tbuckley/cabot-search huggingface dataset:
Global oncology authorship and access patterns.
Authors: Maria Teresa Bourlon, Brenda Jimenez, Charbel Fadi Matar, Emilie M. Gunn, Ophira M. Ginsburg, Gilberto Lopes, Eva Segelov
Journal: Journal of Clinical Oncology (2020)

7061 Background: Global Oncology is a movement to improve equitable access to cancer control and care, recognizing challenges due to economic and social factors between high, middle, and low-income countries (HIC, MIC, LIC). Access to local, regional, and global cancer data and analysis is a major driver for building a global oncology community. The JCO Global Oncology (JCO GO) online open access journal was established in 2015 with the mission to be the voice of research relevant to populations with limited resources. To assess its goals of encouraging global interaction and increasing MIC and LIC engagement, we analyzed authorship and accessing data. Methods: Logged views of articles published in 2018 were identified by DOI, using Google Analytics during the period 01/01/2018 to 06/30/2019. The country of origin of all authors and the location of downloads were classified according to the 218 economies listed in The World Bank Data (WBC) of 2019. Results: 132 articles were published in JCO GO in 2018 with 88152 views, from which the accessing nation was identified for 99%. Views originated from 180 countries: 35% HIC, 51% MIC, and 14% LIC. The most common accessing countries were: USA (37%), India (14%), United Kingdom (3%), Brazil (3%), and Ethiopia (3%). Corresponding authors came from 34 nations: 60% HIC, 32% MIC, and 8% LIC. The most common economies involved in any authorship were: USA (47%), India (10%), Brazil (5%), Mexico (4%), and Nigeria (3%). Reader origin did not differ according to corresponding author WBC. Article authorship was exclusively from one economic category in 49%: 23% HIC 16% MIC, 2% LIC. For 59% of articles, authorship came from mixed economies: 42% HIC + MIC, 11% HIC + LIC, 0% MIC + LIC, 6% HIC + MIC + LIC. Conclusions: JCO GO ’s reach extends to over 80% of the world´s economies. The majority of articles have authors from mixed WBC countries. Areas identified to address are: low level of LIC corresponding authorship; few papers from authors across all economies; no papers from only LMICs authors; low percentage of views by LIC. This information provides focus for global oncology authorities to target interventions to reduce the academic segregation of LICs, such as global oncology funding opportunities, mentorship and policies to encourage interactions and develop MIC and LIC leaders.
Development and validation of a gene expression-based signature predicting efficacy of induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A multicenter cohort study.
Authors: Yuan Lei, Ying-Qin Li, Wei Jiang, Xiao-Hong Hong, Wen-Xiu Ge, Yuan Zhang, Weihan Hu, Ya-Qin Wang, Ye-Lin Liang, Jun-Yan Li, Lei Chen, Fangyun Xie, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Yu-Pei Chen, Ling-Long Tang, Ying Sun, Na Liu, Jun Ma
Journal: Journal of Clinical Oncology (2020)

6522 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene expression signature that can identify patients who will benefit from IC. Methods: We screened chemoresistance-related genes by comparing gene expression profiles of patients with short-term tumor response or non-response to IC (n = 95) using microarray analysis. Chemoresistance-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Results: We identified 43 chemoresistance-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] 0.87, sensitivity = 87.5%, specificity = 75.6%). We then apply the 6-gene signature to classify patients into the benefit group and the no-benefit group. In the benefit group, patients could benefit from IC in terms of failure-free survival (hazard ratio [HR] 0.54 [95% confidence interval 0.34-0.87]; p = 0.01), while patients in the no-benefit group could not (HR 1.25 [95%CI 0.62-2.51]; p = 0.53). In the clinical trial cohort, the developed 6-gene signature was also highly accurate at predicting the response to IC (AUC = 0.82; sensitivity = 87.5%; specificity = 71.8%). Additionally, IC conferred failure-free survival benefits only on patients in the benefit group (HR 0.37 [95%CI 0.18-0.75], p = 0.004) and not on those in the no-benefit group (HR 0.70 [95%CI 0.27-1.82]; p = 0.46). In the external independent cohort, similar results were observed. Conclusions: The 6-gene signature can help select patients who will benefit from IC and thus lay a foundation for a more individualized therapeutic strategy for LA-NPC patients.
A phase II study of vorolanib (CM082) in combination with toripalimab (JS001) in patients with advanced mucosal melanoma.
Authors: Lu Si, Xinan Sheng, Lili Mao, Caili Li, Xuan Wang, Xue Bai, Zhong Hui Qi, Zhihong Chi, Chuanliang Cui, BIN LIAN, Bixia Tang, Xieqiao Yan, Li Zhou, Siming Li, Rong Duan, Huayan Xu, Li Mao, Lieming Ding, Jun Guo
Journal: Journal of Clinical Oncology (2020)

