tbuckley/cabot-search huggingface dataset:
Overall survival modeling and association with serum biomarkers in durvalumab-treated patients with head and neck cancer.
Authors: Vadryn Pierre, Xiang Guo, Ignacio Gonzalez-Garcia, Nassim Morsli, Alejandro Javier Yovine, Weimin Li, Rajesh Narwal, Lorin Roskos, Paul Baverel
Journal: Journal of Clinical Oncology (2020)

6549 Background: Optimal patient selection for immunotherapy remains a challenge as most patients fail to respond. We aim to assess baseline factors for association with long-term survival from durvalumab treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) 1,2 . Methods: Pooled longitudinal tumor size, survival, and dropout data from four trials (1108: NCT01693562, CONDOR: NCT02319044 , HAWK: NCT02207530, and EAGLE: NCT02369874) involving 467 HNSCC patients were used to develop tumor size-driven hazard models. A panel of 66 serum protein biomarkers at baseline and 4 relevant clinical markers from 346 out of 413 patients treated with durvalumab (all studies except 1108) were initially screened to select a pool of 21 candidate covariates. The criteria for dimensionality reduction comprised correlation strength between biomarkers and pharmacological hypotheses pertaining to a prior analysis 3 (inflammation, immunomodulation, tumor burden and angiogenesis). Results: The final tumor model highlighted that high tumor burden, elevated LDH and neutrophil-lymphocyte ratio were associated with faster tumor growth while patients with lower baseline tumor burden had an increase in net tumor shrinkage. For overall survival, the model suggested that high levels of immunomodulators (IL23, Osteocalcin), low inflammation (IL6, NLR), low tumor burden, and low angiogenesis factors (von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1)) were associated with survival benefits for patients treated with durvalumab. Specifically, these patients had baseline serum IL23 &gt; 2.1 pg/mL and Osteocalcin &gt; 32 pg/mL or serum PAI-1 &lt; 229 pg/mL and serum IL6 &lt; 5.4 pg/mL which corresponded to a hazard ratio estimate (HR and 95%CI) of 0.36 (0.27- 0.47), logrank p-value: 2.3x10 −14 . The median (n, 95%CI) overall survival time for the patients with favorable biomarker profile was 14.6 months (n = 129, 11.2-21.4) vs. 4.4 months (n = 217, 3.6-5.3). Conclusions: Our results corroborate the prior hypothesis highlighting the prognostic value of inflammation, disease burden, tumor angiogenesis, and immunomodulatory factors on the clinical outcomes of HNSCC patients treated with durvalumab 3 . Collectively, we identified a serum biomarker profile of HNSCC patients with median survival times exceeding 1 year which may potentially be used for patient enrichment following further validation in prospective studies. References: 1 Yanan CPT 2017, 2 Baverel, 2018 ENA, 3 Guo, X, 2019 Asco P6048 Clinical trial information: NCT01693562, NCT02319044, NCT02207530, NCT02369874 .
原发性鼻结核一例并文献复习
Authors: 黄绍萍, 卢水华, 钱雪琴
Journal: BMJ (2010)

患者女,59岁.因鼻塞、流涕、鼻咽部异物感10年余于2009年1月12日在我院就诊.患者10年来反复鼻塞、流涕,鼻咽部异物感,偶有涕中带血丝及血块,辗转就诊于多家医院诊治,并多次行纤维鼻咽喉镜检查,均提示鼻咽部粘连、鼻中隔偏曲,诊断为慢性鼻炎、慢性鼻窦炎,经治疗无好转,2008年3月手术治疗,效果仍不佳.本院就诊前2 d行结核菌素试验强阳性,考虑鼻结核的可能,来我院诊治。
Circulating mitochondrial DNA (mtDNA) variants to predict metastatic progression of rectal cancer.
Authors: Anne Hansen Ree, Paula A Bousquet, Tonje Bjørnetrø, Anniken Jørlo Fuglestad, Torben Lüders, Ying Esbensen, Christin Johansen, Hedvig V Juul, Else Marit Inderberg, Christian Kersten, Kathrine Røe Redalen, Sebastian Meltzer
Journal: Journal of Clinical Oncology (2020)

