tbuckley/cabot-search huggingface dataset:
The alteration of TERT in 10,000 Chinese patients with solid tumors.
Authors: Jie Lin, Yuehua Li, Hao Zou, Li Zhang, Yanbin Xiao, Qi Pan, Bo Tang, Huan Wu, Jiaochun Shi, Weifeng Wang
Journal: Journal of Clinical Oncology (2020)

e13655 Background: The reactivation of telomerase reverse transcriptase ( TERT) is one of the characters that make cancer cells immortal. TERT expression has been shown in various human cancers.However, the landscape of TERT alterations in Chinese patients with solid tumors still remains unclear. Here, we illustrated the profile of TERT variations of Chinese solid tumor patients by using next generation sequencing (NGS)-based targeted sequencing. Methods: Formalin fixed, paraffin embedded (FFPE) tumor tissues and matching blood samples were collected from 9874 Chinese patients and subjected to a NGS-based panel at a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. All classes of alterations were assessed. Results: FFPE samples from 9874 Chinese solid tumor patients included lung cancers (39.7%), liver cancers (12.5%), colorectal cancers (10.8%), gastric cancers (5.7%), pancreatic cancers (4.9%), biliary tract tumors (4.6%), and other 18 cancer types (21.7%) were assessed. And 1187 (12.0%) out of 9874 cancer samples had TERT variations. TERT variations occurred in all types of cancer with various frequencies: urothelial neoplasms (52.0%), central nervous system tumors (40.0%), melanomas (38.9%), liver cancers (30.7%), thyroid tumors (24.3%), cervical cancers (20.6%), biliary tract tumors (16.3%), head and neck tumors (14.6%), soft tissue tumors (12.2%) and lung cancers (10.3%). Substitution was the most common variation of TERT and accounted for 58.7% of all the alterations, followed by gene amplification (38.8%) and fusions (2.4%). There were 86.8% of substitution variations presented in TERT promoter region comprising of c.-124C &gt; T (70.7%) and c.-146C &gt; T (13.1%). Patients with TERT alterations included 414 females and 773 males with a median age of 59 years old (range: 8-88). Tumors included stage IV (34.0%), stage III (22.2%), stage II (12.7%), stage I (18.7%) and stage 0 (12.3%). TERT variations were correlated with patients’ age (p = 0.00083) and gender (p = 5.59×10 −7 ). There was no significant correlation of TERT alterations with the highly mutated TP53. The frequencies of TERT alterations were similar in patients with mutated and wild type TP53 (12.7% vs 11.1%). Conclusions: Our study revealed that 12.0% Chinese solid tumor patients harbored TERT alterations, especially two hotspots mutations (c.-124C &gt; T and c.-146C &gt; T) in the promoter region. TERT variations had a correlation with patients’ age and gender, but no correlation with hotspot TP53 mutations.
Fenofibrate and statin therapy, compared with placebo and statin, slows the development of retinopathy in type 2 diabetes patients of 10 years duration: the ACCORD study
Authors: David, Matthews, 马红雨（译）, 杨彩哲（校）
Journal: BMJ (2011)

内容 糖尿病性视网膜病变是糖尿病患者最常见的微血管并发症，无论在发达国家或发展中国家，它都是导致失明的首要原因。既往有研究显示强化血糖控制和严格的降压治疗可延缓视网膜病变的发展，而这一结果也得到了大量试验结果的验证。在视网膜病变的成因中血脂的作用并不是很明确。毫无疑问，降低血脂可以减少心血管事件的发生率，但对微血管病变的效果就不那么确定。非诺贝特干预降低糖尿病事件（FIELD）研究显示卅非诺贝特在糖尿病视网膜病变进展中的有益作用。
Effect of linguistic acculturation on self-efficacy and anxiety in caregivers of Latina breast cancer survivors.
Authors: Ilana Schlam, Claudia Campos, Ysabel Duron, Migdalia Torres, Ivis Sampayo, Kristi D Graves
Journal: Journal of Clinical Oncology (2020)

