tbuckley/cabot-search huggingface dataset:
Assessing long-term survival improvement of immune-checkpoint inhibitors (ICI) anticancer agents approved by the Food and Drug Administration: A meta-analysis of randomized controlled trials (RCTs).
Authors: Louis Everest, Kelvin K. Chan, Ronak Saluja, Monica Shah, Vivian Nguyen
Journal: Journal of Clinical Oncology (2020)

e15062 Background: Conventional anticancer drugs have been developed to improve overall survival (OS) and/or progression-free survival (PFS) in the palliative intent setting. However, long-term survival is often limited by acquired biologic resistance. In contrast to conventional anticancer drugs, ICIs putatively preserve long-term survival in a small subset of patients. However, in the absence of a gold-standard definition, long-term survival improvement has not been adequately quantified. Long-term survival rate difference has been proposed as a method of quantifying long-term survival. However, there a paucity of literature demonstrating statistical improvements in survival rate. Therefore, the objective of the study was to quantify the improvement in long-term survival rate in OS and PFS improvement in ICIs compared with non-ICIs. Methods: The FDA Hematology/Oncology Approvals &amp; Safety Notification web page was searched for RCTs cited in oncology drug approvals between 01-2011 and 06-2019. The most recent OS and PFS updates were used when available. OS and PFS curves were digitized to reconstruct pseudo individual patient data as per established methods. Survival rate improvement at 1, 2 and 3 years were calculated as differences between the experimental arm and control arm. Survival rate improvements across RCTs at 1, 2 and 3 years were pooled using a random-effects model and the results were compared between ICI and non-ICIs. Subgroup analyses were conducted for melanoma and non-small cell lung cancer. Results: We identified 130 RCTs (22 ICIs, 108 non-ICIs) for analysis. The absolute OS rate improvement was 9.5% in ICIs and 4.9% in non-ICIs at 1-year (difference = 4.6%, p &lt; 0.001), 10.3% in ICIs and 4.9% in non-ICIs at 2-years (difference = 5.3%, p &lt; 0.001), and 10.2% in ICIs and 5.1% in non-ICIs at 3-years (difference = 4.6% p 0.006). The absolute PFS rate improvement was 10.3% in ICIs and 17.7% in non-ICIs at 1-year (difference = -7.3% p &lt; 0.001), and 8.9% in ICIs and 15.5% in non-ICIs at 2-years (difference = -6.6% p &lt; 0.001). Conclusions: Long-term OS survival rate improvements, while statistically significant were only modestly higher in ICIs compared to non-ICIs. PFS survival rate differences were statistically lower in ICIs compared to non-ICIs. While ICIs represent an important shift towards long-term survival, greater emphasis should be placed on rigorously evaluating long-term survival rate improvement and reporting of future novel therapies.
Disease-free survival as a surrogate for overall survival in neoadjuvant trials of gastroesophageal adenocarcinoma: Pooled analysis of individual patient data from randomized controlled trials.
Authors: Ulrich Ronellenfitsch, Katrin Jensen, Svenja Seide, Meinhard Kieser, Matthias Schwarzbach, Tracy E Slanger, Bryan Burmeister, David Paul Kelsen, Donna Niedzwiecki, Guillaume Piessen, Christoph Schumacher, Susan Urba, Cornelis J. H. Van De Velde, Marc Ychou, Ralf Dieter Hofheinz, Sylvie Lorenzen
Journal: Journal of Clinical Oncology (2020)

