tbuckley/cabot-search huggingface dataset:
Comprehensive molecular profiling of advanced cancers in a real-world setting using an ultrasensitive amplicon-based next-generation sequencing (NGS) liquid biopsy assay.
Authors: Jonathan Poh, Kao Chin Ngeow, Michelle Pek, Daniel Tan, Jing Shan Lim, Yukti Choudhury
Journal: Journal of Clinical Oncology (2021)

3062 Background: Molecular profiling of circulating tumor DNA (ctDNA) by NGS has demonstrated the value of liquid biopsy in informing treatment decisions and monitoring disease progression in cancer patients. Here we report results from the real-world clinical application of an ultrasensitive amplicon-based NGS liquid biopsy assay for advanced cancers. Methods: Plasma cell-free DNA (cfDNA) from 1,338 consecutive samples (51.3% lung, 15.6% breast, 8.4% colorectal, 26.8% from 18 other cancer types; 86.3% of cancer samples were metastatic) underwent real-world testing in a Singapore-based, CAP-accredited, CLIA-certified laboratory from Jan 2018 – Nov 2020. Genomic alterations were analyzed using an amplicon-based NGS assay that detects alterations in 80 cancer-related genes, microsatellite instability (MSI) and cancer-causing viruses, with previously validated cfDNA detection limits of 0.1% variant allele frequency (VAF) for SNPs and indels, 5% tumor fraction, and 2 IU/mL plasma, respectively. Results: ctDNA was successfully detected in 70.0% of cancer samples (76.3% from metastatic and 24.7% from localized tumors) for a total of 977 unique variants. Across ctDNA-positive samples the median VAF was 1.4%, and 8.5% of all reported variants had VAFs between 0.01 – 0.09%. The most frequently altered genes were TP53 (48.8%), EGFR (36.9%), KRAS (17.4%), PIK3CA (15.3%), and APC (9.5%). In ctDNA-positive lung cancer, 74.6% of samples (66.5% EGFR+) harbored ≥1 actionable target, with 29.9% of patients treated with a first- or second-generation EGFR tyrosine kinase inhibitor harboring an EGFR T790M resistance mutation. Among breast cancers, ESR1 or PIK3CA alterations predicting drug resistance/response were detected in 44.2% of HR+ cases. In colorectal cancer, alterations implicated in anti-EGFR resistance ( NRAS, KRAS, BRAF, ERBB2) were found in 50.0% of samples. Profiling of cfDNA also enabled cancer monitoring, even among cancers with low genetic biomarker prevalence. 50% of nasopharyngeal cancer samples were Epstein-Barr virus-positive while 35.7% of liver cancer samples were Hepatitis B virus-positive, enabling an additional yield of 14.3% and 7.1% respectively, over ctDNA detection. cfDNA profiling of cancers of unknown primary origins informed potential tumor origins via the detection of tumor type-specific alterations such as mutations in AR, ESR1, GNAS, EGFR genes, viral biomarkers, and MSI. Conclusions: The use of a comprehensive pan-cancer liquid biopsy panel with rational inclusion of actionable and driver genes resulted in detection of ctDNA in the vast majority of clinical cases processed routinely. These findings support the utility of ultrasensitive amplicon-based NGS liquid biopsy assays in probing cancer drug sensitivity/resistance, tumor burden monitoring, and molecular characterization of tumors.
Association of HLA loss of heterozygosity with allele-specific neoantigen expansion in response to immunotherapy.
Authors: Rachel Marty Pyke, Charles Abbott, Steven Dea, Nikita Bedi, A. Dimitrios Colevas, Eric Levy, Simo V. Zhang, Michael Snyder, Datta Mellacheruvu, John B. Sunwoo, Richard Chen, Sean Michael Boyle
Journal: Journal of Clinical Oncology (2021)