12121 Background: Latina breast cancer survivors and their caregivers face unique challenges. Acculturation is the acquisition of the cultural elements of a dominant society. Higher acculturation in Latino survivors is positively correlated with self-efficacy in patient-provider communication and improved patient-reported outcomes. There is a paucity of research on how language acculturation affects caregiver and patient outcomes. We examined associations over time between linguistic acculturation among caregivers of Latina survivors and outcomes of caregiver self-efficacy and anxiety. Methods: We partnered with four community-based organizations that serve Latino families facing cancer. We enrolled 136 Latina breast cancer survivors and their caregivers for a randomized trial comparing a dyadic coping intervention to usual care (e.g., support groups). Participants completed surveys including demographic and clinical information, the short acculturation scale for Hispanics, caregiver inventory to assess self-efficacy and PROMIS domains of anxiety at baseline and 6-months after the intervention. Results: In multivariate linear regressions models, we examined the effect of acculturation on caregiver self-efficacy and anxiety, controlling for demographics (patient and caregiver age, caregiver education, employment), patient treatment history (chemotherapy and surgery) patient and caregiver language preference (Spanish or English) and intervention arm (intervention vs. usual care). Greater caregiver self-efficacy at 6-months was associated with younger patient age (t=-2.93, p=.004), older caregiver age (t=2.63, p = .01), female caregiver gender (t=2.79, p = .006) and higher acculturation (t=2.01, p=.04), controlling for baseline self-efficacy, patient language and randomization group. Caregiver anxiety was not related to caregiver acculturation or patient language preferences. Conclusions: Caregivers’ language acculturation was significantly associated with their self-efficacy over time, suggesting that caregivers with lower acculturation experience lower confidence in their provision of care for Latina survivors. These findings are particularly salient because participants for this study were enrolled from organizations with bilingual services. Caregivers of Latina survivors without access to these community resources may face even more striking challenges. Future work can explore how caregivers’ confidence relates to survivors’ adherence to care and patient outcomes over time.
Treatment in patients with cat receiving LMWH: Learnings from predicare, a non-interventional prospective cohort study.
Authors: Florian Scotte, Silvy Laporte, Céline Chapelle, Anne Lamblin, Guy Meyer
Journal: Journal of Clinical Oncology (2020)

e24154 Background: Venous thromboembolism (VTE) is a difficult to treat condition in cancer patients with a persisting risk of recurrent VTE (rVTE). We conducted a prospective multicenter observational cohort study in VTE cancer patients treated with tinzaparin for 6 months in order to validate the Ottawa score. The Ottawa score is composed of 5 items, female (+1), lung (+1), breast (-1), cancer stage I (-2) and previous VTE (+1). Methods: Adult cancer patients with recent diagnosis of documented VTE treated with tinzaparin for 6 months were included. The primary endpoint was the rVTE within the first 6 months. Other endpoints were symptomatic rVTE and major bleeding (MB). All events were adjudicated by a Central Adjudication Committee. To validate the Ottawa score, the area under the curve (AUC) and its 95% CI were calculated on receiver operating characteristic curve analysis. Results: 409 patients were included; median age: 68 years; pulmonary embolism: 60.4%; lung cancer: 31.3%; digestive cancer: 18.3%; stage IV cancers: 67.0%. According to Ottawa score, 58% were classified at high clinical probability of recurrence (score ≥ 1). Among all patients, during the 6 months treatment period, 7.3% and 3.7% had rVTE and MB, respectively. 9.1% had rVTE for patients with a score ≥ 1 compared to 5 % for other patients (score &lt; 1). AUC of the Ottawa score was 0.60 (95% CI 0.55-0.65). Conclusions: This prospective cohort of patients with cancer receiving tinzaparin for VTE reported that the Ottawa score did not accurately predict rVTE. Clinical trial information: NCT03099031 .
Effects of age on outcomes in men receiving treatment for metastatic castration-resistant prostate cancer (mCRPC): Analysis of Medicare fee for service (FFS) claims data.
Authors: Tanya B. Dorff, Rana R. McKay, Carl A. Olsson, Kate Fitch, Scott Flanders, Celestia S. Higano
Journal: Journal of Clinical Oncology (2020)

