tbuckley/cabot-search huggingface dataset:
Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.
Authors: Shaheer Khan, Jose Lutzky, Alexander Noor Shoushtari, Joanne M. Jeter, Cody Chiuzan, Naomi Sender, Lauren Esther Blumberg, Alexandra Nesson, Shahnaz V. Singh-Kandah, Susana Hernandez, Grazia Ambrosini, Oliver Surriga, Gary K. Schwartz, Richard D. Carvajal
Journal: Journal of Clinical Oncology (2020)

10075 Background: Uveal melanomas (UM) measuring at least 12mm in base diameter with a class 2 signature as defined by gene expression profiling (DecisionDx-UM) are characterized by high metastatic risk, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk. The growth factor receptor Met is highly expressed in UM. We have previously shown that crizotinib, an inhibitor of Met, is an effective adjuvant therapy in preclinical models (Surriga et al, Mol Cancer Ther 2013). We therefore conducted a phase II study of adjuvant crizotinib in high-risk UM. Methods: Eligibility included: primary lesion ≥12mm in base diameter; class 2 by DecisionDx-UM testing; definitive therapy within 120 days before starting crizotinib; and, no evidence of metastatic disease. Patients (pts) received 12 four-week cycles of crizotinib (250 mg twice daily). Surveillance imaging (chest CT and MRI abdomen/pelvis) were performed q3 months. The primary endpoint was distant relapse-free survival (RFS). Secondary endpoints were overall survival (OS) and toxicity. We hypothesized that the addition of crizotinib would increase the 32 month RFS from 50% to 75% (α = 0.05; β = 0.11). Results: As of 1/31/2020, 34 pts had enrolled and received at least one dose of study drug with median age of 60 (range, 26-86); 41% female; and median ECOG PS 0 (range, 0-1). 2 pts could not be evaluated for the primary endpoint due to early withdrawal and loss to follow-up. The median time from primary treatment to crizotinib initiation was 60 days (range, 0-106). All pts experienced a treatment-related adverse event (AE) of any grade. 11/34 (32%) experienced a grade 3 or 4 AE, the most common being transaminase elevation (n = 8/11). 9 pts (28%) did not complete the full 48-week treatment course due to disease recurrence (n = 5) or toxicity (n = 4). An additional 5 pts required dose reduction due to hepatic toxicity or diarrhea. 15/32 evaluable pts developed distant disease relapse, with 14 developing relapse within 32 months. With a median duration of follow up of 28.7 months, the median RFS was 30.6 months (95% CI: 27.8-58.5%). The median OS was not reached. Conclusions: The use of adjuvant crizotinib in patients with high-risk UM did not reduce rates of relapse in this multicenter, single arm trial. 9/32 (28%) pts required dose modification or discontinuation due to AE which may have limited efficacy. Further investigations of adjuvant treatment options are warranted. Clinical trial information: NCT02223819.
A shared tumor-antigen RNA-lipoplex vaccine with/without anti-PD1 in patients with checkpoint-inhibition experienced melanoma.
Authors: Carmen Loquai, Jessica Cecile Hassel, Petra Oehm, Evelyna Derhovanessian, Robert Alexander Jabulowsky, Maike Gold, Doreen Schwarck-Kokarakis, Sebastian Attig, Katarina Cuk, Isabel Vogler, Julian Sikorski, Melanie Leierer, Heidrun Mitzel-Rink, Matthias Miederer, Stephan Grabbe, Jochen Utikal, Andreas Pinter, Roland Kaufmann, Ugur Sahin, Oezlem Tureci
Journal: Journal of Clinical Oncology (2020)

