tbuckley/cabot-search huggingface dataset:
Concordance between blood- and tumor-based detection of RAS mutations to guide therapy in metastatic colorectal cancer.
Authors: Elena Brozos, Ramón Lago, Marta Covela Rúa, Ana Fernández Montes, Juan De la camara, Sonia Candamio Folgar, Laura Muinelo, Yolanda Vidal, Maria Francisca Vazquez, Rosa López, Cristina Blanco, Isabel Ferreirós, Rafael Lopez
Journal: Journal of Clinical Oncology (2020)

217 Background: The study of RAS using circulating tumor DNA (ctDNA) provides a good alternative for the detection and monitoring of RAS mutations during therapy course. Liquid biopsy has the advantage of being less invasive than conventional tissue biopsy. Therefore, it is necessary to determine the degree of concordance of RAS status between plasma and tissue samples from mCRC patients. Methods: We conducted a study to evaluate RAS concordance in several hospitals in Galicia, Northwest of Spain. We analyzed samples from 380 patients with mCRC in Galicia. RAS genotyping in plasma was performed using OncoBEAM RAS CRC kit, Sysmex and compared with the PyroMark Q24 System, Qiagen for FFPE-tissue analysis. Clinical data were collected from electronical reports from each patient. We analyzed the clinical features that can be related with discordant cases. Results: The overall percent of agreement was 83%, with a positive concordance of 79% (143/180 patients) and a negative concordance of 87% (116/132 patients). Taking into account the clinical features of the patients, those with only liver metastasis showed a higher level of concordance (88,8%) and the highest level was in the group of patients that presented liver metastasis and another location (91,3%). On the other hand, patients with only peritoneal disease showed the lowest level of agreement (68,2%), and the absence of liver metastasis was a significant factor of discordance of RAS (71% vs 28%, p&lt;0.0001). Conclusions: The high overall concordance between plasma and tissue RAS mutation support the liquid biopsy technology as an alternative to tissue testing for RAS characterization in mCRC patients, especially in patients with liver metastasis and less in those with peritoneal disease. These results reinforce the use of liquid biopsy as a non-invasive tool for guiding targeted therapy in our patients. [Table: see text]
Identification of Cardiovascular Monosodium Urate Crystal Deposition in Patients With Gout Using Dual-Energy Computed Tomography
Authors: Fabio Becce, Brian Ghoshhajra, Hyon K. Choi
Journal: JAMA Cardiology (2020)

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Do socioeconomic factors really have an impact on early detection of hepatocellular carcinoma and colorectal cancer?
Authors: Anas Albawaliz, Yousaf Zafar, Anahat Kaur, Sheshadri Madhusudhana, Anuj Shrestha
Journal: Journal of Clinical Oncology (2020)

60 Background: Improving surveillance in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) is an important topic in the field of gastroenterology and oncology due to significant benefit associated with early detection and better outcomes. Multiple studies have been undertaken to assess the association between the socioeconomic status of the population and adherence to HCC/CRC screening. Most of these studies used self-reporting surveys and faced limitations due to reporting bias. We aimed to assess the relevance of socioeconomic factors in the diagnosis of HCC and CRC in Jackson County, Missouri by means of a census-based survey. Methods: We retrospectively studied 190 HCC and 690 CRC cases at our institution using a census-based analysis, which consisted of geocoding home addresses of patients and then attaching block level census variables for household occupancy, education level and household income. Statistical analysis was performed using Cox proportional hazard model and ordinal logistic regressions. Results: We did not find a statistically significant association between socioeconomic factors and adherence to surveillance guidelines for HCC and CRC. USPSTF-2019 guidelines for CRC and AASLD-2018 guidelines for HCC screening were taken into account. Variables that were analyzed included high school education or better (p = 0.5), four-person households with one or more workers (p = 0.08) and income less than 25 thousand dollars (p = 0.58). Study results were risk adjusted for age, race, and gender. Separate ordinal logistic regression analysis was done to also adjust for the stage at the time of eventual cancer diagnosis, no statistically significant result was obtained. Conclusions: Our study showed no association between demographic variables and participation in HCC or CRC surveillance. The study is limited by a relatively small sample size confined to local patients seen at our institution. Multicenter census-based surveys and meta-analyses need to be conducted to determine whether socioeconomic factors really have an appreciable impact on early screening and detection of HCC and CRC.
Publisher Correction: K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8+ T cell activation
Authors: Mingjin Yang, Taoyong Chen, Xuelian Li, Zhou Yu, Songqing Tang, Chen Wang, Yan Gu, Yanfang Liu, Sheng Xu, Weihua Li, Xuemin Zhang, Jianli Wang, Xuetao Cao
Journal: Nature Immunology (2020)
Respiratory-gated magnetic resonance image guided radiation therapy for hepatocellular carcinoma: A pilot study.
Authors: Hyun-Cheol Kang, Jin Ho Kim, Eui Kyu Chie
Journal: Journal of Clinical Oncology (2020)

