tbuckley/cabot-search huggingface dataset:
Changes in cancer detection and false-positive recall in mammography using artificial intelligence: a retrospective, multireader study
Authors: Hyo-Eun Kim, Hak Hee Kim, Boo-Kyung Han, Ki Hwan Kim, Kyunghwa Han, Hyeonseob Nam, Eun Hye Lee, Eun-Kyung Kim
Journal: The Lancet Digital Health (2020)

BackgroundMammography is the current standard for breast cancer screening. This study aimed to develop an artificial intelligence (AI) algorithm for diagnosis of breast cancer in mammography, and explore whether it could benefit radiologists by improving accuracy of diagnosis.MethodsIn this retrospective study, an AI algorithm was developed and validated with 170 230 mammography examinations collected from five institutions in South Korea, the USA, and the UK, including 36 468 cancer positive confirmed by biopsy, 59 544 benign confirmed by biopsy (8827 mammograms) or follow-up imaging (50 717 mammograms), and 74 218 normal. For the multicentre, observer-blinded, reader study, 320 mammograms (160 cancer positive, 64 benign, 96 normal) were independently obtained from two institutions. 14 radiologists participated as readers and assessed each mammogram in terms of likelihood of malignancy (LOM), location of malignancy, and necessity to recall the patient, first without and then with assistance of the AI algorithm. The performance of AI and radiologists was evaluated in terms of LOM-based area under the receiver operating characteristic curve (AUROC) and recall-based sensitivity and specificity.FindingsThe AI standalone performance was AUROC 0·959 (95% CI 0·952–0·966) overall, and 0·970 (0·963–0·978) in the South Korea dataset, 0·953 (0·938–0·968) in the USA dataset, and 0·938 (0·918–0·958) in the UK dataset. In the reader study, the performance level of AI was 0·940 (0·915–0·965), significantly higher than that of the radiologists without AI assistance (0·810, 95% CI 0·770–0·850; p<0·0001). With the assistance of AI, radiologists' performance was improved to 0·881 (0·850–0·911; p<0·0001). AI was more sensitive to detect cancers with mass (53 [90%] vs 46 [78%] of 59 cancers detected; p=0·044) or distortion or asymmetry (18 [90%] vs ten [50%] of 20 cancers detected; p=0·023) than radiologists. AI was better in detection of T1 cancers (73 [91%] vs 59 [74%] of 80; p=0·0039) or node-negative cancers (104 [87%] vs 88 [74%] of 119; p=0·0025) than radiologists.InterpretationThe AI algorithm developed with large-scale mammography data showed better diagnostic performance in breast cancer detection compared with radiologists. The significant improvement in radiologists' performance when aided by AI supports application of AI to mammograms as a diagnostic support tool.FundingLunit.
Identification of Novel CD74-NRG2α Fusion From Comprehensive Profiling of Lung Adenocarcinoma in Japanese Never or Light Smokers
Authors: Shinji Kohsaka, Takuo Hayashi, Masaaki Nagano, Toshihide Ueno, Shinya Kojima, Masahito Kawazu, Yuichi Shiraishi, Satsuki Kishikawa, Yoshiyuki Suehara, Fumiyuki Takahashi, Kazuhisa Takahashi, Kenji Suzuki, Kazuya Takamochi, Hiroyuki Mano
Journal: Journal of Thoracic Oncology (2020)

IntroductionStudies are yet to characterize the differences in molecular profiles of lung adenocarcinoma (LUAD) among divergent ethnic groups. Herein, we conducted comprehensive molecular profiling of LUAD in never or light smokers from Asia to discover novel targetable mutations and prognostic biomarkers of this distinct disease entity.MethodsWe analyzed 996 cases of Japanese LUAD and performed whole-exome sequencing and RNA-seq in 125 cases of Japanese LUAD negative for the driver oncogenes defined by conventional laboratory testing. We also investigated the clinical and pathologic characteristics among the 996 cases.ResultsDriver oncogenes were identified in 88 cases (70.4%) with specific hotspot mutations differing from those in The Cancer Genome Atlas study. Two actionable novel fusions of FGFR2 and NRG2α were also identified. Clustering on the basis of mRNA expression profiles, but not genetic mutational ones, could predict patient prognosis. The risk score generated by the expression of a three-gene set was a strong prognostic marker for overall survival and progression-free survival in our cohort, and was further validated using The Cancer Genome Atlas cohort. Among the 996 cases, each driver alteration is distributed across all histologic subtypes. Adenocarcinoma in situ was identified to harbor driver mutations, suggesting that these alterations are early events in the pathogenesis of LUAD. ERBB2 mutations were over-represented in young adults.ConclusionsThis study indicates the value of applying gene expression profiling for predicting the prognosis after a surgical operation, and that the identification of actionable mutations is important for optimizing targeted drugs in Japanese LUAD.
Clinical significance of MUC4 isoforms in pancreatic cancer patients.
Authors: Christopher M Thompson, Andrew Cannon, Prakash Kshirsagar, Rakesh Bhatia, Surinder Batra, Sushil Kumar
Journal: Journal of Clinical Oncology (2020)

