tbuckley/cabot-search huggingface dataset:
PhaseI/IIa Study evaluating the safety, efficacy of K-001 in advanced pancreatic ductal adenocarcinoma.
Authors: Jiujie Cui, Haiyan Yang, Donghui Chen, Jiong Hu, Haiyan Zhang, Feng Jiao, Min Liu, Jue Liu, Li-Wei Wang
Journal: Journal of Clinical Oncology (2020)

e16770 Background: K-001 is a potent, oral anticancer drug made from active ingredients of marine microorganisms. Its former phase I study did not observe the dose limited toxicity (DLT). Thus, further phase I/IIa trial was conducted to determine maximum tolerated dose (MTD), safety profile and antitumor effects of K-001 in advanced pancreatic ductal adenocarcinoma (PDAC). Methods: This open-label phase I/IIa study involved a dose-escalation to determine maximum tolerated dose (MTD), recommended dose (RD) of K001 in patients with pancreatic ductal adenocarcinoma, followed to obtain preliminary evidence of efficacy in patients who could potentially benefit from treatment. Results: Doses from 1350mg to 2160mg twice daily were evaluated. No dose-limiting toxic effects were observed. Totally, 47 adverse events (AE) were observed which included 27 (57.4%) grade 1 AEs, 17 (36.2%) grade 2 AEs and 3 (6.4%) grade 3 AEs. Only 2 AEs which were indigestion and gastrointestinal flatulence were affirmed to research drug and both grade 2. These two AEs were both symptoms of digestive system. For grade 3 AEs, The AEs were not dose dependent. Twelve patients were assessable for response. Clinical activity was observed at all doses tested with durable Response Evaluation Criteria in Solid Tumor (RECIST) . The objective RECIST response rate (ORR) was 0% (complete response + partial response) and the disease control rate (DCR) was 83.3% (10 of 12). Conclusions: K001 has promising efficacy and light side-effect profile. The activity observed demonstrates clinical benefit in pancreatic ductal adenocarcinoma, justifying the conduct of further studies. Clinical trial information: NCT02720666 .
Concurrent cetuximab (CTX) and nivolumab (NIVO) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Results of phase II study.
Authors: Christine H. Chung, Marcelo Raul Bonomi, Conor Ernst Steuer, Michael J. Schell, Jiannong Li, Matthew Johnson, Jude Masannat, Juan C. Hernandez-Prera, Caitlin McMullen, J Wadsworth, Krupal Patel, Julie Ann Kish, Jameel Muzaffar, Kedar Kirtane, James William Rocco, Nabil F. Saba
Journal: Journal of Clinical Oncology (2020)

