tbuckley/cabot-search huggingface dataset:
Delivery by Dendritic Mesoporous Silica Nanoparticles Enhances the Antimicrobial Activity of a Napsin‐Derived Peptide Against Intracellular <i>Mycobacterium tuberculosis</i>
Authors: Bastian Beitzinger, Fabian Gerbl, Thomas Vomhof, Roman Schmid, Reiner Noschka, Armando Rodriguez, Sebastian Wiese, Gilbert Weidinger, Ludger Ständker, Paul Walther, Jens Michaelis, Mika Lindén, Steffen Stenger
Journal: Advanced Healthcare Materials (2021)

Tuberculosis remains a serious global health problem causing 1.3 million deaths annually. The causative pathogen Mycobacterium tuberculosis (Mtb) has developed several mechanisms to evade the immune system and resistances to many conventional antibiotics, so that alternative treatment strategies are urgently needed. By isolation from bronchoalveolar lavage and peptide optimization, a new antimicrobial peptide named NapFab is discovered. While showing robust activity against extracellular Mtb, the activity of NapFab against intracellular bacteria is limited due to low intracellular availability. By loading NapFab onto dendritic mesoporous silica nanoparticles (DMSN) as a carrier system, cellular uptake, and consequently antimycobacterial activity against intracellular Mtb is significantly enhanced. Furthermore, using lattice light-sheet fluorescence microscopy, it can be shown that the peptide is gradually released from the DMSN inside living macrophages over time. By electron microscopy and tomography, it is demonstrated that peptide loaded DMSN are stored in vesicular structures in proximity to mycobacterial phagosomes inside the cells, but the nanoparticles are typically not in direct contact with the bacteria. Based on the combination of functional and live-cell imaging analyses, it is hypothesized that after being released from the DMSN NapFab is able to enter the bacterial phagosome and gain access to the bacilli.
Predicting 180-day mortality for women with ovarian cancer using machine learning and patient-reported outcome data.
Authors: Chris Sidey-Gibbons, Charlotte C. Sun, Cai Xu, Amy Schneider, Sheng-Chieh Lu, Ishwaria Mohan Subbiah, Alexi A. Wright, Larissa Meyer
Journal: Journal of Clinical Oncology (2021)

e13555 Background: Contra to national guidelines, women with ovarian cancer often receive aggressive treatment until the end-of-life. We trained machine learning algorithms to predict mortality within 180 days for women with ovarian cancer. Methods: Data were collected data from a single academic cancer institution in the United States. Women with recurrent ovarian cancer completed biopsychosocial patient-reported outcome measures (PROMs) every 90 days. We randomly partitioned our dataset into training and testing samples with a 2:1 ratio. We used synthetic minority oversampling to reduce class imbalance in the training dataset. We fitted training data to six machine learning algorithms and combined their classifications on the testing dataset into a voting ensemble. We assessed the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) for each algorithm. Results: We recruited 245 patients who completed 1319 assessments. The final voting ensemble performed well across all performance metrics (Accuracy = .79, Sensitivity = .71, Specificity = .80, AUROC = .76). The algorithm correctly identified 25 of the 35 women in the testing dataset who died within 180 days of assessment Conclusions: Machine learning algorithms trained using PROM data offer state-of-the-art performance in predicting whether a woman with ovarian cancer will reach the end-of-life within 180 days. We highlight the importance of PROM data in ML models of mortality. Our model exhibits substantial improvements in prediction sensitivity compared to other similar models trained using electronic health record data alone. This model could inform clinical decision making and improve the uptake of appropriate end-of-life care. Further research is warranted to expand on these findings in a larger, more diverse sample.
Single-operator metal stent deployment for malignant biliary obstruction using a novel thumbwheel delivery system
Authors: Tadahisa Inoue, Mayu Ibusuki, Rena Kitano, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda
Journal: Endoscopy (2021)

