tbuckley/cabot-search huggingface dataset:
Evaluation of standardized patients by examiners in Objective Structured Clinical Examination (OSCE)
Authors: Yao Liu, Xiangjie Zhang, Zhigang Pan, Shanzhu Zhu
Journal: BMJ (2015)

Objective
To evaluate the simulation of standardized patients (SP) in objective structured clinical examination (OSCE) for general practice residency training.


Methods
The simulation levels of 15 SPs were evaluated by 37 examiners with a rating scale of OSCE Examiner Feedback on SP performance from Melbourne University School of Medicine. The evaluation was conducted in history-taking and doctor-patient communication stations of OSCE for general practice residency training.


Results
The overall scores of SP performance were high and most examiners considered that the performance of SP was realistic and consistent. Among 9 items of rating scale, more than 90% of the examiners considered that SP performance met or completely met the requirements of OSCE, except the item of preparation for clothing and making up before role playing. Six items of performance in history-taking station and 4 items in doctor-patient communication station reached 100% satisfaction from the examiners. T test was used to compare the difference of SP performance between the morning and afternoon, and there was no significant difference (P>0.05).


Conclusion
The study showed for this group of SPs, the realistic degree and consistency of performance meet the requirements of OSCE, and its stability is not affected by long time continuous performance.


Key words: 
Educational measurement; Patient simulation; Objective structured clinical examination; General practitioners
Longitudinal and personalized detection of circulating tumor DNA (ctDNA) for monitoring efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma (HCC).
Authors: Chih-Hung Hsu, Shan Lu, Alex Abbas, Yinghui Guan, Andrew X. Zhu, Alexey Aleshin, Kyung-Hun Lee, Michael Sangmin Lee, Amit Mahipal, Baek-Yeol Ryoo, Beiying Ding, Jessica Spahn, Wendy Verret, Aiwu Ruth He, Yulei Wang
Journal: Journal of Clinical Oncology (2020)

3531 Background: ctDNA has emerged as a promising biomarker for noninvasive monitoring of treatment response and disease progression in many tumor types. However, the clinical use of ctDNA in patients with HCC has not been established. Here, we evaluated longitudinal and personalized detection of ctDNA for monitoring the treatment response to atezolizumab (atezo) + bevacizumab (bev) in patients with unresectable HCC not previously treated with systemic therapy. Methods: A subset (n = 48) of 104 patients with HCC who enrolled in Arm A of GO30140 (NCT02715531; Phase 1b) and received atezo + bev treatment were included in this study. These patients had 10 CR, 11 PR, 12 SD and 15 PD per IRF-assessed RECIST 1.1. Serial plasma samples were collected at baseline (Cycle [C]1 Day [D]1), during treatment (C2D1, C4D1) and at disease progression. Somatic mutations in individual tumors were identified via whole exome sequencing of archival tumor tissues or fresh biopsies collected before treatment. Personalized ctDNA assays (Signatera 16-plex multiplex PCR next-generation sequencing assay) specific to each patient’s tumor mutational signatures were successfully designed for 47 of 48 patients. Results: At C1D1, a median of 25.7 ng of cell-free DNA was extracted from 2-mL plasma samples. ctDNA was detected in 45 of 47 patients (96%), with a median of 70.6 mean tumor molecules/mL of plasma (MTM/mL) and a median of 1.8% mean variant allele frequency (mean VAF) in plasma. Higher ctDNA levels detected at C1D1 appeared to be associated with increased tumor burden ( P &lt; 0.03). Dynamic changes in ctDNA levels post-treatment were associated with response at C4D1. ctDNA status changed from positive at baseline to negative in 7 of 10 CR (70%), 3 of 11 PR (27%), 1 of 11 SD (9%) and 0 of 11 PD (0%) patients. Longer PFS was observed in patients whose ctDNA became undetectable post-treatment. The median PFS in patients with ctDNA present vs cleared at C4D1 was 6.5 months and not reached, respectively (HR, 12 [1.7-93], log-rank P &lt; 0.00029). Conclusions: Our study showed that Signatera, a personalized and tumor-informed ctDNA assay, could be used as a sensitive method for detecting ctDNA in patients with unresectable HCC. More importantly, our results illustrate the promise of ctDNA as an emerging biomarker that may potentially help to monitor treatment responses and disease progression in patients with HCC.
Value of Hiquid-based cytology and colposcopy in screening for cervical lesion among urban community women of Beijing
Authors: Chao Zhao, Zheng Tu, Shu-hui Cui, Jian-liu Wang, Li-hui Wei
Journal: BMJ (2008)