532 Background: Hypofractionated RT has shown encouraging results in hepatocellular carcinoma (HCC) patients. However, HCC adjacent to the gastrointestnal (GI) tract should be carefully treated using the high-precision irradiation technique due to risk of radiation damage. We evaluated the feasibility of a respiratory-gated magnetic resonance image guided radiation therapy (RgMRg-RT) for hepatocellular carcinoma (HCC). Methods: Thirty-three patients with HCC underwent RgMRg-RT in our hospital from 2015 to February 2019, including patients with Child-Pugh A/B7 cirrhosis and unresectable tumors near the gastrointestinal tract. The median radiation dose was 50 Gy (range, 25–60) and median fraction number was 5 (range, 4–15). Gating was performed based on real-time magnetic resonance image without an external surrogate. Results: The median follow-up period was 11.7 months (range, 3.6–37.9 months). The rates of local control of the target tumor at 6 months and 1 year were 90.2 and 86.9%, respectively. The overall survival rates at 6 months, 1, and 2 years were 84.3, 76.3, and 61%, respectively. The median distances from gross tumor to the esophagus, stomach, duodenum and colon were 6.1 (range, 1.9-14.3), 6.4 (0-13.4), 3.8 (0-13.5) and 4cm (0.3-13), respectively. A total of 15 tumors (45.5%) were located within 2 cm of the gastrointestinal tract and 9 tumors (27.3%) within 1cm. Grades 3 treatment‐related bleeding was observed in one patient and one patient had radiation‐induced liver disease. Conclusions: Hypofractionated RgMRg-RT was a safe and potentially ablative therapy for HCC. RgMRg-RT is a good alternative treatment for patients with HCCs that are unsuitable for surgical resection or local ablative therapy.
Levels of specific DNA fragments in the blood and their association with stages of melanoma
Authors: N. Calbet‐Llopart, M. Potrony, G. Tell‐Martí, C. Carrera, A. Barreiro, P. Aguilera, S. Podlipnik, S. Puig, J. Malvehy, J.A. Puig‐Butillé
Journal: British Journal of Dermatology (2020)

