tbuckley/cabot-search huggingface dataset:
Combined Cell-free DNA and RNA Profiling of the Androgen Receptor: Clinical Utility of a Novel Multianalyte Liquid Biopsy Assay for Metastatic Prostate Cancer
Authors: Heidi Fettke, Edmond M. Kwan, Maria M. Docanto, Patricia Bukczynska, Nicole Ng, Lisa-Jane K. Graham, Kate Mahon, Christine Hauser, Winston Tan, Xiao Hong Wang, Zhixin Zhao, Tiantian Zheng, Kemin Zhou, Pan Du, Jianjun Yu, Yong Huang, Shidong Jia, Manish Kohli, Lisa G. Horvath, Arun A. Azad
Journal: European Urology (2020)
Genomic profiling of breast cancer brain metastases reveals targetable alterations.
Authors: Sheheryar Kairas Kabraji, Liam F. Spurr, Melissa E Hughes, Yvonne Y. Li, Jose Pablo Leone, Ana Christina Garrido-Castro, Romualdo Barroso-Sousa, Janet Files, Gregory Kirkner, Bruce E. Johnson, Eric P. Winer, Andrew D. Cherniack, Nancy U. Lin
Journal: Journal of Clinical Oncology (2020)

2525 Background: Genomic characterization of breast cancer brain metastases (BCBMs) has thus far been limited. The objective of this study was to describe the landscape of genomic alterations in patients (pts) with BCBMs. Methods: Targeted next-generation DNA sequencing of &gt; 300 cancer-related genes (OncoPanel) was prospectively performed on primary and metastatic (met) tumors in 321 pts with a diagnosis of BCBM between August 2016 and April 2019 at Dana-Farber Cancer Institute (table). Enrichment analysis of genomic alterations was performed using a two-sided Fisher exact test and differences in tumor mutation burden (TMB) between groups were assessed using two-sided Mann-Whitney U test. Multiple comparison correction was performed using the Benjamini-Hochberg procedure. Results: All subtypes were represented in BCBM (25 HR+/HER2-; 24 HR+/HER2+; 27 HR-/HER2+; 18 TNBC; 5 unknown; n = 99) and extracranial (EC) samples: (96 HR+/HER2-; 32 HR+/HER2+; 22 HR-/HER2+; 41 TNBC; 31 unknown; n = 222). BCBMs were found most commonly to have mutations or copy number alterations in TP53, ERBB2, PIK3CA, GATA3, PTEN, ESR1, CDH1, BRCA2, ARID1A, BRCA1 (&gt;5% frequency, table). Two pts acquired ERBB2 amplification (amp) between the matched primary breast sample and brain met. In pair-wise comparisons of BCBMs to unmatched primaries or EC mets, only ERBB2 amp was significantly enriched (table, † = adjusted p &lt; 0.05). There was no significant difference in TMB between BCBM and EC mets (median 9.12 vs 7.26, p = 0.15). In contrast, TMB was significantly higher in BCBMs compared to unmatched primaries (median 9.12 vs 7.26, p=0.005). Conclusions: BCBMs display similar mutations and copy number alterations compared to primary tumors and EC mets in pts with BCBM. These data suggest that BCBMs contain actionable genomic alterations that are most often also reflected in EC disease. Alterations in ERBB2, PIK3CA/PTEN, and BRCA1/2 represent potentially targetable alterations in pts with BCBM. [Table: see text]
Absorbable biomedical membrane-embedded intrauterine device in prevention of recurrence after hysteroscopic adhesiolysis for severe intrauterine adhesion
Authors: Wenjie Yan, Xiangli Pang, Jie Pi, Yi Zhang, Liu Liu, Yang Mu
Journal: BMJ (2016)

Objective
To assess the effects of absorbable biomedical membrane-embedded intrauterine device (IUD) in prevention of recurrence after hysteroscopic adhesiolysis for severe intrauterine adhesions (IUA).


