tbuckley/cabot-search huggingface dataset:
The role of targeted therapy (TKI) in the treatment of advanced hepatocellular carcinoma (aHCC) in the era of immunotherapy: Real-world data using AI analytics from an academic medical center.
Authors: Rachel Su Jen Wong, Jiaxuan Wu, Alisha Joan Leen, Glenn Jin Chong Tey, Yugarajah Asokumaran, Gloria Chan, Chidambaram Siddappan, Anand Devaprasath Jeyasekharan, Cheng Ean Chee, Wei-Peng Yong, Kee Yuan Ngiam, Raghav Sundar
Journal: Journal of Clinical Oncology (2020)

e16623 Background: The management of aHCC has evolved dramatically in recent years, with new agents like immunotherapy receiving regulatory approval. As we begin incorporating these drugs into routine clinical practice, data on real-world sequencing of therapies and clinical outcomes are needed. Methods: We utilised the DISCOVERYAI platform, a virtual machine containing de-identified patient electronic health records to review HCC patients treated at the National University Health System, Singapore from January 2015 to December 2019. We then identified those who received systemic therapy and correlated their clinical outcomes. Results: In total, 395 HCC patients were identified; 75 received surgery, 174 received loco-regional therapy and 102 referred for consideration of systemic therapy. Of those considered for systemic therapy, median age was 65 years (range 23-87); 88% male (n = 90); hepatitis B/hepatitis C/non-hepatitis, 41(40.2%)/ 10(9.8%)/ 51(50.0%). 75.5% (n = 77) of them received systemic therapy with a TKI and/or immunotherapy. 39% (n = 30) of these received second-line treatment. Child-Pugh score at start of treatment was A5/A6/B7/B8, 38(49.3%)/ 32(41.6%)/ 5(6.5%)/ 2(2.6%) respectively. In the first-line, 66% (n = 51) received TKI and 34% (n = 26) received immunotherapy. Amongst those treated with first-line TKI, 45% (n = 23) received second-line therapy; 65% (n = 15) immunotherapy, 35% (n = 8) another TKI. Of those treated with first-line immunotherapy, 27% (n = 7) received second-line TKI. At a median follow-up of 35 months, first-line median progression-free survival (mPFS) for TKI vs immunotherapy was 3.7 vs 3.1 months (HR 0.73; 95% CI, 0.40-1.33; p = 0.31). mPFS for second-line immunotherapy vs TKI was 4.0 vs 2.9 months (HR 0.43; 95% CI, 0.19-0.96; p = 0.04). When comparing sequencing of therapies, the combined first and second mPFS for TKI-immunotherapy/TKI-TKI/immunotherapy-TKI is 9.5/7.6/7.6 months respectively (log-rank test, p = 0.71). Those patients that received both immunotherapy and TKI had significantly higher overall survival (OS) compared to those receiving only immunotherapy or only TKI or none (mOS NR vs 10.1 vs 13.2 vs 4.7 months; p &lt; 0.001). Conclusions: TKI remains an important pillar of treatment in aHCC in the era of immunotherapy. While immunotherapy provides long durable responses and benefit in a minority of patients, the majority appear to benefit from TKI. Biomarker studies are needed to discern treatment algorithms for aHCC.
Combined recombinant humanized anti-PD-1 monoclonal antibody (JS001) and nab-paclitaxel/gemcitabine (AG) as the first-line therapy for patients with advanced pancreatic adenocarcinoma: Preliminary results of an open-label, phase Ib/II clinical study.
Authors: Ke Cheng, Zhiping Li, Dan Cao
Journal: Journal of Clinical Oncology (2020)

