tbuckley/cabot-search huggingface dataset:
Olaparib treatment in patients (pts) with platinum-sensitive relapsed (PSR) ovarian cancer (OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: Phase II LIGHT study.
Authors: Karen Anne Cadoo, Fiona Simpkins, Cara Amanda Mathews, Nashwa Kabil, James Bennett, Carol Aghajanian
Journal: Journal of Clinical Oncology (2020)

6013 Background: In Study 19 (NCT00753545), olaparib capsules demonstrated improvement in progression-free survival (PFS) vs placebo in the PSR OC maintenance setting, irrespective of BRCAm status (Ledermann et al. Lancet Oncol 2014). LIGHT is the first prospective study to evaluate olaparib tablet treatment in PSR OC pts by BRCAm and HRD status. Methods: This is an open-label, non-randomized study (NCT02983799) that assessed efficacy and safety of olaparib monotherapy (300 mg BID) in pts with PSR, high-grade serous/endometrioid epithelial OC and ≥1 prior line of platinum chemotherapy. Pts were assigned to one of four cohorts: germline (g) BRCAm; somatic (s) BRCAm; HRD+ve (non-BRCAm); HRD–ve; by Myriad BRACAnalysis CDx and myChoice tests. HRD+ve was a score ≥42. Primary endpoint was objective response rate (ORR). Secondary endpoints included: disease control rate (DCR) and investigator-assessed PFS (RECIST v1.1). Primary analysis was to be ~6 months (mo) after the last pt was enrolled. Results: Data cut off was 8/27/19. Of 271 pts treated (median of 31.7 weeks [2.1–96.0]), 270 had measurable disease at baseline and were included in efficacy analyses (Table). The most common treatment-emergent adverse events (AEs) were nausea (66%) and fatigue (62%).Serious AEs and Grade ≥3 AEs were experienced by 25% and 44% of pts, respectively. AEs leading to olaparib dose interruptions, reductions and discontinuations occurred in 33%, 24% and 4% of pts, respectively. Conclusions: Olaparib treatment demonstrated activity across all cohorts. As observed in the maintenance setting, similar efficacy was seen in the gBRCAm and sBRCAm cohorts. For non-BRCAm pts, longer median PFS and higher ORR were observed in the HRD+ve cohort. Olaparib treatment was well tolerated with no new safety signals identified and a safety profile consistent with that seen in the PSR and first-line settings. Clinical trial information: NCT02983799. [Table: see text]
弥漫性泛细支气管炎12例临床分析
Authors: 曹兆华
Journal: BMJ (2010)

近十年来,弥漫性泛细支气管炎(diffuse panbronchiolitis,DPB)被国际公认为是一种以两肺弥漫性细支气管慢性炎症为特征、引起严重呼吸功能障碍的疾病.因临床医生对其认识不足,常误诊为慢性支气管炎、支气管扩张、哮喘、肺气肿等呼吸系统疾病.现回顾性分析本院2003年2月至2009年4月收治的DPB患者资料。
Evaluating progression-free survival in black and white women with triple-negative breast cancer in pooled clinical trials from a synthetic control database (SCD) and real-world electronic medical records (EMR).
Authors: Mark Layton Watson, Kevin Holcomb, Lisa Newman, Janna Andrews, Lisa Ensign, Aaron Galaznik, Bryant Fields, Sheila Diamond, Nicole Pollard
Journal: Journal of Clinical Oncology (2020)