e18030 Background: Human leukocyte antigen loss of heterozygosity (HLA LOH) restricts immune recognition of tumors by limiting the major histocompatibility complex (MHC) presentation of neoantigens to T cells and correlates with reduced response to immune checkpoint blockade therapy (ICB) in non-small cell lung cancer. To explore the mechanism behind the impairment of HLA LOH on ICB, we analyzed the relationship between the antigen presentation pathway, neoantigen presentation and response to ICB in a head and neck squamous cell carcinoma (HNSCC) cohort. Methods: Following baseline sample collection, a cohort of 14 HNSCC patients recieved a single dose of PD-1 inhibitor. The primary tumor mass was definitively resected approximately one month later. If resection was impractical, a second biopsy was taken. Response to therapy was evaluated using RECIST criteria. Each pre- and post-intervention tumor sample and normal PBMC sample were profiled using Personalis’ ImmunoID NeXT Platform, an HLA-enhanced exome/transcriptome platform. HLA LOH was detected using a digital PCR validated machine learning algorithm (DASH). Neoantigen presentation was computationally predicted using a machine learning algorithm (SHERPATM) trained on mono-allelic immunopeptidomics data. Results: We found that 50% of the HNSCC cohort had HLA LOH, a larger percentage than in a large pan-cancer cohort (23%, n=611) and a distinct HNSCC cohort (40%, n=20). Further, two patients had B2M LOH and one patient had a deleterious mutation in an HLA allele. Despite the high frequency of somatic alteration in the antigen presentation pathway, we did not find an association between HLA LOH and ICB response. However, if HLA LOH was still shaping tumor evolution in response to ICB, we would expect to see immune pressure against subclonal tumor populations with neoantigens presentable by the retained HLA alleles but not the deleted HLA alleles. Indeed, we found that significantly more novel post-treatment neoantigens were predicted to bind to deleted HLA alleles compared to their homologous alleles (p=0.045). Conclusions: Given the high prevalence of HLA LOH across tumor types, a greater understanding is needed regarding the impact of HLA LOH on tumor evolution during ICB treatment. Though HLA LOH does not correlate with response to ICB, the consistent shift in neoantigen composition suggests that it acts as an evolutionary force in resistance to response during immunotherapy.
Comorbidities at time of diagnosis as a predictor of more or less aggressive treatment modalities in early-invasive breast cancer.
Authors: Sreejata Raychaudhuri, Jaclyn M Kyko, Julie J. Ruterbusch, Jennifer Lynn Beebe-Dimmer, Ann G. Schwartz, Michael S. Simon
Journal: Journal of Clinical Oncology (2021)

e12591 Background: Comorbidities and advanced age have been shown to play important roles in breast cancer treatment and outcomes. Reduced doses of chemotherapy, worse treatment-related side-effects, poor performance status in patients with significant comorbidities, and the biological interplay between other diseases and cancer may also play roles. We evaluated the relationship between age and pre-existing comorbidities and receipt of local and systemic therapy in a cohort of African American (AA) women with early invasive breast cancer. Methods: The study population included 1,169 AJCC stage I-III invasive breast cancer survivors from the Detroit Research on Cancer Survivors (ROCS) study, a large cohort of AA cancer survivors. Comorbidities (both individual diseases and a combined count that was categorized as low/medium/high comorbidity burden), age at diagnosis, and other demographic variables were obtained from self-reported standardized questionnaires. Cancer-related variables including treatment were obtained from the Metropolitan Detroit Cancer Surveillance System registry. Recommended treatment was subdivided into localized (surgery ± radiation; N = 1,156), hormonal (N = 848) and chemotherapy (N = 680). Logistic regression estimated the associations between age and pre-existing comorbid conditions and the receipt of recommended treatments. Adjusted models included variables that were selected a priori and were significant predictors in univariate analysis. Results: Most women received recommended localized treatment (82.6%), hormone treatment (73.7%), and chemotherapy (79.9%). There were no differences in receipt of localized treatment based on age or comorbidity burden in adjusted analyses. However, arthritis and depression were significantly associated with not receiving recommended localized treatment (Odds ratio (OR): 0.66, 95% CI: 0.47, 0.93 and OR: 0.53, 95% CI: 0.36, 0.78, respectively). Women with a history of obesity (BMI ≥30) were more likely to receive recommended hormone therapy (OR: 1.64, 95% CI: 1.19, 2.26), while women with congestive heart failure were less likely (OR: 0.46, 95% CI: 0.23, 0.90). Receipt of recommended chemotherapy was less likely for those with increasing age (P trend &lt; 0.01) and increasing comorbidity burden (P trend = 0.02). Those with a history of arthritis (OR: 0.66, 95% CI: 0.44, 0.99) and hypercholesterolemia (OR: 0.62, 95% CI: 0.41, 0.95) were also less likely to receive recommended chemotherapy. Conclusions: Advanced age and presence of pre-existing co-morbid medical conditions appears to influence the receipt of chemotherapy, while individual conditions were associated with receipt of local treatment or hormone therapy in a cohort of AA survivors, suggesting the importance of providing comprehensive medical care for all women with early invasive breast cancer.
Association of febrile neutropenia (FN) risk factors (RFs) with incident FN in U.S. commercial and Medicare advantage patients receiving intermediate-risk chemotherapy for non-myeloid cancers between 2009 and 2019.
Authors: Edward C. Li, Elizabeth J. Bell, Kimberley J. Campbell, Lincy S. Lal, Jesse Peterson-Brandt, Gary H. Lyman
Journal: Journal of Clinical Oncology (2021)