10040 Background: Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1) with clinical activity in metastasis melanoma but not in its mucosal subtype. In this phase II study (NCT03602547), we investigated the safety and efficacy of CM082 in combination with JS001 in patients (pts) with advanced mucosal melanoma. Methods: The study enrolled pts from 18 to 75 years-old with histologically confirmed metastatic mucosal melanoma, ECOG PS 0-1, no prior systemic anti-cancer treatment. Eligible pts were treated with CM082 tablet (150 or 200 mg once daily) combined with JS001 (240mg every 2 weeks, IV, Q2W) until confirmed disease progression or unacceptable toxicity. Clinical response was evaluated every 8 week. The primary endpoint was overall response rate (ORR) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of remission (DOR), and time to first remission (TTR) according to RECIST v1.1 and iRECIST. The safety was also assessed. Results: Between July 2018 and April 12, 2019, 40 pts (19 pts in 150mg group; 21 pts in 200mg group) were enrolled and 38 pts were evaluable for tumor response (150mg n = 18, 200mg n = 20), with 4 (22.2%) confirmed partial response (PR), 6 (33.3%) stable disease (SD) and 8 (44.4%) progression disease (PD) in the 150mg CM082 group; 3 (15%) PRs (including 2 unconfirmed), 10 (50%) SD, and 7 (35%) PD were reported in the 200mg CM082 group. Tumors shrank in 10 pts (56%) in the 150mg group and 10 pts (50%) in the 200mg group. At data cut-off (November 28, 2019), 29 pts had PFS events (150mg n = 12; 200mg n = 17). The median PFS was 5.7 (95% CI 2.0, NE) months and 5.6 (1.9, 7.7) months in the two groups, respectively. The most common treatment-related adverse events (AEs) were grade 1 or 2, including leukopenia, elevated LDH, increased ALT, neutropenia, increased AST, and elevated GGT. Common grade 3 or higher adverse events ( &gt; 10%) were increased ALT (12 pts, 30%), increased AST (11 pts, 27.5%), neutropenia (6 pts, 15%) and elevated GGT (6 pts, 15%). Eight pts had 9 serious AEs (SAEs). The study is still ongoing and more data will be presented in the future. Conclusions: PFS benefit was observed in both 150mg and 200mg subgroups. This study demonstrated potentially improved efficacy with predictable toxicities of CM082 in combination with JS001 therapy, which may be an effective treatment option for pts with advanced mucosal melanoma. Clinical trial information: NCT03602547.
A single institution study on the demographics and response rates of Hispanic women with HER2+ disease.
Authors: Michelle Cholankeril, Keia Smith
Journal: Journal of Clinical Oncology (2020)