Blood plasma contains DNA fragments from dying cells, called cell‐free circulating DNA (cfDNA). In cancer patients, a fraction of their blood cfDNA comes from dying tumour cells. Therefore, key genetic alterations (mutations) from tumours might be detected in plasma from cancer patients. The analysis of cfDNA is a promising tool for the treating cancer patients, since the information from the tumour might be obtained from a blood sample, avoiding the use of ‘invasive’ methods such as tissue biopsies (samples taken by surgery, for example). Melanoma is an aggressive type of skin cancer. Each year more than 250,000 new cases are diagnosed worldwide. The p.V600E mutation in the BRAF gene (BRAFV600E) is detected in approximately 50% of melanomas. Currently, the analysis of the BRAFV600E mutation in plasma from melanoma patients can be used to monitor their disease progression. Besides tumours, the BRAFV600E mutation is frequently detected in moles on the skin, which are a risk factor to developing melanoma. To date, no information exists about the role of dying cells from moles in the detection of BRAFV600E in plasma. This study, from Spain, aimed to assess the robustness of the BRAFV600E test in plasma. The authors analysed plasma from 146 people without melanoma and from 33 melanoma patients with BRAFV600E melanomas. Melanomas are categorized from stage I to stage IV, with stage 1 as the earliest melanoma and stage IV as the most advanced. Stage I and II melanomas are present in the skin only and have not spread elsewhere in the body. Stage III have spread towards or have reached the draining lymph glands (nodes) and Stage IV melanomas are those that have spread beyond the closest draining lymph glands to other parts of the body. In this study, cell‐free circulating BRAFV600E was detected in 71% of patients with stage IV melanoma and 15% with stage III, whereas it was only detected in 1.4% of people without melanoma. The results of the BRAFV600E test in an individual were not influenced by the number of moles they had or clinical characteristics of moles (such as an unusual appearance). Additionally, they observed that melanoma patients with advanced disease showed a higher amount of BRAFV600E in plasma. Altogether, these findings indicate that the BRAFV600E test is an effective and robust tool for use with melanoma patients. This summary relates to the study: Detection of cell‐free circulating BRAFV600Eby droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance
Impact of biliary metal and plastic stents on preoperative staging for pancreatic cancer.
Authors: Hachem Hachem, Sanjay S. Reddy, Jeffrey Tokar, Eileen O'Halloran, Jennifer Higa, Abby Sapp, Albert Civitarese, Michael Bartel
Journal: Journal of Clinical Oncology (2020)

646 Background: Multiple studies have shown the superiority of biliary metal compared with plastic stents for pre-operative (preop) biliary drainage in pancreatic cancer (PDAC). Despite the importance of preop cross-sectional imaging, particularly in the era of neoadjuvant treatment, there is no data on the impact of such stents on the quality of preop cross-sectional imaging. We hypothesis, that biliary metal stents negatively impact the accuracy of preop cross-sectional imaging in pancreatic cancer, with unknown impact for the adequacy of surgical candidacy. Methods: Data of all patients undergoing pancreatic resection for PDAC between 1/1/2012 and 1/1/2018 was retrospectively abstracted. Clinical staging based on preop cross-sectional imaging following biliary stent placement (within 2 months prior surgical resection) was compared with the surgical pathology (staging gold standard). Accuracy of clinical and surgical pathology staging was compared. Logistic regression was performed to control for biliary stent type, neoadjuvant treatment and patient baseline characteristics including BMI and type of imaging. Results: 312 patients underwent pancreatic resections. 118 patients required preop biliary drainage in setting of PDAC, including 92 ERCPs of which 83 were successful (46 plastic and 37 metal stents). 76 patients underwent neoadjuvant chemoradiation therapy. Surgical pathology revealed following stages: 0 n = 4, 1A n = 5, 1B n = 8, 2A n = 20, 2B n = 24, 3 n = 1, 4 n = 14. 96% underwent preop CT and 4% MRI pancreas protocol imaging. Exact correlation between clinical and surgical pathology was present in only 48% of cases (57% plastic, 46% metal stent), with 28% of clinical T overstaging, 4% clinical T understaging, 16% clinical N understaging and 4% unable to stage due to artefacts. More importantly, 8% patients were incorrectly staged to be surgical candidates (14% plastic, 6% metal). Controlling for stent type, neoadjuvant treatment and BMI did not impact preop cross-sectional imaging accuracy. Conclusions: Despite their impact on preop cross-imaging biliary metal stents did not negatively impact the accuracy and patient selection for surgical candidacy compared with biliary plastic stents in PDAC.
Homologous recombination deficiency (HRD) scoring in pancreatic ductal adenocarcinoma (PDAC) and response to chemotherapy.
Authors: Grainne M. O'Kane, Rob Denroche, Sarah Louise Picardo, Amy Zhang, Spring Holter, Robert C. Grant, Michael Allen, Yifan Wang, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Mustapha Tehfe, James Joseph Biagi, Julie Wilson, Faiyaz Notta, Sandra Fischer, George Zogopoulos, Steven Gallinger, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2020)