e17590 Background: Because elderly patients may exhibit differences in immune activation, we evaluated outcomes in men receiving first line treatment for mCRPC with sip-T or oral agents (ie, abiraterone acetate or enzalutamide) by age. Methods: Claims data from the 2013-2017 Centers for Medicare and Medicaid Services Fee for Service 100% Medicare Identifiable Database for Parts A, B and D were examined. We evaluated with index dates in 2014 and 3 years of follow-up. Patients were categorized by age (Table) and agent use as per Healthcare Common Procedure Coding System codes and National Drug Codes. First line use of sip-T vs oral agents was examined as was any line use of sip-T vs oral agents (without sip-T). Kaplan-Meier methodology was used to assess survival with Cox proportional hazards regression modelling used to calculate hazard ratios (HR). Results: Mean ages of men receiving sip-T and orals were 76 and 78 years, respectively. Most (84%) were white. Regardless of line of use, the risk of death among men receiving sip-T was lower than the risk in men receiving orals, except in men over 90 years old (Table). Conclusions: Based on these claims data, benefits of sip-T use were evident across all ages except for the men 90+ years old with decreasing differences between agents with increasing age, as would be expected. While the oral agents may be perceived as more convenient, greater survival with sip-T suggests that clinicians should consider use of sip-T therapy for mCRPC, irrespective of age. [Table: see text]
A proteomic biomarker discovery platform for predicting clinical benefit of immunotherapy in advanced melanoma.
Authors: Yuval Shaked, Michal Harel, Eran Issler, Ella Fremder, Eyal Jacob, Nili Dahan, Haim Bar, Ruth Halaban, Mario Sznol, Ofer Sharon
Journal: Journal of Clinical Oncology (2020)

10037 Background: Immune checkpoint inhibitor-based immunotherapies that target CTLA-4 and the PD-1/PD-L1 axis have revolutionized the treatment of advanced melanoma due to their remarkable clinical benefit. However, only a limited number of patients respond to treatment. Therefore, biomarkers to identify appropriate candidates who will benefit from such therapy are needed. Our previous studies have identified therapy-induced, host-mediated mechanisms that drive resistance to a variety of cancer treatment modalities. Here, we explored whether assessing the systemic host-mediated response to immunotherapy can serve as a basis for predicting clinical outcome in melanoma patients. Methods: The cohort consisted of 34 advanced melanoma patients receiving anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combination therapy. Clinical benefit was assessed. Plasma samples were obtained from patients at baseline and 2-4 weeks after a single treatment. Proteomic profiling of plasma samples was performed using ELISA-based protein arrays. A generalized linear model (GLM) was applied to a subset of the cohort (n = 13) to identify a proteomic signature that can predict clinical response to treatment. The predictive signature was then tested on the entire cohort (n = 33), excluding one patient with stable disease. Results: We identified a 10-protein signature that accurately distinguishes between responders and non-responders with an area under the curve (AUC) of 0.84 (confidence interval: 0.69-0.99, p-value 5.56E-04), and sensitivity and specificity of 0.94 and 0.79, respectively. These results are currently being validated in a larger cohort in an ongoing prospective study (PROPHETIC trial, NCT04056247). To explore the biological basis of resistance to immunotherapy, we performed a pathway enrichment analysis. Multiple mechanisms of resistance were identified in the non-responder group, including signaling pathways associated with immunosuppression and inflammation. Comparison between the two treatment modalities revealed pathways unique to each treatment, implying important differences between the two regimens. Conclusions: Our study provides insights into mechanisms of resistance to immunotherapy and paves the way towards the discovery of novel predictive biomarkers for patient stratification in melanoma.
Composition of urinary stones in Taizhou of Zhejiang province
Authors: Licai Mo, Xianguo Cai, Xia Yao, Jun Lu, Bokang Chen
Journal: BMJ (2017)

Objective
To analyze the composition of urinary stones in Taizhou of Zhejiang province.