Methods
A prospective study was carried out among 125 patients who underwent hysteroscopic adhesiolysis for severe IUA from February 2013 to January 2015. Foley catheter was placed immediately after surgery and removed 7 days later. Then patients were randomly divided into three groups: group A (40 cases) received round IUD insertion after catheter removal; froup B (41 cases) received IUD placement and intrauterine injection of sodium hyaluronate; group C (44 cases) received absorbable biomedical membrane-embedded IUD insertion. All patients received two artificial cycles (oral estradiol valerate, 9 mg/d) the first day after surgery. Hysteroscopy was carried out two months later to assess the repair of endometrium. Patients who were cured or whose condition was greatly improved received three-dimensional transvaginal ultrasound examination in the first natural cycle. Thickness of endometrium, uterine volume and blood flow index were compared.


Results
Cure rate and effective rate in group C were significantly higher than that in groups B and A [43%(19/44) vs. 22%(9/41) and 20%(8/40), χ2=6.89, P=0.03, 86%(37/44) vs. 56%(26/41) and 65%(23/40), χ2=9.78, P=0.01]. The improvement rate of menstruation was higher in group C compared with groups B and A [84%(37/44) vs. 63%(26/41)and 58%(23/40), χ2=7.73, P=0.02]. Average endometrium thickness, uterine volume and blood flow index were also significantly improved in Group C[(8.4±1.1) vs.(7.2±1.5) and (7.6±1.1) mm, F=5.42, P=0.01, (4.3±0.3) vs.(3.9±0.4) and (4.0±0.6) cm3, F=7.12, P=0.00, 28.0±4.0 vs. 24.6±4.7 and 23.4±4.0, F=5.40, P=0.01]. No significantly differences were observed between group B and group A in terms of the above indices.


Conclusion
Insertion of absorbable biomedical membrane embedded-IUD has a good therapeutic effect and can better prevent adhesion recurrence in patients with severe intrauterine adhesion after adhesiolysis.


Key words: 
Uterine diseases; Intrauterine adhesions; Intrauterine device; Treatment
肺功能检查的临床应用
Authors: 郑劲平
Journal: BMJ (2011)

肺是人体最重要的器官之一,通过吸人氧气、排出二氧化碳而完成人体的气体代谢.肺功能检查是运用呼吸生理知识和现代检查技术来了解和探索人体呼吸系统的功能状态,在临床上是胸肺疾病诊断、严重度评估、治疗和预后评估的重要检查,被广泛应用于呼吸内科、外科、儿科、麻醉科、流行病学、潜水及航天医学等领域,亦是健康体检的重要内容之一。
The potential target of double negative T cells in cancer immunotherapy.
Authors: Kazumi Okamura, Satoshi Nagayama, Tomohiro Tate, Kazuma Kiyotani, Yusuke Nakamura
Journal: Journal of Clinical Oncology (2020)

e15180 Background: Double negative T cell (DNT) is defined by the expression of CD3 (or TCRαβ) with the absence of CD4, CD8 and iNKT cell markers. DNTs account for 1-3% of the total peripheral lymphocytes. Although healthy donor cells derived allogeneic DNTs were reported to have anti-tumor effects in several cancer models, the function of DNTs in tumor microenvironment is not well understood. In this study, we aim to characterize DNTs in cancer tissues and lymph nodes of colorectal cancer patients including their immunological functions. Methods: A total of 14 colorectal cancer tissues and regional lymph nodes were collected and examined for the proportion and the immunological functions of DNTs by FACS analysis. Results: DNTs, which were defined in this study as TCRαβ positive with CD4-, CD8- and CD56- T cells, were detected in colorectal cancer tissues. DNT cells account for more than 5% of TCRαβ-positive populations in 12 cases and out of which 7 cases were more than 20% observed in this study. In all of these 7 cases, DNT cells were also found to be higher in the tumor tissues than in non-metastatic lymph nodes. In addition to colorectal cancer, DNTs were found to be more than 5% of TCRαβ-positive populations in cancer tissues in 3 out of the 6 cases of ovarian and uterine cancer cases.To further evaluate the potential immunological functions of DNTs, expression of cell membrane protein markers were evaluated. CD3ε expression was down regulated in almost all of the DNTs. The CD107a expression of DNTs were higher than that of CD8 + T cells in tumor tissues. When co-culturing DNTs with tumor cells, CD107a expression of DNTs was significantly upregulated. Notably, the intracellular production of perforin and granzyme B were lower than CD8 + T cells. Fas-L expression were found to be higher on DNT cells compared to other T cell populations, suggesting DNT might possess cytotoxic activity in the tumor microenvironment. It is known that upregulation of Fas expression is caused by T cell activation and subsequently induces T cell apoptosis. The upregulation of Fas expression was also observed in DNT cells from non-metastatic lymph nodes. In contrast, Fas expression of DNT cells in tumor tissues was observed to be lower than CD4 + or CD8 + T cells, suggesting that DNT could escape from apoptosis. This downregulation of Fas expression was speculated to be one of the reasons for the accumulation of DNTs in tumor tissues. Conclusions: Although the function of DNTs was still not well elucidated, the accumulation of DNT cells in tumor microenvironment suggests DNTs could be a potential target for cancer immunotherapy.
Variety of clinical trial enrollment by actionable tumor suppressor genotype.
Authors: Monica Avila, Chetna Wathoo, Jia Zeng, Clark Andersen, Ying Yuan, Timothy A Yap, Jordi Rodon Ahnert, Funda Meric-Bernstam
Journal: Journal of Clinical Oncology (2020)