e16792 Background: To determine evaluate the safety and efficacy of nab-paclitaxe, gemcitabine (AG) and Recombinant Humanized Anti-PD-1 Monoclonal Antibody (JS001) for patients with advanced pancreatic ductal adenocarcinoma (PDAC). Methods: This was a single-arm, open-label, phase 1b/2 clinical trial of nab-paclitaxel plus gemcitabine plus Anti-PD-1 Monoclonal Antibody in which 11 patients with previously untreated advanced PDAC were enrolled from December 2018. Patients were treated with nab-paclitaxel 125 mg/m2 on days 1 and 8 plus gemcitabine 1000 mg/m2 on days 1 and 8 plus fixed dose of JS001 240mg on day 1 of a 21-day cycle until progression or toxicity or receiving maintance therapy. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Results: 11 chemotherapy naïve PDAC patients with a median age of 52 years old were treated. 5 were men and all patients had an ECOG of 0 or 1. Grade 3/4 events were observed in 27.3% of patients (2 patients presented hematological toxicity ), and JS001 was discontinued because of asymptomatic elevated cardiac biomarkers and hypothyroidism as immunotherapy-related toxicities in a female patient, no patient was discontinued AG therapy because of chemotherapy-related adverse events. Of the 11 evaluable patients, the disease control rate (partial response [PR] + stable disease[SD]) was 81.8%. There were 2 patients with PR and 1 patient with complete response respectively, and overall response rate (ORR) was 27.3%. The median progression-free survival (PFS) was 7 months and all patients survive at the last following-up in Jan-2020. All patients were proficient mismatch repair (pMMR) status. Whole-exome sequencing was performed on 7 patients, no immunotherapy-associated gene was detected, and next comprehensive analysis of somatic alterations was ongoing. Conclusions: Combined JS001 and AG can be safely given to chemotherapy naïve PDAC patients. Efficacy appears to be promising over previously reported results for standard AG chemotherapy every 28 days gemcitabine and nab-paclitaxel dosing. Comprehensive data available was ongoing to analysis the potential effect to efficacy of the combination.
Survival in adult and pediatric patients with medulloblastoma: A 2018 SEER-based analysis.
Authors: Hanna Moisander-Joyce, Anoushka Sinha, Shannon Fernandez-Ledon, Davon Lee, Satoki Hatano, Justine Kahn, James Garvin, Stergios Zacharoulis, Robyn D Gartrell-Corrado
Journal: Journal of Clinical Oncology (2020)

e14529 Background: Medulloblastoma (MB) is a malignant neuroectodermal tumor accounting for 30% of pediatric and only 1% of adult brain tumors. In previous studies comparing survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database no difference has been found. However, diagnostic subgroup analyses have been limited. Methods: We examined survival in children (age 0-19) and adults (20-79) coded as MB in the 2018 SEER database (2000-2016). We used Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n = 1,728). ICD 9473, supratentorial PNET (sPNET, n = 97) is biologically distinct and therefore it was analyzed separately. Results: We found that 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n = 488, 79.1%) (HR = 0.97, CI: 0.79 – 1.17, p = 0.50). Furthermore, subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n = 222, p = 0.09), large cell MB (n = 73, p = 0.46), or MB NOS (n = 1330, p = 0.10). Yet, children with sPNET had improved 5-year survival (n = 65, 72.3%) compared to adults (n = 29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p = 0.02,). These findings indicate that while survival in patients with MB is similar across age groups, children with sPNET have improved outcomes. Conclusions: In summary, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment (chemotherapy or radiation). For sPNET, the apparent improved outcomes for children merit further detailed investigation and will be re-evaluated using the new 2016 World Health Organization classification.
Association of hospital type and patient volume growth with timely cancer treatment.
Authors: Zachary AK Frosch, Nicholas Illenberger, Nandita Mitra, Daniel J. Boffa, Matthew A. Facktor, Heidi Nelson, Justin E. Bekelman, Lawrence N. Shulman, Samuel U Takvorian
Journal: Journal of Clinical Oncology (2020)