Methods
Clinical data of 1 022 patients with urinary stones admitted in Taizhou Hospital of Zhejiang province were retrospectively reviewed. The samples of urinary stones were collected and analyzed by infrared spectrophotometry.


Results
There were 722 males and 300 females with a male to female ratio of 2.4∶1 and with a mean age of (53.4±13.6) years (14-88 years). Among 1 022 patients, the stones with single composition were found in 299 cases (29.3%); the most common single-component was anhydrous uric acid (15.9%), followed by calcium oxalate monohydrate (12.0%). The mixed stones were found in 723 cases (70.7%); the most common mixture was calcium oxalate monohydrate, calcium oxalate dehydrate and carbonate apatite mixture (316 cases, 30.9%). Calcium oxalate (58.9%, 602/1 022) was the most common major component and frequently seen in upper urinary tract stones, followed by uric acid (21.8%, 223/1 022). Uric acid calculi was predominant component in male patients(χ2=30.97, P=0.00), while the rate of infection stones was higher in women (χ2=60.69, P=0.00). The mean age of patients with uric acid stones was 59.4 years, which was older than that with other components (t=7.62, P=0.00). The uric acid stones were more common in upper urinary tract stones(χ2=42.97, P=0.00). The mean age of patients with infection stones was 49 years, which was younger than that with other types of stones(t=4.87, P=0.00).


Conclusion
Mixed stones with calcium oxalate monohydrate, calcium oxalate dehydrate and carbonate apatite are the predominant urinary stones in Taizhou of Zhejiang province, while the most common single-component stones are anhydrous uric acid stones. Location, age and sex are associated with the types of urinary stones.


Key words: 
Urinary calculi; Stone composition; Spectrum
Reduce the prevalence of obesity from the grassroots level
Authors: Xueyao Yin
Journal: BMJ (2020)

肥胖症发病率呈上升趋势，增加了多种慢性疾病的发病风险。《肥胖症基层诊疗指南（2019年）》的制订，为基层医疗机构的医生对肥胖症进行合理的诊疗及管理提供了具体指导，提高肥胖症的正确诊断，选择个体化治疗方案，将有助于预防肥胖症相关慢性病，提高患者生命质量。
Cancer cachexia syndrome in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): Results from a single-institution, prospective, observational study.
Authors: Dimitrios Mavroudis, Konstantinos Rounis, Dimitrios Makrakis, Alexandra Georgiou, Nikolaos Galanakis, Chara Papadaki, Lampros Vamvakas, Alexandros-Pantelis Tsigkas, Meropi Kontogianni, Ioannis Gioulbasanis, Sofia Agelaki
Journal: Journal of Clinical Oncology (2020)

