tbuckley/cabot-search huggingface dataset:
Weight-Based Dosing of Pembrolizumab Every 6 Weeks in the Time of COVID-19
Authors: Daniel A. Goldstein, Mark J. Ratain, Leonard B. Saltz
Journal: JAMA Oncology (2020)

cology or medicine-and consider if we should do it even if there is no pandemic.We believe this is an opportunity to choose wisely, be thoughtful, and critically appraise the evidence for everything we do as physicians.We do realize that thinking in terms of value or priorities may slowly fade away once the pandemic recedes and the pressure to make these critical decisions wanes.However, it would be a mistake to dismiss the careful and thoughtful decisions about how we deliver cancer care and what treatments we prescribe during this pandemic crisis as short-term changes only.They represent an opportunity to rethink how our cancer system should function using meaningful patient outcomes and value at the center of decision-making.If we revert to practice as usual postpandemic with testing, imaging, and treatments, we would have lost the opportunity to learn from the lessons this pandemic has brought to the fore.The ability to work and adapt to working in a resource-limited setting is an important skillset for us all to develop.Truly, no matter where we work, we are all global oncologists because at the time of pandemic, we are all resource limited.The COVID-19 pandemic and our global response to it is the defining public health crisis of our time.Let us learn from it-not only about how to manage global infectious disease threats that will come in future, but also about what in oncology and other areas of medicine are the important interventions, with outcomes of meaning to patients, that we should focus on delivering .
Infection of Ureaplasma urealyticum in patients with cervical intra-epithelial neoplasia
Authors: Di-kai Zhang
Journal: BMJ (2008)

One hundred and twenty four patients with cervical intra-epithelial neoplasia(CIN group)and 300 women in routine health check(control group)were recruited in the study.Ureaplasma urealyticum(UU)DNA in cervical secretions was detected by fluorescent quantitative PCR(FQ-PCR),and detectopm pf HPV was also performed in 103 CIN cases.The positive rate of UU was 64.5%in CIN group and 38.7%in control group(P＜0.05).The results demonstrated that UU infection may be associated with cervical intra-epithelial neoplasia,especially for high-grade lesions;and there may be interaction between UU and HPV infection in development of CIN.

Key words: 
Ureaplasma urealyticum; Cervical intra-epithelial neoplasia
Application effect of fine needle aspiration cytology and sentinel lymph nodes stain assisted by contrast-enhanced ultrasound in early breast cancer
Authors: Huiming Zhang, Xianquan Shi, Weihua Liu, Xuejing Wei, Zihan Wang, Zhicheng Ge, Daqing Zhang, Yinguang Gao, Zhongtao Zhang, Xiang Qu
Journal: International Journal of Surgery (2020)
Cumulative steroid doses and response rates to immune checkpoint inhibitors in metastatic cancer.
Authors: Karine Tawagi, Diana Maslov, Victoria Simenson, Helen Yuan, Cameron Parent, Adi Bamnolker, Richa Goel, Zoe Blake, Madhav KC, Marc Ryan Matrana, Daniel H. Johnson
Journal: Journal of Clinical Oncology (2020)