e18607 Background: FN after myelosuppressive chemotherapy may result in significant morbidity/mortality and increase healthcare costs due to interventions such as hospitalization. For patients receiving chemotherapy at intermediate-risk of FN, guidelines recommend assessing patient-specific FN RFs to decide whether to provide primary prophylaxis. However, there is a paucity of real-world data that quantifies the FN risk based on patient RFs when receiving intermediate-risk chemotherapy. Thus, we examined the association of FN RFs with incident FN in the first and subsequent cycles in patients at intermediate-risk of chemotherapy-induced FN within the real-world. Methods: This retrospective cohort study used the Optum Research Database to identify US commercial and Medicare Advantage patients with a non-myeloid malignancy who were treated between 01 Jan 2009 and 31 Dec 2019 with a first-line intermediate-risk chemotherapy regimen. The following FN RFs were identified based on ICD or procedure codes on claims during the 6 months prior to chemotherapy, unless otherwise stated: radiation, neutropenia, liver dysfunction, renal dysfunction, age &gt; 65 years, metastases to the bone, and surgery during the 30 days prior. FN was defined as ICD codes for neutropenia and fever on a claim. Patients without previous FN were followed for FN from five days after index through the earliest of the following: 1) FN, 2) 31 Dec 2019, 3) death, 4) health plan disenrollment, or 5) end of chemotherapy line or cycle (depending on time frame of interest). Cox regression was used to calculate HRs for incident FN. Results: The study included 13,937 patients, and the most common RFs were 1) recent surgery (84%), 2) age &gt; 65 (67%), and 3) liver dysfunction (31%). Compared to patients with no individual RFs, each additional RF was associated with a greater risk of FN during both the first and subsequent cycles, although confidence intervals were large (Table). Conclusions: Among patients at intermediate-risk of chemotherapy-induced FN, patients with more individual RFs for FN had a higher risk of FN during both the first and all cycles. These results underscore the importance of RF analysis in prophylaxis decisions for patients at intermediate-risk of chemotherapy-induced FN.[Table: see text]
Sarcopenia Is a Clinically Relevant and Independent Predictor of Adverse Outcomes after Allogeneic Hematopoietic Cell Transplantation
Authors: Saro H. Armenian, Dongyun Yang, Jennifer Berano Teh, Brandyn Lee, Howard Chang, Mascarenhas Kristen, Lee Sean, Iukuridze Aleksi, Jack Ji Xie, Jessica Scott, Lee Jones, F. Lennie Wong, Stephen J. Forman, Ryotaro Nakamura
Journal: Blood (2017)
Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning
Authors: Naixin Liang, Bingsi Li, Ziqi Jia, Chenyang Wang, Pancheng Wu, Tao Zheng, Yanyu Wang, Fujun Qiu, Yijun Wu, Jing Su, Jiayue Xu, Feng Xu, Huiling Chu, Shuai Fang, Xingyu Yang, Chengju Wu, Zhili Cao, Lei Cao, Zhongxing Bing, Hongsheng Liu, Li Li, Cheng Huang, Yingzhi Qin, Yushang Cui, Han Han-Zhang, Jianxing Xiang, Hao Liu, Xin Guo, Shanqing Li, Heng Zhao, Zhihong Zhang
Journal: Nature Biomedical Engineering (2021)
Uterine transplantation and donation in transgender individuals; proof of concept
Authors: Alireza Hamidian Jahromi, Sydney R. Horen, Amir H. Dorafshar, Michelle L. Seu, Asa Radix, Erica Anderson, Jamison Green, Lin Fraser, Liza Johannesson, Giuliano Testa, Loren S. Schechter, Loren Schechter
Journal: International Journal of Transgender Health (2021)

