB after 3 months and at the end of treatment: in case of positivity will be switched to FOLFIRI. ctDNA+/- patientswill receive a de-escalated treatment with CAPE for 3 months. 3 LB will be performed within 3 months and in case of positivity the patient will be switched to FOLFIRI. Patients with ctDNA-/- will be subjected to an interventional follow-up comprising 2 further LB and in case of positivity they will be switched to CAPOX treatment. PEGASUS is piggybacked to AlfaOmega (NCT04120935), a Master Observational Protocol that will follow patients from diagnosis to 5 years or recurrence/death (whichever comes first), collecting clinical data, radio-images and biological samples. AlfaOmega provides a clinical and logistic ecosystem for the seamless integration of PEGASUS clinical results with the biological underpinning of colon cancer. Clinical trial information: NCT04259944 .
Masterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies.
Authors: Erika Paige Hamilton, Manish R. Patel, Jordi Rodon, David S. Hong, Alison M. Schram, Pasi A. Janne, Patricia LoRusso, Jasgit C. Sachdev, Sai Hong Ou, Elizabeth A Buck, Matthew O'Connor, Nigel Waters, Karsten Witt, Carl Cook
Journal: Journal of Clinical Oncology (2020)

TPS3665 Background: A significant unmet need exists for drugs targeting allosteric ErbB mutations (non-canonical mutations outside the ATP binding site). Current EGFR and HER2 tyrosine kinase inhibitors or mAbs have limited antitumor activity against allosteric mutations, resulting in toxicity before adequate drug exposure (Connell and Doherty, 2017). BDTX-189 is a potent and selective orally available irreversible inhibitor targeting unique oncogenic driver mutations of ErbB kinases in EGFR and HER2, while sparing WT EGFR. Preclinical studies demonstrated antitumor activity across a range of allosteric ErbB mutants, including extracellular domain allosteric mutations of HER2 as well as EGFR and HER2 kinase domain exon 20 insertions (Buck, 2019). This first-in-human trial (NCT04209465) is aimed to determine the recommended phase 2 dose (RP2) and schedule (Phase 1, P1), and evaluate the efficacy (Phase 2, P2) of BDTX-189. P1 primary objective is to determine the RP2 dose and schedule of monotherapy BDTX-189. Secondary objectives include assessment of safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) effects in tumor, and preliminary efficacy. The P2 primary objective is to assess antitumor activity of monotherapy BDTX-189. Methods: The study will enroll patients (pts) ≥18 yrs with histologically or cytologically confirmed locally advanced or metastatic solid tumors with no standard therapy available or for whom standard therapy is unsuitable or intolerable. P1 dose-escalation will use a BOIN design (Yuan, 2016) and will enroll ≤ 88 pts with allosteric HER2 or HER3 mutation; EGFR or HER2 exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or EGFR exon 19 deletion or L858R mutation. BDTX-189 will be dosed orally (PO) initially QD in 3 wk cycles. Regimen optimization will use PK, PD and safety data and may explore a BID schedule. An expansion cohort of ≤12 pts will further evaluate safety and preliminary efficacy of BDTX-189 prior to P2. P2, utilizing a Simon 2-stage design, will enroll ≤100 pts with NSCLC with EGFR or HER2 exon 20 insertion mutations (cohort 1); breast cancer with an allosteric ErbB mutation (cohort 2); tumors (except breast) with S310F/Y mutation (cohort 3); and other allosteric ErbB mutations not defined in cohorts 1-3 (cohort 4). Assessments include safety, tolerability, DLTs, evaluation of MTD, PK, PD, and preliminary antitumor activity. Enrollment began 1/2020. Clinical trial information: NCT04209465 .
Feasibility of anticoagulation therapy after mechanical valve replacement in grass-root health institutions
Authors: Longhui Guo, Jingchao Zhang, Chao Liu, Wenyi Wang, Liwen Wu
Journal: BMJ (2015)

Objective
To assess the feasibility of anticoagulation therapy after mechanical valve replacement in grass-root health institutions.


Methods
One hundred and sixty one patients with mechanical valve replacement received anticoagulation therapy with warfarin, including 79 cases receiving the therapy in grass-root health institutions (test group) and 82 cases in the tertiary hospitals (control group). The patients were followed up for 12 months after operation; the rate of anticoagulation efficacy, the anticoagulation-related complications, and the anticoagulation-related cost were documented and compared between two groups.