4533 Background: Disease-free survival (DFS) is an appealing surrogate endpoint for overall survival (OS) in trials on neoadjuvant or adjuvant cancer therapy, because it is available faster and with less follow-up effort. The aim of this study was to assess if DFS can be a valid surrogate endpoint for OS when comparing neoadjuvant treatment followed by surgery to surgery alone for gastroesophageal adenocarcinoma. Methods: Individual patient data (IPD) from eight randomized controlled trials (n = 1,126 patients) which compared neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma were used for the analysis. Correlation between OS-time and DFS-time was calculated. Kaplan-Meier survival curves and corresponding hazard ratios (HRs) for treatment effects were separately determined for each trial. Subsequently, HRs were pooled in a meta-analysis using a random-effects model. An error-in-variables linear regression model was used to compare observed and predicted values. The minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS was estimated by calculating the surrogate threshold effect. Results: OS-time correlated strongly with DFS-time. HRs for OS and DFS were highly similar for all single trials. The meta-analysis yielded almost identical overall HRs for treatment effects on OS and DFS. The determination coefficient for the association between HRs for OS and DFS was 0.912 (95% confidence interval 0.75-1.0), indicating a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect was calculated at 0.79, indicating that a future trial yielding a hazard ratio for the treatment effect on DFS &lt; 0.79 could be expected with a 95% probability to yield a hazard ratio for the treatment effect on OS &lt; 1. Conclusions: DFS and OS strongly correlate both after neoadjuvant therapy followed by surgery and after surgery alone for gastroesophageal adenocarcinoma. Likewise, the treatment effects on the two endpoints are very similar. Consequently, DFS can be regarded an appropriate surrogate endpoint for OS in trials on neoadjuvant therapy for gastroesophageal adenocarcinoma.
Breast and cervical cancer screening disparities among transgender patients.
Authors: Oluwadamilola Temilade Oladeru, Sung Jun Ma, Joseph Miccio, Katy Wang, Kristopher Attwood, Anurag K Singh, Daphne A. Haas-Kogan, Paula M Neira
Journal: Journal of Clinical Oncology (2020)

7024 Background: Over a million Americans identify themselves as transgender and this population is growing. Transgender status was a pre-existing condition prior to the Affordable Care Act (ACA), and transgender individuals faced unique disparities in gender-specific cancer screening in part due to discrimination in health insurance coverage. Modern literature for transgender adults’ adherence to cancer screening is limited. To fill this knowledge gap, we conducted a cross sectional study to investigate transgender individuals’ self-reported adherence to cancer screening and access to primary care compared to cisgender individuals. Methods: The Behavioral Risk Factor Surveillance System database was queried for transgender (either male-to-female [MTF] or female-to-male [FTM]) and cisgender adults from 2014-2016 and 2018. Primary endpoints were adherence to breast and cervical cancer screening guidelines and access to primary health care. Those with prior hysterectomy, breast and cervical cancer were excluded. Multivariable logistic regression was performed to evaluate the association of transgender status with cancer screening and healthcare access, after adjusting for demographic characteristics and survey weights. Results: A total of 219,665 and 206,446 participants were eligible for breast and cervical cancer screening, respectively. Of those, 614 (0.28%) and 587 (0.29%) transgender participants were eligible for each cancer screening type, respectively, representing a weighted estimate of nearly 200,000 transgender participants total. When compared to cisgender counterparts, transgender participants were less likely to adhere to breast cancer screening (FTM: OR 0.47, p &lt; 0.001; MTF: OR 0.04, p &lt; 0.001) and to have received any breast cancer screening (FTM: OR 0.32, p &lt; 0.001; MTF: OR 0.02, p &lt; 0.001). Similarly, FTM participants were less likely to adhere to cervical cancer screening (OR 0.42, p &lt; 0.001) and to have received any cervical cancer screening (OR 0.26, p &lt; 0.001). In addition, transgender participants were more likely to have no primary care physician (FTM: OR 0.79, p &lt; 0.001; MTF: OR 0.58, p &lt; 0.001) and to be unable to see a physician when needed within the past year due to medical cost (FTM: OR 1.44, p &lt; 0.001; MTF: OR 1.36, p &lt; 0.001). Conclusions: Despite the implementation of the ACA, limited primary care access and poor adherence to breast and cervical cancer screening are evident for transgender populations. Further research efforts to improve the utilization of preventive cancer services are needed for this underserved population.
Effect of continuous positive airway pressure (CPAP) therapy on heart rhythm and blood pressure variability in primary hypertensive patients with obstructive sleep apnea/hypopnea syndrome (OSAHS)
Authors: Jianwei Luo, Li Zeng
Journal: BMJ (2015)

Objective
To investigate the effect of continuous positive airway pressure therapy (CPAP) on heart rhythm and blood pressure variability in primary hypertensive patients with obstructive sleep apnea/hypopnea syndrome (OSAHS).