2022 Background: Studies have suggested superior outcomes for patients with cancer treated at National Cancer Institute (NCI) and academic hospitals, leading some to advocate for complex cancer care to be delivered at regional referral centers. However, growing demand at such centers may exceed their capacity to provide timely treatment, which could be detrimental to patient outcomes. We evaluated the relationship between hospital type, the average annual growth rate in patient volume (PV), and time to treatment initiation (TTI) trends. Methods: We used the National Cancer Database to identify patients undergoing initial treatment for a new diagnosis of cancer (breast, lung, prostate, colorectal, melanoma, bladder, non-Hodgkin lymphoma, renal, uterine or pancreatic) in 2007-2016. The exposure was hospital type (NCI, academic, community or integrated network). The primary outcome was TTI over time. We estimated both the average annual growth rate for PV and adjusted TTI trends by hospital type using linear mixed effects models, including a hospital type-by-time interaction and, when modeling TTI, a patient volume-by-time interaction. Results: We identified 4,218,577 patients treated at 1351 hospitals (49% at 897 community, 23% at 177 academic, 14% at 50 NCI and 14% at 227 integrated network hospitals). Over the study period, PV grew by 40% at NCI and 25% at academic hospitals, compared to 8% at community hospitals (p-value for trend both &lt; 0.001). Meanwhile, mean TTI increased by 3.2 days at community, remained stable at academic (+0.3 days) and decreased by 4.3 days at NCI hospitals (p-value for trend both &lt; 0.001 vs community). A higher annual PV growth rate was associated with a statistically but not clinically significant TTI increase (0.05 days for each 100 patient/year increase in the growth rate, p = 0.001). Conclusions: Patients with newly diagnosed cancer are increasingly receiving treatment at NCI and academic hospitals. While TTI at NCI and academic hospitals is longer than in the community, PV growth has been possible without delaying cancer treatment. Further study is needed to determine whether continued growth at this rate is sustainable. [Table: see text]
Retrospective Analysis of Budd-Chiari Syndrome in 135 Patients
Authors: Hua Yang, Qian Chen, Shan-zhu Zhu
Journal: BMJ (2008)

A total of 135 patients diagnosed with Budd-Chiari syndrome(BCS)during August 2004 and February 2007 were reviewed and analyzed retrospectively.The results showed that 105 subiects (77.8%)caused by malignances,while 29 participants(21.5%)had no definite pathogens.The most commonly seen symptom included jaundiee(69.6%),followed by ascites(48.2%),abdominal distention (40.7%)and lower extremity edema(37.0%).Hisher levels of STB,PT and γ-GT were determined.Color Dopple ultrasound,CT and MRI could be helpful in diagnosing BCS;angiography remained the most accurate measurement.Main treatment strategies were stent implantation and/or balloon dilation.BCS is a clinical syndrome with no typical symptoms.which makes its management very difficult.A complete understanding of the condition will help reduce misdiagnosis.Angiography and stent implantation are primary ways to diagnose or treat BCS.

Key words: 
Hepatic vein thrombosis; Diagnosis; Treatment
肺栓塞误诊一例分析
Authors: 孙宏伟, 罗静, 贾宁
Journal: BMJ (2009)

患者女,70岁,因胸闷、气短1个月,加重伴喘憋10 d于2008年10月16日入院.该患者1个月前无明显诱因间断出现胸闷、气短,活动后症状加重,无胸痛及咯血,无大汗、恶心及呕吐,无晕厥及黑朦。
Effect of STK11 mutations on efficacy of PD-1 inhibition in non-small cell lung cancer (NSCLC) and dependence on KRAS mutation status.
Authors: Biagio Ricciuti, Kathryn Cecilia Arbour, Jessica Jiyeong Lin, Natalie Vokes, Amir Vajdi Hoojghan, Yvonne Y. Li, Andrew D. Cherniack, Gonzalo Recondo, Giuseppe Lamberti, Deepti Venkatraman, Hira Rizvi, Jacklynn V. Egger, Andrew J. Plodkowski, Sara Khosrowjerdi, Subba R Digumarthy, Mizuki Nishino, Lynette M. Sholl, Justin F. Gainor, Matthew David Hellmann, Mark M. Awad
Journal: Journal of Clinical Oncology (2020)