Results
The international normalized ratio (INR) tests were performed for 1 021 times in test group and 717 times were up to anticoagulation standard (70.2 %, 717/1 021), while INR tests in control group were performed for 965 times and 688 times were up to standard (71.3%, 688/965); there were no significantly differences in efficacy rate between two groups (P>0.05). There were no significant differences in rate of bleeding events and thrombosis between two groups [16.5% (13/79) vs. 12.2% (10/82), 6.3%(5/79) vs. 4.9%(4/82), respectively, χ2=0.596, P=0.44, χ2=0.161, P=0.69]. The anticoagulation-related cost per month and per patient in test group was significantly lower than those in control group [(63.1±12.8) vs. (176.6±16.4) yuan, t=48.716, P<0.05].


Conclusion
Compared with the tertiary hospital, the anticoagulation therapy in grass-root institutions can accomplish the similar clinical outcomes and significantly reduce the medical cost in patients with mechanical valve replacement.


Key words: 
Heart valve prothesis implantation; Warfarin; Anticoagulation therapy; Hospitals, general; Hospitals, community
Validity of patient-reported outcomes to describe the symptom experience of patients enrolled on phase I clinical trials.
Authors: Ramy Sedhom, Betty R. Ferrell, Nora Ruel, Marianna Koczywas, Vincent Chung, Thomas J. Smith
Journal: Journal of Clinical Oncology (2020)

12107 Background: Symptoms are common among patients enrolled in phase I trials. To integrate the patient perspective, the National Cancer Institute developed a patient-reported outcomes version of the CTCAE (PRO-CTCAE) to capture symptomatic adverse events (AEs) directly from patients; however, the tool has not been used often in early phase trials or in palliative care studies. Our overall objective was to assess the validity of PRO-CTCAE items to previously validated assessments of quality of life (FACT-G) and psychological distress (Distress Thermometer). We utilized data from a randomized trial testing a palliative care intervention for patients with cancer enrolled on phase I trials. Methods: Patients (n = 481) were accrued to the parent study prior to initiating a Phase I clinical trial with data collected at baseline, 4, and 12 weeks. We determined the correlation of PRO-CTCAE with Distress Level, FACT-G total and subscale domain scores. Aggregate scores using PRO-CTCAE were calculated to explore the effect of overall symptom frequency, severity, and interference by calculating the total of all scored items classified within each of those domains. We used these metrics to identify associations between this and other validated tools. Results: Patients were predominantly female (56.8%), over age 60, and 30.7% were minority populations. Correlations between PRO-CTCAE items and corresponding FACT-G (total and subscales) and Distress levels reached statistical significance for all items (p &lt; 0.001). Importantly, many of symptoms captured would have been missed using HRQOL assessment tools. Some of these symptoms affected nearly 50% of patients and were frequently rated as severe or very severe. The correlation coefficient for Distress Level for all PRO-CTCAE items was small to moderate (Pearson r = 0.33 to 0.46). Pearson’s correlation coefficient for FACT-G total was moderate ( r = -0.45 to -0.69). Mood items of the PRO-CTCAE had stronger associations (Pearson r &gt; 0.5). PRO-CTCAE symptom interference scores had the strongest correlation with Distress (Pearson r = 0.46) and FACT-G Total (Pearson r = -0.69). Conclusions: Patients entering Phase I trials are willing to report on symptoms they experience as a result of advancing disease and adverse effects from experimental treatment. Evidence demonstrates favorable validity of PRO-CTCAE in a heterogeneous US sample of patients undergoing cancer treatment on phase I trials. The granular assessment of symptomatic AEs may be on increasing importance as we enter a new therapeutic era in oncology. Clinical trial information: NCT01828775 .
Progress in identification and protection of parathyroid gland during thyroidectomy
Authors: Lu Huang, Chao Li, Yongcong Cai, Ronghao Sun, Wei Wang, Jian Jiang, Yuxiu Zhou, Chunyan Shui, Qiaoli Li, Jing Tu, Ke Wang
Journal: BMJ (2019)

Thyroid cancer is a common head and neck malignant tumor, it has become a malignant tumor of the highest incidence in young women in China. The treatment of thyroid cancer is a surgery-based comprehensive therapy, and the protection of the parathyroid gland during surgery has always been a major problem for clinicians. The methods for protection of parathyroid glands are in situ preservation or immediate parathyroid autotransplantation according to whether or not the blood supply can be maintained. To identify the parathyroid gland is the key issue of the protection during thryoidectomy. This article reviews the recent progress of the identification and protection of parathyroid glands at home and abroad.