Objective To study the value of liquid-based cytology and colposcopy in screening for cervical lesion among urban community women of Beijing.Methods A total of 795 women aged 20～54 years with sexual activity living in Zhanlanlu Community of Beijing were screened for cervical lesion Cervcal specimen was collected for thin-layer,liquid-based cytology test (LCT) from each of the participants in gynecologic examination.Colposcopy and biopsy were performed for the women with positive LCT.Results Forty-five of 795 (5.7%) women were positive for LCT[≥ASC-US (atypical squamouscell of undetermined significance)],with 33 of ASC-us,eight of low-grade squamous intraepithelial lesion (LSIL),three of high-grade squamous intraepithelial lesion (HSIL),one of atypical glandular cells (AGC).Five of 45 women with positive LCT refused to accept colposcopy.Among 40 women with colposcopy and biopsy,chronic cervicitis was diagnosed in 11(27.5%),cervical condyloma acurninatum in 14(35.0%),cervical intraepithelial neoplasia (CIN) 1 in seven(17.5%),CIN 2 in three (7.5%),CIN 3 in four(10.0%),and early invasive cervical cancer in one(2.5%).In 750 women with negative LCT,cervical condyloma acuminature was diagnosed in two(0.3%),CIN 1 in five(0.7%)and low-grade glandular intraepithelial lesion (LGIL) bin one(0.1%).Sensitivity and specificity of LCT screening for cervical lesion(≥CIN 1)were 71.4%and 94.2%,respectively,with positive and negative predictive values of 37.5%and 99.2%.respectively,and those screening for cervical lesion more than CIN 2 were 100.0%, 96.0%,20.5%and 100.0%,respectively.Conclusions More attention should be paid to early screening for cervical lesion in urban community women.LCT combined with colposcopy and biopsy provide very helpful information in screening for early cervical cancer.

Key words: 
Uterine cervical neoplasms;  Cytological techniques;  Colposcopy
Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the childhood cancer survivor study and the St. Jude Lifetime Cohort.
Authors: Matthew R. Trendowski, Jessica Baedke, Yadav Sapkota, Omar El Charif, Heather E. Wheeler, Wendy M. Leisenring, Leslie L. Robison, Melissa M. Hudson, Lindsay M. Morton, Kevin C. Oeffinger, Lois B. Travis, Rebecca M. Howell, Yutaka Yasui, Gregory T. Armstrong, Smita Bhatia, M. Eileen Dolan
Journal: Journal of Clinical Oncology (2020)

10550 Background: Cranial radiation therapy (CRT) for pediatric cancer often results in ototoxicity in the form of hearing loss and tinnitus. We sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with cranial radiation. Methods: Relationships between age at last observation, sex, cumulative CRT dose and self-reported ototoxicity were evaluated for hearing loss and tinnitus among 1,991 (tinnitus) and 2,198 (hearing loss) survivors in the Childhood Cancer Survivor Study who received CRT. Logistic regression evaluated associations with non-genetic risk factors and comorbidities as well as SNP dosages in GWAS of CRT-related tinnitus (cases: 146; controls: 1,845) and hearing loss (cases: 270; controls: 1,928). Results: Males were more likely to report CRT-related tinnitus (9.4% vs. 5.4%; p = 5.81x10 −4 ) and hearing loss (14.0% vs. 10.7%; p = 0.02) than females after adjusting for dose and age at last observation. Survivors with tinnitus or hearing loss were more likely to experience persistent dizziness or vertigo (tinnitus: p &lt; 2.00x10 −16 ; hearing loss: p = 6.35x10 −9 ), take antidepressants (tinnitus: p = 0.02; hearing loss: p = 0.01) and report poorer overall health (tinnitus: p = 9.40x10 −7 ; hearing loss: p = 1.30x10 −6 ) compared to survivors without tinnitus or hearing loss after age-adjustment. GWAS of CRT-related tinnitus revealed a prominent signal in chromosome 1 led by rs203248 (p = 1.50x10 −9 ), while GWAS of CRT-related hearing loss identified rs332013 (p = 5.79x10 −7 ) in chromosome 8 and rs67522722 (p = 7.78x10 −7 ) in chromosome 6 as approaching genome-wide significance. Replication analysis in an independent cohort of pediatric cancer survivors (SJLIFE) indicated that rs67522722, intronic to ATXN1, a gene associated with the neurodegenerative disorder spinocerebellar ataxia type 1, was significantly associated with CRT-related hearing loss (p = 0.03). Enrichment analysis and LD score regression with previous GWAS results of cisplatin-related hearing loss and tinnitus in testicular cancer survivors showed no detectable enrichment in genetic architecture with CRT-related hearing loss and tinnitus, respectively. Conclusions: Radiation-associated ototoxicity was associated with sex, several neuro-otological symptoms, increased antidepressant use and poorer self-reported health. GWAS of CRT-related hearing loss identified rs67522722 that was replicated in an independent cohort of pediatric cancer survivors.
Value of MRI enhanced scanning in diagnosis of meningeal carcinomatosis
Authors: Gui-hua Ni, Xiang-yang Tian, Wei-dong Zhao, Lin-fang Chen
Journal: BMJ (2011)