e15674 Background: In the last decade, genomics has been increasingly used for therapeutic management of cancer. In precision oncology, genes that can be directly or indirectly targeted with therapeutic agents are considered “actionable”. However, not all alterations affect gene function and alterations in tumor suppressor genes are especially challenging to interpret. The objective of this study was to determine frequency of trial enrollment in patients with “actionable” tumor suppressor alterations and determine whether this varied by genotype and tumor type. Methods: A single-institution retrospective review was performed on patients with metastatic, advanced, or recurrent solid tumors perceived to likely benefit from genomic profiling. Between 1/2015 and 1/2020, the top 5 tumor suppressor alterations CDKN2A, BRCA1/2, PTEN, ATM and NF1 were considered most common “actionable” tumor suppressor genes among patients reviewed by MD Anderson Precision Oncology Decision Support system. Once literature-based or inferred actionability of the tumor-suppressor alteration was determined, a clinical record review was performed to assess an institution-specific annotation detailing trial availability. This annotation matches somatic genomic alteration based on therapeutic significance and availability of matched investigative therapy based on available literature at the time. From here, patient demographics and trial enrollment was extracted from the electronic medical record. Results: 424 patients were categorized as having actionable alterations that had a trial available for enrollment based on genomic characteristics. Of these, 61 patients (14%) enrolled in a matched trial. Primary reasons for non-enrollment for a specific alteration were: enrollment in non-targeted therapeutic trial (39%), treatment with another stand of care therapy (32%), or enrollment in another genomically matched trial targeting another genomic alteration (14%). There was variability in enrollment by disease type approaching statistical significance (p = 0.073). CDKN2A alterations were the most common while BRCA1/2 had the highest rate of matched enrollment (39.5%). Conclusions: In this cohort of patients, the presence of an actionable tumor-suppressor alteration was associated with trial enrollment varying by genotype. Further work is needed to determine the impact of decision support on trial enrollment as well as strategies to increase actionability by building genomically-driven combination therapy trials.
RESILIENT part II: an open-label, randomized, phase III study of liposomal irinotecan injection in patients with small-cell lung cancer who have progressed with platinum-based first-line therapy.
Authors: Luis G. Paz-Ares, David R. Spigel, Yuanbin Chen, Maria Jove, Oscar Juan-Vidal, Patricia Rich, Theresa M. Hayes, M Vanesa Gutierrez Calderon, Reyes Bernabe Caro, Alejandro Navarro, Afshin Dowlati, Bin Zhang, Yan Moore, Haofei Tiffany Wang, Jaba Kokhreidze, Santiago Ponce Aix, Paul Bunn
Journal: Journal of Clinical Oncology (2020)