Methods
Ninety seven patients with OSAHS and primary hypertension were randomly divided into treatment group (n=49) and control group (n=48). Patients in control group receive antihypertensive medication only, while patients in treatment group received antihypertensive medication in combination with CPAP therapy for 4 weeks. The dynamic electrocardiogram (ESG) and ambulatory blood pressure for 24 h were measured before and after treatment in both groups.


Results
After CPAP treatment, the night index of standard deviation of the average NN intervals (SDANNnight) in treatment group was (89.0±21.4) ms, while the day and night index of square root of the mean squared differences of successive NN intervals (rMSSDday and rMSSDnight) was (35.9±17.2) ms and (45.7±18.3) ms respectively. Compared with those before treatment, the index of SDANNnight was decreased and the indexes of rMSSDday and rMSSDnight were increased (P<0.01). Compared with control group, the SDANNnight was decreased, and the rMSSDday and rMSSDnight were increased (P<0.01, P<0.05). After CPAP treatment, the night index of low-frequency power (LFnight) in treatment group was (15.3±5.7) ms, which was lower than that before treatment, and the night index of high-frequency power (HFnigh) was (16.3±8.1) ms, which was higher than that before treatment (P<0.01); the LFnight in treatment group was decreased and the HFnight was increased (P<0.01). After CPAP treatment, the day and night indexes of systolic blood pressure (SBPday and SBPnight) and the night indexes of diastolic blood pressure (DBPnigh) t in treatment group were (136.1±13.4) mmHg, (128.7±9.8) mmHg (1 mmHg=0.133 kPa), and (83.7±7.2) mmHg respectivley, which were all lower than those in control group (P<0.05 or P<0.01). The incidences of morning peak blood pressure and non-dipper hypertension in control group were significantly higher than those in treatment group (P<0.01).


Conclusion
CPAP therapy can effectively adjust the heart rate and blood pressure levels in patients with OSAHS and primary hypertension, especially in the night.


Key words: 
Sleep apnea, obstructive; Continuos positive airway pressure; Hypertension
Amyloidosis secondary to ankylosing spondylitis: case report and literature review
Authors: Xinxin Han, Yu Chen, Chuiwen Deng, Linyi Peng, Xuejun Zeng, Wen Zhang, Xiaofeng Zeng, Fengchun Zhang
Journal: BMJ (2019)

Three patients diagnosed as amyloidosis secondary to ankylosing spondylitis (AS) in Peking Union Medical College Hospital are reported. All 3 cases had renal abnormalities, 2 cases were complicated with cardiac abnormalities, 1 case was complicated with gastrointestinal abnormalities and 1 case was complicated with skin moss-like changes. Eleven cases of AS with amyloidosis were retrieved from Wanfang database and Pubmed database from 1997 to 2017. In total 14 cases, the male and female ratio was 5∶2, the mean age of AS onset was (29.6±10.5) years, and the mean age of amyloidosis diagnosed was (44.0±10.5) years. Eight patients presented with edema and severe proteinuria, 2 cases showed diarrhea, 2 cases showed dyspnea, while 2 cases had no obvious symptoms. Thirteen cases had renal abnormalities and 1 case had only heart involvement. Of the 13 patients with renal involvement, 2 cases were complicated with cardiac abnormalities, 2 cases complicated with gastrointestinal abnormalities, 2 cases complicated with skin abnormalities.The mean ESR was (83.7±22.6) mm/1 h,C reactive protein was (89±59) mg/L at onset. After the diagnosis of amyloidosis, 9 patients were treated with TNF-α inhibitors, 3 cases received symptomatic therapy, 1 case underwent renal transplantation and 1 case were treated with peritoneal dialysis. In 9 patients treated with TNF-α inhibitors, 8 cases were relieved and 1 case lost follow-up. Three patients who received symptomatic treatment all died, while patients receiving kidney transplantation and peritoneal dialysis were in stable condition. The study indicates that secondary amyloidosis often occurs in young male AS patients who have long course and poorly controlled disease, the kidney is the most common affected organ. TNF-α inhibitors may be effective for treatment of amyloidosis secondary to AS.