A 57-year-old-man with multiple liver metastases associated with colonic cancer developed obstructive jaundice. Computed tomography and magnetic resonance cholangiopancreatography revealed a hilar bile duct stricture and intrahepatic bile duct dilatation. Therefore, endoscopic placement of a metal stent was planned. As the right hepatic lobe was largely occupied by tumors, unilateral placement in the left intrahepatic duct was attempted. After biliary cannulation, a 0.025-in. guidewire was placed over the stricture. Subsequently, a novel metal stent with a 5.4-Fr thumbwheel delivery system (Yabusame; Kaneka Medix, Osaka, Japan) ([Fig. 1]) was advanced through the stricture over the guidewire. Thereafter, the operator held the delivery system in the right hand and the shaft of the delivery system above the working channel of the duodenoscope in the left hand ([Fig. 2]). The metal stent was gradually released using the thumbwheel, while the stent’s position was adjusted by pulling the shaft. Finally, the stent was deployed in an optimal position across the stricture ([Video 1]). The patient’s symptoms improved rapidly without any adverse events.
A pan-cancer study on characteristic of <i>CDK4/6</i> amplification between Chinese and Western patients.
Authors: Yamin Zhang, Zilin Cui, Rui Shi, Xiaolong Liu, Yang Li, Taiyan Guo, Xia You, Qin Zhang, Qianqian Duan, Chuang Qi
Journal: Journal of Clinical Oncology (2021)

e15074 Background: CDK4/6 kinases associate with cyclin D proteins during transition from G1 to S phase of the cell cycle. Amplification of CDK4/6 may elicit the activity of cyclin D, which hyperphosphorylates RB, ultimately leading to uncontrolled cell proliferation. Currently, three CDK4/6 inhibitors are used in breast cancer, ovarian cancer and sarcoma. Herein, we investigate the prevalence of CDK4/6 amplification in Chinese and Western cancer patients, hope to find more cancer subtypes with CDK4/6 amplification. Methods: Next-generation sequencing data and clinical data were collected from 10828 TCGA pan-cancer patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 4181 Chinese pan-cancer patients (Chinese cohort). CDK4 and CDK6 amplification were calculated on the two cohorts following the same criteria. Results: In total, 182 (4.4%) of the 4181 Chinese patients and 529 (4.9%) of the 10828 Western patients had CDK4 amplification, 133 (3.2%) of the 4181 Chinese patients and 475 (4.4%) of the 10828 Western patients had CDK6 amplification. In Western cohort, the top 5 CDK4 amplification-associated cancer types were sarcoma, glioblastoma multiforme, lung adenocarcinoma, ovarian carcinoma, and adrenocortical carcinoma, and the top 5 CDK6 amplification-associated cancer types were esophageal carcinoma, ovarian carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, sarcoma. In Chinese cohort, the top 5 CDK4 amplification-associated cancer types were lung adenocarcinoma, melanoma, sarcoma, stomach carcinoma, liver cancer, and the top 5 CDK6 amplification-associated cancer types were lung adenocarcinoma, stomach carcinoma, liver cancer, melanoma, glioma. In addition, CDK4 amplification in Chinese cohort, 22 (11%) of the 203 Chinese bone and soft tissue sarcoma patients had CDK4 amplification, and 4 (2%) of the 203 had CDK6 amplification. Bone and soft tissue sarcoma types with CDK4 / 6 amplification including soft tissue sarcoma, bone cancer, fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, liposarcoma, synovial sarcoma. Conclusions: Our study provided a characteristic of CDK4/6 amplification in Chinese and Western pan-cancer patients. Analysis revealed frequent CDK4 / 6 amplification in lung cancer, sarcoma, stomach carcinoma, ovarian carcinoma and liver cancer. It is suggested patient with these cancer types may potentially benefit from CDK4/6 inhibitor.
A Transient Induction of Blood-Circulating Bile Acid Is a Therapeutic Marker and Target of Chemotherapy-Oriented Myelosuppression
Authors: Valgardur Sigurdsson, Youichi Haga, Hajime Takei, Chizuko Okamatsu-Haga, Visnja Radulovic, Mark Van Der Garde, Mitsuyoshi Suzuki, Svetlana Soboleva, Hiroshi Nittono, Akira Ohara, Kenichi Miharada
Journal: Blood (2017)
The real-word evidence of first-line treatment of pembrolizumab in advanced NSCLC.
Authors: Pin Li, Shirish M. Gadgeel, Laila Poisson
Journal: Journal of Clinical Oncology (2021)

