tbuckley/cabot-search huggingface dataset:
Phase II prospective trial of primary lung tumor stereotactic body radiation therapy (SBRT) followed by concurrent mediastinal chemoradiation and adjuvant immunotherapy for locally-advanced non-small cell lung cancer (NSCLC): Planned toxicity analysis.
Authors: John H Heinzerling, Kathryn Finch Mileham, Myra M. Robinson, James Thomas Symanowski, Raghava Reddy Induru, Roshan Sudhir Prabhu, Dean A. Gant, Sridhar E. Pal, Daniel Ernest Haggstrom, Edward S. Kim, Stuart Burri, Charles B. Simone
Journal: Journal of Clinical Oncology (2020)

e21047 Background: The care of pts with locally-advanced NSCLC has continued to evolve. Dose escalation with conventional radiation and concurrent chemotherapy has failed to improve outcomes and is associated with low primary tumor control rates and high toxicity rates. We initiated a phase II study to evaluate full dose SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes followed by adjuvant immunotherapy in patients (pts) with unresectable locally-advanced NSCLC. Methods: Eligible pts included peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions with concurrent chemotherapy (physician choice of carboplatin/paclitaxel or cisplatin/etoposide). Pts without disease progression after chemoradiation then received adjuvant durvalumab (PACIFIC trial). Planned analysis of early toxicity was performed given this is the first prospective trial to replace conventional fractionation and deliver full dose SBRT to the primary tumor in the locally advanced setting. Results: From May 2017 to January 2020, 35pts were enrolled. Median follow up is 7.9 months (range 0-27 months). Toxicity related to either SBRT or mediastinal radiation was lower than previous published prospective trials with a grade 2 radiation pneumonitis incidence of only 17%. There was no ≥grade 3 pneumonitis. Grade 3 esophagitis was observed in 1 pt (3%) with grade 2 esophagitis in 37%. No grade ≥3 toxicity has been attributed to SBRT with 26% of pts experiencing a grade 2 toxicity from SBRT. Overall incidence of grade ≥3 pulmonary toxicity attributed to any therapy was 9%. One pt died of neutropenic sepsis due to legionella while on therapy attributed to chemotherapy. No major cardiac events were reported to date. Conclusions: Full dose SBRT to the primary tumor followed by standard chemoradiation to the involved lymph nodes appears to have a favorable toxicity profile when compared with conventional dose escalation and to previously published experiences with SBRT boost following chemoradiation in the treatment of locally advanced NSCLC. Our trial continues to enroll with a target of 56 pts. Clinical trial information: NCT03141359 .
Relationship between waist circumference and prevalence of metabolic syndrome in Beijing elderly residents
Authors: Jian-rong He, Xue-ping Du
Journal: BMJ (2012)

Total 7594 elderly subjects from three urban districts in Beijing were enrolled in the study with randomized cluster sampling design. Physical examination and fasting plasma glucose test were undertaken for all participants.Based on the diagnosis criteria from The Guidelines of Dyslipidemia Control for Chinese Adults in 2007,the prevalence of metabolic syndrome (MS) was 26.57％ (2018/7594) and the prevalence of central obesity was 42.04％ ( 3193/7594 ).Using waist circumference ( WC ) as independent variable and MS prevalence as dependant variable,we developed a “Central obesity-Metabolic Syndrome”multiple regression model.The results showed that among those having WC higher than cutoff point,with each 3.3 cm reduction of WC,the prevalence of MS decreased by 4.5％.Therefore,central obesity can be used an important clinical target of MS for both prevention and treatment purposes.