The clinical data and findings in MRI enhanced scanning of 16 patients with meningeal carcinomatosis were analyzed retrospectively.Meningeal carcinomatosis with subacute- or chronic-onset deteriorated progressively presenting the characteristics of intracranial hypertension and meningeal irritation.Fourteen out of 16 patients showed abnormal linear and strip signal enhancement of meninges by enhancement scanning.Meningeal carcinomatosis presented in diversified patterns and contrast-enhanced MRI is of referential value for the diagnosis of the disease.

Key words: 
Meningeal neoplasm;  Magnetic resonance imaging
Are the demographics of recurrent oropharyngeal and oral cavity squamous cell carcinoma changing?
Authors: Jeffrey Means, Douglas Stram, Jed Abraham Katzel
Journal: Journal of Clinical Oncology (2020)

e18537 Background: In the current era of human papillomavirus (HPV)-related oropharyngeal cancer and decreasing alcohol and tobacco use, the demographic factors associated with recurrent head and neck cancer may be evolving. We evaluated clinical and demographic factors in a cohort of patients with recurrent and non-recurrent Oral Cavity (OC) and Oropharyngeal Squamous Cell Carcinoma (OPSCC) in order to evaluate which factors are associated with tumor recurrence and how these factors are modified by HPV status. Methods: From a cohort of 3201 patients diagnosed with OC and OPSCC at Kaiser Permanente Northern California between 1/1/2008 and 6/30/2019, 235 recurrent cases were identified. Clinical and demographic factors were extracted from electronic medical records. We calculated frequencies of demographic and clinical factors stratified by recurrence and HPV status, and reported p-values using the chi-square test for independence. Results: HPV-related cases were more likely to be male (84% vs. 64%), younger (80% ≤70 years old vs. 55%), have fewer comorbidities (61% with non-cancer Charlson index &lt; 1 vs. 47%), and higher cancer stage (88% with a stage &gt; 1 vs. 42%) than HPV-unrelated cases. Recurrent HPV-unrelated cases were more likely to be Asian (14% vs. 8%), and from higher income census tracts (75% from tracts with median household income &gt; $60,000 vs. 66%) than recurrent HPV-related cases. Chi-square p-values of &lt; 0.001. Recurrence and HPV status did not appear to be associated with prior smoking and alcohol abuse. Conclusions: Our cohort verifies that HPV-related OPSCC patients are more likely to be younger, male, and with lower Charlson scores, while recurrent HPV-unrelated OC and OPSCC may be more common among Asians and individuals from higher-income census tracts. This may have important implications for future clinical trial design and surveillance for recurrence. [Table: see text]
Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial
Authors: David A. Palma, Robert Olson, Stephen Harrow, Stewart Gaede, Alexander V. Louie, Cornelis Haasbeek, Liam Mulroy, Michael Lock, George B. Rodrigues, Brian P. Yaremko, Devin Schellenberg, Belal Ahmad, Sashendra Senthi, Anand Swaminath, Neil Kopek, Mitchell Liu, Karen Moore, Suzanne Currie, Roel Schlijper, Glenn S. Bauman, Joanna Laba, X. Melody Qu, Andrew Warner, Suresh Senan
Journal: Journal of Clinical Oncology (2020)