e18731 Background: For advanced non-small cell lung cancer (NSCLC), evidence from clinical trials indicates the superiority of pembrolizumab (P) than chemotherapy (C) in PD-L1 positive patients and superiority of P+C than C among PD-L1 unselected patients. Meta-analysis from different clinical trials stated P+C failed to improve overall survival (OS) or progression-free survival (PFS) compared with P alone. This study used real-world data of PD-L1+ patients with advanced NSCLC to compare treatment effect of P with P+C. Methods: A retrospective analysis of adult patients diagnosed between 2015-2020 with stage IV NSCLC with PD-L1+ and without EGFR/ALK mutation was examined using de-identified Syapse Learning Health Network(LHN). We compared the patients with first-line (1L) treatment of pembrolizumab + carboplatin + chemo (P+C) and patients with 1L treatment of P only (P). Patient characteristics and survival outcomes including real-world OS (rwOS) and real-world time to next treatment (rwTTNT) were collected. Results: 485 patients were included: 231 on P+C and 254 on P. The two groups are similar in race, primary tumor histology and ECOG, and P are older in age and have more female. The median rwOS for P+C is longer than P (13.2 vs 11.0 month), 1 year survival probability is higher (55% vs 49%), but 2 year survival probability is lower (34% vs 39%). Coxph model shows no significant difference between two groups (HR=0.89, 95% CI 0.69-1.14, p=0.34). Subgroup analysis of patients age≥75 shows median rwOS for P+C is shorter than P (8.7 vs 13.2 month), 1 year survival probability is lower (46% vs 51%). Coxph model shows no significant difference between two groups (HR=1.32, 95% CI 0.81-2.16, p=0.27). In each treatment group, the median rwOS for female is longer than male (13.2 vs 7.9 month in P, 15.8 vs 12.2 month in P+C), and 1 year survival probability is higher (52% vs 45% in P, 59% vs 53% in P+C). Coxph model shows no significant difference between female and male (HR=0.81, 95% CI 0.58-1.15, p=0.23 in P; HR=0.90, 95% CI 0.62-1.30, p=0.57 in P+C). Conclusions: Among patients with PD-L1+ advanced NSCLC, there is no significant difference in rwOS for patients with 1L treatment of P+C or P alone.[Table: see text]
Analysis of breast cancer screening results in urban areas of Henan Province.
Authors: Guo Lan-Wei
Journal: Journal of Clinical Oncology (2021)

10543 Background: Breast cancer is the most common female cancer in China. Reasonable and effective screening is an important means to reduce the mortality of breast cancer. This study was to evaluate the compliance and efficacy of breast cancer screening in urban areas of Henan province from 2013 to 2019. Methods: A cluster sampling method was used to select the residents of 40-74 years old in Henan province to investigate the risk factors and breast cancer risk assessment. For subjects with high risk of breast cancer, those aged 40-44 conduct breast ultrasound examination; those aged over 45 conduct breast ultrasound combined with mammography examination. BI-RADs classification was used as the evaluation standard in both examinations. BI-RADS 3 class was defined as suspicious and BI-RADS≥4 class was defined as positive. Chi-square test was used to analyze the compliance rate and breast cancer detection rate among different groups. Results: A total of 29 111 residents at high risk for breast cancer were recruited in this study. They were 55.03 ± 7.91 years old, of which 13 760 took the following breast ultrasound or mammography examination, yielding a participation rate of 47.27% (13 760/29 111). The detection rates of suspected positive patients, positive patients and breast cancer patients were 23.40% (3 220/13 760), 2.55% (351/13 760) and 0.30% (41/13 760), respectively. Among the screening population, the highest detection rate of suspected positive patients was found in the 45-49 age group [27.79% (935/3 365)], the highest detection rate of positive patients was found in the 50-54 age group [2.98% (97/3 257)], and the highest detection rate of breast cancer was found in the 65-69 age group [0.49% (5/1 012)]. The detection rate of breast cancer positive patients by breast ultrasound combined with mammography examination was 2.95% (316/10 728), which was significantly higher than that of breast ultrasound alone [1.99% (213/10 728)] or mammography examination alone [1.25% (134/10 728)]. Conclusions: Breast ultrasound combined with mammography examination as a means of screening for breast cancer can significantly increase the detection rate of breast cancer positive patients. The next step should be to improve the compliance of the population, as well as the organization's implementation and service capabilities of the screening provider, to improve screening effectiveness.
Every three weekly irinotecan for refractory/relapsed small cell lung cancer.
Authors: Snigdha Nutalapati, Donglin Yan, Rachael Morgan, Aman Chauhan
Journal: Journal of Clinical Oncology (2021)