e15113 Background: STK11 mutations ( STK11m) have been associated with resistance to ICI in KRAS-mutant ( KRASm) NSCLC. Whether STK11m status also impacts clinical outcomes to ICI in KRAS wild-type (wt) NSCLC is unknown. Methods: We analyzed clinical outcomes of patients (pts) with NSCLC treated with ICI according to KRAS and STK11 mutation status in independent discovery (DFCI+MGH) and validation (MSKCC) cohorts. TCGA and xCell data were interrogated to identify differences in tumor gene expression and tumor immune cell subsets, respectively, according to KRAS/ STK11 co-mutation status. Results: Of 1195 pts with advanced nonsquamous NSCLC treated with ICI, 447 (37.4%) had a KRASm, 252 (21.1%) had pathogenic STK11 mutations, and 128 (10.7%) had concurrent KRASm and STK11m. ICI outcomes for the discovery and validation cohorts in KRASm and KRASwt cases by STK11 mutation status are shown in Table. In the combined cohort (discovery+validation), STK11m was associated with significantly worse outcomes to ICI among KRASm cases: ORR 10.2% vs 30.7%, P &lt; 0.001; median progression-free survival (mPFS): 2.0 vs 4.8 months (mo), HR:0.49 [95%CI:0.39-0.61], P &lt; 0.0001; median overall survival (mOS): 6.1 vs 16.9 mo, HR:0.50 [95%CI:0.39-0.63], P &lt; 0.0001. In multivariable analysis, STK11m was associated with significantly shorter PFS (HR:0.56, P = 0.002) and OS (HR:0.57, P = 0.006). By contrast, STK11m had no impact on ICI outcomes among KRASwt cases: ORR 24.2% vs 19.2%, P = 0.21; mPFS: 2.5 vs 2.8 mo, HR:0.98 [95%CI:0.79-1.21], P = 0.89; mOS: 12.0 vs 11.5 mo, HR:1.06 [95%CI:0.85-1.33], P = 0.57. Among KRASwt cases, STK11m had no impact on ICI outcomes among both smokers and never smokers, when analyzed separately. Gene ontology analysis from TCGA revealed that among KRASm but not KRASwt NSCLC, STK11m was associated with the downregulation of MHC class II-related genes (P = 0.02). Cell subset transcriptome analysis showed significantly lower proportions of M1 macrophages among KRASm/ STK11m but not among KRASwt/ STK11m NSCLCs (P &lt; 0.01). Conclusions: STK11m are associated with resistance to ICI in KRASm but not KRASwt NSCLC. STK11m/ KRASm vs STK11m/ KRASwt NSCLC have distinct immunophenotypes. [Table: see text]
Relationship between human papillomavirns and cervical carcinoma
Authors: Bin Yu
Journal: BMJ (2009)

Objective To explore the relationship between high-risk human papillomavirus (HPV) DNA and biological behavior of cervical carcinoma. Methods Sixty-six patients of cervical carcinoma with cytological examinations and 103 patients of cervical carcinoma followed-up after surgical operation were selected for high-risk HPV DNA test with second-generation hybrid capture technique (HC2 Ⅱ). Results ①HPV DNA was positive in 62 and negative in four of 66 patients of cervical carcinoma with an overall prevalence of 94%. ②There was no significant difference in positive HPV DNA of patients with cervical carcinoma between their varied clinical stages and pathologic grades. But, HPV positivity and HPV DNA load in patients with myometrial invasion were higher than those in patients without invasion (P < 0. 05).③ HPV DNA conversed to negative in 99 of 103 patients (96%) with cervical carcinoma after surgical operation from positivity before operation. Conclusions High-risk HPV infection may correlate with angiogenesis, invasion and metastasis of cervical carcinoma and HC2 Ⅱ can be used as an effective method to detect HPV DNA.

Key words: 
Papillomavirus infections;  DNA, viral;  Nucleic acid hybridization;  Uterine cervical neoplasms
Evaluation of hypertension group-interference-management model in the community
Authors: Keming Wu, Lan Zhu, Jianbo Wang, De'an Liu
Journal: BMJ (2014)

Objective
To evaluate the effectiveness of hypertension group-intervention-management model in the community.


Methods
Four hundred hypertensive patients in the community were randomly assigned into intervention group and control group (n=200 in each) in January 2011. Patients in intervention group received group-intervention management for 6 months, those in control group received routine management service. Self-efficacy, Community-support, Coping skill, Health status and Blood pressure control (including blood fat, waist-to-hip ratio, body mass index) scales were adapted to evaluate the effectiveness of intervention.


Results
There were no significant differences in demography index between 2 groups.Patients in intervention group showed greater improvement in Self-efficacy(SE to manage symptom, disease and exercise), Health status(health self-evaluation, energy, low spirit and health distress) scores compared to control group(all P 0.05).


Conclusion
The community-based group-interference model is more effective than the routine management service for management of hypertensive patients in the community.