e19069 Background: Hispanics have 20% lower incidence of breast cancer than the general US population. Despite this, breast cancer is the leading neoplasm seen in Hispanics and is a significant cause of their mortality. Our study reports the incidence and outcome of HER2 breast cancer, use of a neoadjuvant regimen, and surgery type in the Hispanic population at our urban institution. Methods: This study reports on 37 women that were diagnosed with HER2+, non-metastatic breast cancer from 2015-2019. We report this as a single institution, community program that provides equal access healthcare and delivery. Our data was investigated and compiled using our facility’s cancer registry. The patient sample included 20(54%) Hispanics, 13(35%) African Americans, 3(8.0%) Caucasians and 1(3%) Asian. Of the 20 Hispanic women, 85% were Estrogen Receptor (ER) positive and 48% were Progesterone Receptor (PR) positive. Eleven (55%) of the 20 Hispanic patients(pts) received neoadjuvant chemotherapy (NAC), which included regimens containing Trastuzamab (H) with or without Pertuzumab(P). Our remaining 9 pts receiving adjuvant therapy were investigated for response as well. Results: Our Hispanic pts receiving NAC had an overall complete response rate of 45% and a partial response rate of 55%. There appeared to be no significant difference in response rate in Hispanic women between the HP group versus H. NAC pts had fewer partial mastectomies performed than those not receiving NAC. Hispanic NAC patients were found to have significantly more sentinel lymph node dissections (SLND) 7(88%) versus axillary lymph node dissections 1(16%) compared to other ethnicities receiving NAC. Non NAC Hispanic patients had 56% sentinel lymph node dissections, compared to 44% complete axillary dissections. Conclusions: The results indicate that there is a significant Hispanic population at our facility that harbor the HER2 oncogene. These pts seem to have a promising response to the NAC regimen in regards to SLND. We hope to have a larger patient sample through a multi-institution study, with statistical analysis to support our current findings. More studies should be performed on Hispanic women with HER2 disease, as data with this subset of population is lacking. The NAC regimen should be greatly considered and implemented in the treatment in those looking to downstage axillary disease. We hope to further investigate treatment options for Hispanic pts to gain greater pathological responses, leading to improved progression free and disease free survival that match that of other ethnic groups.
The effect of antibiotic use on immune-checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.
Authors: Mohammad Khan, Nathan Radakovich, Brian I. Rini, Omar Y. Mian, Moshe Chaim Ornstein, Shilpa Gupta
Journal: Journal of Clinical Oncology (2020)

e17116 Background: There is emerging evidence that antibiotic (Abx) use may be associated with poor response to immune-checkpoint inhibitors (ICIs) in patients (pts) with some solid tumors. However, this has not been studied in metastatic urothelial carcinoma (mUC). We examined the effect of Abx use on outcomes in pts receiving ICIs for mUC. Methods: We retrospectively reviewed adult pts receiving ICIs for mUC treated at Cleveland Clinic between 2015 and 2020. Pts included in the study received &gt; / = 3 cycles of ICI therapy with either azetolizumab or pembrolizumab. Abx use was defined as at least 3 days of Abx in the 60 days preceding or following ICI initiation. PFS and OS were estimated using the Kaplan-Meier method and a Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI). Results: A total of 69 pts with mUC receiving ICI therapy were included. The Abx-treated group consisted of 22 pts (32%) and the Abx-untreated group was 47 pts (68 %). 30 pts had Abx 60 days prior to ICI initiation and 20 patients had Abx within 60 days of ICI initiation. Abx use 60 days prior to ICI was not associated with PFS (HR = 0.91, 95% CI = 0.42-1.95) or OS (HR = 0.52, 95% CI = 0.33-1.68). Abx use during the first 60 days of ICI use was associated with decreased PFS (HR = 2.23, 95% CI = 1.03-4.86) but not OS (HR = 2.01, 95% CI = 0.89-4.53). Notably, there was no effect on response rates. The most commonly used Abx prior to treatment were: fluoroquinolones (30%); cephalosporins (26%); non-cephalosporin beta lactams (17%); and trimethoprim-sulfamethoxasole (13%). The most commonly used Abx after treatment initiation were: fluoroquinolones (17% of patients); cephalosporins (13%); non-cephalosporin beta lactams (12%); and trimethoprim-sulfamethoxasole (9%). Our study was insufficiently powered to address the effect of different antibiotic classes on outcomes. Conclusions: In our study, Abx use within first 60 days of treatment with ICIs was associated with decreased PFS and a trend toward decreased OS in pts with mUC but not in pts receiving Abx 60 days prior to ICI therapy. While the numbers are small, this is the first report exploring the effect of Abx on ICI response in mUC and further studies in larger databases are warranted.
Are there inequities in reconstruction after mastectomy in breast cancer patients related to race or insurance status?
Authors: Paul J. Chuba, Maria T. Vlachaki, Sean Koerner, William Stefani, Jeffrey Falk
Journal: Journal of Clinical Oncology (2020)