e21644 Background: Cancer cachexia syndrome (CCS) is a multifactorial inflammatory syndrome affecting a large subset of patients (pts) with NSCLC which in preclinical models negatively impairs antitumor immunity. We conducted a prospective, observational study to investigate the effect of CCS and sarcopenia on the efficacy of ICIs in NSCLC. Methods: CCS was defined as weight loss of &gt; 5% in the last 6 months or any degree of weight loss &gt; 2% in combination with BMI &lt; 20% or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia. Skeletal muscle index was calculated using slice-o-matic tomovision software in the abdominal CT scan before starting ICIs. Results: 83 pts were included in the analysis. Median follow up was 9.5 months. Median age was 66 years, 61.4% had non-squamous histology, 20.5% received ICIs as first and the remaining as second-line therapy. 20.5% of pts experienced partial response (PR), 31% had stable disease (SD) and 48.2% had disease progression (PD). Median progression-free survival (PFS) was 4.4 months and median overall survival (OS) was 10.33 months. 43.4% of the whole group were categorized as having CCS, whereas 63.3% of 30 pts evaluated using tomovision had sarcopenia. CCS negatively affected response rates (p = 0.003) but not response duration (p = 0.266). CCS was associated with reduced PFS (2.46 vs 5.77 months, p = 0.006) and OS (4.8 vs 14.53 months, p = 0.001). In the multivariate analysis, CCS independently predicted for shorter OS (HR = 2.01; CI: 1,14-3,54; p = 0.014). Sarcopenia was also associated with reduced OS (5.4 vs 17.9 months, p = 0.012). Analysis on the whole pt population will be presented at the conference. Conclusions: CCS is associated with lower response rates and independently predicts for shorter OS in pts with NSCLC treated with ICIs. Further research on CCS could better define its role as a potential biomarker and a research platform for maximizing immunotherapy efficacy.
Comparative analysis of characteristics, survival trends, and associated malignancies of B-cell and T-cell prolymphocytic leukemia: A surveillance, epidemiology, and end results (SEER) based study1998 to 2016.
Authors: Doaa Attia, Sara Aly Attia
Journal: Journal of Clinical Oncology (2020)

7558 Background: Prolymphocytic leukemia (PLL) compromises two subsets; B-cell and T-cell, accounting for less than 2% of mature lymphocytic leukemia. Both of them are rare lymphoid neoplasms with a very aggressive clinical course and poor prognosis. Methods: We used SEER program dataset between 1998 and 2016. We divided the patients into 2 groups: B-PLL and T-PLL and identified them using ‘ICD-O-3 histology recode: 9833/3 and 9834/3 respectively. We used SPSS software (version 26, IBM, NY, USA) to calculate overall survival using Kaplan-Meier methods and compare the survival between the two subtypes using the log-rank test. We also used multivariable covariate-adjust cox models to determine the impact of age, sex, race, cause of death, and associated primary malignancies on survival in both types. Results: A retrospective cohort study of 783 patients (295 B-PLL and 488 T-PLL) with overall survival rate of 22.5% (30.2% B-PLL and 18% T-PLL). The overall median survival for PLL was 16 months (95 CI, 13.745-18.255). The median survival of B-PLL (25 months, 95%CI, 15.733-34.267) was much better than T-PLL (14 months, 95%CI, 11.922-16.078). The mean age was 68.7±15.3. Patient age was an independent factor in determining the survival and inversely associated with survival time in both types (p &lt; 0.0001). The survival rate was worst ) among age groups older than 79, between 70-79 years (8.9%, 18.9%) respectively. Although white male patients were more affected in both types, neither sex nor race significantly affected survival (P 0.554, 0.062 respectively). 64.7% of PLL patients died due to cancer. Patients with cancer-related death had significantly shorter survival time in both T-PLL group (HR = 0.351, 95% CI 0.241-0.512) and B-PLL group (HR = 0.682, 95% CI 0.491-0.945). We also found that 24.4% of B-PLL and 19% of T-PLL patients have another associated primary malignancy. Among hematological malignancies, non-hodgkin lymphoma was the commonest. Although associated solid tumors were less common, Prostate cancer and breast cancer were the commonest for both types and lung/bronchus malignancies were more associated with T-PLL. Conclusions: T-PLL subtype has worse prognosis. Age is the most important independent predictor of survival in both types. Although most of affected patients were white males, race and gender have no impact on survival. Non-hodgkin lymphoma is the commonest primary associated malignancy followed by breast and prostate cancer in both types.
Mutational profiles and clinical outcomes in metastatic colorectal carcinoma patients with different metastases sites.
Authors: Xi Zhang, Zhang Jing, Yingmei Li, Shifu Chen
Journal: Journal of Clinical Oncology (2020)