3136 Background: Cancer vaccines are considered unsuitable for patients with advanced tumours and have not been clinically successful. Methods: Lipo-MERIT is an ongoing phase 1/2 trial (NCT02410733) with melanoma FixVac, a liposomal RNA vaccine targeting four non-mutant shared tumour-associated antigens (TAAs) (MAGE-A3, NY-ESO-1, tyrosinase, TPTE). Patients with stage IIIB-C and IV melanoma are eligible. The trial comprises 7 dose escalation and 3 dose expansion cohorts, the latter with FixVac alone or combined with anti-PD1. Eight doses of FixVac are administered i.v. weekly/bi-weekly followed by optional continued monthly treatment. This abstract summarizes the findings of an exploratory interim analysis (cut-off JUL2019) of 89 patients. Results: 42 of 89 patients had measurable disease at baseline and were eligible for assessment of best objective overall response. All but one patient were stage IV and had undergone previous lines of treatment, 41 patients were checkpoint-inhibitor (CPI)-experienced, and 35 had been exposed to both anti-CTLA4 and anti-PD1 therapy. In the vaccine monotherapy group (n = 25) three patients experienced a partial response (PR) and 7 patients had stable disease (SD). An additional patient showed a complete metabolic remission of metastatic lesions based on [ 18 F]-FDG PET/CT imaging. In the group of patients treated with melanoma FixVac and PD1 blockade, 6 of 17 patients developed a PR. Patients with PR showed induction of poly-epitopic and strong CD4 + and CD8 + T cell immunity against the vaccine antigens. The number of antigen-specific cytotoxic T cells in some responders reached up to low 2-digit percentages of circulating CD8 + T cells and was maintained at high levels by continued vaccination. Overall, 75% of the 50 patients tested by ex vivo IFNg ELISpot analysis and all 20 patients tested by IFNg ELISpot after in vitro stimulation showed vaccine-induced immune responses against at least one vaccine antigen. Typically, antigen-specific T cells ramped up within the first 4-8 weeks to single-digit and low double-digit percent fractions of circulating CD8 + T cells. Immune responses were of effector memory phenotype and their strength and frequency did not depend on disease status at baseline (measurable versus non-measurable disease), on vaccine dose or on treatment (FixVac alone versus in combination with anti-PD1). Conclusions: FixVac alone and in combination with anti-PD1 mediates durable objective responses in pre-treated, CPI experienced patients with advanced progressing melanoma. Clinical trial information: NCT02410733 .
Satisfaction measurement tools and their application on community health service
Authors: 刘宇婧, 崔树起
Journal: BMJ (2009)

满意度调查工具是了解居民医疗需求及其满意度的重要手段,目前,国外已经有多种通用的标准化患者满意度调查工具,但国内还未开发出具有影响力的测量工具.现对国内外满意度测量工具及其应用情况加以评述。
癌症防治的全科医学思考
Authors: 曹水
Journal: BMJ (2005)

癌症的病因及影响因素较为复杂.由于人口老龄化、乡镇工业化、居住城市化、环境污染、职业危害以及人们健康意识淡薄、不良的生活习惯、行为方式等原因,造成环境、社会、心理、行为、遗传、生物等诸多促发因素的普遍存在,致使癌症的发病率、死亡率逐年上升.解决的途径就是要认真贯彻 ,以大卫生观念,创新理论,调整思路,改变目前防癌工作中,以中、晚期患者治疗为主的被动局面。
CARD: Overall survival (OS) analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel versus abiraterone or enzalutamide.
Authors: Bertrand F. Tombal, Daniel Castellano, Gero Kramer, Jean-Christophe Eymard, Johann S. De Bono, Cora N. Sternberg, Karim Fizazi, Christian Wulfing, Aristotelis Bamias, Joan Carles, Roberto Iacovelli, Bohuslav Melichar, Asgerdur Sverrisdottir, Christine Theodore, Susan Feyerabend, Carole Helissey, Elizabeth Poole, Ayse Ozatilgan, Christine Geffriaud-Ricouard, Ronald De Wit
Journal: Journal of Clinical Oncology (2020)

5569 Background: The CARD trial (NCT02485691) compared cabazitaxel vs. an androgen receptor targeted agent (ART; abiraterone/enzalutamide) in mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), in any order. These post hoc analyses assessed OS from various time points and the impact of prognostic factors. Methods: Patients with mCRPC previously treated with docetaxel and progressing ≤ 12 months on prior abiraterone/enzalutamide were randomized 1:1 to cabazitaxel (25 mg/m 2 IV Q3W + daily prednisone + prophylactic G-CSF) vs. abiraterone (1000 mg PO + daily prednisone) or enzalutamide (160 mg PO). OS was calculated from date of diagnosis of metastatic disease, date of mCRPC, and start of 1st, 2nd or 3rd life-extending therapy (LET). A stratified multivariate Cox regression analysis assessed the impact of 14 prognostic factors on OS using a stepwise model selection approach with a significance level of 0.10 for entry into the model and 0.05 for removal. Results: In the CARD study (N = 255), median OS was longer with cabazitaxel vs. abiraterone/enzalutamide (13.6 vs 11.0 months; HR 0.64, 95% CI 0.46–0.89; p = 0.008). OS was numerically improved for cabazitaxel vs. abiraterone/enzalutamide when assessed from the time of diagnosis of metastatic disease or mCRPC, or from start of 1st or 2nd LET (Table). In the multivariate analysis, low hemoglobin, high baseline neutrophil to lymphocyte ratio, and high PSA values at baseline were associated with worse OS. In presence of these factors, the OS benefit observed with cabazitaxel versus abiraterone/enzalutamide remained significant (HR 0.63, 95% CI 0.42–0.94, p = 0.022). Conclusions: Cabazitaxel numerically improved OS vs. abiraterone/enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), whatever the time point considered. The robustness of this OS benefit was confirmed by stratified multivariate analysis. Sanofi funded. Clinical trial information: NCT02485691 . [Table: see text]
妇产科几种常见阴道感染的诊断、治疗与预防
Authors: 糜若然, 瞿全新
Journal: BMJ (2006)