Key words: 
Metabolic syndrome X;  Waist circumference
Incidence of brain metastases in patients receiving neoadjuvant chemotherapy (NAC) with trastuzumab and pertuzumab (HP) in HER2-positive early breast cancer (BC).
Authors: Emanuela Ferraro, Andrea Veronica Barrio, Sujata Patil, Mark E. Robson, Chau T. Dang
Journal: Journal of Clinical Oncology (2020)

e12653 Background: The addition of pertuzumab in the neoadjuvant setting has become a standard of care in stage II-III HER2-positive BC. In the Katherine study the incidence of brain metastases (BM) at the follow-up of 3-years was 5.9 % in patients (pts) with residual disease who received TDM1. The aim of this study was to assess the incidence of BM in pts who received NAC with HP at a single center who were found to have pathological complete response (pCR) (ypT0/is ypN0) versus non-pCR at the time of surgery. Methods: Chart review on HER2-positive pts treated with NAC and HP between September 1, 2013 to May 1, 2018 was conducted. Only surgical specimens of pts whose pre-NAC specimens were internally reviewed for HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were included in this analysis. Data on BM as component of distant recurrence along with invasive disease-free (IDFS) and overall survival (OS) were collected. Results: 540 pts were identified. Cases with no internally verified-HER2 status (387), equivocal status (10) and discordant internal assessment (13) were excluded. 130 pts with preoperative HER2 status confirmed by dedicated breast pathologists were included. Clinicopathological features are described in Table. pCR was achieved in 77/130 (60%) of cases, residual disease in 53/130 (40%). The median follow-up was 2.83 (0.35-5.3) years. The rate of BM as first presentation of distant disease was 3.8 % (3/77) and 3.7 % (2/53) in pts with pCR and non-pCR, respectively. Median time to development BM was 35 (13-58) months and 11.7 (9-14) months in the pCR group and non-pCR, respectively. Conclusions: In our cohort, the combination of HP was associated with a high pCR rate. At a median follow-up of 2.8 years, the incidence of BM appeared to be similar in pts who achieved pCR versus non-pCR. The data of IDFS and OS will be reported. Further data are needed to validate our findings before designing clinical trials to test prophylactic strategies to prevent BM. [Table: see text]
Intensive chemotherapy in patients with high grade myelodysplastic syndromes (MDS): A systematic review and meta-analysis.
Authors: Raed Benkhadra, Tarek Nayfeh, Veli Bakalov, Christie Hilton, Cyrus Khan, Larry Prokop, Mithun Vinod Shah, Hassan Alkhateeb, Mark Robert Litzow, M. Hassan Murad, Aref Al-Kali
Journal: Journal of Clinical Oncology (2020)

e19530 Background: Intensive chemotherapy (IC) regimens are rarely used in patients with myelodysplastic syndromes (MDS) for many reasons including advanced age at diagnosis, the frailty of these patients, the presence of several comorbidities and potentially increased mortality when such regimens are used. Additionally, very little literature exists on its safety and long-term benefit in this population. Aim: To evaluate the safety and effectiveness of IC regimens in patients with MDS. Methods: We searched MEDLINE, Embase, Scopus and Cochrane databases from each database's inception from 1990 to January 27 th , 2020. Keywords include: “MDS”, “induction chemotherapy” and “remission induction”. Studies evaluating different IC regimens with MDS were included. IC studies for patients with relapsed/ refractory MDS were excluded. Studies that combined acute myeloid leukemia (AML) and MDS outcomes were excluded. The random-effects model was used to pool relative risks and incidence rates. Main endpoints were overall remission rates (ORR), 30- and 60-days mortality, 1-year, 2-year and 5-year overall survival (OS). Results: Characteristics: From 2001 records, we included 13 studies [1,164 patients, median age 60.1 years (range, 17-88), males 58.9%, 58.4% patients had abnormal cytogenetics, median bone marrow blasts 17.8% (range 4 -29%), 4 studies were randomized]. Induction outcome: IC regimes included “7+3, FLAG, s-HAM, and few other regimens. Response: ORR was 55%, including 52% CR rate. Safety: 30- and 60-days mortality were 7%, 15%, respectively. Survival outcome: median survival was 11.6 months, 1-year, 2-year and 5-year OS were 48%, 21% and 5%, respectively. Randomized studies comparison: adding growth factors to IC did not show statistically significant effects on outcomes regarding induction mortality, ORR and OS (p-value &gt; .05). Conclusions: IC is rarely used in MDS patients and its use is associated with high mortality rates and low long-term survival. Limitations to our studies include the long span of this review over 3 decades and the difficulty of using published studies that combines MDS and AML patients’ outcome. More studies are needed in this population of interest in the future.
Relationships between worry about dying in patients with advanced cancer and their illness understanding, treatment preferences, and advance care planning.
Authors: Rachel Rodenbach, Andrew Althouse, Thomas J. Smith, Douglas B. White, Edward Chu, Marie Bakitas, Yael Schenker, Robert M Arnold
Journal: Journal of Clinical Oncology (2020)