e12615 Background: Patients with invasive or in-situ breast cancers may increasingly be offered bilateral mastectomy with reconstruction with a view towards achieving symmetry and risk reduction. We investigated whether this treatment option was offered equally based on race and insurance status. Methods: Rates of mastectomy and reconstruction were studied among 4703 patients diagnosed or treated at Ascension St John Hospital, Ascension Macomb Oakland Hospital, and Ascension Providence Hospital between 2005 and 2015. Data collected included demographics, tumor characteristics, insurance (primary payer), first course of surgical treatment, vital status, and cause of death. Cases coded as contralateral mastectomy and reconstruction were considered as representative of “bilateral mastectomy” and reconstruction. Results: Insurance status could be definitively categorized as HMO/PPO, fee for service (FFS), Medicare, or Medicaid in 2375 breast cancer patients. Medicaid HMO was categorized as Medicaid and Medicare with or without supplemental insurance was categorized as Medicare. For simplicity, cases coded as uninsured, other, and NOS were not analyzed further. A total of 406 of 2375 (17.0%) were coded as contralateral mastectomy with reconstruction. Smaller numbers of Medicare cases had contralateral mastectomy and reconstruction (7.3%) compared to 23.3% for HMO/PPO, 26.3% for FFS, and 16% for Medicaid, presumably related to older age. Within each insurance category, similar proportions of Caucasian and African American women were treated with contralateral mastectomy (Table) compared to all patients (Table). Conclusions: Patients having Medicaid insurance had lower rates of contralateral mastectomy and reconstruction compared to HMO/PPO and FFS cases. African American race did not appear to be associated with lower rates of this surgery within the Ascension St John, Ascension Macomb Oakland, and Ascension Providence hospitals. [Table: see text]
Association of CD4+ T lymphocyte count with HBV replication and progression of liver diseases in patients infected with HIV and HBV
Authors: Rongrong Yang, Xi'en Gui, Yong Xiong, Shicheng Gao
Journal: BMJ (2016)

The clinical data of 459 patients, who were first diagnosed as HIV/HBV co-infection from January 2007 to December 2013, were retrospectively analyzed. Among all patients, there were 89 cases with CD4 < 50/μl, 134 cases with CD4 50-200/μl and 236 cases with CD4﹥200/μl , when HIV infection was diagnosed. In these three groups with different CD4 levels, the HBV DNA positive rates were 49.3% (37/75), 50.5% (54/107) and 33.7%(66/196); the HBV viral load were (6.37±1.71) log10 copies/ml, (5.82±1.86) log10 copies/ml and (4.36±1.64) log10 copies/ml; the rates of abnormal liver function were 29.2%(26/89), 29.1%(39/134) and 10.6%(25/236); the occurrence rates of end-stage-liver-diseases were 16.9% (15/89), 14.9% (20/134) and 5.1%(12/236); the mortality rates were 10.1% (9/89), 9.7%(13/134) and 3.8%(9/236), respectively. The HBV DNA positive rates, HBV viral load, the rates of abnormal liver function, the occurrence rates of end-stage-liver-diseases and the mortality rates in CD4﹥200/μl group were lower than that in CD4 < 50/μl group and 50-200/μl group. The results suggest that for HIV and HBV co-infection patients, HBV replication level and prognosis of liver diseases are associated with CD4+ T lymphocyte count.


Key words: 
Human immunodeficiency virus proteins; Hepatitis B virus; CD4 positive T-lymphocytes
Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series
Authors: 徐小微, 吴晓鑫, 蒋贤高, 徐凯进, 应灵军, 马春莲, 李世波, 王华英, 张胜, 高海女, 盛吉芳, 蔡洪流, 裘云庆, 李兰娟
Journal: BMJ (2020)

目的
为了研究浙江省新型冠状病毒感染患者的临床特征。


研究设计
回顾性病例研究。


研究地点
浙江省7家医院。


研究对象
从2020年1月10至1月26日收集的62例确诊患者的临床资料。


主要结局指标
采用临床病例表形式采集每个病例的临床特征，包括体温、暴露史、潜伏期等信息。如果信息存在疑问，在杭州的研究人员会与各地负责的医师联系核实。


结果
62例患者中位年龄41岁，只有1例患者进重症监护病房接受治疗，没有患者死亡。根据我们的数据，患者均无华南海鲜市场暴露史，所有患者都是通过人传人而感染。发病时常见的症状和患者数如下：发热48例（77%），咳嗽50例（81%），咳痰35例（56%），头痛21例（34%），肌痛或疲劳32例（52%），腹泻3例（8%），咯血2例（3%）。只有2例患者（3%）在入院时即有呼吸困难。在我们的数据中，发现患者从暴露到发病的中位时间是4天（四分位间距3～5天）。从症状开始到第一次入院时间为2天（四分位间距1～4天）。