阴道感染的定义是由正常存在于阴道的微生物及外界微生物在医疗操作或在性接触中进入阴道而引起的感染,是日常门诊工作中最多见的生殖道感染.[1].其正确诊断和治疗在门诊实际工作中很重要,现就以下几种常见阴道感染进行讨论。
Landmark analysis of immunotherapy duration and disease free survival in advanced melanoma patients with a complete response.
Authors: Grayce N. Selig, Alexander Chan Chi Huang, Giorgos C. Karakousis, Wei Xu, Cathy Zheng, Mary Carberry, Lydia Giles, Kristin Kreider, Suzanne McGettigan, John Nicholas Lukens, Lynn Mara Schuchter, Ravi K. Amaravadi, Tara C. Mitchell
Journal: Journal of Clinical Oncology (2020)

10054 Background: Checkpoint blockade improves survival in patients with melanoma, with durable complete responses (CR) after stopping therapy. Based on data from KEYNOTE-001, immunotherapy is often continued for 24 months in patients with confirmed CR. Outcomes with treatment of less than 24 months hav not been adequately evaluated and reported. If equally efficacious, shorter courses would potentially reduce health care costs and toxicity. Methods: 45 patients with locally advanced stage III and IV melanoma who received immunotherapy (pembrolizumab, nivolumab or ipilimumab/nivolumab) as 1 st line or subsequent therapy, achieved a CR, and stopped therapy were identified under an IRB approved protocol at Penn. Disease Free Survival (DFS) was defined as time from declaration of CR until recurrence or date of analysis (1/15/20). Landmark DFS from time of CR was analyzed based on duration of therapy (less than or greater than 7 months, based on early trial requirements to treat patients with confirmed CR for at least 6 months). Rationale for stopping (toxicity or CR) was also analyzed. Results: Of 45 patients with CR, 27 (60%) were treated less then 7 months (median 4.8, range 1 day to 6.7 months) and 18 (40%) were treated for greater than 7 months (median 12.4, range 7.5 to 24.2 months). Patients who were treated for less than 7 months had a median DFS from time of CR of 30.4 months (95% CI 23.7 to 37.2, range 2.9 to 65.7 months). Patients treated for greater than 7 months had a median DFS of 28.0 months (95% CI 18.9 to 37, range 8.5 to 73.7 months). Patients who stopped due to toxicity (N = 17, 40%) had a median treatment duration of 3.7 months. Their median DFS from time of CR was 30.4 months (95% CI 20.7 to 40.1, range of 2.9 to 65.7 months). Patients who stopped due to CR (N = 28, 60%) had a median treatment duration of 8.5 months. Their median DFS was 27.6 months (95% CI 21.2 to 34 range 7.2 to 73.7 months). Two of 27 (7.4%) patients treated for less then 7 months and 3 out of 18 (16%) patients treated greater than 7 months recurred after stopping. One out of 17 (5.8%) recurred after stopping for toxicity vs. 4/28 (14.3%) who stopped after CR. Conclusions: Patients who stop therapy at less than 7 months have CRs that are equally durable as those treated longer than 7 months, without reduction in landmark DFS. Patients who stopped therapy due to toxicity and then achieved a CR had no difference in DFS compared to patients treated until CR. There was no significant difference in recurrence after achieving a complete response in patients treated for a longer vs shorter treatment course.
Is the incidence of breast cancer increasing? Using the NCDB and autoregressive integrated moving average models (ARIMA) to forecast breast cancer to 2030.
Authors: Leah Elson, Nadeem Bilani, Elizabeth Blessing Elimimian, Rafael Arteta-Bulos, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2020)