e16132 Background: High rates of systemic failure after curative-intent therapy in locally advanced rectal cancer (LARC) call for new diagnostic tools to improve risk-based treatment stratification. We hypothesized that blood mtDNA polymorphisms, generated by the high mtDNA mutation rate when the mitochondrial biogenesis is mobilized during clonal immune cell activation, correlate with systemic immune control of LARC dissemination and thus can be used as diagnostic marker. Methods: 41 LARC patients given neoadjuvant (chemo)radiotherapy had DNA extracted from whole blood (WB) sampled at the time of diagnosis, for high-throughput full-length mtDNA sequencing followed by annotation of mtDNA variants using the curated reference genome (mitomap.org). The composition of peripheral blood mononuclear cell (PBMC) subpopulations was analyzed by high-dimensional single-cell mass cytometry. Metastatic events were recorded over 24-60 months of follow-up after completion of the multimodal treatment. Results: The total number of WB-mtDNA variants was strikingly different across the study cases but without correlation to patient’s age, body mass index, or metformin use, which may affect mitochondrial function, or to the disease extension at presentation or the local tumor response to the neoadjuvant therapy. All patients had microsatellite-stable tumor. The higher the number of variants in MT-RNR2, encoding one of the two ribosomal subunits of mitochondria, the better distant metastasis-free survival (DMFS). For each patient, two MT-RNR2 sites were homoplasmic for either the normal or a deletion (3105AC &gt; A, 3106CN &gt; C) variant, categorizing the patients into two groups that comprised the same cases for both mtDNA sites. Nine of a total of 10 DMFS events occurred during the 18 first months of follow-up in one of the patient groups ( n = 23). The single event in the other group ( n = 18) appeared in a patient who had declined primary tumor surgery. In the former group, a low number of variants in the ribosomal subunit MT-RNR1 identified all patients who had metastatic progression. These patients had reduced PBMC frequency of CD8 + (cytolytic) T cells that were positive for CXCR4 ( p = 0.001), a chemokine receptor that promotes their homing to tumor sites. Conclusions: The WB-ribosomal mtDNA polymorphisms reflected systemic immune cells endowed with cytolytic and tumor-homing properties. The actual mtDNA variants were single-base alterations and might thus be analyzed by PCR and developed as a feasible assay for metastatic risk assessment in rectal cancer. Clinical trial information: 01816607 .
A Randomized Trial of Convalescent Plasma for COVID-19—Potentially Hopeful Signals
Authors: Arturo Casadevall, Michael J. Joyner, Liise-Anne Pirofski
Journal: JAMA (2020)

Ling Li, MD, PhD; Wei Zhang, MD; Yu Hu, MD, PhD; Xunliang Tong, MD, PhD; Shangen Zheng, MD; Juntao Yang, PhD; Yujie Kong, MD; Lili Ren, PhD; Qing Wei, MD; Heng Mei, MD, PhD; Caiying Hu, MD; Cuihua Tao, MD; Ru Yang, MD; Jue Wang, MD; Yongpei Yu, PhD; Yong Guo, PhD; Xiaoxiong Wu, MD; Zhihua Xu, MD; Li Zeng, MD; Nian Xiong, MD, PhD; Lifeng Chen, MD; Juan Wang, MD; Ning Man, MD; Yu Liu, PhD; Haixia Xu, MD; E. Deng, MS; Xuejun Zhang, MS; Chenyue Li, MD; Conghui Wang, PhD; Shisheng Su, PhD; Linqi Zhang, PhD; Jianwei Wang, PhD; Yanyun Wu, MD, PhD; Zhong Liu, MD, PhD
Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction
Authors: Xinpeng Yao, Yi Liu, Jie Gao, Liang Yang, Duo Mao, Christina Stefanitsch, Yang Li, Jun Zhang, Lailiang Ou, Deling Kong, Qiang Zhao, Zongjin Li
Journal: Biomaterials (2015)
Effect of genetic testing results on patient-reported quality of life among patients undergoing panel testing for newly diagnosed ovarian cancer.
Authors: Sarah S. Lee, Melissa Kristen Frey, Deanna Gerber, Zachary Phillip Schwartz, Jessica Martineau, Kathleen Lutz, Erin Reese, Emily Dalton, Anne Olsen, Julia Girdler, Bhavana Pothuri, Leslie R. Boyd, John Patrick Curtin, Douglas A. Levine, Stephanie V. Blank
Journal: Journal of Clinical Oncology (2020)