The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking.We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an α of .20 (wherein P < .20 indicates a positive trial). Secondary end points included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial.Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P = .006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P = .001). There were no new grade 2-5 adverse events and no differences in QOL between arms.With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.
The genomic landscape of immune-related genes and its correlations with TMB and PD-L1 expression in Chinese NSCLC.
Authors: Linxin Zheng, Weifeng Li, Wenzhuan Xie, Mengli Huang
Journal: Journal of Clinical Oncology (2020)

e21056 Background: Understanding the genomic landscape of immune-related genes (IRGs) of patient with Non-Small Cell Lung Carcinoma (NSCLC) may provide critical insight and facilitate development of novel strategies for cancer therapy. Methods: Targeted next generation sequencing (NGS) was performed on tissue obtained from patients with NSCLC using a 381-gene panel. The IRGs were mainly based on a published article that summarized the genes related to activated T cells, immune cytolytic activity and IFN-γ release. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations (CNV) and gene fusions were assessed. Mutational profiles of IRGs and its correlations with Tumor mutation burden (TMB) and PD-L1 expression in NSCLC patients were analyzed from the 3D Medicine database. Results: Genomic data of 2,510 patients with NSCLC were analyzed via tissue detection [median age 62 years, (IQR: 54 - 69 years)]. 4.26% (107 / 2,510) of the patients had at least one characterized altered IRGs. The most frequently mutated IRGs identified for all genomic alternations occurred in PDCD1LG2 (40%), FAS (27%), LCK (23%), CD274 (21%), CD74 (3%), and missense mutations were the mainly mutant types of PDCD1LG2 and LCK, and copy number gains were showed in PDCD1LG2 and CD274. TMB levels in NSCLC patients with IRGs mutations were higher than in wild-type patients (mean TMB: 14.17 mut/MB vs 9.27 mut/MB, P &lt; 0.001). 65.42% (70/107, 9.35% for PD-L1 &gt; = 1% and &lt; 5%, 28.97% for PD-L1 &gt; = 5% and &lt; 50%, 27.10% for PD-L1 &gt; = 50%) of patients harboring PD-L1-positive ( &gt; = 1%), and the proportion of patients with mutations in IRGs does not exceed 10% in each subgroup. Results of Pearson Chi-square test showed that the PD-L1 expression had different between two groups ( Χ 2 = 13.3774, P = 0.0038), patients harboring IRGs mutation had a significantly higher level of PD-L1 than those wide-type patients (P = 0.001). Conclusions: Genomic landscape of IRGs significantly correlated with that of PD-L1 expression. Further analyses using more precisely IRGs and different stage NSCLC samples are requisite to support a role for IRGs as an target to immune therapy of cancers.
A randomized phase II/III study of paclitaxel/cisplatin versus cisplatin/5-fluorouracil in neoadjuvant chemoradiotherapy (CRT) followed by surgery for patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Ta-Chen Huang, Chih-Hung Hsu, Jason C. Cheng, Chia-Chi Lin, Jhe-Cyuan Guo, Hung-Yang Kuo, Feng-Ming Hsu, Pei-Ming Huang, Kuan-Yin Ko, Jang-Ming Lee
Journal: Journal of Clinical Oncology (2020)

TPS4650 Background: Meta-analyses have shown the survival benefit of cisplatin/5-fluorouracil (PF) neoadjuvant CRT over surgery alone for patients with locally advanced ESCC. The CROSS study has demonstrated the statistically significant survival benefit of paclitaxel/carboplatin neoadjuvant CRT for patients with locally advanced esophageal cancer, especially ESCC. A network meta-analysis based on published phase III trials suggested that paclitaxel/platinum might be superior to PF as neoadjuvant CRT in patients with ESCC (Huang et al: Jpn J Clin Oncol. 2015;45:1023–8). However, a direct comparison of two CRT regimens in a prospective randomized clinical trial has not been performed in ESCC. We designed this clinical trial to test the hypothesis that paclitaxel-platinum is superior to PF as neoadjuvant CRT in patients with locally advanced ESCC. Methods: This single center open-label phase 2/3 study randomizes patients with histologically confirmed ESCC, T3/4aN0M0 or T1-3N1-3M0 (AJCC 7 th edition), in 1:1 ratio, to receive TP (paclitaxel, 50 mg/m2/week; cisplatin 30 mg/m2/week; for 5 weeks) or PF (cisplatin 75 mg/m2, d1; 5-FU 1,000 mg/m2, d1-4; on week 1 and week 5)-neoadjuvant CRT (180 cGy/d, 5 days/week, for 5 weeks). Esophagectomy will be performed 6 to 10 weeks after completing CRT. All patients must be eligible to esophagectomy, with tumor length ≤8cm and tumor radial ≤5cm, with adequate organ functions, and have ECOG performance status of 0-2. In the phase 2 stage, 128 patients will be enrolled, assuming the pathologic complete response (pCR) rate of TP and PF as 45% and 25%, respectively, with a power of 80% and one-sided 10% significance level. If the primary endpoint of pCR is met, additional 120 patients will be enrolled for the phase III stage with overall survival as the primary endpoint, assuming the hazard ratio of TP versus PF as 0.65 with a power of 80% and a 5% significance level. The trial started patient enrollment in May, 2017. As of Jan of 2020, 52 of planned 128 patients for phase II part have been enrolled. Clinical trial information: NCT03623737 .
Efficacy and safety of apatinib plus docetaxel for non-squamous non-small cell lung cancer with bone metastases.
Authors: Aimin Zang, Guoguo Sun
Journal: Journal of Clinical Oncology (2020)