12080 Background: Patients with advanced cancer often worry about dying, yet little is known about the role their fears play regarding future care. We aimed to explore relationships between patients’ worry about dying and their illness understanding, treatment preference, and advance care planning. Methods: This cross-sectional study uses baseline data from a community-based, primary palliative care intervention trial. Patients had metastatic solid tumors, an Eastern Cooperative Oncology Group performance status of 0-2, and their oncologist “would not be surprised” if they died in the next year. Using patients’ response to “I worry about dying” (not at all, a little bit, somewhat, quite a bit, or very much) from the Functional Assessment of Chronic Illness - Palliative Care survey instrument, univariate and multivariate analyses assessed associations with illness understanding (report of being terminally ill or not), treatment preference (life-extending vs. symptom-focused), and advance care planning (completion of an advance directive or not). We also performed sensitivity analyses substituting “I feel scared about my future” (strongly disagree, disagree, agree, or strongly agree) from the Herth Hope Index for “I worry about dying.” Results: Of 672 patients, 54% were female, 94% white, and 69% currently receiving chemotherapy. 47% reported worrying about dying “not at all,” while 9.7% worried “quite a bit” or “very much.” In regression analysis, those who worried “quite a bit” or “very much” were more likely to describe themselves as terminally ill (adjusted odds ratio (AOR)=1.98, 95% CI=1.10-3.54, p=0.021) and more likely to prefer life-extending treatment over symptom-focused care (AOR=2.61, 95% CI=1.30-5.22, p=0.007) compared with patients who reported not worrying about dying. They also were less likely to have completed an advance directive (AOR=0.49, 95% CI=0.25-0.94, p=0.032). The same relationships were observed using patients’ response to “I feel scared about my future.” Conclusions: Patients with advanced cancer who worry more about dying can affirm they are terminally ill and are more likely to want life-extending treatment over symptom care while less likely to engage in advance care planning. Understanding these patients’ decision making is critical to ensuring that their values are known and understood near the end of life.
脑膜癌五例临床分析
Authors: 陈育英, 王玉芬
Journal: BMJ (2009)

脑膜癌是指颅外癌肿向脑膜弥漫性转移而脑实质内无转移的一类具有特殊临床表现的疾病.回顾性分析我院2005年6月至2008年9月间收治的5例脑膜癌病患者的临床表现及诊断,以加深对该病的认识。
社区全科医生在老年人心血管病诊断中易发生的失误
Authors: 王悦宁, 黄鸿, 陈珍
Journal: BMJ (2008)

随着社区医疗的广泛开展,很多老年人会首先选择去社区医疗中心就诊.现将我院近年来收治的老年人心血管病在社区诊断中有代表性的失误举例分析如下,以期吸取经验教训,提高社区全科医生的诊断水平。
Clinical conditions and outcomes of medical patients cared at the Polyclinic of Beijing 2008 Olympic and Paralympic Village
Authors: Dong Wu
Journal: BMJ (2009)