Key words: 
Spondylitis, ankylosing; Amyloidosis
Musashi 2 (MSI2) expression as an independent prognostic biomarker in non-small cell lung cancer (NSCLC).
Authors: Alexander Deneka, Leonid Kharin, Nikolay S. Karnaukhov, Mark Voloshin, Tamara G. Ayrapetova, Elena Ratner, Alexey Sabirov, Yulia Topchu, Alexandra Mazitova, Zinaida Abramova, Veronika Yugai, Elena M. Frantsiyants, Oleg Ivanovich Kit, Yanis Boumber
Journal: Journal of Clinical Oncology (2020)

e21583 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world, and metastasis is the most common cause of death in lung cancer patients. Musashi-2 (MSI2) is a member of RNA-binding protein family and regulates mRNA translation of numerous intracellular targets, and influences multiple biological processes, including maintenance of stem cell identity. Previously we reported that MSI2 is upregulated in the metastasis-competent NSCLC murine and human cell lines, drives NSCLC metastasis, and is progressively elevated in lung cancer patient samples. This study assessed MSI2 as potential clinical biomarker in NSCLC. Methods: The current study included 40 patients with NSCLC, of whom 15 presented with stage II and III respectively (37,5% each), and 10 patients (25%) had stage IV. All patients received treatment in accordance with the NCCN guidelines, and did not participate in clinical trials. All patient samples were obtained before treatment started. We used immunohistochemical (IHC) approach to measure MSI2 expression on the protein level in matching specimens of normal versus tumor tissues, and primary tumor vs. metastasis, followed by correlative analysis in relation to clinical outcomes. In parallel, clinical correlative analysis of MSI2 mRNA expression was performed in silico using publicly available datasets (TCGA/ICGC) as of January 2020. Results: MSI2 protein expression in patient samples was significantly elevated in NSCLC primary tumors and metastatic sites versus normal tissue (p = 0.03). MSI2 elevated expression positively correlated with a decreased progression free survival (PFS) (p = 0.026) at all stages and overall survival at stage IV (p = 0.013). Elevated MSI2 expression on RNA level was observed in primary tumor versus normal tissue samples in TCGA (p &lt; 0.0001), and positively correlated with decreased OS (p = 0.028). No correlation was observed between MSI2 expression and age, sex, smoking, and treatment type. Conclusions: Elevated MSI2 expression in primary NSCLC tumors is associated with poor prognosis and can be used as a novel potential prognostic biomarker in NSCLC patients. Future studies in an extended patient cohort are strongly warranted.
Real-world survey of pneumonitis/radiation pneumonitis among patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy after durvalumab approval: A multicenter retrospective cohort study (HOPE-005/CRIMSON).
Authors: Go Saito, Yuko Oya, Yoshihiko Taniguchi, Hayato Kawachi, Daichi Fujimoto, Hirotaka Matsumoto, Shunichiro Iwasawa, Hidekazu Suzuki, Takayuki Niitsu, Eisaku Miyauchi, Takashi Yokoi, Miho Mitsui, Takeshi Uenami, Yoshihiko Sakata, Daisuke Arai, Asuka Okada, Satoshi Hara, Shunsuke Teraoka, Masaki Kokubo
Journal: Journal of Clinical Oncology (2020)