741 Background: Whole genome sequencing (WGS) can reveal patterns of substitution base signatures and structural variation consistent with tumours deficient in homologous recombination repair. We evaluated the published HRDetect score and a novel HRD hallmark score (HS) in patients receiving combination chemotherapy (cCT) on the COMPASS trial for advanced PDAC. Methods: The HRD-HS incorporates 10 genomic characteristics of HRD-PDAC with a score ≥ 4 defining HRD. HRD-HS and an HRDetect score ≥0.7 were applied to WGS data and overall survival (OS) and response (ORR) evaluated. Sensitivity and specificity were ascertained. Results: As of 05/19, 205 eligible patients (pts) were enrolled and 186 received cCT including modified FOLFIRINOX n = 108 (58%) or cisplatin/gemcitabine n = 2 (1%) and gemcitabine/nab-paclitaxel n = 76 (41%). HRD-HS had a sensitivity of 87.5% and specificity of 100% in detecting HRD-PDAC. In contrast, HRDetect (≥0.7) had sensitivity of 51.9% and specificity of 100%; sensitivity increased to 73.7% when using a cutoff score of ≥0.99. 23/186 (12%) pts were classified as HRdetect hi and median OS was 15.3months (mo) vs 8.7mo in HRDetect lo pts (HR 0.44 95% CI 0.27-.70, p = 0.009). In platinum treated pts, median OS was 18.1mo (HRDetect hi ) vs 9.3mo (HRDetect lo ) (HR 0.38 95%CI 0.21-0.69, p = 0.02). HRD-HS predicted the longest median OS for platinum of 21.0mths. ORR in HRDetect hi was not different to HRDetect lo pts treated with cCT, however in those receiving platinum the ORR was 50% vs 19% respectively (p &lt; 0.001). Of the false positives by HRDetect, 46% had a non-BRCA1 tandem duplicator phenotype (TDP). The TDP group comprised 8% of all patients enrolled. HRD-PDAC was caused by inactivation of BRCA1/2, PALB2, RAD51C and XRCC2; all germline variants were pathogenic. Pathogenic ATM and CHEK2 germline variants were present in 3 pts with evidence of a second somatic hit or LOH, none of these identified as HRD by either classifier nor considered a TDP. Conclusions: HRD-HS most correctly identified HRD-PDAC however the HRDetect score classifies additional patients sensitive to cCT, especially platinum. The TDP cohort may be responsive to DNA damaging agents warranting further evaluation. Clinical trial information: NCT02750657.
RECIST v1.1 and irRECIST outcomes in advanced HCC treated with pembrolizumab (pembro).
Authors: Julien Edeline, Mark Karwal, Andrew X. Zhu, Richard S. Finn, Stéphane Cattan, Sadahisa Ogasawara, Chris Verslype, Vincenzo Dadduzio, Laetitia Fartoux, Arndt Vogel, Olivier Rosmorduc, Gontran Verset, Stephen Lam Chan, Jennifer J. Knox, Bruno Daniele, Ann-Lii Cheng, Gregory V. Goldmacher, Erin Jensen, Abby B. Siegel, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2020)

528 Background: IO can cause pseudoprogression (PP): apparent tumor growth followed by stability or favorable response. We assess PP in aHCC treated with pembro (KEYNOTE-224 [ph 2], NCT02702414; KEYNOTE-240 [ph 3], NCT02702401). Methods: aHCC pts with PD on/intolerance to sorafenib received pembro 200 mg IV Q3W until unacceptable toxicity, study withdrawal, 2 y of therapy, or RECIST v1.1 PD; if pt clinically stable at PD, physician could continue therapy and repeat scans to confirm PD per irRECIST. PP=RECIST v1.1 PD then irRECIST response other than PD. Data cutoff: Jan 02, 2019 (KEYNOTE-240); Feb 13, 2018 (KEYNOTE-224). Results: 245/382 pembro-treated pts had RECIST v1.1 PD: 138 irRECIST repeat scan; 105 PD; 33 (8.6%; 33/382) outcomes other than PD. Of 33 PP, 29 had SD, 3 PR, 1 CR (irRECIST; 29 had this at first irRECIST scan; 4 [2 SD, 2 PR] at subsequent scan). For initial RECIST v1.1 PD, 16/33 PP had PD at first postbaseline scan (pembro cycles 2-4); 17/33 PP had PD at pembro cycles 4-18. Median (range) time to RECIST v1.1 PD in the 33 PP was 80 (37-378) days. OS shown in Table. KEYNOTE-240 had 135 PBO-treated pts: 8 (5.9%) PP; small samples bar meaningful interpretation. Conclusions: PP in aHCC, per irRECIST, has a similar incidence to other cancers (eg, melanoma) and does not seem to correlate with OS. Data may help physicians assess when to continue pembro after PD. Clinical trial information: NCT02702414, NCT02702401. [Table: see text]
Evaluation of the current treatment strategies for pancreatic neuroendocrine tumors.
Authors: Kenneth Lee Meredith, Taylor Maramara, Paige Blinn, Jamie Huston, Ravi Shridhar
Journal: Journal of Clinical Oncology (2020)