6515 Background: While anti-Programmed Death-1 (anti-PD-1) inhibitors have efficacy, only some patients (pts) with R/M HNSCC achieve clinically significant benefits. We designed the study to determine the 1-year overall survival (OS) rate of concurrent CTX and NIVO in patients who had progressed on at least one prior treatment for their R/M HNSCC. Methods: Pts were treated with CTX 500 mg/m2 IV on Day (D) -14 as a lead-in followed by CTX 500 mg/m2 IV and NIVO 240 mg/m2 IV on D1 and D15 every 28-D cycle (C). Pts with CTX infusion reaction or who did not receive C1D1 for any reason were non-evaluable and replaced. NIVO dose reduction was not allowed but withheld/discontinued based on adverse event (AE) severity. Results: Total 47 pts are enrolled. 2 pts are non-evaluable. 45 evaluable pts are analyzed. Median age is 64 (24-77). ECOG performance status at baseline is 0 (9, 20%), 1 (33, 73%), and 2 (3, 7%). Primary sites are oral cavity 10 (22%), oropharynx 24 (53%), hypopharynx 3 (7%), larynx 6 (13%), and unknown primary 2 (4%). p16 status is available in 33 (73%). Prior treatments before the study enrollment are: chemotherapy (CT) 42 (93%), no CT 3 (7%), radiotherapy (RT) 38 (84%), no RT 7 (16%), checkpoint inhibitors (CPI) 23 (51%), and no CPI 22 (49%). PD-L1 combined positive scores (CPS) is available in 30 (67%). Median follow up time for overall survival (OS) is 12.6 months. The most common grade 3 treatment-related AE (TRAE) occurring ≥2 are fatigue 6 (13%) and rash-acneiform 2 (4.4%). The only grade 4 TRAE is CTX infusion reaction in 1 (2.2%). The most common grade 3 immune-related AE (IRAE) occurring ≥2 is fatigue 3 (6.7%). No grade 4 IRAE is observed. The median progression-free survival (PFS) and median OS are summarized in Table. Pts with no prior exposure to CPI have favorable PFS and OS relative to pts with prior CPI (PFS: HR 0.49, 95% CI 0.25-0.97, p=0.04 and OS: HR 0.5, 95% CI 0.22-1.14, p=0.09). Conclusions: Our data suggest the combination of CTX and NIVO is active in pts without prior CPI exposure and overall well tolerated in all pts. These preliminary results support further evaluation of the combination in CPI naïve pts. Clinical trial information: NCT03370276 . [Table: see text]
Patient-reported outcomes (PRO) in the GARNET trial in patients (pts) with advanced or recurrent dMMR/MSI-H endometrial cancer (EC) treated with dostarlimab.
Authors: Rebecca Sophie Kristeleit, Cara Amanda Mathews, Andres Redondo, Joice Huang, Laurie Eliason, Ellie Im, Jubilee Brown
Journal: Journal of Clinical Oncology (2020)

e18032 Background: PRO enable direct measurement of the experiences of patients with cancer. Anti-programmed death 1 (PD-1) therapies have shown favorable PRO in lung cancer but a data gap remains in EC. Dostarlimab is an investigational anti-PD-1 monoclonal antibody which has shown promising activity in GARNET in advanced mismatch repair deficient (dMMR) EC pts (with an ORR of 42.9% and a disease control rate of 58.6%), and a low incidence of symptomatic grade ≥3 treatment-related adverse events (anemia [2·9%], colitis [1·9%], and diarrhea [1·9%]). Here, we report on PRO measures collected from pts with dMMR/microsattelite instability high (MSI-H) EC in the single-arm GARNET trial. Methods: Pts with dMMR/MSI-H EC confirmed by local tests, with recurrent or advanced disease that progressed on a platinum regimen were enrolled. Pts received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment was an exploratory endpoint and was measured by the EORTC Quality of Life Questionnaire (QLQ-C30), a validated instrument used to evaluate quality of life, functioning, disease symptoms, and treatment-related side effects. PRO were collected at each dose administration, end of treatment, and follow-up. A mixed-model for repeated measures was used to assess change from baseline, accounting for time and baseline ECOG scores. The threshold to determine clinically meaningful group-level change was ±10 points. Results: PRO data were available for 43 pts. Compliance rates were high at 98%. Relative to baseline, pts reported meaningful improvements in pain, insomnia, and social and emotional functioning over the trial duration. Appetite, nausea, vomiting, constipation, diarrhea, and physical and role functioning were stable over the trial duration. Quality of life and global health status were also maintained. Conclusions: PRO from 43 pts enrolled in the GARNET trial show that disease- and treatment-related symptoms and quality of life are improved or maintained while receiving treatment. These data, along with with the efficacy and safety profile of dostarlimab, strongly support the use of dostarlimab in dMMR/MSI-H advanced EC. Clinical trial information: NCT02715284.
Frailty and neurocognitive decline in young adult survivors of childhood cancer: A longitudinal analysis from the St. Jude lifetime cohort.
Authors: AnnaLynn Williams, Kevin R. Krull, Carrie R Howell, Pia Banerjee, Tara M. Brinkman, Sue C. Kaste, Robyn Partin, MS, Deokumar Srivastava, Gregory T. Armstrong, Leslie L. Robison, Melissa M. Hudson, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2020)