9039 Background: Durvalumab was approved as a consolidation therapy after chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) and established as the standard of care. However, since the approval of durvalumab, little has been reported on the frequency, severity, or clinical course of pneumonitis/radiation pneumonitis throughout the course of CRT. Methods: We conducted a 17-center, retrospective cohort study of consecutive patients with locally advanced NSCLC who received concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy between May 2018 and May 2019. Results: A total of 275 patients were included; their median age was 69.9 (range, 40.3-87.5), mean V 20 was 19.4% (range, 1.4-37.9), and mean "mean lung dose" was 10.9 Gy (range, 1.5-31.3). Of these, 204 patients received durvalumab consolidation therapy (74.2%). Median follow-up time from the initiation of CCRT was 8.4 months (range, 1.5-15.7). During follow-up, 225 patients (81.8%) developed any-grade pneumonitis/radiation pneumonitis. Of these, more than half (134 of 225) were asymptomatic (grade 1), 18 (6.5%) were ≥grade 3, and 4 patients (1.5%) had fatal pneumonitis/radiation pneumonitis. By the time of initial assessment of response to CCRT, 64 (23.3%) patients had developed radiation pneumonitis. Logistic regression revealed that only V 20 ≥25 % was an independent risk factor of symptomatic (≥grade 2) pneumonitis/radiation pneumonitis (OR: 2.74, 95% CI: 1.35-5.53, p = 0.0045). Of the 275 patients, 67 were treated with corticosteroids for pneumonitis/radiation pneumonitis (24.7%), and 14 (5.1%) needed home oxygen therapy after the treatment of pneumonitis/radiation pneumonitis. Among patients treated with corticosteroids, 21 patients received durvalumab rechallenge. Of the 21 patients, 6 (29%) showed pneumonitis/radiation pneumonitis relapse, of which 3 (14%) resulted in suspension of durvalumab rechallenge, but none were fatal. Conclusions: Although over four-fifths of the patients treated with CCRT after the approval of durvalumab developed pneumonitis/radiation pneumonitis, more than half of them were asymptomatic, and ≥grade 3 events accounted for 6.5%. Sometimes patients needed corticosteroid therapy, which was in many occasions effective, and some also underwent durvalumab rechallenge. V 20 was an independent risk factor of symptomatic pneumonitis/radiation pneumonitis.
Clinicopathology characteristics of idiopathic membranous nephropathy in elderly patients
Authors: Qianqian Xu, Li Zhuo, Guming Zou, Hongmei Gao
Journal: BMJ (2018)

Objective
To investigate the clinicopathological characteristics of idiopathic membranous nephropathy (IMN) in elderly patients.


Methods
Clinicopatholigical data of 400 patients with IMN identified by renal biopsy from January 2006 to December 2016 were analyzed retrospectively. The patients were divided into three groups: the young (≤44 years old), the middle-aged (45-59 years old) and the elderly (≥60 years old) , and the clinicopathological characteristics were compared among three groups.


Results
The average age of the elderly group was( 64.9±4.3)years, the elderly group had worse renal function than the young group (F=784.60, P=0.000) and the middle-aged group [estimated glomerular filtration rate(eGFR)were (91.1±25.9) 、(119.8±37.0) and (102.5±33.2) ml·min-1·1.73 m-2,F=21.74, P=0.000]. The incidence of hypertension was higher in the elderly group than the other two groups [40.0%(32/80) vs. 19.6%(30/153) and 22.2%(37/167), χ2=12.76, P=0.003]. The incidence of MN with ischemic nephropathy and tubulointerstitial lesion in the elderly group was higher than in the young group[15.0%(12/80) vs. 5.8%(9/153), χ2=5.31, P=0.021].


Conclusion
The elderly patients with IMN are likely to be complicated with hypertension, ischemic nephropathy and tubulointerstitial lesions indicating poorer prognosis, so more attention should be paid to the early diagnosis and treatment of these comorbidities.