Objective To investigate clinical service delivered at the Polyclinic of Beijing 2008 Olympic and Paralympic Village and outcomes of the medical patients visited there.to provide experiences in medical care service for other mass-gatherings in the future.Methads Clinical data of all the medical patients evaluated at the Polyclinic during July 27 to August 27 and during August 29 to September 19,2008 were reviewed retrospectively.with univariate and multivariate analyses.Results In total.1537 and 1206 medical patients visited the Polyclinic at the Olympic and Paralympic Village,respectively.Proportion of athletes visited was hisher during the Paralympic Games than that during the Olympic Games(14.2% vs.9.8%,P<0.01).We reeeived 775 patients(50.4%)with acute respiratory tract disorders,including 16 cases(1.0%)with asthma,during the Olympic Games,and 686(56.9%),including eight cases (0.7%)with asthma,during the Paralympic Games,and antibiotics were prescribed for 149(9.7%)and162(13.4%)of them,respectively.Twelve(0.8%)patients were hospitalized during the Olympic Games and four(0.3%)during the Paralyrnpie Games,and age equal to or nlore than 55 years and digestive disease were independent risk factors for hospitalization,with odds ratios(ORs) of 5.3 and 9.5 and their 95% confidence intervals(Cls)of 1.4-19.6 and 2.5-36.4,respectively.Conclusions Acute respiratory disorder was the most connnon cause for medical visits in the Polyclinic.Asthma did not play a significant role to iniluence athletes'performance in the Beijing 2008 Olympic and Paralympic Games.Antibiotic prescription in the Polyclinic had been controled to an acceptable level.Conditions in elder patients and those with digestive disorder tended to be severe.deserving more attention infuture's mass gathering.

Key words: 
Internal Medicine; Mass gathering; Retrospective studies
Error propagation in simulated treatment comparisons for multiple myeloma: Results from a simulation.
Authors: Eric Mackay, Justin Slater, Paul Arora, Kristian Thorlund, Audrey Beliveau, Devon J Boyne, Darren Brenner
Journal: Journal of Clinical Oncology (2020)

e20523 Background: Comparing the effectiveness of multiple myeloma treatments presents a challenge due to the limited number of head-to-head trials with which to conduct indirect treatment comparisons. This is particularly true when subgroup analysis is of interest. In comparative effectiveness research Simulated Treatment Comparisons (STCs) are becoming increasingly common in the absence of head-to-head trials. STCs use estimates from limited IPD to adjust for covariate imbalance between trials, however the uncertainty from these estimates is generally ignored when estimating relative treatment effects. This study demonstrates the need to account for this uncertainty when conducting STCs for indications such as multiple myeloma. We introduce an STC method that accounts for the uncertainty due to covariate adjustment, and demonstrate its effectiveness via simulation. Methods: We simulated two single arm studies (N = 300 for both), each containing age and overall survival. We assume study 1 has individual patient data available, and study 2 only has aggregate age data and a digitized Kaplan-Meier curve. We compute a covariate adjustment term based on the mean age difference between the studies and the age coefficients from fitting a parametric survival model to the observed study 1 IPD. We then estimate the variance of this adjustment term via bootstrapping and incorporate this uncertainty into a Bayesian STC model which estimates the relative treatment effect for the two study datasets converted to a digitized Kaplan-Meier format. Results: The proportion of 95% credible intervals (CrI) that captured the true treatment effect was 86.8% without error propagation, whereas 92.0% of CrI’s captured the true treatment with error propagation. 94.9% of CrI’s contained the true treatment effect when using survival regression with the complete IPD. Conclusions: Failing to account for uncertainty from the covariate adjustment when conducting simulated treatment comparisons generally leads to underestimating the uncertainty of the relative treatment effect. This method better captures the uncertainty introduced when conducting an STC and has the potential to yield more reliable estimates of the comparative effectiveness of multiple myeloma treatments.
Clonal dominance of EGFR and efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC.
Authors: Xinghao Ai, Rongrong Chen, Jiuwei Cui, Jiexia Zhang, Wen Lin, Congying Xie, Xiaohua HU, Junping Zhang, Xiaodong Jiao, Chuangzhou Rao, Weihua Yang, Lianpeng Chang, Xuefeng Xia, Xin Yi, Shun Lu
Journal: Journal of Clinical Oncology (2020)