Key words: 
Parathyroid glands; Parathyroid protection; Surgical procedures, operative, thyroid gland
Factors associated with frequent insomnia among breast cancer survivors.
Authors: Agnes Kwak, Allison L. McDonough, Rachel Jimenez, Yvonne Y. Lei, Dana Haggett, Katherine T. Johnston, Laura Spring, Beverly Moy, Jeffrey M. Peppercorn
Journal: Journal of Clinical Oncology (2020)

e24098 Background: Insomnia is common among breast cancer (BC) survivors and often goes unrecognized and untreated. We sought to evaluate the association between frequent insomnia and potentially modifiable contributing factors to inform development of a comprehensive clinical program to address insomnia among patients with breast cancer. Methods: We adapted a 1-page survey from the National Comprehensive Cancer Network Guidelines for Survivorship, which was administered to BC survivors at oncology or primary care follow-up visits at our academic center and community based sites. The survey included 23 plain-language statements regarding symptoms, lifestyle concerns, and financial worries. Patients reported the frequency of concerns using a 5-point Likert scale (0 = never to 5 = always). We evaluated the frequency of insomnia and association between insomnia and 6 common concerns hypothesized to contribute among this population: emotional distress, fatigue, pain, hot flashes, fear of cancer recurrence, and healthcare-related financial stress. Prevalence of symptoms was dichotomized, grouping “very often” and “always” as “frequent”, and “sometimes,” “rarely”, and “never” as “infrequent”. Descriptive analysis was performed and associations between insomnia and other concerns were evaluated with Fisher’s exact test. Results: Among 192 patients (median age 59, range 34-92), 46 (24%) reported frequent insomnia (“I have problems falling or staying asleep”). Most patients (58%) reported experiencing insomnia at least “sometimes”, while 20% answered “rarely” and 23% “never”. Overall, 14% of survivors reported frequent anxiety/depression, 15% fatigue, 27% pain, 19% hot flashes, and 23% fear of recurrence. Only 6% of patients reported frequent financial worries due to healthcare costs. Emotional distress (p=0.016), fatigue (p≤0.001), pain (p≤0.001), hot flashes (p=0.017), and fear of recurrence (p≤0.01) were each associated with frequent insomnia. Conclusions: BC survivors who experience frequent insomnia are more likely to report emotional distress, fatigue, pain, hot flashes, and fear of recurrence, compared to those with infrequent insomnia. A clinical program designed for the management of insomnia may benefit from targeting these potentially contributing factors.
Disparities in advanced-stage breast cancer: The socioeconomic and geographic contributions.
Authors: Kelli Clemons, William Forehand, Hongyan Xu, Li Fang Zhang, Priyanka Raval
Journal: Journal of Clinical Oncology (2020)

134 Background: Socioeconomic disparities in healthcare have been well documented in America, with cancer being a critical area. One in four deaths are caused by cancer, and the effects on different communities are not equal. Clinical observations suggest that poorer socioeconomic circumstances lead to more frequent, later stage diagnoses and worse outcomes. The aim of this project was to quantify the sociodemographic and geographic contributions to disparities in advanced, metastatic breast cancer within the Augusta population and surrounding areas. Methods: Records of patients managed for breast cancer at the Georgia Cancer Center between Jan 2009- Jun 2019 were reviewed. 80 patients who presented with early stage breast cancer (clinical stage I) without positive lymph nodes were compared with 80 patients who presented with advanced, metastatic disease (clinical stage III-IV). Their race, breast cancer characteristics, insurance status, geographic proximity to a mammography site or major healthcare facility, and time interval between diagnosis and treatment were compared. Results: Results show that 73.75% early stage patients had private insurance, while 41.25% late stage patients had private insurance (p value &lt; 0.0001). Results also show that 25.0% of late stage patients had annual mammography screenings, while 77.78% of early stage patients had regular screening for mammograms (p value &lt; 0.0001). 80.6% of patients that received regular mammograms had private insurance, while the remaining 19.4% of those patients had public insurance. No statistical difference was shown in late and early stage presentation based on HER2 and/or triple negative (ER-, PR-, HER2-) status. Conclusions: There is a significant outcome of advanced, metastatic breast cancer in patients that do not have private insurance and in those that do not receive regular mammograms. Our findings support the importance of investing resources into alleviating differences in various socioeconomic populations as they relate to the amount and quality of cancer healthcare available. While the incidence of mortality in breast cancer is decreasing nationwide, disparities in morbidity and mortality will most likely continue unless there is an aggressive effort towards addressing said differences.