e13102 Background: Previous studies have shown a lower survival rate in Black women with breast cancer compared with other ethnic groups, largely explained by the increased incidence of triple negative breast cancer (TNBC). In this study we further explore relative survival by race within a TNBC population. By using pooled clinical trial data, we seek to control for variation in patient assessment on outcomes. We further use a real-world electronic medical records (EMR) data source to compare the representativeness of pooled trial findings to patients receiving care not on trial. Methods: Phase II and III open-label breast cancer studies having completed their primary analysis were selected from the Medidata Enterprise Data Store (MEDS), comprised of over 19,000 historical clinical trials, for de-identified aggregate analyses. The Synthetic Control Database (SCD) for this study contains 749 patients with TNBC enrolled in second line and higher treatment trials between 2010 and 2017. De-identified Oncology EMR data was sourced from the Guardian Research Network (GRN) of integrated delivery systems from 2010 to 2018, and contained 1877 patients. Baseline characteristics were assessed between pooled trial and real-world data cohorts. Patients were stratified by race. Progression-free survival (PFS) was assessed using a Kaplan-Meier analysis. We conducted further analysis to assess the impact of additional factors that may influence the aggressive progression of TNBC response in Black women and TNBC disparity. Factors included, but were not limited to: age, stage at diagnosis, baseline benign neutropenia, Body Mass Index (BMI) and genetic factors (BRCA). Results: The TNBC SCD population was 73.0% White, 6.8% Black, and 20.2% Non-White Non-Black (NWNB). The real-world distribution, by contrast was 79%, 10%, and 11%, respectively, with patients predominantly stage 2 at diagnosis. Median BMI at diagnosis was 28.6, 32.6 and 27.1. Unadjusted progression-free survival (PFS) was directionally lower in Black patients in a Kaplan-Meier assessment with a Median PFS of 105 days vs 144 days for all others. Conclusions: A representative pool of cross trial TNBC patients demonstrated lower PFS in Black patients compared to their non-Black counterparts. Based on these findings, further investigation to explore potential biological and treatment factors associated with racial disparity in TNBC is warranted.
The validity and predictive value of blood-based biomarkers in prediction of response in the treatment of non-small cell lung cancer: A systematic review.
Authors: Maarten J. IJzerman, Freek Anne van Delft, Hendrik Koffijberg, Valesca P. Retel, Michel van den Heuvel
Journal: Journal of Clinical Oncology (2020)

e15053 Background: With the introduction of targeted therapies and immunotherapy, molecular diagnostics gained a more profound role in the management of non-small cell lung cancer (NSCLC). Currently, tissue biopsies (TB) are used as primary source for molecular testing and generally require an invasive procedure. The introduction of liquid biopsies (LB) not only decreases patient burden, but it also allows for more frequent testing. Which might be of value in the monitoring of treatment response. This study aimed to systematically search for studies reporting on the use of LB, the correlation between LB and TB, and finally the predictive value in the management of NSCLC. Methods: A systematic literature search was performed using Scopus and PubMed, including results published in English after 01-01-2014. Articles were included when 1) describing the predictive value of a LB with regard to overall and/or progression-free survival, or 2) describing the validity of a marker by comparing LBs to TBs regarding sensitivity, specificity, or concordance. Results: 1705 articles were identified in the search, 1323 articles were excluded after title and abstract screening, leaving 382 articles for full-text evaluation. Of the 137 articles included after full-text evaluation, 78 articles described the validity, and 65 articles described the predictive value of LBs. In studies describing the predictive value of LBs, the majority of articles reported on the predictive value of biomarkers in relation to targeted therapies (n = 31). In studies describing the validity of LBs, the majority of studies report on EGFR mutations including, exon 19 deletion (n = 23) and L858R (n = 26). Looking at the validity of LBs, we saw a large variation in reported sensitivity (range 20-100%), specificity (range 30-100%), and concordance (range 40-99%). Conclusions: Although a variety of blood-based biomarkers has been investigated, most studies have limited their evaluation to sensitivity and specificity of liquid biopsies to determine EGFR mutation status compared to tissue and the subsequent targeting of EGFR tyrosine kinase inhibitors based on the mutation status found in LBs of NSCLC patients. The first adoption of LBs in practice is expected to involve the detection of EGFR mutations by LB analysis in addition to TBs.
A multicenter phase II trial of the combination cisplatin/ docetaxel/durvalumab/tremelimumab as single-cycle induction treatment in locally advanced HNSCC (CheckRad-CD8 trial).
Authors: Markus Hecht, Antoniu-Oreste Gostian, Markus Eckstein, Sandra Rutzner, Jens von der Grün, Thomas Illmer, Matthias G. Hautmann, Thomas Brunner, Simon Laban, Gunther Klautke, Balint Tamaskovics, Axel Hinke, Benjamin Frey, Sabine Semrau, Arndt Hartmann, Claus Roedel, Wilfried Budach, Udo S Gaipl, Heinrich Iro, Rainer Fietkau
Journal: Journal of Clinical Oncology (2020)