10555 Background: Among young adult childhood cancer survivors, 8% meet the criteria for frailty, an aging phenotype associated with poor health. Frailty is associated with neurocognitive decline in the elderly general population, but this association has not been examined in young adult survivors of childhood cancer. Methods: Childhood cancer survivors (N = 845, mean [SD] age 30 [7] years, 22 [7] years post diagnosis, 52% male) were clinically evaluated for prefrailty/frailty (defined as ≥2/≥3 of muscle wasting, muscle weakness, low energy expenditure, slow walking speed, exhaustion) and completed neuropsychological assessments at baseline and five years later. Linear regression models estimated mean differences in neurocognitive decline in prefrail/frail survivors vs. non-frail survivors adjusting for age, sex, race, CNS therapy (cranial radiation, intrathecal chemotherapy, neurosurgery), and baseline neurocognitive performance. P-values were adjusted for multiple comparisons using false discovery rate (FDR). Results: 18% and 6% of survivors were prefrail and frail at baseline. Baseline frailty was associated with declines in visual-motor processing speed, short-term memory, and sustained attention (Table). Prefrailty and frailty were associated with declines in focused attention and executive function (Table). No significant associations were observed between prefrailty or frailty and decline in global cognition, academics, motor processing speed, long-term memory, verbal learning, or verbal fluency despite significant baseline cross-sectional associations. Conclusions: Young adult prefrail and frail survivors had greater declines in attention and executive function compared to non-frail survivors, domains commonly associated with aging. These findings suggest that interventions designed to mitigate components of frailty may also mitigate or prevent neurocognitive decline. [Table: see text]
Feasibility of a digital medicine program in optimizing opioid pain control in cancer patients (SWOG S1916).
Authors: Sherry Shen, Riha Vaidya, Amy Darke, Joseph M. Unger, Mina S. Sedrak, Barbara Segarra-Vazquez, Cynthia Law, Kendrith M. Rowland, Justin D. Floyd, Jeannine M. Brant, Mark Allen O'Rourke, Anna Catherine Beck, Scott David Ramsey, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2020)

TPS12126 Background: The undertreatment of pain in patients with advanced or metastatic cancer is well described in cancer research. Overcoming barriers that prevent successful use of opioid analgesics for cancer pain requires a clear understanding of how individuals use oral medications at home. The Proteus Discover is a digital medicine program (DMP) consisting of an FDA-approved ingestible sensor made of dietary minerals co-encapsulated with patients’ medications, a wearable sensor patch, and a mobile device app that enables patients to electronically transmit their medication adherence patterns. Use of the DMP has demonstrated improved clinical outcomes vs. usual care in patients with diabetes and hypertension, shown superiority over directly-observed therapy in tuberculosis and has been studied in the treatment of patients with hepatitis C, HIV, cancer and severe mental illness, but it has not been previously studied with opioids or in monitoring cancer-related pain. Methods: We are conducting a multicenter pilot study at SWOG NCORP sites to test the feasibility of using the DMP to monitor opioid use in the treatment of metastatic cancer pain. Eligible patients must have a diagnosis of metastatic cancer, have a baseline Brief Pain Inventory worst pain score of ≥3, be deemed by their physician to need initiation or up-titration of oxycodone-acetaminophen for pain control, and be able to read English. Primary outcomes include: (1) study accrual of 60 patients within six months of study activation at all participating sites; (2) patient retention defined as ≥50 patients completing the study, and; (3) adherence to the DMP defined as ≥66% of patients wearing the sensor patch for ≥28 days of the 42-day observation period. Secondary outcomes include change in Brief Pain Inventory pain scores, opioid medication consumption, number of safety alert triggers for high consumption, hospital or emergency room visits for pain, activity levels, and frequency of changes to the pain control regimen. The study will enroll patients at six sites; the first patient was enrolled on 1/20/2020. If successful, this study will inform design of a randomized controlled trial of the DMP vs. usual care in optimizing medication utilization and controlling cancer-related pain. Clinical trial information: NCT04194528 .
A型肉毒毒素治疗痉挛性斜颈18例
Authors: 邓晓玲, 王世凤
Journal: BMJ (2006)