According to the Center for Disease Control (CDC)’s yearly Behavioral Risk Factor Surveillance System (BRFSS) report, approximately 25 million individuals worldwide, including 1–1.4 million adults ...
Clinical parameters combined with radiomics features to predict the efficacy of immunotherapy for advanced non-small cell lung cancer.
Authors: Qian Zhao, Linlin Wang
Journal: Journal of Clinical Oncology (2021)

e21187 Background: Many tools have been developed to predict the efficacy of immunotherapy, such as LIPI, EPSILoN and mLIPI scores. The aim of this study was to determine the ability of to predict outcomes in Chinese aNSCLC patients treated with ICIs.With the development of imaging technology, radiomics has increasingly received a great deal of attention. We use 3D-slicer to delineat the ROI in the patient's CT image, extract a large number of features, and further screen out the radiomics features that have predictive value for the outcome. Methods: We retrospectively enrolled 317 patients with histologically proven aNSCLC (IIIB–IV) treated with ICIs. The discriminative ability of the predictive models was evaluated by AUC in the ROC analysis. Patients were randomly divided into training and validation cohorts using a 2：1 ratio. We used the semi-automatic segmentation method of the 3D-slicer platform to delineate the ROI of the tumor’s lesion area and extract 854 image features for each patient. In the training set of patients, the LASSO algorithm was used to screen the radiomic features.Hosmer-Lemeshow tests (H-L tests) were conducted to determine the fit of the prediction models. PFS and OS curves were generated using the Kaplan-Meier method and differences were assessed using log-rank tests. Univariate and multivariate analyses were performed using Cox proportional-hazards regression models. The glmnet R package was used for the LASSO regression method. The rms, Hmisc R packages used for C-index. Results: Among the 317 patients included in the study, the median OS and PFS were 14.2 months and 5.6 months, respectively and the ORR was 23.1%. The AUC values of LIPI, mLIPI, and EPSILoN scores for predicting PFS were 0.649 (95% CI: 0.588–0.709), 0.765 (95% CI: 0.713–0.818]), and 0.637 (95% CI: 0.567–0.698), respectively (P &lt; 0.001 for all models). The AUC value of mLIPI scores was significantly higher than that of LIPI and EPSILoN scores (P &lt; 0.05). The C-index of mLIPI was 0.645 (95% CI: 0.617-0.673). In this study, 5 radiomics features with predictive value were selected from radiomics features. The C-indexs of the radscore were 0.643 (95% CI: 0.602–0.684) and 0.632 (95% CI: 0.571–0.693). Then we combined mLIPI and radscore to obtain a mixed model. The C-index of the combination mLIPI scores with radscore for predicting PFS was 0.810 (95% CI: 0.770–0.849) and 0.706（CI: 0.633–0.778) in the training and validation cohorts, respectively. Conclusions: By externally validating LIPI, mLIPI, and EPSILoN scores, we found that all three of these predictive models could identify different prognostic subsets of patients treated with ICIs to statistically significant degrees. We also found that mLIPI had the highest accuracy among the three models. With the addition of radiomics features, the prediction performance of the mixed model has been further improved.
Part 2: International Collaboration in Resuscitation Science
Authors: Vinay M. Nadkarni, Jerry P. Nolan, John E. Billi, Leo Bossaert, Bernd W. Böttiger, Douglas Chamberlain, Saul Drajer, Brian Eigel, Mary Fran Hazinski, Robert W. Hickey, Ian Jacobs, Walter Kloeck, William H. Montgomery, Peter T. Morley, Robert E. O'Connor, Kazuo Okada, Michael Shuster, Andrew H. Travers, David Zideman
Journal: Circulation (2010)
Diagnosis and management of migraine in ten steps
Authors: Anna K. Eigenbrodt, Håkan Ashina, Sabrina Khan, Hans-Christoph Diener, Dimos D. Mitsikostas, Alexandra J. Sinclair, Patricia Pozo-Rosich, Paolo Martelletti, Anne Ducros, Michel Lantéri-Minet, Mark Braschinsky, Margarita Sanchez del Rio, Oved Daniel, Aynur Özge, Ayten Mammadbayli, Mihails Arons, Kirill Skorobogatykh, Vladimir Romanenko, Gisela M. Terwindt, Koen Paemeleire, Simona Sacco, Uwe Reuter, Christian Lampl, Henrik W. Schytz, Zaza Katsarava, Timothy J. Steiner, Messoud Ashina
Journal: Nature Reviews Neurology (2021)