6519 Background: PD-1/PD-L1 inhibitors are efficient in head and neck squamous cell cancer (HNSCC). Combination with anti-CTLA4 agents may enhance anti-tumor activity compared to anti-PD-1/PD-L1 monotherapy in different tumor types. In the CheckRad-CD8 trial the typical induction treatment consisting of Cisplatin/Docetaxel was combined with Durvalumab/Tremelimumab. Patients with pathological complete response (pCR) in the re-biopsy after induction treatment or at least 20% increase of intratumoral CD8 density in the re-biopsy compared to baseline entered radioimmunotherapy with concomitant Durvalumab/Tremelimumab. Methods: In this prospective multicenter phase II trial, patients with HNSCC stage III-IVB received a single cycle of Cisplatin 30mg/m² d1-3, Docetaxel 75mg/m² d1, Durvalumab 1500mg fix dose d5 and Tremelimumab 75mg fix dose d5. Objectives of this interim analysis were to quantify the effect of the induction treatment on intratumoral CD8 density and the pCR rate and to generate safety data. Results: Between Sep 2018 and Dec 2019, 57 patients were enrolled. Median age was 59 years, 22 patients (37%) were current smokers, 27 patients (47%) had oropharyngeal tumors (52% p16 positive). The median pre-treatment intratumoral CD8 density was 335 CD8+ cells/mm². After induction treatment 27 patients (47%) had a pCR in the re-biopsy and further 25 patients (44%) had a relevant increase of intratumoral CD8+ cells (median increase by factor 3.0). Response according to RECIST criteria was CR in 1 (2%), PR in 19 (33%) and SD in 20 patients (35%) (17 patients not evaluable). Adverse events (AE) grade 3-4 appeared in 39 patients (68%) and mainly consisted of leucopenia (43%) and infections (28%). 6 patients (11%) developed grade 3-4 immune-related AEs. In multivariable analysis the intratumoral CD8 density was the only independently significant predictor of pCR (odds ratio 1.0013 per cell/mm², 95%-CI 1.00023-1.0023, p=0.017). 42 patients (74%) continued with Durvalumab/ Tremelimumab concomitant to radiotherapy. Conclusions: Single cycle induction treatment with Cisplatin/Docetaxel/Durvalumab/Tremelimumab is feasible and achieves a high pCR rate. CD8 density may have a predictive role for further treatment planning in locally advanced HNSCC. Clinical trial information: NCT03426657 .
ISS stage and network risk score to predict benefits of multiple myeloma treatment options.
Authors: Yu Liu, Li Wang, Haocheng Yu, Samir S. Parekh, Eric Schadt, Jun Zhu
Journal: Journal of Clinical Oncology (2020)

e20511 Background: Multiple myeloma (MM) is molecularly heterogeneous with many treatment regimens developed targeting different aspects of the disease. Multi-omics studies are now widely available, facilitating a precision medicine approach for personalized MM treatments. However, data from these studies vary with respect to treatment regimens, patient age, disease stage, and genomic alterations, thus complicating identification of treatment effects. Methods: From a Multiple Myeloma Molecular Causal Network (M3CN) model we previously described, we identified a prognostic subnetwork (prognNET) associated with survivals of newly diagnosed MM (NDMM) patients. We derived a network risk score (NRS) for each patient by inferring their molecular state with respect to prognNET, and partitioned patients into NRS low, medium, and high groups (referred as NRS L/M/H ). We validated NRS L/M/H to be significantly associated with progression free survival (PFS) and overall survival (OS) in single variate and multi-variate Cox regression models including age and ISS stage in TT2,3,4 and HOVON studies. Results: To determine the impact of NRS in an independent contemporary dataset, we examined NDMM patients with RNAseq data in the MMRF-CoMMpass study. Among young patients (age &lt; 65), ones with combined therapies (CoTs) as the first line therapy (n = 363) had better survival than ones on proteasome inhibitors (PIs) (n = 93) (p = 0.027 and 0.002 for PFS and OS). When stratified by ISS stage and NRS, there was no significant difference between CoTs and PIs except that in the stage I-NRS L group, patients on PIs had better PFS than ones on CoTs (p = 0.016). This suggests that NRS may be able to discriminate ISS stage I patients that do not need CoT. Similarly, we studied the ability of NRS to discriminate patients that benefit from autologous stem cell transplant (ASCT). In a model combining age, ISS stage, NSR, and induction treatment, ASCT was associated with better survival. When stratified young patients on CoTs by ISS stage and NRS, only the stage II-NRS M and stage III-NRS M patients benefited from ASCT in term of PFS (p = 0.01 and 0.005) and OS (p = 0.004 and 0.04). Conclusions: Stage and NRS group should be considered in personalizing treatment options for NDMM patients.
临床与护理路径在急性阑尾炎患者的应用
Authors: 项蕾蕾, 孙媛, 葛恒发
Journal: BMJ (2011)