痉挛性斜颈(spasmodic torticollis,ST)是因颈部肌肉不随意性持续性强直或阵挛性收缩,产生头和颈部向一侧扭转或阵发性倾斜,常伴局部疼痛.ST是神经系统肌张力障碍性疾病之一.我院自2001年6月至2003年7月采用肌电图引导下A型肉毒毒素(BTX-A)局部注射治疗ST患者18例,取得良好疗效,现报告如下。
Single-institution analysis of ablations versus partial nephrectomies for small renal masses.
Authors: Fionna Sun, Zachary Dreyer, Pranav Moudgil, Diane Studzinksi, Stephen Vartanian
Journal: Journal of Clinical Oncology (2020)

e17074 Background: Renal cell carcinoma (RCC) has the highest mortality rate of the genitourinary cancers with detection rising annually for small ( &lt; 4cm) renal masses (SRM). Nephron-sparing partial nephrectomy (PN) is recommended over other approaches such as ablations (Abl). This study aims to evaluate the outcomes and costs associated with treating patients with SRM RCC that undergo PN, laparoscopic cryoablation (lcryo), or various percutaneous ablations-cryoablation (pcryo), microwave (pmv), and radiofrequency (prf). Methods: A retrospective chart review of 295 patients that had either a PN or Abl from 2010-2019 at Beaumont Hospital- Royal Oak was performed. 189 patients with SRM were analyzed. Data collected included demographics, comorbidities, pathology, 30-day ED readmission, recurrence rate, and hospital-billed costs and charges. Data was analyzed using Mann-Whitney, chi-square, unpaired t-tests, Kruskal Wallis post-test, and Dunn’s multiple comparison test. Results: 133 patients with an index Abl (6 lcryo, 73 pcryo, 44 pmv, and 10 prf) and 56 patients with an index PN were analyzed. Mean tumor size for Abl (2.34cm; 90% biopsy-confirmed RCC) and PN (2.48cm; 87% histology confirmed RCC) was comparable. The populations undergoing PN or Abl were similar for both demographics and comorbidities except for age at index procedure (PN 58, Abl 71, p &lt; 0.01). Length of stay (LOS) following index procedure differed with an avg PN LOS = 2.74 days and Abl LOS 0.52 (p &lt; 0.01). 55% of PN patients presented to the ED within 30 days (38% readmitted) whereas only 8% of Abl patients did (42% readmitted)(p &lt; 0.01). The recurrence rate for PN compared to Abl was 23% to 14%, respectively (p = 0.14), with an average follow-up time of 4.95 years for PN and 2.78 years for Abl (p &lt; 0.01). Total hospital charge analysis showed PN being 1.57 the charge of all Abl types (p &lt; 0.01) while cost analysis demonstrated PN being more costly than Abl as a whole by 2.79x (p &lt; 0.01). When evaluating ablation subtypes, trends were noted lcryo being comparable to PN in both charge and cost while percutaneous interventions pmv, pcryo, and prf displayed lower charge and cost when compared to both PN and lcryo. Conclusions: With treatment decisions for SRM RCC are multifactorial, this single-site study demonstrated similar populations with comparable pathologies undergo both PN and Abl procedures. Complication and readmission rates differ between PN and Abl and consideration should be made for these variables as well as the costs associated with each procedure type when managing SRM RCC.
Functional hotness score based on three genes predicts long-term survival of triple-negative breast cancer independent from tumor mutational burden.
Authors: Eriko Katsuta, Li Yan, Mateusz Opyrchal, Pawel Kalinski, Kazuaki Takabe
Journal: Journal of Clinical Oncology (2020)