结论
截止2020年2月初，与武汉市新型冠状病毒感染患者相比，浙江省患者的病情相对较轻。
Impact of community comprehensive intervention on healthy behavior and self-rated health status among family caregivers of disabled elderly
Authors: Wei Xu, Chenguang Qian, Xinmei Liu, Li Chen, Juan Du
Journal: BMJ (2017)

Objective
To investigate the effect of community comprehensive intervention on health behavior and self-rated health status among family caregivers of disabled elderly.


Methods
One hundred and twenty family caregivers of disabled elderly were selected from community health service centers of Beijing Dongcheng District, and were given 6 month-comprehensive community intervention (intervention group); 121 family caregivers of disabled elderly from another community were selected as the control group. The knowledge and skills of caregiving, health behaviors (daily exercise time, daily relaxation time) and self-rated health status were evaluated before and 6 months after intervention.


Results
The knowledge and skill scores in intervention group were improved by 50.781 points, the daily exercise time and daily relaxation time were prolonged by 0.491 h and 0.837 h, respectively after the intervention (all P 0.05).


Conclusion
Community comprehensive intervention improves the knowledge and skills of caregiving, and the health behaviors among family caregivers of disabled elderly, but the intervention measures does not impact the self-rated health status of family caregivers.


Key words: 
Disability; Aged; Community health services; Family caregivers
Assessment of current approaches of starting dose selection and dose escalation for oncology biologics in first-in-patient trials.
Authors: Kai Hsin Liao, Xiaoying Chen, Darrin M. Beaupre, Donghua Yin, Chandrasekhar Udata
Journal: Journal of Clinical Oncology (2020)

e14093 Background: Current approaches for starting dose selection for first-in-patient (FIP) trials of oncology biologics vary according to pharmacological properties and modality of the investigational agent. For biologics with immune agonistic properties, the FIP starting dose is typically based on the minimal anticipated biological effect level (MABEL). For non-immune activating biologics, the starting dose is typically based on allometric scaling of a threshold toxic dose determined in the most appropriate animal species. The aim of this work is to assess the performance of current approaches of FIP starting dose selection and dose escalation for oncology biologics. Methods: FIP clinical trials for oncology biologics licensed by the US FDA from 2010 to 2019 were analyzed to extract information related to starting dose and dose escalation. Source materials for the relevant FIP trials included the Drugs@FDA database, PubMed, and conference proceedings. The data were further analyzed to evaluate parameters related to appropriateness of the starting dose and dose escalation efficiency, which include the number of cohorts to reach the maximum tolerated dose [MTD] (or, when MTD was not identified, the highest human dose [HHD]) and the ratio of MTD/HHD to starting dose. Results: The 26 oncology biologics licensed by the US FDA between 2010 and 2019 included 8 ADCs/immunotoxins, 7 checkpoint inhibitors and 11 other biologics (monoclonal antibody, fusion protein or CD3 bispecific construct). The majority (69%) of these biologics were well tolerated without MTD identified in the FIP trials. All 26 FIP trials with biologics appeared to follow ICH S9 Guidance for starting dose selection, and the dose increment ranged from 1.2- to 10-fold. These FIP trials had a median of 6 cohorts (range: 3-10) to reach MTD (or HHD) from the starting dose. About 50% of these trials involved ≥ 6 cohorts to reach MTD (or HHD). The MTD/HHD to starting dose ratio was &gt; 100 for 4 of the biologics. The median label dose to starting dose ratio was 10 (range: 1-3200), suggesting that a large number of patients in these FIP trials received subtherapeutic dose levels. Conclusions: Current approaches of starting dose selection and dose escalation led to a very low starting dose and many dose escalation cohorts for the FIP trials of a large portion of recently licensed oncology biologics. There exist opportunities to improve current approaches to increase FIP trial efficiency and reduce the number of patients receiving subtherapeutic dose levels in these trials.