Key words: 
Nephrosis; Glomerulone-phritis, membranous; Pathological conditions, signs and symptoms; Age groups
Mutational analysis of radiation-induced subsequent thyroid cancers in pediatric patients.
Authors: Jennifer Hess, Alexandra Maria Walsh, Kristian Schafernak
Journal: Journal of Clinical Oncology (2020)

e22531 Background: The genetic landscape of radiation induced pediatric thyroid cancers is unclear. Radiation (RT) induced thyroid cancers frequently demonstrate tumorigenesis driven by fusion oncogenes. However, data is limited to children exposed to radioactive contamination after the Chernobyl nuclear accident. Little is known about the genetic landscape of subsequent pediatric thyroid cancers after RT exposure for the treatment of a primary malignancy or conditioning regimens prior to bone marrow transplantation (BMT). The objective of this study was to assess the prevalence of different mutations in a small cohort of pediatric patients who developed a subsequent thyroid cancer after RT exposure for the treatment of a primary disease. Methods: This is a single-center retrospective study. Thyroid tissue blocks from 10 pediatric patients who underwent thyroidectomy between 2010 and 2019 for subsequent thyroid cancers after RT for treatment of a primary malignancy or BMT were analyzed for genetic alterations using targeted next-generation sequencing for alterations in 112 genes linked to thyroid cancer. Thyroid cancers included 7 papillary (PTC) and 3 follicular thyroid carcinomas (FTC). Results: Ten samples (6 females) were genotyped. The mean age at thyroid cancer diagnosis was 15.7 years (range 11–22 years) at a mean of 10.3 years (range 6 – 19 years) after RT exposure. The mean RT dose was 2618 cGy (range 400 – 10,080 cGy) delivered to the head, neck, and/or chest. Mutations were noted in 6/10 (60%) of patients. Mutations were detected in 6/7 (85.7%) of PTC cases: EMLA/NTRK in 2 cases, STRN/ALK in 2 cases, RET in 1 case, and CCDC30/ROS in 1 case. A DICER.1 c.5438A &gt; C p.E1813A was also identified in a patient with an EMLA/NTRK fusion. Of 3 FTC patients, (2/3) 67% had copy number alterations, but no mutations were observed. BRAF V600E mutations were not present in any tissues analyzed. Conclusions: An exceedinlgy rare ROS fusion was identified. Multiple RT induced thyroid lesions were positive for classic therapeutic targets including NTRK3, ALK, ROS1, and RET fusions, demonstrating a potential role for tyrosine kinase inhibitor therapy for refractory, recurrent or metastatic disease. All cases were negative for mutant BRAF V600E consistent with the pathogenesis of RT induced thyroid cancers primarily activated by fusions rather than point mutations. Larger, pediatric cohorts with RT induced thyroid cancers followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed.
农村与城市社区卫生服务的特点分析
Authors: 刘春生
Journal: BMJ (2011)

我在农村从事社区卫生服务10余年以来，深感农村基层卫生服务的重要。随着社区卫生服务的开展，新型农村合作医疗的建立，农村的卫生医疗水平有了长足的进步，农民因此受益匪浅。我体会，农村与城市有许多不同的特点，表现在地理环境、医疗资源、文化水平、经济条件、生活习惯、饮食结构、体力劳动、医疗需求、医疗保障等方面，因而，农村社区卫生服务也会不同于城市社区卫生服务，谈谈我的一些看法。
上呼吸道感染用药的合理选择
Authors: 张晓林
Journal: BMJ (2007)

我国约有75%的人每年至少有过一次上呼吸道感染,在社区卫生服务站上呼吸道感染患者约占门诊患者量的1/4～1/3.但是,全科医生是怎样选择治疗上呼吸道感染药物的呢?我做过的一个调查结果显示,89.6%的全科医生认为感冒药既然是非处方药,就十分安全,患者可以按照自己的情况选择自己喜欢的药物;只有10.4%的医生认为虽然是非处方药,但在服用中也会发生不良反应。