e12583 Background: Cytotoxic T-lymphocytes (CTLs) infiltration into tumor is a positive prognostic factor in breast cancer. Infiltration of CTLs are believed to be driven by mutation-induced neoantigens, thus, higher tumor mutation burden (TMB) is considered an important predictor of tumor immunogenicity and response to immunotherapy, but the association between intratumoral CTL counts and TMB in the overall cancer prognosis remains unclear. Methods: Utilizing publicly available breast cancer cohorts, we established Functional Hotness Score (FHS), based on CD8A, GZMB and CXCL10 gene expression levels of bulk tumors. The associations of FHS and breast cancer patient prognosis as well as distinct immunity markers were analyzed. Results: Breast cancer patients with high-FHS tumors demonstrated significantly better survival. FHS was lower in metastatic breast cancer. Among breast cancer subtypes, triple-negative breast cancer (TNBC) showed the highest FHS. FHS predicted patient survival not in hormone receptor (HR)-positive but in HR-negative, especially TNBCs. The high-FHS TNBCs enhanced not only CD8+ T cell infiltration, but also a broader type-1 anti-cancer immunity. The patients with the high-FHS patients showed better prognosis not only in high-TMB tumors but also in low-TMB TNBCs. The combination of high-TMB with high-FHS identified the unique subset of patients who did not recur over time. Conclusions: In conclusion, TNBCs with high-FHS based on the expression levels of CD8A, GZMB and CXCL10 showed improved prognosis with higher anti-cancer immunity regardless of TMB, and constituting an independent prognostic marker of survival, particularly robust when combined with TMB.
Results analysis of emergency skill contest using emergency care simulator among family physicians in Shenzhen
Authors: Guang-qiang Lai, Xiao-hui Zhang, Peng Kang
Journal: BMJ (2012)

A clinical emergency skill contest using emergency care simulator (ECS) was carried out on May 2011.Total 30 family physicians in 10 teams from Shenzhen community health centers participated in the contest.The performance and the scores of each item were analyzed.The overall score was 61.3 ± 11.9.The average score for general treatment was 33.0 ± 6.9 with a score rate of 66％ (33/50) ; the average score for cardiopulmonary resuscitation was 23.2 ± 7.2 with a score rate of 57.5％ (23/40) ; the average team score was lowest (5.0 ± 1.1 ) with a score rate of 50.0％ (5/10).The results indicate that family physicians should strengthen clinical skill training of emergency care,particularly in on-site response and teamwork.

Key words: 
Clinical competence;  Community health services
Circulating tumor DNA analysis to detect minimal residual disease and predict recurrence in patients with resectable pancreatic cancer.
Authors: Liu Yang, Jiahong Jiang, Song Ye, Yaping Xu, Dongsheng Huang
Journal: Journal of Clinical Oncology (2020)

e16799 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death, partly due to the high recurrence rates for patients with resectable PDAC. Current postoperative surveillance methods including monitoring of clinical symptoms, tumor markers and CT imaging, lack sensitivity and specificity to identify minimal residual disease (MRD). Methods: We investigated whether the detection of circulating tumor DNA (ctDNA) could identify MRD and predict relapse in postoperative patients with PDAC. In this study, we performed panel-captured sequencing to detect somatic mutations. Matched tissue samples were obtained to verify mutation. Results: A total of 27 patients and 65 plasma samples were included. Among the somatic mutations, KRAS and TP53 were the most recurrent genes in both tissue and plasma samples. The detectable rate of ctDNA increased with the stage of PDAC. The maximal variant allele fraction (VAF) of ctDNA had a positive correlation with tumor largest diameter (p = 0.0101). Patients with ctDNA-positive status postoperatively had a markedly reduced disease-free survival (DFS) compared to those with ctDNA-negative status (HR, 5.20; p = 0.019). Positive vascular invasion significantly influenced disease-free survival (DFS) (p = 0.036), and positive postoperative ctDNA status was an independent prognostic factor for DFS (HR = 3.60; 95% CI, 1.15-11.28; p = 0.028). Conclusions: Postoperative ctDNA detection provides strong evidence of MRD and identifies patients with a high risk of relapse. ctDNA detection is a promising approach for personalized patient management during postoperative follow-up.
爆发性1型糖尿病二例
Authors: 翟秀军, 宋道远, 刘秀梅
Journal: BMJ (2009)