e15133 Background: Steroids are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether steroids have an effect on immune checkpoint inhibitor (CPI) efficacy compared patients receiving steroids vs. no steroids. This comparison may be confounded by different rates of irAEs and a known association of irAEs with higher response rates to CPIs. There is a paucity of CPI efficacy data in relation to the total dose of concomitant steroids. Methods: We retrospectively collected data from patients treated with CPIs alone, who received steroids during their CPI treatment at a single institution. IrAEs were defined using the CTCAEv5 criteria. Response rate (RR) and progression were defined per RECIST v1.1. Kaplan Meier and Cox proportional hazard regression methods were used to estimate the survival probability and hazard ratios (HR). Results: We identified 260 patients with stage IV cancer who received steroids concurrently with CPI treatment. A total of 111 patients (42.7%) received ≥1000mg prednisone equivalence during the course of their CPI treatment, and the remaining 149 patients (57.3%) received &lt; 1000mg PED. There was no difference in progression free survival (PFS) between the two cohorts [HR of 0.923 for &lt; 1000 mg PED group; p = 0.6016] or in overall survival (OS) [0.854 for &lt; 1000 mg PED group, p = 0.3308]. Median PFS for the &lt; 1000mg group was 5.9 months (mo), vs 6.3 mo in the ≥1000mg group. Median OS for the &lt; 1000mg group was 15.76 mo, vs 11.53 mo in the ≥1000mg group. The RR was numerically higher in the prednisone &lt; 1000mg cohort at 29.53% vs 20.72% in the ≥1000mg cohort, however not statistically significant (p = 0.1082). Basic characteristics including sex, race, tumor type, and smoking status, were similar between the two groups. There was a statistically significant difference in BMI distribution and steroid indication (irAE indication higher in &gt;1000 mg PED cohort than non-irAE) between the two groups. Conclusions: PFS, OS, and RR were not different between patients who received &gt;1000mg vs. &lt; 1000mg PED during CPI therapy. These data suggest that even high doses and protracted courses of corticosteroids may not hinder CPI efficacy. However, differences in our primary endpoint PFS may be confounded by difference in BMI and rates of irAEs between each cohort, which are both known to be associated with improved CPI efficacy. Further analyses to account for these differences along with how timing of steroid initiation affects CPI-efficacy will be completed by time of presentation.
Lenvatinib (LEN) plus pembrolizumab (PEMBRO) for early-line treatment of advanced/recurrent endometrial cancer (EC).
Authors: Vicky Makker, Matthew H. Taylor, Carol Aghajanian, Ana Oaknin, James Mier, Allen Lee Cohn, Margarita Romeo, Raquel Bratos, Marcia S. Brose, Christopher DiSimone, Mark Messing, Lea Dutta, Min Ren, Emmett V. Schmidt, Robert Orlowski, Jodi Alicia McKenzie, Kathryn Gillis, Antonio Casado Herraez
Journal: Journal of Clinical Oncology (2020)

6083 Background: As part of an ongoing phase Ib/II study (NCT02501096) in patients (pts) with selected solid tumors, LEN (20 mg PO QD) + PEMBRO (200 mg IV Q3W) displayed substantial and durable antitumor activity in advanced EC. In previously treated EC that was not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR; n=94 pts), the objective response rate (ORR) by independent imaging review (IIR) per RECIST 1.1 was 38.3% (95% CI 28.5–48.9). In this post hoc analysis, we assessed 2 subgroups of pts with previously treated, advanced, non MSI-H or dMMR EC who received LEN + PEMBRO in an early-treatment setting. Methods: Pts were examined in 2 subgroups: (1) Pts with only 1 prior line of cytotoxic therapy regardless of surgical stage or setting (adjuvant treatment for local-regional disease or treatment for metastatic disease); and (2) pts from subgroup 1 with local-regional disease at diagnosis who received only adjuvant cytotoxic therapy. There were no restrictions on prior hormonal or chemoradiation therapies in either subgroup. Tumor responses were assessed by IIR per RECIST 1.1. Results: Subgroup 1 included 63 pts and subgroup 2 had 21 pts. ORR (95% CI) was 41.3% (29.0–54.4) for subgroup 1 and 57.1% (34.0–78.2) for subgroup 2. Additional efficacy outcomes are summarized in the table. In subgroup 1, treatment-related adverse events (TRAEs) occurred in 62 (98%) pts (42 [67%] ≥ grade 3). TRAEs led to study-drug interruption of one or both drugs in 43 (68%) pts and dose reductions of LEN in 42 (67%) pts; 12 (19%) pts discontinued one or both drugs due to a TRAE. Serious TRAEs occurred in 18 (29%) pts and 2 (3%) pts died from a TRAE. The safety profile for subgroup 2 was generally similar to the profile for subgroup 1. Conclusions: The efficacy of LEN + PEMBRO for early-line treatment of advanced non MSI-H or dMMR EC appears promising. No new safety signals have emerged. A phase III study of LEN + PEMBRO vs paclitaxel + carboplatin for first-line treatment in advanced or recurrent EC is underway. Clinical trial information: NCT02501096. [Table: see text]
Genetic counseling referrals after next generation sequencing testing.
Authors: Rafael Gonzalez, Emma Ryan, Catherine Watson, Gloria Broadwater, Noah D. Kauff, Laura J Havrilesky, Andrew Berchuck, John H. Strickler, Edgardo Castellar, Carolyn S. Menendez, Michelle Green, Kyle C Strickland, Rebecca A. Previs
Journal: Journal of Clinical Oncology (2020)