本研究结合急性阑尾炎手术患者资料,总结多中心临床路径构建和应用与护理路径相互作用及影响的效果. 一、对象与方法 1.对象来源:将2010年1月至6月688例急性阑尾炎手术患者资料用信封法随机分为两组,试验组354例(中途退出24例),男210例,女144例,平均年龄(37±6)岁;发病到入院时间(7.6±1.1)h,手术距发病时间(8.2±0.5)h。
A phase II study of ERK inhibition by ulixertinib (BVD-523) in metastatic uveal melanoma.
Authors: Elizabeth Iannotti Buchbinder, Justine Vanessa Cohen, Rizwan Haq, F. Stephen Hodi, Donald P. Lawrence, Anita Giobbie-Hurder, Deb Knoerzer, Ryan J. Sullivan
Journal: Journal of Clinical Oncology (2020)

10036 Background: Uveal melanoma is a rare and aggressive subset of melanoma that is minimally responsive to traditional therapies. Greater than 80% of uveal melanomas have a mutation in GNAQ or GNA11 which lead to downstream signaling through the MAPK pathway. This has led to efforts to treat uveal melanoma with MEK inhibition with mixed results. Ulixertinib (BVD-523) is a potent and reversible small molecule ATP-competitive inhibitor of both ERK1 and ERK2 protein kinases which has undergone phase I testing. Methods: We performed a phase II study to determine the efficacy and safety of BVD-523 in patients with metastatic uveal melanoma. This was conducted as a Simon two-stage design with a total sample size of 25 patients (pts) and an initial evaluation of efficacy after 13 pts. Two responses were required to continue to the second stage. Results: From April 2018 to April 2019 thirteen pts were enrolled. Pts were predominantly female (69%) with a median age of 64 yrs. (34 -76). Sites of metastasis included liver (84.6%) and lung (30.8%). Grade 3 and 4 toxicities associated with therapy were consistent with BVD-523 and other ERK inhibitors and included LFT elevation, hyponatremia, pruritis, amylase elevation, anemia and rash. The best response, per RECIST 1.1, was stable disease (SD) in 4 pts, and disease progression (PD) in 7 patients. Two patients were unevaluable for response due to withdrawing themselves from the study. Median time to progression was 2.0 months (90% CI: 1.8 – 3.6 mos.). There were eight deaths due to disease progression with a median survival time of 6.9 months (90%CI: 3.2 to 8.3 mos.). Analysis of correlative data from pre- and on-treatment biopsies exploring the change in expression of key signaling proteins relating to treatment is underway. Conclusions: ERK inhibition with ulixertinib (BVD-523) did not demonstrate activity in patients with metastatic uveal melanoma. The toxicities observed on study were consistent with what would be expected with MAPK pathway inhibition. Clinical trial information: NCT03417739.
慢性疲劳综合征的中医治疗
Authors: 张孟仁
Journal: BMJ (2012)

慢性疲劳综合征以长期持续疲劳为突出表现,可伴有低热、头痛、咽喉痛、肌肉关节痛、注意力不集中、记忆力下降、睡眠障碍和抑郁等非特异性表现,一般体格检查和常规检查无明显异常[1-2].慢性疲劳综合征的病因及发病机制未完全阐明,可能与感染、免疫异常、内分泌代谢紊乱、精神神经障碍有关.因其会严重影响患者的工作效率和生存质量,日益受到医学界高度关注。
Changing paradigm in oncology clinical trials: Cox-TEL—Adjustment made ready for early crossover and tail tale.
Authors: Emily Pei-Ying Lin, Chih-Yuan Hsu, Pan-Chyr Yang, Yu Shyr
Journal: Journal of Clinical Oncology (2020)

e15067 Background: Approvals of immune checkpoint inhibitors (ICI) were made based on positive clinical trial results analyzed by the Cox proportional hazards (PH) model. With ICI data, however, long tails and early crossover in survival curves, which violate the Cox PH assumption, can lead to misinterpretation of clinical significance of findings. Here we introduce the Cox-TEL and show the differences of study results before and after Cox-TEL adjustment using KEYNOTE 042 and 045 as examples. Methods: Cox-TEL is built on the mathematical foundation of Taylor expansion. As an easily implemented alternative of PH cure model, it not only infers associations between survival probabilities of the two study arms among patients without long-term survival (poor-responders), but also estimates differences in proportion (DP) between arms among patients in the long-tail segment of the survival curve (true-responders). Results: In KEYNOTE 042, the Cox-TEL HRs for death were statistically insignificant across all subgroups. The trend of DP, on the other hand, is positively related to that of PD-L1 TPS and inverted related to that of Cox HR when the PD-L1 ≥50% cohort is covered. In KEYNOTE 045, the Cox-TEL HRs suggested that for the poor-responders, pembrolizumab did not do better than chemotherapy in terms of overall survival (OS) and might do harm to the patients in terms of progression-free survival (PFS). For the true-responders, DPs of OS and PFS were both statistically significant (Table). Conclusions: Our data demonstrated the biases derived from insufficient data analyses and strengthened the necessity of analytic model revisits in the new oncology era of which cure for advanced cancers is no longer impossible. [Table: see text]
Optimizing management of the oncological patient with pulmonary embolism: Validation of the epiphany index—PERSEO study.
Authors: Manuel Sánchez Cánovas, Mónica Cejuela Solís, Irma De la Haba Vacas, David Gómez, Diego Casado Elía, Ana Fernandez Montes, Roberto Morales Giménez, Mercedes Biosca, David Fernández Garay, Virginia Arrazubi, Silvia Sequero, Cristina Sánchez Cendra, Remedios Otero Candelera, Marina Justo de la Peña, Diana Moreno, Eva Martinez De Castro, Laura Ortega, Andres J. Muñoz Martín, Paula Jiménez-Fonseca, Alberto Carmona Bayonas
Journal: Journal of Clinical Oncology (2020)