e16020 Background: To compare the difference of genomic and survival of first metastases site between first metastases site of metastatic colorectal cancer (mCRC) in liver and other sites (bone, brain, lung, and so on). Methods: Genomic mutations and clinic data of 113,4 CRCs (consisting of 533 metastases) were collected from TCGA database. According to first site(s) of metastases, patients were categorized into group 1 (liver as first metastases site, n = 405) and group 2 (other organs as first metastases site, n = 128). OS curves were estimated with Kaplan-Meier method, p values were calculated by fisher exact test. Results: Mutation frequency in GNAS (2.34%), KRAS (37.78%), BRAF (16.41%) and proportion of MSI-high (8.5%) was significantly higher in group2. Compared with group2, group1 showed significantly higher mutation rate of APC (78.52%) and TP53 (77.28%). We assessed overall survival in the two groups. OS was significantly better for patients in group1 than in group2 (HR 0.57, 95% CI 0.41-0.79, p = 0.00075). Conclusions: According to the results of this study, mCRC patients showed different mutational signatures with respect to the site of first metastases, and presented higher OS rate in liver metastases group. Our findings provided new knowledge to understand the biological progress of different metastases and develop new prognostic markers for metastatic colorectal cancer.
Epidemiological profile of cancers among adolescent and young adult patients of a Haitian cancer program.
Authors: Joseph Bernard, Pascale Constant, Rebecca Henderson, Lynn Gabrielle Alexis, Doukens Patrick Gilbert, Lenz Sacha Christyl Pierre, Vincent A. DeGennaro
Journal: Journal of Clinical Oncology (2020)

e13589 Background: The epidemiology of cancer among adolescents and young adults (AYA) has been a relatively neglected topic, particularly in the developing countries. The main objective of this study was to present the epidemiology of cancer among this subpopulation in Haiti’s largest cancer program. Methods: A retrospective study was conducted on patients aged 15 to 39 years old with pathological and/or clinical diagnosis of cancer at the cancer clinic of Innovating Health International (IHI) in Port-au-Prince, Haiti from January 2016 to December 2019. The chart review collected variables such as age, gender, date of diagnosis, cancer type and outcome to present this epidemiological profile of AYA cancers. Results: Among the two thousand two hundred and ninety-eight (2298) cancer cases managed during this study period, 20.1% (n = 461) were adolescents and young adults. 82% of these patients were female and 18% male. 25.2% (n = 116) were less than 30 years old. Breast cancer was the most common type (n = 222, 48.2%%), followed by gynecological cancers (n = 70, 15.1%) with cervical cancer representing 61.4% of the cases (n = 43), hematological malignancies (n = 44, 9.5%) with lymphomas (n = 31) as the most common type, sarcomas (n = 43, 9.3%), head and neck cancers (n = 24, 5.2%), gastrointestinal cancers (n = 22, 4.8%), cutaneous cancers (n = 10, 2.2%), urological cancers (n = 5, 1.1%), thyroid cancer (n = 5, 1.1%) and CNS tumors (n = 2, 0.4%). 3.0% of the AYA patients (n = 14) presented with a cancer of unknown primary (CUP). In the &lt; 30 y/o subgroup blood cancers, breast cancer, sarcomas, and head and neck malignancies were respectively the most common types, while in the ≥ 30 y/o subgroup, breast and gynecological cancers were the most common, followed by sarcomas, GI and blood cancers. No case of lung cancer was received for the AYA population. The overall mortality rate was 30.6% and 12.8% of the patients were lost to follow-up. Conclusions: Cancers among AYA patients represented 20.1% of the cancer population, with a different epidemiological profile for the &lt; 30 y/o and ≥ 30 y/o subgroups. The CNS tumors, leukemias and urological cancers were most likely under-represented due to low referral, misdiagnosis or early mortality.