TPS9081 Background: Although small cell lung cancer (SCLC) is often sensitive to established first-line therapies, many patients relapse and develop drug resistance, and second-line therapies are limited. RESILIENT (NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability, and efficacy of liposomal irinotecan monotherapy in patients with SCLC who progressed with platinum-based first-line therapy. Preliminary data from the dose-ranging part of the study (part 1) showed that liposomal irinotecan 70 mg/m 2 administered every 2 weeks was well tolerated and had promising antitumor activity (Paz-Ares et al. ASCO 2019; poster 318). Here, we present the design of the second, larger part of the study, which will evaluate the efficacy and safety of liposomal irinotecan versus topotecan in the same patient population. Methods: Part 2 of RESILIENT is a phase 3, open-label study with a planned sample size of 450. Patients are randomly allocated 1:1 to intravenous liposomal irinotecan or intravenous topotecan. Liposomal irinotecan is administered every 2 weeks at 70 mg/m 2 (free-base equivalent) and topotecan is administered for 5 consecutive days every 3 weeks at 1.5 mg/m 2 . As of January 2020, 80 patients have been enrolled in part 2 of the trial. Tumor assessments are performed using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Response Assessment in Neuro-oncology criteria for CNS lesions; symptom improvement is measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Safety assessments include monitoring for adverse events. The primary endpoint is overall survival (OS) and secondary endpoints are progression-free survival (PFS), objective response rate, and proportion of patients reporting symptom improvement. Patients will continue study treatment until disease progression, unacceptable toxicity or study withdrawal and will then be followed for survival until death or study end (when all patients have died, withdrawn consent or are lost to follow-up). Clinical trial information: NCT03088813.
Spontaneous negative conversion of anti-GBM antibody in a case of acute kidney injury
Authors: Chenhao Li, Chao Zhang, Yan Cui, Ying Zhao
Journal: BMJ (2019)

报道1例以急性肾损伤伴抗GBM抗体阳性为主要表现的病例，经肾活检示IgA肾病（Lee分级：Ⅰ~Ⅱ级），未使用免疫抑制治疗的情况下，抗GBM抗体自动转阴，且肾功能及尿量恢复正常，分析了相关原因。为提高临床医生对此类疾病诊断思路、相关机制的认识提供参考。
Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up
Authors: Jerome Paillassa, Edouard Cornet, Stephanie Noel, Cecile Tomowiak, Stephane Lepretre, Sandrine Vaudaux, Jehan Dupuis, Alain Devidas, Bertrand Joly, Charlotte Petitdidier-Lionnet, Stephanie Haiat, Clara Mariette, Catherine Thieblemont, Didier Decaudin, Patricia Validire-Charpy, Bernard Drenou, Jean-Claude Eisenmann, Mario Ojeda Uribe, Agnès Olivrie, Mohamed Touati, Olivier Lambotte, Olivier Hermine, Jean-Michel Karsenti, Pierre Feugier, Willy Vaillant, Jean Gutnecht, Eric Lippert, Fabienne Huysman, Kamel Ghomari, Marouane Boubaya, Vincent Levy, Jeremie Riou, Gandhi Damaj, Aline Tanguy-Schmidt, Mathilde Hunault-Berger, Xavier Troussard
Journal: Blood Cancer Journal (2020)

In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.
Uptake of first-line immune checkpoint inhibitors among medically frail patients with advanced solid malignancies.
Authors: Ravi Bharat Parikh, Roger B. Cohen, Eun Jeong Min, E. Paul Wileyto, Fauzia Riaz, Cary Philip Gross, Qi Long, Ronac Mamtani
Journal: Journal of Clinical Oncology (2020)