1515 Background: Next generation sequencing (NGS) testing of tumor tissue or blood is performed to identify ‘actionable’ mutations that might guide patient care. NGS testing might incidentally identify germline mutations associated with cancer syndromes. No distinction is made between germline and somatic alterations on NGS reports, thus confirmatory germline testing is required. In this quality improvement (QI) initiative, we evaluated the frequency of referrals to genetic counseling (GC) for patients with potentially heritable germline mutations identified through NGS testing. Methods: We generated a list of high-risk mutations (HRMs) which merit GC referral based on NCCN guidelines. NGS test results for 3,400 consecutive patients with solid tumor malignancies were reviewed by the molecular tumor board from 1/2014-9/2019 and were screened for pathogenic HRMs. Basic demographic, oncologic, and GC data were retrospectively abstracted for each patient. The outcomes of interest were the frequency of HRMs identified through NGS testing, the proportion of patients subsequently referred to GC, and the proportion of patients ultimately diagnosed with a hereditary cancer syndrome. Results: 472 individual patients (14%) had NGS testing with one or more HRM identified; 465 patients were evaluable which corresponded to 519 HRMs that were included in the analysis (Table). Malignancies included were gastrointestinal 199 (42.8%), lung 83 (17.8%), genitourinary/renal 56 (12.0%), breast 49 (10.5%), gynecologic 35 (7.5%), and other 43 (9.2%). 75 (16.1%) patients had germline testing prior to NGS testing. Of those patients without prior germline genetic testing, 62 (15.9%) were referred to GC, and 19 (4.9%) patients were diagnosed with a hereditary cancer syndrome. Conclusions: Tumor NGS testing identifies HRMs that may represent an undiagnosed heritable germline mutation. Providers ordering NGS tests should review results for HRMs, refer to GC when appropriate, and offer confirmatory germline testing for patients and their families. [Table: see text]
The multicultural mind as an epistemological test and extension for the thinking through other minds approach
Authors: George I. Christopoulos, Ying-yi Hong
Journal: Behavioral and Brain Sciences (2020)

Abstract The multicultural experience (i.e., multicultural individuals and cross-cultural experiences) offers the intriguing possibility for (i) an empirical examination of how free-energy principles explain dynamic cultural behaviors and pragmatic cultural phenomena and (ii) a challenging but decisive test of thinking through other minds (TTOM) predictions. We highlight that TTOM needs to treat individuals as active cultural agents instead of passive learners.
Symptom burden as a predictor of emergency room use and unplanned hospitalization in patients with head and neck cancer: A population-based study.
Authors: Christopher Noel, Rinku Sutradhar, Julie Hallet, Jonathan Crawford Irish, Natalie Coburn, Antoine Eskander
Journal: Journal of Clinical Oncology (2020)

12084 Background: Symptoms are common in oncology patients, though they remain undetected and untreated by clinicians in up to 50% of cases. Integrating patient reported outcomes (PRO) within routine clinical practice has been suggested as a way to improve detection. In order to inform an effective and efficient PRO symptom screening program, we sought to determine whether outpatient symptom scores could predict emergency room use and unplanned hospitalization (ER/Hosp) in a cancer patient population. Methods: This was a population-based study of patients diagnosed with head and neck cancer who had completed at least one outpatient Edmonton Symptom Assessment System (ESAS) assessment between January 2007 and March 2018 in Ontario. Logistic regression models were used to determine the relationship between reported outpatient ESAS scores and ER/Hosp use in the 14-day period following ESAS completion. A generalized estimating equations approach was incorporated to account for possible patient-level clustering. Results: There were 11,761 unique patients identified with a total of 73,282 ESAS assessments. There were 5,203 ER/Hosp outcome events. In adjusted analysis, the odds of ER/Hosp use increased log linearly with ESAS score (1.23 per 1 unit increase in index ESAS score, [95% confidence interval (CI) 1.22 – 1.25]). This corresponds to a 9.23 (95%CI 7.22-11.33) higher odds of ER/Hosp use for the maximum index ESAS score of 10. Seven of the nine ESAS symptom scores were significantly associated with ER/Hosp use with pain, appetite and shortness of breath demonstrating the strongest association. Conclusions: ESAS scores are independently associated with 14-day ER/Hosp in head and neck cancer patients. Appropriate and timely management of symptom burden may reduce rates of ER/Hosp. [Table: see text]
Molecular correlation of the activity of evofosfamide (EVO) in combination with sunitinib (SUN) in pancreatic Neuroendocrine Tumors (pNETs) in the SUNEVO GETNE Trial.
Authors: Carlos López-López, Teresa Alonso Gordoa, Marta Benavent, Jaume Capdevila, Alex Teule, Ana Custodio, Isabel Sevilla, Maria Santos, J. Lanillos, Cristina Rodríguez-Antona, Rocio Garcia-Carbonero, Enrique Grande
Journal: Journal of Clinical Oncology (2020)