1584 Background: This study compared patient-reported stress, anxiety, and depression between newly diagnosed ovarian cancer patients with pathogenic genetic testing results versus patients with non-informative results (i.e., variants of uncertain significance (VUS) or negative). Methods: Patients underwent genetic testing (GT) via a facilitated referral pathway (Frey et al, Gynecol Oncol 2020) through which they were referred for genetic counseling and GT by their gynecologic oncologist within six weeks of diagnosis from 10/2015 to 5/2019. English-speaking patients completed three quality of life (QoL) instruments: Impact of Events Scale (IOES), State-Trait Anxiety Questionnaire (STAI), Hospital Anxiety and Depression Scale (HADS) immediately pre-and post-GT and 6 months post GT. Two-way mixed ANOVA was performed to analyze effect of GT results on QoL over time with significance p &lt; 0.05. Results: One hundred ten patients were enrolled in the pathway and 83 (76%) patients underwent GT. Among these, 15 (18%) had potentially actionable pathogenic mutations ( BRCA1-8, BRCA2-4, MSH2-2, MRE11A-1); 26 (31%) had VUS results; 3 (4%) had both a pathogenic mutation and a VUS result; and 42 (51%) had negative results. Sixty patients (72%) completed QoL assessments pre and post GT, and 37 (44%) patients at 6-9 months post GT. For all patients, GT results did not affect QoL scales across our time points. By mean scores across all-comers, patients demonstrated mild stress at each time point and clinically significant anxiety immediate post-GT. All patients had a statistically significance decrease in HADS depression scores over time from pre-GT to 6 months post-GT (mean score 4.98 vs 2.97, p = 0.020). Patients with VUS had lower HADS mean anxiety scores across time (3.62) compared to patients with pathogenic (7.44) or negative mutations (6.83, p = 0.029). For patients without mutations, there was a significant decrease in clinically significant anxiety by STAI-state score at 6 months (p = 0.002) and a decrease in borderline anxiety by HADS scores at 6 months (p = 0.005). This effect was not present for patients with pathogenic mutations or VUS. Conclusions: A pathogenic result does not impact QoL scales immediately pre or post GT or at 6 months post GT, though patients with negative mutations were more likely to show a decrease in anxiety over time. Patients should be recommended GT at time of diagnosis of ovarian cancer without concern of increased stress, anxiety, or depression based on GT results.
Outcomes for black versus white women with stage IV breast cancer enrolled on investigator-initiated clinical trials at Emory.
Authors: Princess Ekpo, Mylin Ann Torres, Manali Rupji, Jeffrey M. Switchenko, Preeti Subhedar, Keerthi Gogineni, Manali A. Bhave
Journal: Journal of Clinical Oncology (2020)

1086 Background: Black women are 40% more likely to die from their breast cancer compared to White women. Inadequate representation of Blacks in clinical trials may contribute to health care inequity. Emory’s Winship Cancer Institute (WCI) in Atlanta serves a significant Black population and has a unique opportunity to engage these underrepresented patients in clinical trials. We aimed to assess clinical outcomes in Black versus White women with metastatic breast cancer (MBC) enrolled on investigator-initiated clinical trials (IITs) at Emory. Methods: Black and White women with MBC enrolled on IITs conducted at WCI between 1/2009 and 1/2019 were retrospectively evaluated. Descriptive statistics were generated for all patient characteristics. Univariate analyses and a multiple logistic regression model were used to assess the effect of age and race on clinical response, length of time on trial, number of therapy lines prior to trial enrollment, and toxicity on trial. Overall survival was assessed using Kaplan Meier analysis. Results: Sixty-two women with MBC were included [White, n = 41 (66%), and Black, n = 21 (34%), p = 0.55]. Over 90% of women were enrolled on phase II clinical trials and received targeted therapy. Mean age at clinical trial consent was 53.2 and 55.9 years in Black and White women, respectively (p = 0.36). While the majority of women had hormone-receptor positive disease, a higher percentage of Blacks had triple negative breast cancer (29% vs. 17% in Whites, p = 0.39). Black women had fewer lines of systemic therapy prior to trial enrollment (2.86 vs. 4.3, respectively, p = 0.017) and were enrolled on trial for less time than White women (5.67 mo vs. 7.83 mo, respectively, p = 0.22). There were no differences in toxicity rates among patients enrolled on IITs based on race. Black women were more likely to have progressive disease (PD) on trial (45% in Blacks vs. 20% in Whites, p = 0.05). While there was no significant difference in overall survival (p = 0.482), there was a trend towards shorter survival in Black women (51.3 mos vs. 64 mos, respectively). Conclusions: Black women with MBC who enrolled on IIT trials at Emory had worse treatment response and a trend towards poorer survival compared to White women. More research is needed to determine whether this is due to adverse biology. These results reinforce the need for exploration of biomarkers of response by race and ethnicity and improved representation of Blacks in clinical trials to inform real world efficacy.
Real-world data of a cohort of patients with EGFR mutated metastatic non-small cell lung cancer (NSCLC), follow up of 52 months in Fundación Santa Fe de Bogota.
Authors: Aylen Vanessa Ospina Serrano, Luis Pino, Javier Segovia, Ivan Camilo Triana
Journal: Journal of Clinical Oncology (2020)