e13612 Background: The observed increase in the incidence rate of BC has been described due, in part, to higher, effective public health campaigns for screening, higher sensitivity among diagnostic testing modalities as well as an aging population. While the mortality rate associated with breast cancer has reported to fall by 1.8% every year since 2007, the disease burden itself has continued to grow and increased breast cancer rates will contribute to the strain already experienced within the United States healthcare system infrastructure. Therefore, the authors sought to use a large, national registry to develop a time series model that might help forecast the approximate breast cancer incidence rate, to the year 2030, as captured by the National Cancer Database (NCDB). Methods: In this time series forecast, autoregressive integrated moving average models (ARIMA) were constructed based on 2004-2016 historic breast cancer incidence rates, as reported by the NCDB. Multiple models were generated, using differing autoregressive parameters, and the most predictive model was chosen using the lowest Bayesian Information Criteria (BIC), and mean absolute percentage error (MAPE). Similar methodology has already been published to predict prostate cancer incidence. The best fit model was applied to forecast annual incidence in the NCDB to the year 2030. Statistics were performed using modeling systems in SPSS, version 26. Results: For this model, 12 years of NCDB breast cancer diagnoses were used, which included n = 1,924,425 cases, overall. Using ARIMA modeling, a best fit, stationary average was identified with autoregressive and difference terms of 1 (ARIMA (1,1,0), coefficient = 0.598; P = 0.028). Of the multiple models tested the model with the lowest BIC was chosen, with a MAPE of 4.71%. The best fit model forecasted n = 325,048 new breast cancer diagnoses to be captured annually by the NCDB, by 2030. Conclusions: In this analysis, the annual breast cancer incidence within the NCDB is predicted to increase by 21%, by 2030. This forecast, while slightly lower than previously reported by the National Cancer Institute, utilizes more recent historical data that reflects a period of leveling-off in disease incidence, during 2014-2016, as reported to the NCDB. This innovative model can be utilized to proactively plan public health strategies and allocate appropriate resources focused on reducing the burden of cancer.
Comparison of tumor mutational burden across eight types of human cancer.
Authors: Peng Chen, Cuicui Zhang, Zhaoting Meng, Xing Zhang, Minhui Ge, Huijuan Qin
Journal: Journal of Clinical Oncology (2020)

e15170 Background: Tumor mutational burden (TMB) is an impressive predictive biomarker for immune checkpoint inhibitors therapy, and immunotherapy is one of the most promising methods for cancer treatment. However, the profile of TMB in various types of cancers was still poorly understood. Methods: In this study, genomic profiling of DNA was performed using next generation sequencing from a 539 genes panel in tumor tissues. The TMB was defined as the numbers of SNVs including synonymous and nonsynonymous mutations, and InDels per megabase in coding regions of sequenced genome. TMB-H was defined as highest mutation load quintile (top 20%) in each cancer type. The values of TMB of 874 patients were compared among eight main tumor types including 174 patients with liver cancer, 32 patients with bile duct cancer, 54 patients with gastric cancer, 119 patients with colorectal cancer, 27 patients with pancreatic cancer, 32 patients with melanoma, 25 patients with glioma and 411 patients with lung cancer cases by multiple independent samples nonparametric Kruskal-Wallis H test via SPSS v22.0. Results: The median values of TMB in liver cancer, bile duct cancer, gastric cancer, colorectal cancer, pancreatic cancer, melanoma, glioma and lung cancer were 10.29, 8.09, 11.03, 10.29, 5.88, 7.35, 5.88 and 7.35 Muts/Mb, respectively. The cut-off values of TMB-H in corresponding eight solid tumors were 16.18, 19.12, 19.85, 16.18, 10.29, 13.24, 10.29 and 18.38 Muts/Mb, respectively. Based on nonparametric Kruskal-Wallis H test, there were significant differences of median TMB values across eight independent tumor types (χ 2 = 26.752, p = 3.693×10 −4 ). Significant differences between patients with colorectal cancer and pancreatic cancer ( p = 0.005) or lung cancer ( p = 0.011) were observed via pairwise comparisons. Conclusions: Our study proved the presence of significant differences across eight cancer types, deepened the knowledge of the cancer-specific of TMB, provided useful information in immunology therapy for East Asian patients with solid tumors. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Assessing the relationship in relapsed-refractory multiple myeloma between response, progression, and survival between pooled clinical trial subjects and a real-world electronic medical record data source.
Authors: Mark Layton Watson, Charlie Hurmiz, Jordan Smith, Suresh Marada, Aaron Galaznik, Sheila Diamond, Bryant Fields, Ruthanna Davi
Journal: Journal of Clinical Oncology (2020)