Abstract Migraine is a disabling primary headache disorder that directly affects more than one billion people worldwide. Despite its widespread prevalence, migraine remains under-diagnosed and under-treated. To support clinical decision-making, we convened a European panel of experts to develop a ten-step approach to the diagnosis and management of migraine. Each step was established by expert consensus and supported by a review of current literature, and the Consensus Statement is endorsed by the European Headache Federation and the European Academy of Neurology. In this Consensus Statement, we introduce typical clinical features, diagnostic criteria and differential diagnoses of migraine. We then emphasize the value of patient centricity and patient education to ensure treatment adherence and satisfaction with care provision. Further, we outline best practices for acute and preventive treatment of migraine in various patient populations, including adults, children and adolescents, pregnant and breastfeeding women, and older people. In addition, we provide recommendations for evaluating treatment response and managing treatment failure. Lastly, we discuss the management of complications and comorbidities as well as the importance of planning long-term follow-up.
Corrigendum to Dual-modality endoscopic probe for tissue surface shape reconstruction and hyperspectral imaging enabled by deep neural networks [Medical Image Analysis 48 (2018) 162-176/2018.06.004]
Authors: Jianyu Lin, Neil T. Clancy, Ji Qi, Yang Hu, Taran Tatla, Danail Stoyanov, Lena Maier-Hein, Daniel S. Elson
Journal: Medical Image Analysis (2021)
Red Blood Cell Transfusions Shape Macrophages Towards an Anti-Inflammatory Functional Phenotype and Impair the Immune Response to Infectious Cues
Authors: Francesca Vinchi, Milene Costa da Silva, Richard Sparla, Heike Weidner, Martina Rauner, Emanuela Tolosano, Uwe Platzbecker, Martina U. Muckenthaler
Journal: Blood (2017)
SIROF stabilized PEDOT/PSS allows biocompatible and reversible direct current stimulation capable of driving electrotaxis in cells
Authors: José Leal, Nicole Jedrusik, Sebastian Shaner, Christian Boehler, Maria Asplund
Journal: Biomaterials (2021)

Electrotaxis is a naturally occurring phenomenon in which ionic gradients dictate the directed migration of cells involved in different biological processes such as wound healing, embryonic development, or cancer metastasis. To investigate these processes, direct current (DC) has been used to generate electric fields capable of eliciting an electrotactic response in cells. However, the need for metallic electrodes to deliver said currents has hindered electrotaxis research and the application of DC stimulation as medical therapy. This study aimed to investigate the capability of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) on sputtered iridium oxide film (SIROF) electrodes to generate stable direct currents. The electrochemical properties of PEDOT/PSS allow ions to be released and reabsorbed depending on the polarity of the current flow. SIROF stabilized PEDOT/PSS electrodes demonstrated exceptional stability in voltage and current controlled DC stimulation for periods of up to 12 hours. These electrodes were capable of directing cell migration of the rat prostate cancer cell line MAT-LyLu in a microfluidic chamber without the need for chemical buffers. This material combination shows excellent promise for accelerating electrotaxis research and facilitating the translation of DC stimulation to medical applications thanks to its biocompatibility, ionic charge injection mechanisms, and recharging capabilities in a biological environment.
Association of the COVID-19 pandemic with patterns of cancer services.
Authors: Robin Robin Yabroff, Xiao-Cheng Wu, Serban Negoita, Jennifer Stevens, Linda Coyle, Jingxuan Zhao, Brent Mumphrey, Ahmedin Jemal, Kevin C. Ward
Journal: Journal of Clinical Oncology (2021)

1514 Background: The COVID-19 pandemic led to delays in medical care in the United States. We examined changes in patterns of cancer diagnosis and surgical treatment in 2020 using real-time electronic pathology report data from population-based SEER cancer registries in Georgia and Louisiana. Methods: Bi-weekly numbers, distributions, and patterns of pathology reports were compared between January 1 st and December 31 st in 2020 and the same period in 2019 by age group and cancer site. Results: During 2020, there were 29,905 fewer pathology reports than in 2019, representing a 10.2% decline. Absolute declines were greatest among adults aged ≥50 years (N=23,065); percentage declines were greatest among children and young adults ≤18 years (38.3%). By cancer site, percentage declines were greatest for lung cancer (17.4%), followed by colorectal (12.0%), breast (9.0%) and prostate (5.8%) cancers. Biweekly reports were statistically significantly lower in 2020 than in 2019 from late March through the end of December in most biweekly periods. The nadir was the month of April 2020 – the number of reports was at least 40% lower than in April 2019. The number of reports in 2020 compared with 2019 also declined sharply in early November (26.8%) and late December (32.0%). Numbers of reports in 2020 never consistently exceeded those in 2019 after the first decline. Patterns were similar by cancer site, with variation in magnitude and duration of declines. Conclusions: Significant declines in cancer pathology reports from population-based registries during 2020 suggest substantial delays in screening, evaluation of signs and symptoms, diagnosis, and treatment services for cancers with effective screening tests as well as in cancer sites and age groups without effective screening tests as an indirect result of the COVID-19 pandemic. Ongoing evaluation will be critical for informing public health efforts to minimize any lasting adverse effects of the pandemic on cancer screening, diagnosis, treatment, and survival.[Table: see text]