e19287 Background: In Colombia, clinical information about EGFR mutated metastatic NSCLC is deficient. The goal of this study is to describe the characteristics and outcomes of a cohort of patients as a real-world evidence from a single institution from Colombia. Methods: This is an observational study of a cohort of patients with EGFR mutated metastatic NSCLC. We did follow up for 52 months and analyzed molecular, clinical and epidemiological characteristics, progression free survival (PFS), overall survival (OSm) and treatment related complications. Results: Sixteen patients were included. 81.2% were female and 18.2% male patients. All patients with ECOG 0-2. Previous smoking history was reported in 31.2%. 25% of the patients had brain metastasis and 18.7% had high volume disease (three or more sites of metastasis). The mutations reported were: 62.5% exon 19 deletion, 31.2% L858R mutation, 0.06% exon 19 insertion, 12.5% truncal T790M mutation. The PFS and the OSm for the whole cohort were 14.6 months and 25 months respectively. As a first line of treatment 25% of the patients received erlotinib (PFS 11.7m and OSm 26.6m), 37.5% gefitinib (PFS 12m and OSm 14.6m), 25% afatinib (PFS 16.6m and OSm has not been reached) and 12.5% osimertinib without progression, during 10.5m of follow up. After 52 months, 50% of the patients had progressed. After the progression, rebiopsy was performed in all patients, T790M mutation was detected in 50%, and 50% of these patients died with OSm of 3m with a fast clinical worsening. In relation with grade 3-4 toxicity it was one case of hepatotoxicity with afatinib, with gefitinib 2/6 patients had diarrhea, with erlotinib one case of hematotoxicity and with osimertinib 1/6 patients developed hepatotoxicity. Conclusions: The clinical characteristics of our cohort was similar to previous reports in the literature. Additionally, molecular behavior was concordant with other reports in Latin America, with a higher incidence of exon 19 deletion. Gefitinib was the most frequent treatment used, probably due to non-availability of other therapies such as afatinib or osimertinib in our country until 2018 and 2019 respectively. There were no differences in PFS or OSm according to anti-EGFR treatment and molecular behavior. The OS was lower than reported in clinical trials in gefitinib treatment group, this finding requires validation in bigger cohort of patients, but is real world data that can partially explain these results.
Analgesic treatment for patients with advanced cancer at home
Authors: 王庆善, 王莉, 孙建纯, 杨云辉, 赵双莉, 门桂芹
Journal: BMJ (2004)

目的 对居家镇痛治疗的晚期癌性疼痛患者进行镇痛效果的观察和评估.方法选择512例经病理证实的晚期癌症患者,以世界卫生组织三阶梯止痛原则为指导,在家中镇痛药物为主,辅以其他麻醉技术和心理疏导进行综合镇痛治疗.镇痛效果采用数字分级法、生存质量评估和卡诺夫斯基功能状态评分评估.结果 512例患者中途退出3例;497例药物镇痛有效,有效率97.1%;出现顽固性疼痛12例,辅以经静脉病人自控镇痛术和神经阻断术镇痛成功.患者治疗前后数字分级法、生存质量评估和卡诺夫斯基功能状态评分均明显改善(均P＜0.05).结论晚期癌性疼痛患者居家镇痛治疗安全可靠、镇痛有效,患者生活质量明显提高。
Germline alterations other than <i>BRCA</i> in triple negative breast cancer (TNBC) patients who underwent neoadjuvant therapy (NAT) on a prospective clinical trial.
Authors: Banu Arun, Li Zhao, Roland L. Bassett, Alastair Mark Thompson, Jason B White, Rachel M. Layman, Angelica Gutierrez Barrera, Vicente Valero, Naoto T. Ueno, Jennifer Keating Litton, Jianhua Zhang, Elizabeth Ravenberg, Rosalind P Candelaria, Gaiane M Rauch, Debu Tripathy, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2020)