e16706 Background: MEN1, DAXX, ATRX, and PI3K/AKT/mTOR pathway genes are frequently mutated in pNETs. Sunitinib is approved and widely used in the metastatic setting but unfortunately, no validated predictive biomarker has been identified to guide therapy yet. The SUNEVO phase II trial of the Spanish Task Force Group for Neuroendocrine and Endocrine Tumours (GETNE) trial combined the pro-drug of EVO under SUN-induced hypoxic conditions. Methods: We performed an exploratory analysis aimed to identify somatic mutations associated with the clinical benefit of pNET patients treated with SUN+EVO combination. Seventeen treatment-naïve pts with pNETS were included in the SUNEVO trial, and 4 (23.5%) achieved a partial response (by RECIST 1.1). Tumor DNA from 10 FFPE tumor samples were successfully sequenced with an enrichment panel (Nimblegen, Roche) including 42 cancer-related genes and TERT promoter region. Median coverage was 793x. Coding non-synonymous and loss-of-function variants were considered for the analysis. Final analysis included tumor samples from the 10 patients with NGS results. Results: Somatic mutations were found in MEN1 (70%), DAXX (30%), ATRX (20%), SETD2 (20%) and PTEN (10%). Mutations in the telomere maintenance genes DAXX and ATRX were concordant with mutual exclusivity. The loss of MEN1 was associated with a greater number of mutations (p = 0.019). Patients with complete and partial response showed heterogeneous genetic profiles. Conclusions: The molecular alterations of the patients in the SUNEVO trial were consistent with those previously described for metastatic pNETs. No clear association between molecular defects and treatment response was found. Clinical trial information: NCT02402062 .
The association between IDO activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic body radiotherapy.
Authors: Yaoyao Zhu, Min Hu, Qinghua Xu, Yaping Xu
Journal: Journal of Clinical Oncology (2020)

e21054 Background: Immunity affects the efficacy of radiotherapy of lung cancer patients. Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that converts tryptophan (T) into heparin (K), which can promote immune suppression and assist tumor cells in immune evasion. The purpose of this study was to quantitatively analyze the immune activity of IDO in serum before and after SBRT, and to explore the changes in immune activity of IDO mediated by SBRT and its relationship with patient's survival. Methods: High-performance liquid chromatography and mass spectrometry were used to determine serum K and T in 30 patients with early non-small cell lung cancer before and after SBRT treatment. K: T stands for IDO activity. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Cox proportional hazards model was used for univariate and multivariate analyses. Results: The median follow-up time was 37.4 months. The median PFS was 37.5 (95% CI, 31.0-44.0) months. The median survival was not reached. In all patients, lower post/pre kynurenine ratio correlated significantly with better PFS (HR = 0.31, 95% CI = 0.11-0.90, P = 0.032). The lower K: T ratio at post-RT received longer OS (HR = 0.27, 95% CI = 0.079-0.95, P = 0.042). In multivariate analysis, smoking &lt; 30 packs / year (P = 0.030), higher BED (P &lt; 0.001), and lower post/pre kynurenine (P = 0.043) were associated with better PFS. Lower K: T ratio post-RT (P = 0.040) and higher BED (P &lt; 0.001) were significantly associated with better OS. Conclusions: SBRT could alter IDO-mediated antitumor immune activity. The lower level of post/pre kynurenine ratio was significantly related with better PFS. The lower K: T ratio at post-RT was related with better OS. This study shows that IDO is a potentially valuable biomarker for monitoring the immune status and predicting survival in early NSCLC patients after SBRT.
心搏骤停和猝死的基本概念
Authors: 冯庚
Journal: BMJ (2005)

编者按心搏骤停是临床上常见的危重症之一,由于大多数心搏骤停发生在院外,因此对该症患者的院前急救是急救医学中最重要的研究课题之一.由于多种原因,该项研究尚未取得突破性的进展,在世界范围内其抢救成功率很低.因此如何加强复苏理论和技术的研究,提高复苏成功率,是摆在所有医护人员面前的艰巨任务,同时也是我们刊登心搏骤停院前急救系列讲座的初衷.这套讲座共分9讲,第1讲为概论,介绍心搏骤停的基本概念和相关问题,之后依次介绍心搏骤停的病因和临床表现、心搏骤停的心电图检查和物理检查、初级复苏的若干问题、高级复苏的基本措施和复苏程序、气管插管的相关技术、怎样在复苏后维护患者的基本生命体征、怎样在院前对患者进行正确的脑复苏和脑保护、院前常用复苏药物.讲座将介绍目前最先进的复苏理论、方法和进展,突出其实用性和可操作性.欢迎大家共同参与讨论,结合实际提出自己的观点,力求从交流中得到裨益,提高院前复苏的理论和技术水平。
Novel HPV-E7 immune modulators to activate HPV-specific T cells to eliminate cervical cancer.
Authors: Lihua Shi, Di Zhang, Susan Tam, Man-Cheong Fung
Journal: Journal of Clinical Oncology (2020)