e20525 Background: Despite new treatments, Relapsed-Refractory Multiple Myeloma (RRMM) remains an incurable disease 1 . In a recent study by Moreau et al, there was a demonstrated survival benefit to treatment with pomalidomide in RRMM patients 2 . To better understand how the relationships between initial depth of response and long-term prognosis can inform clinical decision making and guide new compound development, we performed an analysis of standardized clinical trial patient pool data compared with Real-World Data (RWD), across multiple studies. Methods: Pooled clinical trial data was obtained from a Study Data Tabulation Model (SDTM) dataset (n=1,815) from the Medidata Enterprise Data Store. De-identified Oncology EMR data was sourced from the Guardian Research Network™ (GRN)5 of integrated delivery systems from 2010-2018, with robust clinical endpoint extraction and curation to enable outcomes comparisons (n=962). Subject selection was refined based on the inclusion/exclusion criteria from the NIMBUS trial 2 . Response, Progression-free survival (PFS), and Overall Survival (OS) were extracted. Patients were stratified by age, gender, and prior regimens. Log-rank tests were conducted to compare PFS and OS in patient sub-populations at 90, 180, and 240 days from most recent treatment start. Cox proportional hazard models assessed predictors of survival. Rates were estimated for common adverse events, including leukopenia, neutropenia, and thrombocytopenia. Factors associated with neutropenia were assessed using logistic regression. Results: Within pooled trial and RWD patients, the majority were on regimens with proteasome inhibitors, followed by immunomodulators, and approximately one third on monoclonal antibodies. Within the pooled trial analysis, survival rates were consistent with published literature rates, at ~4 months and ~12 months, respectively. EMR data analysis showed overall longer times to progression with an increased depth of response, with similar associations. Frequency-Factored Time-to-Progression also decreased. Conclusions: The use of SDTM for pooled clinical trial analyses, together with real-world data, can overcome individual trial sample size limitations and biases. Together this approach can expand the range of populations, relative treatment comparisons, and clinical events that can be studied to more comprehensively understand the complexity of the oncology treatment landscape.
Clinician perspectives of complementary and integrative medicine (CIM) at an academic cancer center.
Authors: Marium Husain, Sherise C. Rogers, Dori Klemanski, Michelle Fullmer, Catherine Hreachmack, Kathi Kemper, Julie Stephens, Payal Chandarana Desai, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2020)

e24047 Background: Surveys suggest up to 87% of patients with cancer use complementary and integrative (CIM) therapies such as herbal medicine, acupuncture, massage and mind-body practices. These therapies may assist with symptoms of pain, nausea and anxiety. However, several studies have demonstrated that many clinicians do not inquire about CIM use, which may be due to lack of education and/or limited evidence-based data. We sought to explore the perspectives of clinicians at an academic comprehensive cancer center on the use of CIM therapies. Methods: Physicians and advanced practice providers (APPs) who practice medical oncology, hematology, radiation oncology, surgical oncology and neuro-oncology in a Midwest tertiary comprehensive cancer center were asked to participate in a 9-question online survey which inquired about their personal knowledge and recommendation for 21 different CIM therapies (not all are offered at the cancer center). Responses were summarized using descriptive statistics. Results: The response rate for this survey was 24.5% (n = 49). Responders were from the following specialties: hematology (n = 17; 35%); solid tumor (n = 18; 37%); both hematology and solid tumor (n = 8; 16%), surgical oncology (n = 3; 6%); gynecologic oncology (n = 2; 4%) and radiation oncology (n = 1; 2%). Sixty-seven percent were attending physicians and hematology/oncology fellows (n = 33), and 33% were APPs (n = 16). Median age range was 30-39 years (range 20-59). The most recommended CIM therapy for cancer treatment-related effects was massage (80%), followed by deep breathing (55%). The least recommended CIM therapies were traditional Chinese medicine (TCM) and Ayurvedic medicine (2%), followed by vitamins/minerals and homeopathy (both 6%). Participants requested more education on CBD/CBD oil (59%) and herbs/botanicals (49%). Up to 14% of respondents already had education on five integrative therapies. Conclusions: Hematology/oncology clinicians do not routinely recommend most CIM therapies, except for massage therapy. Efforts should be made to educate clinicians regarding CIM therapies used by patients with cancer as well resources that appraise the efficacy, safety, and potential drug interactions of these therapies. Education could encourage informed decision-making and improved patient-clinician communication and satisfaction.