1546 Background: Previous studies have related germline BRCA mutations to pathologic complete response (pCR) in TNBC cohorts. However, prospective data is lacking on the frequency of non- BRCA germline mutations and pCR in TNBC patients who received neoadjuvant therapy (NAT). The aim of this study was to describe germline alterations in comparison with pCR in a prospective cohort of TNBC receiving NAT. Methods: Pre-NAT blood was drawn from patients enrolled in a clinical trial of genomically tailored NAT (ARTEMIS: NCT: 02276443, per eligibility patients had to have negative clinical BRCA tetsing). Germline DNA was extracted and sequenced on a HiSeq4000 sequencer (Illumina, coverage 60X). Reads were aligned to human reference hg19. Variants were filtered against public databases of normal cohorts: esp6500, 1000 genome, ExAC with a frequency cutoff at 1% in any ethnicity. Two integrative scores were used to evaluate the deleteriousness of the missense variants and the variants predicted to be damaging by both scores were included in the analyses. A 105 pan-cancer susceptibility gene panel was selected based on literature data and commercially available gene panels. NAT included anthracycline and taxane based chemotherapy +/- targeted therapy based on tumor genomic expression. Univariate logistic regression models were used to fit pCR for individual mutations, excluding genes mutated in fewer than three patients. All statistical analyses were performed using R version 3.6.1. with a significance of p=0.05. Results: Germline results and pCR were available for 152 patients. Median age was 55 yrs (range: 24-77). 7.9% were stage (st) I, 65.8% st II, 26.3% st III. 55 pts (36%) had pan-cancer associated germline mutations, whereas 33 (21%) had a breast-cancer associated mutation. Greater than 1% mutations were seen in seventeen genes (Table). There was no significant difference in pCR rate after NAT among pts with different germline mutations versus without mutation. Conclusions: Breast cancer related germline mutations other than BRCA in TNBC are relatively common supporting at least a breast panel (not only BRCA1/2) testing. Treatment implications of different germline mutations and their impact on pCR is ongoing on an extended series. [Table: see text]
Pros and cons of probiotics in immunocompromised individuals
Authors: Yanfang Wu
Journal: BMJ (2017)

Probiotics as intestinal flora regulators are increasingly applied in clinical practice; however, the administration of probiotics in immunocompromised individuals is rarely reported. This article is aimed to review the benefits and risks of probiotics in immunocompromised individuals, such as HIV-infected individuals and patients with malignant tumors. The research evidence shows that probiotics can reduce the occurrence of different types of diarrhea, regulate the intestinal immune status and decrease the incidence of complications in immunocompromised patients. Randomized controlled clinical trials have shown that the risk of adverse events is not significantly increased in immunocompromised patients compared to those with intact immune status and the probiotics-related infections are only presented in case reports.


Key words: 
Probiotics; Acquired immunodeficiency syndrome; Neoplasms
Post-PACIFIC trial era: Patterns of outcomes and toxicities from a single private institution in a developing country.
Authors: Daniel Przybysz
Journal: Journal of Clinical Oncology (2020)

e21005 Background: Despite the twenty-first century, NSCLC remains the leading cause of cancer related deaths in a great variety of nations around the globe. However, the scenario has changed dramatically in the past 5 years. Immunotherapy features have opened a gigantic range of combinations now possible towards a better suited treatment for these patients. And we have seen results as we have never before - even in developing countries. Therefore, the goal of this study was to retrospectively analyze the patterns of outcomes, toxicities and safeness in the post-PACIFIC trial era, reporting results on patients that underwent chemoradiation followed by immunotherapy. Methods: We retrospectively collected and analyzed data on patients diagnosed with locally-advanced NSCLC treated in a single private institution in Rio de Janeiro, Brazil, between January 2017 and May 2019. All electronic medical records were accessed in order to obtain demographics, treatment and follow-up pattern data. Patients that received full chemoradiation treatment were included. Patients that did not meet the inclusion criteria were excluded from the study. Results: 121 patients were analyzed. 38 did not meet the inclusion criteria, and were excluded. The median age was 73.5y (50-95). 55% (46) were females. 59% (49) patients were smokers, 12% non-smokers. 29% of them did not have that info on their EMR. Adenocarcinoma was the most common histologic subtype (67%). All patients received chemotherapy regimen according to the best suited to patient, being carbo-taxol the most commonly used one (73%). All patients received radiation therapy, and the mostly used scheme was 60Gy in 30 fractions (38.5%). During a medium follow-up of 1.2 years on Durvalumab, 8 patients died (9.6%), none of them being a treatment-related death. Most toxicities presented during treatment and follow-up were mucositis (62.5%), cough (52%), cutaneous rash (48.8%). Other minor toxicities were nauseas (22.9%) and hematologic (14.5%). No grade 5 toxicity was reported. Conclusions: This study carries limitations inherent to retrospective analysis. Yet, we found the utmost importance on understanding how our patient population is responding to this new era of NSCLC-oncology. Despite all issues related within a developing nation, we showed that our results are compatible with the current data published. The treatment of locally advanced NSCLC brings exciting results and a big hope for these patients.