742 Background: Pancreatic adenocarcinoma (PC) is a highly aggressive cancer with a 5-year survival rate around 9% with majority of patients diagnosed at advanced stage. Prior studies describe transcriptomic alterations during tumorigenesis, of which novel and progressive expression of mucins are significant. Mucins are large secreted or membrane-tethered glycoproteins that have been shown to be of pathogenic importance in PC. Methods: We explored differential expression and survival outcomes based on mucin expression using TCGA PC patients (n = 150). RNA-Seq. reads were realigned to all known mucin splice variant (SV) sequences. Hazard ratios (HR) were calculated for all SVs (n = 123), and SVs with significant HRs were plotted on Kaplan-Maier survival curves comparing expression about the median. The MUC4 SV (MUC4Δ6) was selected for validation in patient tumor samples (n = 17) due to PC tumor cell-specific expression and in-frame deletion of a single exon. After discovery of significant mucin SVs, we designed a gold-nanoparticle (GNP) assay to specifically detect MUC4Δ6 in circulation from PC patient plasma. Results: In the absence of significant mucin-based survival differences, we expanded our analysis to include mucin SV transcripts. Through hazard and survival analyses, we identified 3 MUC1 SVs with better survival (SV1 HR = .61, p = .033; SV2 HR = .64, p = .05; SV3 HR = .62, p = .04), and one each of MUC4 (HR = 1.93, p = .028) and MUC16 (HR = 1.90, p = .027) with worse prognosis. In a validation cohort, we found 10 samples had a high cellularity (HC) gene signature. Expression of MUC4Δ6 was 4804.7 copies/100,000 GPI copies in the HC population and expressors above the median had a median survival of 397 days compared to1964.5 days (p = .191) in low expressors. Our novel GNP assay detected MUC4∆6 transcripts at minimum concentrations of 100 fM with a synthetic RNA. Uniquely, our assay detects the MUC4∆6 SV but not wild-type variant. Conclusions: We were able to determine that expression of specific mucin SV are prognostic in PC patients. We developed technology to detect MUC4Δ6 transcript in circulation using a novel GNP assay. Future studies will seek to stabilize the nanoparticles and modify them for potential diagnostic purposes in a clinical setting.
The efficacy and safety of lenvatinib in patients with intermediate-stage hepatocellular carcinoma: A nationwide multicenter study in Japan.
Authors: Kaoru Tsuchiya, Masayuki Kurosaki, Azusa Sakamoto, Hiroyuki Marusawa, Chikara Ogawa, Masahiko Kondo, Kouji Joko, Keiji Tsuji, Hiroyuki Kimura, Shuichi Wada, Haruhiko Kobashi, Yasushi Uchida, Koichiro Furuta, Takehiro Akahane, Atsunori Kusakabe, Hideo Yoshida, Tomomichi Matsushita, Takehiko Abe, Tetsuro Sohda, Namiki Izumi
Journal: Journal of Clinical Oncology (2020)

548 Background: Lenvatinib (LEN) has been used in patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. We conducted a nationwide multicenter study and especially focused on the efficacy and safety in the patients with intermediate-stage u-HCC. Methods: A total of 240 patients received LEN from March 2018 at 15 sites in Japan was enrolled. Tumour assessments in accordance with modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Results: In this study, 88 of 240 (36.7%) patients were BCLC stage B. Among them 76 (86.3%) patients received TACE before LEN and the median number of TACE was 2 (1-10). Only 4 patients were TKI experienced and other 84 (95.5%) patients received LEN as a 1st line therapy. The median pretreatment ALBI score was -2.35 and 75 (85.2%) patients were Child-Pugh A. In this cohort, 73 (83.0%) patients were beyond up-to-seven criteria and the median pretreatment AFP was 38.2 (2-12870) ng/mL. The median observation time was 8.5 months and 16 patients died. The median progression free survival was 8.7 months, and the median overall survival (OS) was not reached. Objective response rate (ORR) and disease control rate (DCR) were 48.5% and 80.3%. AFP decrease ( &gt; 20%) after 1 month was observed in 52 (59.0%) patients. Child-Pugh B patients (n = 13) had significantly shorter OS than Child-Pugh A (p = 0.02) and median OS in Child-Pugh B patients was 8.8 months. The patients received &gt; 6 times TACE before LEN had significantly shorter OS than patients received ≤ 6 times TACE (p = 0.02). Additional TACE was performed in 8 patients and The median time of restarting LEN was 19 days. The median ALBI score before additional TACE, Day 1 after TACE and Day 28 after TACE were -2.38, -2.07, and -2.36.There was no severe adverse event associated with additional TACE. The median duration of LEN in patients treated with LEN and additional TACE was 8.5 months. Conclusions: The ORR and DCR of LEN in Child-Pugh A patients with intermediate-stage HCC were 46.6% and 79.3%. The therapeutic strategies for intermediate-stage HCC should be discussed based on the liver function, tumor states, and treatment course about TACE.
A hospital based rapid respiratory response team
Authors: J G Williams, B Critchlow, B Furnival, J Meek, S Furlong, R Smith
Journal: Thorax (1998)