e20584 Background: Current NCCN guidelines support weekly irinotecan regimen for refractory/relapsed SCLC (small cell lung cancer). Despite prior studies that used irinotecan for other solid malignancies included both weekly and three weekly regimens, NCCN do not acknowledge three weekly regimen for SCLC due to insufficient data, especially from United States patient population. We aimed to study clinical efficacy, side effect profile and cost analysis of three weekly irinotecan regimens for refractory/relapsed SCLC. Methods: Retrospective analysis of relapsed/refractory SCLC or high-grade neuroendocrine carcinoma (HGNEC) patients treated with every 3 weekly irinotecan (300 mg/m 2 ) regimen between 2010 and 2020 at NCI-designated Markey Cancer Center/University of Kentucky healthcare was performed. Median PFS and adverse events per CTCAE 5.0 were determined. Results: A total of thirty-eight patients were included in our analysis, 32 with SCLC and 6 with HGNEC. Of 6 patients with HGNEC, primary site included bladder (n=1), prostate(n=1), gastroesophageal junction(n=1) and unknown primary (n=3). Mean age at diagnosis was 58 years. Mean prior line of therapies were 1.8 (range=1 to 4) and mean number of irinotecan cycles were 3.5 (range=1 to 12). Median progression free survival was 2.1 months (95% CI-1.6 to 8.1). Grade (G) 2, 3 and 4 adverse events were noted among 20.5%, 33.3% and 7.8% respectively. G3 and G4 neutropenia was seen in 2.6% and 5.3%; neutropenic fever was noted among 5.3%; G2 and G3 diarrhea among 7.9% and 15.8%; ileus among 5.3%; enterocolitis among 2.6%; G2 and G3 nausea and vomiting among 7.9% and 10.5%; G3 transaminitis among 2.6%; G3 and G4 acute kidney injury was seen among 5.1% and 2.6% respectively. Estimated overall costs (including infusion related expenses, cost of pre-medications and irinotecan) to deliver three 100mg/m 2 doses with every weekly regimen was $661 compared to only $268 for a single 300mg/m 2 dose with every three-weekly regimen. Conclusions: In previously treated patients with refractory/relapsed SCLC, every three weekly irinotecan regimen was found to have comparable efficacy and adverse event profile. Diarrhea, nausea, vomiting and neutropenia are the most common adverse events reported. Moreover, cost effectiveness of every 3 weekly regimen and reduced number of infusions should potentially benefit patients who live far from health care facility as is the case in rural Appalachia and also help reduce financial toxicity.
Deep biopsy via endoscopic submucosal dissection for primary gastric amyloidosis
Authors: Zheng Zhao, Yue Jiao, Bing Yue, Wenjing Wang, Guiping Zhao, Shutian Zhang, Peng Li
Journal: Endoscopy (2021)

Amyloidosis is characterized by interference with multiple organs. It is usually systemic and uncommonly limited to the stomach [1] [2]. Here we report a rare case of primary gastric amyloidosis.
Graphical representations of patient tolerability data: Recommendations from the National Cancer Institute (NCI) Cancer Moonshot Standardization Working Group.
Authors: Gillian Gresham, Gina L. Mazza, Blake Langlais, Bellinda King-Kallimanis, Lauren J. Rogak
Journal: Journal of Clinical Oncology (2021)