611 Background: The management of pancreatic neuroendocrine tumors (PNET) varies between observation (O), pancreatic resection (PR) and enucleation (E). Currently, size, grade and location are used to determine which treatment strategy may be employed. We sought to evaluate each strategy and further clarify the role for surgery. Methods: Utilizing the National Cancer Database we identified patients with pancreatic neuroendocrine tumors. Tumors were stratified based upon size &lt;1cm, 1-2cm and &gt;2 cm. Mann-Whitney U and Kruskal were used to compare continuous variables and Pearson’s Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method. Multivariate analysis (MVA) was performed to identify predictors of survival. All statistical tests were two-sided and p&lt;0.05 was considered significant. Results: We identified 17,921 patients. (&lt;1cm, 1214, 1-2cm, 4325, and &gt;2cm, 12,382) with a median age of 61.5 (18-90). Males more often presented with tumors &gt;2cm, 56% vs 44%, &lt;0.001. Tumors &gt;2cm were more likely to be poorly differentiated (PD), p&lt;0.001, have node positive disease, p&lt;0.001 and less likely to undergo R0 resection, p&lt;0.001. Tumors &lt;1cm and well differentiated (WD) the median and overall 5-year survival in the O group was not reached (NR) (77%) vs 142.6 months (87%) in the surgery groups, p&lt;0.04; in the 1-2 cm WD group 95.7 months and 60% vs NR and 94%, p&lt;0.001. Similarly in the PD tumors &lt;1cm the median and overall survival was 32.9 months and 24% in the O vs NR and 81%, p&lt;001; in the 1-2 cm group 14.8 months and 19% vs NR and 73%, p&lt;0.001. There were no differences in survival in patients undergoing PR or E, p=0.09. MVA revealed age, grade, Charleson Deyo score, tumor size, tumor location, and surgery (PR or E) were all independent predictors of survival. Conclusions: While observation is currently an acceptable option for the management of small &lt;1cm WD PNET, we found an improvement in survival in the patients undergoing surgery. Additionally, 1-2 cm PNET benefited from the surgical approach. Enucleation and pancreatic resection did not differ in overall survival. Surgery for PNET should be considered as the first line treatment of these patients.
Diabetic charcot neuroarthropathy of the knee: Conservative treatment options as alternatives to surgery [Case report]
Authors: Ulrich Illgner, Sieds Van Netten, Carolin Droste, Klaas Postema, Thomas Meiners, Hans Wetz
Journal: Diabetes Care (2014)

In contrast to the well-known Charcot neuroarthropathy (CN) of the foot, CN of the knee is hardly recognized. In a literature search, we only found five articles on total knee arthroplasty for Charcot joints (1–5). We did not find a single article dealing with alternative treatment options or the general clinical course of this disease. We started our study
Atopic dermatitis independently increases sensitization above parental atopy: The MPAACH study
Authors: John W. Kroner, Asel Baatyrbek kyzy, Jeffrey W. Burkle, Lisa J. Martin, Grace K. LeMasters, David I. Bernstein, James E. Lockey, Patrick Ryan, Gurjit K. Khurana Hershey, Jocelyn M. Biagini Myers
Journal: Journal of Allergy and Clinical Immunology (2020)
Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.
Authors: Yu Jin Kim, Won Shik Kim, Sang Woo Kim, Woon Yong Jung
Journal: Journal of Clinical Oncology (2020)

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.