Key words: 
Hypertension; Disease management; Intervention studies
Low protein diet for patients with chronic kidney disease
Authors: Liyang Chang
Journal: BMJ (2016)

Diet therapy is considered as the basic treatment of chronic kidney disease (CKD), and its primary goals are improving metabolic disorder, relieving symptoms and prevent complications, hence to retard renal function lost of CKD patients. However, there have been controversies about the results of clinical studies on nutritional treatment for CKD. This article reviews the effectiveness, safety and compliance of low-protein diet (LPD) for CKD patients, and related clinical management strategies. The article also recommends the feasible diet scheme to provide a reference of clinical LPD therapy for patients with CKD.


Key words: 
Kidney disease, chronic; Nutrition therapy; Diet, protein-restricted
Responding to narrowing discrimination protections: Can hospital policies protect transgender and gender diverse patients with cancer?
Authors: Ash Alpert, Elizabeth Stieglitz Tarras, Amani Sampson, Myla S. Strawderman, Megan Sutter, Gwendolyn P. Quinn
Journal: Journal of Clinical Oncology (2020)

e14126 Background: The U.S. Department of Health and Human Services recently proposed to eliminate federal protections against discrimination in healthcare on the basis of gender identity. This proposal seeks to alter the Patient Protection and Affordable Care Act Section 1557 Rule, which currently prohibits sex discrimination in any health program receiving federal financial assistance. The provisional change poses imminent threats to transgender and gender diverse (TGD) communities who face discrimination in healthcare, and in cancer care specifically. If current federal protections are eliminated, enacting local non-discrimination policies may safeguard TGD individuals’ rights to access safe equitable cancer care. To determine the need for local policy change, we sought to assess the current protections based on gender identity and expression for patients at National Cancer Institute (NCI)-Designated Cancer Centers. Methods: Publicly available hospital non-discrimination policies and Patients’ Bill of Rights were examined from the main affiliated hospitals of each of the 62 NCI-Designated Cancer Centers, excluding laboratories. The policies were classified as clearly including gender identity and expression or not. McNemar’s Test calculated differences between non-discrimination policies and Patient’ Bill of Rights. Results: Of 62 institutions, 30 (48.4%) clearly included gender identity and expression in their hospital non-discrimination policies, whereas 45 (72.6%) included gender identity and expression in their Patients’ Bill of Rights ( p= 0.014). Thirty-seven (59.7%) institutions included gender identity and expression in only one of the documents (Table). Conclusions: NCI-Designated Cancer Centers do not consistently include gender identity and expression in publicly available non-discrimination documents. The discrepancy between Patients’ Bill of Rights documents and hospital non-discrimination policies suggests a difference between what institutions outwardly convey to patients and what they operationalize in their legal documents. Paired outcomes from 62 independent NCI-Designated Cancer Centers. [Table: see text]
Clinical characteristics and outcomes of simultaneous multiple primary lung cancer.
Authors: Ying Liu
Journal: Journal of Clinical Oncology (2020)

e21088 Background: Simultaneous multiple primary lung cancer (sMPLC) is detected increasingly nowadays with the development of image technology. But it has not been well characterized. Methods: All consecutive patients diagnosed as sMPLC according to Martini-Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 were enrolled in our center. The clinical characteristics and outcomes were compared between patients with same histology and different histology. Results: A total of 336 patients were enrolled, consist of 297 (88.4%) patients with same histology and 39(11.6%) patients with different histology. Compared to patients with same histology, patients with different histology were more common male (87.2% vs. 34%, p &lt; 0.001) and diagnosed at an older age (54 [62-69] vs. 59 [52-65], p &lt; 0.001). Also, more than half of them (56.4%) had respiratory symptom or pain before diagnosis and most of them had smoking history (79.5% vs. 19.2%, p &lt; 0.001). During follow-up, 5 patients were lost and 16 patients were died, contributing the 1-, 2-, and 3-year survival of overall patients was 97.7%, 96.1%, and 92.2%, respectively. Importantly, the survival rate was lower in patients with different histology (1-, 2-, and 3-year 88.5%, 75.4, and 64.3%) than same histology (1-, 2-, and 3-year 99.2%, 99.2, and 96.8%) (p &lt; 0.001). Conclusions: Although relative less common in sMPLC, patients with different histology showed different clinical features and worse prognosis. [Table: see text]
Expensive Insulin—The Epicenter of a Large, Life-Threatening Problem
Authors: Laura M. Nally, Kasia J. Lipska
Journal: JAMA Internal Medicine (2020)

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