e18612 Background: Effective communication of treatment tolerability data is essential for clinical decision making and improved patient outcomes, yet standardized approaches to the analysis and visualization of tolerability data in cancer clinical trials are currently limited. To address this need, the Standardization Working Group (SWG) was established within the NCI Cancer Moonshot Tolerability Consortium. This abstract describes the SWG’s initiative to develop a publicly accessible online toolkit with a comprehensive set of guidelines, references, and resources for graphical displays of tolerability data. Methods: A multidisciplinary group of PRO researchers including biostatisticians, clinicians, epidemiologists, and representatives from the NCI and FDA convened monthly to discuss toolkit development and content. Considerations for standardization of graphical displays of tolerability data included (1) types of graphical displays, (2) incorporation of missing data, (3) labeling and color schemes, and (4) software to produce graphical displays. For consistency, considerations of tolerability relied on the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE), which includes 124 items assessing the frequency, severity, interference, and/or presence of 78 symptomatic adverse events. Graphical displays were generated using simulated PRO-CTCAE data and summarized by composite score (range 0-3).Color schemes that were Section 508 compliant and color blindness accessible were created. Surveys were distributed to 68 consortium members to assess preferences and interpretability of the graphical displays. Results: The SWG created graphical displays for PRO-CTCAE data, including bar charts, butterfly plots, and Sankey diagrams and compiled SAS macros and R functions to do so. Graphical displays made available in the toolkit maximize the use of PRO-CTCAE data, incorporate missingness, support between-arm comparisons, and present data longitudinally over treatment cycles or study timepoints. Survey results for labeling and color schemes were summarized and informed a list of short labels for PRO-CTCAE items (e.g., “radiation burns” for “skin burns from radiation”) and standardized color schemes for use in graphical displays. Survey results were also summarized to provide insight into PRO researchers’ ability to accurately interpret the graphical displays. Conclusions: Standardizinggraphical displays is important for improving the communication and interpretation of tolerability data. The type of graphical display used depends on the purpose of the analysis and should be tailored to the intended audience, including patients. This toolkit will provide a comprehensive resource with best practice recommendations.
Real-world progression-free survival among patients with newly diagnosed advanced ovarian cancer: Does maintenance therapy work?
Authors: Jinan Liu, John Chan, Janvi Sah, Eric M. Maiese, Oscar Bee, Jean Hurteau, Premal H. Thaker
Journal: Journal of Clinical Oncology (2021)

e18707 Background: Options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US in recent years, particularly with FDA approvals of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). Olaparib was approved in 2018 for 1L maintenance treatment of patients (pts) with advanced OC with BRCA mutation and in 2020 as combination therapy with bevacizumab for 1L maintenance treatment of pts with homologous recombination deficient (HRd)–positive tumors. Additionally, the FDA approved niraparib in 2020 for maintenance treatment of pts with advanced OC regardless of tumor biomarker status. This study aimed to describe use and outcomes of 1L maintenance vs. active surveillance (AS) among PARPi-eligible pts with OC in a real-world setting prior to the most recent 2020 FDA approvals. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and either primary debulking surgery or interval debulking surgery following neoadjuvant chemotherapy between January 1, 2016, and February 29, 2020, regardless of biomarker status, from the Flatiron Health database, a longitudinal electronic health record-derived database consisting of de-identified patient-level data that are curated via technology-enabled abstraction. The end of the last cycle of 1L PBC was defined as the index date. Pts who started second-line (2L) treatment within 2 months of the index date were excluded. Primary endpoint was time to initiation of 2L systemic therapy (as a surrogate for progression) or death. Inverse probability of treatment weighting and Cox proportional hazard model were used to adjust for baseline differences among pts on maintenance therapy and pts on AS. Results: A total of 463 pts were included in the study, 87.7% from community practices and 12.3% from academic institutions. Of the pts included, 21.0% received maintenance therapy, while 79.0% did not. Of those who received maintenance therapy, 48.5% received bevacizumab, 40.2% received PARPi (olaparib, rucaparib), and 11.3% received paclitaxel. Median progression-free survival (PFS) for pts who received 1L maintenance therapy was 16.1 months, compared with 12.2 months in pts who did not receive 1L maintenance therapy. After adjusting for baseline differences in characteristics and demographics, including age, race, stage of cancer, and BRCA status, pts on maintenance therapy had a statistically significant, 29% lower risk of progression or death than those receiving AS (hazard ratio: 0.71; 95% CI, 0.52–0.99; P= 0.04). Conclusions: In this real-world analysis, the majority of pts did not receive maintenance therapy; however, a PFS benefit was found in those receiving maintenance therapy. Further studies are needed to understand how biomarker status drives practice patterns.