e21741 Background: The skeletal system is one of the most common distant sites of metastatic non-small cell lung cancer (NSCLC) which may lead to skeletal-related events (SREs). Bone metastasis can reduced quality of life. Vascular endothelial growth factor receptor (VEGFR)-targeted therapy is effective against bone metastasis in animal models. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), which is inhibits tumor angiogenesis. Therefore, we aimed to investigate the efficacy and safety of apatinib plus docetaxel for NSCLC with bone metastases. Methods: Eligible patients of NSCLC with bone metastases who received first-line platinum-based chemotherapy. Treated with apatinib (500 mg, qd, orally) plus docetaxel (60mg/m2, q3w, iv) and zoledronic acid (4mg, q3w, iv). Treatment was continued until disease progression or unacceptable toxic effects. Results: Between July 2017 and June 2019, 10 patients were enrolled. All patients available for efficacy and safety evaluation. the objective response rate (ORR) was 50% and the disease control rate (DCR) was 80%. The median progression-free survival (PFS) was 6.5 months, The proportions of patients with SREs were 20%. The most common Grade 1 or 2 adverse events included hypertension (30%, 3/10), fatigue (30%, 3/10), digestive tract reaction (30%, 3/10), leukopenia (20%, 2/10). Conclusions: Apatinib plus docetaxel prolonged PFS and reduced the incidence of SREs, with acceptable toxic effects. The therapeutic regime may be an option for NSCLC with bone metastases. Clinical trial information: NCT03127319.
What happens at radiographic disease progression in patients with metastatic cancer receiving immune checkpoint inhibitors? A single institution analysis.
Authors: Justin Lin, Vaibhav G. Patel, Qian Qin, Bo Wang, George Mellgard, Mahalya Gogerly-Moragoda, Amanda Leiter, Emily J. Gallagher, Xiaobo Zhong, William K. Oh, Matt D. Galsky, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

e15157 Background: Immune checkpoint inhibitors (ICIs) are widely adopted for multiple indications across various malignancies. Despite the surge in their use, what occurs at radiographic progression (rPOD) remains poorly characterized. Herein, we describe patients at our institution that experienced rPOD on ICIs. Methods: We retrospectively reviewed charts of patients (pts) with solid tumors that received at least 2 doses of ICI at our institution from 12/01/2010 to 04/25/2017. Patients’ demographic data, medical history, ICI course, and outcomes were recorded. Characteristics at rPOD included change in tumor size by metastatic site, symptoms, and hospital utilization. Additionally, we characterized outcomes of pts who continued ICIs after rPOD. Fisher’s exact test was performed to identify potential clinical predictors of hospitalization at rPOD. Results: Of the 361 evaluable pts, 238 experienced rPOD. In this cohort, the most common primary sites of disease are: genitourinary (24%), thoracic (24%), skin (21%), and hepatobiliary (15%). At rPOD, 71 (30%) patients were hospitalized within 30 days, with infection (27%) and pain (18%) being the most common reasons. Median survival of pts with hospitalization was 2 months (mos; 95% CI: 0-4), compared to 10 months (95% CI: 8-12) for those not hospitalized (p&lt;0.001). Forty-six (19%) pts continued ICI treatment after rPOD (median duration = 2.8 mos), with eleven (5%) pts continuing for at least 6 months (median duration = 8 mos). Conclusions: In our study of real-world cancer pts treated with ICI, a higher than expected proportion was hospitalized within 30 days after rPOD, and this population had a worse overall survival compared to those that were not. A subgroup of pt with rPOD did not experience clinical progression, and thus treatment was continued, although further benefit was limited to a small subset. Further studies are needed to better understand the underlying mechanism to identify those who benefits from treatment beyond rPOD. [Table: see text]