e18027 Background: Human papilloma virus (HPV) infection can lead to several types of cancers in both men and women. HPV+ tumor cells constitutively express the HPV-E7 antigen which can act as an oncogene to promote tumor growth and malignant transformation. Here, we report the application of novel Tavo Immune Modulator (TIM) biologics molecules which are consisted of a pMHC complex with an epitope peptide derived from HPV-E7 and co-stimulatory modulators of T cell activity. The HPV-E7 TIM molecules can specifically recognize and activate HPV-E7-specific T cells for the elimination of HPV affected cells. Methods: HPV-E7 TIM molecules were engineered as fusion molecules with HLA-A*02:01 MHC complexed with an HPV-E7 (11-20) epitope peptide at the N-termini, and various T cell costimulatory modulators at the C-termini of IgG heavy and light chains. TIM molecules were expressed in Expi293 cells and purified by Protein A affinity chromatography. Specific binding of TIM with HPV-E7 specific T cells was confirmed by immunostaining and flow cytometry. The activation and expansion of antigen specific CD8+ T cells were elucidated in T cell activation and recall assays. Results: HPV-E7 TIM molecules with various T cell co-stimulator molecules were engineered to specifically recognize HPV-specific T cells. Activation of T cells was antigen-specific and depended on the presence of an engineered T cell modulatory component on the TIM framework. The effects of various costimulatory molecules in different combinations on T cell activation were explored and an optimal combination was identified which facilitated high potency antigen-specific T cell activation. Such molecular combinations could facilitate T cell expansion and activation in T cell recall assays. Efficacy of HPV-E7 TIM molecules by inhibiting tumor growth in a syngeneic tumor model is ongoing. Conclusions: This study demonstrates that HPV-E7 TIM molecules selectively recognize and activate HPV-specific CD8+ T cells in the presence of a combination of two T cell costimulatory factors. Such novel biologics provide distinctive approaches in the treatment of HPV-related cancers and warrant further investigation. Additional in vitro and in vivo studies are ongoing to demonstrate the utility in eliminating HPV-infected tumor cells. Full data will be presented at the meeting.
Palliative referrals in advanced cancer patients: Utilizing the Supportive and Palliative Care Indicators Tool and Rothman Index.
Authors: Abigail Sy Chan, Amit Rout, Irina Lev, Amy Yu, Chris D'Adamo, Kenneth David Miller
Journal: Journal of Clinical Oncology (2020)

12102 Backgroun1d: Timely identification of palliative care needs have the ability to reduce hospitalizations and improve QOL. The Supportive &amp; Palliative Care Indicators Tool (SPICT) is used to identify patients with advanced stage medical conditions who may need special care planning. The Rothman Index (RI) detects patients at high risk of acutely decompensating in the inpatient setting and has been validated to assess 24-hour mortality risk. We used SPICT and RI in cancer patients admitted to the hospital and evaluated their roles in recognizing early palliative care needs and 6-month mortality. Methods: Advanced/metastatic cancer patients admitted to our institution from Jan 1, 2019 to June 30, 2019 were retrospectively reviewed. Patient demographics, length of hospital stay (LOS), comorbidities, palliative/hospice care referrals, vital status, initial RI score, and computed SPICT scores were obtained. Worse clinical indicators were defined as SPICT positive if it met &gt; 2 clinical indicators or RI &lt; 60. Univariate and bivariate analyses were performed. Results: A total of 227 patients were included, mean age 68, 34% Caucasians, 63% Blacks, 59% female, median comorbidities of 3, with majority having lung and GI malignancies. A total of 137 (60%) were SPICT +, 47 (21%) had RI &lt; 60, and 38 (17%) concurrent SPICT + and RI &lt; 60. SPICT + patients were more likely to have longer hospital stay, change in code status, more palliative/hospice referrals, and increased mortality. Those with RI &lt; 60 had similar results (Table). SPICT + patients are more likely to have RI &lt; 60 (p = 0.0013). Conclusions: SPICT and RI are valuable tools in predicting 6-month mortality and palliative/hospice care referrals. These can also be utilized to initiate early palliative and goals of care discussions in patients with advanced cancer. [Table: see text]