e21501 Background: Though EGFR mutations in lung cancer are identified most often on the trunks of tumor phylogenetic trees in early stage, whether EGFR would always be the dominant clone in the advanced stage is unknown, as cancer evolution often follows a branched trajectory, with divergent subclones evolving simultaneously. The impact of clonal dominance of EGFR on outcomes with targeted therapies has not been explored. Methods: Paired tumor and plasma samples at diagnosis were obtained from systemic treatment naïve patients with advanced NSCLC in the clinical trial (NCT03059641). cfDNA and tumor DNA were sequenced by target-capture deep sequencing of 1021 genes related to solid tumors, with blood cells as the germline control. Clonal dominance analysis was performed on the basis of the CCF determined for SNVs and clustered in plasma or tumor sequencing data using a modified version of Pyclone. PFS was estimated using Kaplan-Meier method and compared using log-rank test. Results: From February 2017 to December 2019, 300 advanced NSCLC patients were enrolled prospectively from 14 centers cross China. One hundred and fourteen EGFR mutant patients treated with EGFR-TKI were followed until disease progression (PD). The medium follow-up time was 10 month (1-27 months) and 92 (80.7%) patients have reached PD, with the ORR of 74.6% (85/114), mPFS of 10.5 months. Clonal dominance analysis of EGFR showed 76 patients had EGFR as the dominant clone according to tissue NGS results, and 66 patients as the dominant clone according to plasma cfDNA NGS results (p = 0.04). The ORR was significantly higher for patients with EGFR as dominant clone according to plasma cfDNA NGS results (84.8% vs 60.9%, p = 0.016), and PFS was significantly longer (12 vs 8 months, HR = 2.58). There was no difference when using tissue NGS results to analyze EGFR clonal dominance. However, if comparing patients who were defined as EGFR dominant clone by both tissue and plasma (n = 44) with those defined as EGFR nondominant (n = 9), EGFR dominance was associated with higher ORR (84.1% vs 44.4%, p = 0.01), and longer PFS (11 vs 6 months, HR = 9.88) significantly. Moreover, multivariate Cox proportional hazard ratio analysis demonstrated it as an independent prognostic indicator of EGFR-TKIs. Conclusions: Clonal dominance of EGFR in the pretreatment plasma cfDNA is associated with the efficacy of EGFR-TKIs in NSCLC. This study indicated the importance of evaluating clonal dominance in the current clinical practice and future trial designs. Clinical trial information: NCT03059641.
Effect of chronic neurogenic pain on blood levels of hormones in patients with melanoma depending on their gender.
Authors: Viktoria V. Pozdnyakova, Elena M. Frantsiyants, Valeria A. Bandovkina, Ludmila Ya. Rozenko, Maria G. Ilchenko, Elena I. Agarkova, Natalia A. Zakharova, Olga V. Khokhlova, Yuriy V. Przhedetskiy, Viktoria Yu. Przhedetskaya, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e22097 Background: Chronic neurogenic pain (CNP) as a comorbid disease is quite frequent, but its effect on malignant diseases is poorly studied. The risk of cutaneous melanoma in women is higher, but the disease course in men is more severe. The purpose of the study was to reveal the effect of CNP on the levels of sex hormones in the blood of patients with melanoma depending on their gender. Methods: Blood levels of estradiol (E2), estrone (E1), progesterone (P4), testosterone (T) and prolactin (PRL) were measured by ELISA in patients with Т 3-4 N x M 0 melanoma (M): 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: In women with M+CNP, E2 and P4 were decreased by 1.8 times, while E1 was 1.4 times, T – 2 times, PRL – 1.5 times higher, compared to controls. In men with M+CNP, blood levels of estrogens were unchanged, PRL was 2.5 times lower and P4 and T – 1.3 times higher, compared to the corresponding control levels. Conclusions: CNP upregulated blood levels of androgens in both male and female melanoma patients, and caused the inversion of estrogens only in women with the prevalence of E1 over E2. Gender differences in the CNP influence included the elevation of progesterone and a decrease of prolactin in the blood of men, and P4 deficiency with increased prolactin in women with M+CNP. The specific effect of CNP on the hormonal profile in patients with cutaneous melanoma should be considered in choosing antitumor treatment.
Cancer vaccines
Authors: Butterfield Lisa H, 易宗毕
Journal: BMJ (2015)