12085 Background: EPIPHANY is the first algorithm to predict serious complications in both suspected and unsuspected cancer-associated pulmonary embolism (PE), overcoming limitations of previous models. Methods: PERSEO is a prospective multicenter study. We recruited cancer patients with both incidental and symptomatic PE treated between Oct. 2017 and Dec. 2019. The primary aim was to determine the percentage of serious complications in patients at low predicted risk, with at least 3% accuracy. We also compared the predictive parameters of EPIPHANY with other available scores for prediction 15-day serious complications and 30-day mortality. Results: Cohort includes 831 patients (men, 58.6%; median age, 66 years). Most frequent tumors were lung (27.1%), colorectal (19%) and breast (7.8%). 78.6% had stage IV disease, and 77.6% were receiving antineoplastic treatment. EPIPHANY classified 27%, 24% and 49% of patients as low, medium and high risk, respectively. The rate of 15-day serious complications increased significantly across these prognostic categories: 2.67 (95% CI 0.6 - 4.8), 8.9% (95% CI 0.5 - 12.8), and 25.9% (95% CI 21.7 - 30.2), for low, intermediate, and high risk patients, respectively (p&lt;0.001, linear-by-linear test). In comparison with other validated scores, EPIPHANY has a higher negative predictive value, lower negative likelihood-ratio, and comparable sensitivity (Table). Conclusions: The EPIPHANY index is able to identify a subgroup of patients with cancer-associated pulmonary embolism at very low risk of serious complications or short-term mortality, with potential implications for decision making. [Table: see text]
Lenalidomide use in multiple myeloma.
Authors: Denise Meade, Marie Ng, S Alford
Journal: Journal of Clinical Oncology (2020)

e14045 Background: For patients with multiple myeloma (MM), lenalidomide’s (LEN) received its first FDA approval for use in combination with dexamethasone (DEX) for second-line treatment in 2006, and was expanded to first-line treatment in 2015 for patients not eligible for autologous stem cell transplant, and was further expanded for use as monotherapy for maintenance treatment following a transplant in 2017. We aimed to characterize the treatment patterns of LEN and analyze the impact of the expanded approval on the MM treatment. Methods: A MM disease model was built in IBM Access and Value Connect to interrogate patient demographics, payer types, clinical characteristics, clinical outcomes, utilization, costs, and treatment sequencing, informed by United States Food and Drug Administration (FDA) labels for approvals, professional society guidelines, clinical and economic literature review, and subject matter expertise. Patients were selected from IBM Marketscan Commercial and Medicare Claims database and have an approved MM treatment, at least one diagnosis claim for MM within 30 days of treatment, and a minimum of treatment period of 90 days, but do not have claims for other cancers or pregnancy during the study period. Using advanced visual analytics, we identified trends and outcomes in the treatment and performance of MM patients with LEN to evaluate the impact of LEN’s expanded approval. Results: From October 2017 to September 2018, a total of 1,422 MM patients in the database received treatment with LEN, representing 61% of all MM patients for the same period. Of the patients receiving LEN, 38% of patients were being treated with LEN on monotherapy. In comparison, for the same time period only 1% of patients were on LEN-DEX. Patients receiving LEN as a monotherapy had mean monthly all-cause costs of $15,590 vs $32,352 for the same costs for patients receiving LEN as a combination therapy. Conclusions: The expanded indication of LEN in 2017 has likely increased the population of MM patients receiving LEN as a monotherapy. Further analyses to determine whether clinical outcomes have improved for patients on LEN maintenance therapy should be completed given the increased financial costs of combination therapy.