例1 患者女性,49岁.因多饮、多尿、口渴、全身乏力5 d,于2005年3月28 日入院.患者病前半个月感咽痒,刺激性干咳.5 d前,出现多饮、多尿、口渴,全身乏力,食欲不振,喜冷饮,多以水果、果汁充饥.入院前1 d晚餐前血糖21.5 mmoL/L、餐后2 h血糖20.5 mmol/L,次日空腹血糖(FBG)19.8 mmol/L,急诊入院.病后体重下降4 kg.既往无特殊病史,无糖尿病家族史.入院查体:体温、脉搏、呼吸、血压正常,体重指数(BMI)26.心、肺、腹及神经系统尤阳性发现。
Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).
Authors: Alicia Frances Clare Okines, Elisavet Paplomata, Tanya A. Wahl, Gail Lynn Shaw Wright, Stephanie Sutherland, Erik Jakobsen, Frances Valdes, Arlene Chan, Amy Sanders Clark, Alison Katherine Conlin, Maryam B. Lustberg, Jennifer M. Specht, Timothy J. Pluard, Xiaofu Zhu, Ian E. Krop, Karen A. Gelmon, Dennis J. Slamon, Jorge Ramos, Grace An, Erika Paige Hamilton
Journal: Journal of Clinical Oncology (2020)

1043 Background: Tucatinib (TUC) is an investigational TKI, highly selective for HER2 without significant inhibition of EGFR. HER2CLIMB is a randomized trial of TUC vs placebo in combination with trastuzumab and capecitabine in patients (pts) with HER2+ breast cancer (NCT02614794, Murthy NEJM 2019). The most common G ≥3 adverse events (AEs) with higher incidence on the TUC arm (diarrhea, palmar-plantar erythrodysesthesia syndrome [PPE], and elevated liver enzymes) are described herein. Methods: Given that pts on the TUC arm had a longer duration of tx than those on the control arm, time-at-risk exposure-adjusted incidence rates of diarrhea, AST, ALT, and PPE were calculated as the number of pts with an event divided by the total exposure time-at-risk of an initial occurrence of the event among pts in the tx group. Time-to-event analyses were conducted for AST/ALT/bilirubin (in aggregate), diarrhea, and PPE. Results: Diarrhea and elevated AST/ALT/bilirubin on both the TUC and control arms were primarily G1/2 and manageable with dose modifications, and in some cases of diarrhea, with antidiarrheal tx. Median time to diarrhea onset was shorter on the TUC arm compared to control. For AST/ALT/bilirubin and PPE, median time to first onset was Cycles 1 and 2. On the TUC arm, antidiarrheals were used in 49.7% of cycles in which diarrhea was reported (39.8% on the control arm), and when used, the median duration of use on each arm was 3 days per cycle. Prophylactic antidiarrheals were not required per protocol. When adjusted for exposure (time-at-risk exposure-adjusted incidence rate per 100 person-years), the difference in G ≥3 events between tx arms becomes similar for diarrhea and PPE (21 vs 17 and 21 vs 19). The difference in G ≥3 events between arms is reduced for AST and ALT (7 vs 1 and 8 vs 1). Conclusions: TUC with trastuzumab and capecitabine was well-tolerated. Rates of G ≥3 diarrhea and PPE were similar between tx arms. Elevated liver enzymes were higher on the TUC arm, but were transient and reversible. Discontinuation of TUC due to AEs was rare. Clinical trial information: NCT02614794 . [Table: see text]