e19316 Background: There are concerns about use of immune checkpoint inhibitor (ICI) therapy in medically frail patients, for whom ICIs do not have a proven survival or quality-of-life benefit. We compared uptake of first-line ICI treatment in routine practice between frail and non-frail patients with advanced solid malignancies. Methods: This retrospective cohort study used data from the Flatiron Health electronic health record-derived database. We included patients who started first-line systemic therapy from 2014 through 2018 for stage IV non-small cell lung cancer (NSCLC) without a targetable mutation, urothelial cell carcinoma (UCC), renal cell carcinoma (RCC), or hepatocellular carcinoma (HCC). We identified medically frail patients using literature-based criteria: Eastern Cooperative Oncology Group performance status (ECOG) ≥ 2, Elixhauser comorbidity index ≥ 3, or grade ≥3 liver or renal dysfunction as defined by NCI CTCAE v5. We used multivariable logistic regressions to examine associations between frailty and the probability of first-line use of an ICI-containing regimen (monotherapy or combination therapy), adjusted for age, insurance type, academic vs. community practice setting, type of cancer, and year of treatment. Results: Of 23,972 patients in the cohort, 17,122 (71.4%) were white, 10,237 (42.7%) were female, 9,666 (40.3%) were commercially-insured, and 13,144 (54.8%) met criteria for frailty. ICI use steadily increased over time in frail patients: among frail patients diagnosed in the last quarter of 2018, ICI-containing regimens represented 55% of first-line therapy starts in NSCLC; 35% in UCC; 55% in RCC; and 23% in HCC. Frail patients had a slightly higher likelihood of ICI use compared to non-frail patients (adjusted odds ratio [aOR] 1.12, 95% CI 1.04-1.20, p=0.002). This was primarily driven by greater use in patients with high comorbidity (aOR 1.15, 95% CI 1.08-1.23, p&lt;0.001) (Table). Associations were consistent when examining first-line ICI monotherapy use only. Conclusions: First-line ICI use is common and increasing among frail patients with advanced solid malignancies. Prospective evidence is needed to assess the benefit (or lack thereof) of ICI use in medically frail patients. [Table: see text]
Screening for COVID-19 in Asymptomatic Patients With Cancer in a Hospital in the United Arab Emirates
Authors: Humaid O. Al-Shamsi, Eric A. Coomes, Sadir Alrawi
Journal: JAMA Oncology (2020)

This case series examines the results of implementing a universal microbiologic screening strategy for asymptomatic patients with cancer for coronavirus disease 2019 at 1 institution in the United Arab Emirates.
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma.
Authors: Yanal Mufeed Alnimer, Ayman Qasrawi, Khalil Katato
Journal: Journal of Clinical Oncology (2020)

e17080 Background: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (MRCC) is unclear. Two randomized clinical trials (RCT) in the cytokine era demonstrated a survival benefit of CN in MRCC. However, the efficacy of this approach is unknown after the introduction of tyrosine kinase inhibitor (TKI) therapy and immunotherapy (IC) in the frontline setting of MRCC. Methods: We studied the the impact of CN in MRCC on overall survival (OS) using the Surveillance, Epidemiology, and End Results (SEER)-18 registries. The R software was used for statistical analysis. Results: A total of 5488 patients with MRCC between 2010-2016 were identified. The median age was 62 years, 70% were males and 55% underwent partial or total nephrectomy. After a median follow-up time of 36 months, median OS was 12 months. Histology was clear cell (CC) in 79% the cases and 21% were non-clear cell (NCC). On univariate Cox regression, patients with CC histology who underwent CN had a 0.35 [95% confidence interval (CI), 0.33-0.38] lower risk of death compared to those who did not. After adjustment for age, gender, number of sites involved by metastasis (bone, liver, lung and/or brain), grade and administration of chemotherapy, patients who got CN had a 0.33 (CI, 0.29-0.36) lower risk of death compared to those who did not. The following factors were associated with higher risk of death in multivariable Cox proportional hazard ratio (HR) model: number of metastatic sites, HR = 1.50 (CI, 1.43-1.58); grade III vs. II, HR = 1.39 (CI, 1.22-1.59); grade IV vs. II, HR = 2.08 (CI, 1.80-2.39); female gender, HR = 1.16 (CI, 1.07-1.26), those who didn’t receive chemotherapy (or unknown status) with a HR of 1.39 (CI, 1.28-1.50) and increasing age with a hazard ratio of 1.009 (CI 1.005-1.013) for each year increase. With NCC, the following factors were associated with higher mortality: number of metastatic sites, HR = 1.34(CI, 1.24-1.46), older age, HR = 1.01(CI, 1.003-1.014) for each year increase, grade III vs. II,HR = 1.97(CI,1.41-2.77);IV vs. II,HR = 1.98 (CI, 1.41-2.77); and those who didn’t receive chemotherapy with HR = 1.52 (CI, 1.32-1.74). On the other hand, those who had CN had lower mortality, HR = 0.46 (CI, 0.38-0.55). Conclusions: In this large cohort, there was a survival benefit of CN in MRCC. However, our study is limited by the lack of treatment details and possible selection bias for the patients who got CN. TARIBO is an ongoing RCT that aims to identify the benefit from CN in MRCC in the TKI and IC era. Until the trial is concluded, CN should be considered for eligible patients with MRCC, regardless of histology.