癌症疫苗能够刺激机体产生特异性免疫性应答，尤其是针对肿瘤抗原的特异性CD8＋的细胞毒T细胞。1994年到1995年间生产的最早的癌症疫苗主要应用于非突变抗原患者中，结果显示肿瘤相关抗原具有一定的免疫原性，而且能够诱导少数晚期癌症患者产生临床反应。过去10年来，技术的发展使我们能够研发针对癌症患者特异性突变抗原的疫苗。多种癌症疫苗正在研发中，包括多肽、蛋白质、抗原提呈细胞(APCs)、肿瘤细胞和病毒载体疫苗。目前肿瘤的标准治疗包括外科、消融、化疗、放疗，都能诱导机体产生抗肿瘤免疫，因此我们认为这些治疗也具有一定的癌症疫苗的效应。通过监测肿瘤患者接受标准治疗前后免疫应答能力的变化，我们找到了肿瘤免疫的生物标志物。正在进行临床试验的联合治疗方案有望成为改善患者预后的最佳策略。
Safety and feasibility of systemic anticancer therapy in gastrointestinal (GI) cancer patients on hemodialysis (HD): The largest retrospective study.
Authors: Jennifer Park, Kerri McGovern, Leslie Ledbetter, Kristin Kaley, Teresa Rodriguez, Antonia Maloney, Wasif M. Saif
Journal: Journal of Clinical Oncology (2020)

e16139 Background: There is an increasing incidence of malignancies in patients with chronic kidney disease including patients on HD. Minimal reports exist in the literature regarding optimal management of chemotherapy in HD patients. This study investigates the feasibility of chemotherapy for patients with GI malignancies who were on HD. Methods: We collected retrospective data on 37 patients on HD who were treated for a GI malignancy from 2002-2018. Data points collected included demographics, cancer type, treatment regimens, toxicity and treatment outcomes. Results: Of the 37 patients, 28 patients were male and 9 female. Ethnicity consisted of White (25), African American (7), Hispanic (2) and other (4). Diagnoses included colorectal cancer (11), gastric cancer (7), pancreatic cancer (5), carcinoma of unknown primary (3), esophageal cancer (2), gallbladder cancer (2), peritoneal cancer (2), cholangiocarcinoma (2) and others (3). 7 patients received neoadjuvant chemotherapy with 4 undergoing successful resection of tumor. The following chemotherapies were administered post-HD: 5-FU, capecitabine, carboplatin, cisplatin, epirubicin, irinotecan, oxaliplatin and navelbine. Gemcitabine, docetaxel, paclitaxel and etoposide was given prior to HD. Grade &gt; 3 toxicities included anemia, nausea, vomiting and fatigue. Etiology of anemia was partly attributed to renal etiology. Response rate of treatments for HD patients were comparable to that of treatments for patients with normal renal function. 32 patients (86%) completed treatment as planned. Conclusions: Our data constitutes the largest set of patients with GI malignancies who received chemotherapy while on HD. Chemotherapy was feasible and needed a multi-modality approach. Our data calls for larger studies to further investigate pharmacokinetic parameters of cytotoxic drugs in hemodialysis patients to provide strong evidence based guidelines.