An audit of admissions due to respiratory disease to our hospital cited insufficient home support as the precipitating reason for 30% of cases. A hospital based respiratory team consisting of a specialist nurse, physiotherapist and two nurses was established to see if these admissions could be reduced by providing support in the home. Referrals were taken from general practitioners and hospital firms. 130 referrals deemed suitable for home based care by stringent criteria were made between 1.12.97 and 31.5.98, 70 from G.P.'s and 60 from the hospital. Only 7/70 of the G.P. referrals had to be admitted. 12/60 hospital referred patients had to be readmitted for their respiratory disease. The number of patients kept out of hospital represented 10% of the all acute admissions during the study period. By 31.5.98, 49 patients were still being seen at home, 63 had been discharged and 4 were in hospital. 14 patients had died primarily due to their underlying lung disorder.
Lateral lymph node dissection after neoadjuvant (chemo)radiotherapy may improve oncological outcomes in Western patients with low rectal cancer.
Authors: Hidde Maarten Kroon, Songphol Malakorn, Nagendra N Dudi-Venkata, Sergei Bedrikovetski, Jianliang Liu, Brian K. Bednarski, Atsushi Ogura, Cornelis J. H. Van De Velde, Harm Rutten, Geerard Beets, Michelle Thomas, Miranda Kusters, George J. Chang, Tarik Sammour
Journal: Journal of Clinical Oncology (2020)

163 Background: In the West, rectal cancer patients with pre-treatment abnormal lateral lymph nodes (LLN) are commonly treated with neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Few centers perform lateral lymph node dissection (LLND) in addition to this, with the aim of improving oncological outcomes. To date, no comparative data are available in Western patients. Methods: An international multi-center cohort study was conducted comparing six centers from the Netherlands and Australia treating patients with abnormal LLN (≥5mm short-axis) with n(C)RT and TME (LLND- group) versus similarly staged patients from a dedicated cancer center in the USA who underwent a LLND in addition to n(C)RT and TME (LLND+ group). Results: Data were available on 169 patients. LLND+ patients (n = 44) consisted of significantly younger and more female patients with higher ASA-scores and ypN-stages compared to LLND- patients (n = 115). LLND+ patients also had a larger median LLN short-axis and were more likely to receive adjuvant chemotherapy (100 vs. 30%; p &lt; 0.0001). Between groups, the lateral local recurrence rate (LLRR) was 0% for LLND+ vs. 7% for LLND- (p = 0.09) and the local recurrence rate (LRR) was 3% for LLND+ vs. 11% for LLND- (p = 0.13). No significant differences were observed in disease-free survival (DFS, p = 0.94) or overall survival (OS, p = 0.42). Sub-analysis of patients who underwent adjuvant chemotherapy (LLND- patients: n = 35) demonstrated clinically relevant though non-statistically significant trends towards a lower LLRR (0% for LLND+ vs. 6% for LLND-; p = 0.07), LRR (3% for LLND+ vs. 14% for LLND-; p = 0.06), DFS (p = 0.19) and OS (p = 0.17) in favour of the LLND+ group. Conclusions: Lateral lymph node dissection in addition to neoadjuvant (chemo)radiotherapy may improve oncological outcomes in Western patients with low rectal cancer and abnormal lateral lymph nodes.
Development of a new patient‐reported outcome measure to assess activities and participation in people with systemic sclerosis: the Cochin 17‐item Scleroderma Functional scale
Authors: C. Daste, H. Abdoul, F. Foissac, A. Papelard, S. Alami, L. Kwakkenbos, M.‐E. Carrier, M.‐M. Lefèvre‐Colau, B.D. Thombs, S. Poiraudeau, F. Rannou, L. Mouthon, C. Nguyen
Journal: British Journal of Dermatology (2020)

Patient-reported outcome measures (PROMs) aimed at assessing people with systemic sclerosis (SSc) have rarely involved the target population in the item- and domain-generation stage of the instrument construction.To develop a new PROM assessing activities and participation in people with SSc.A provisional International Classification of Functioning, Disability and Health (ICF)-based 65-item questionnaire previously developed from interviews of people with SSc was sent by email to all patients followed in the internal medicine department of Cochin hospital (n = 184) and enrolled in the Scleroderma Patient-centered Intervention Network Cohort. Items were reduced according to their metric properties. Dimensional structure of the questionnaire was assessed by principal component analysis, convergent and divergent validities by Spearman's rank correlation coefficient, internal consistency by Cronbach's α, and reliability by a test-retest method using the intraclass correlation coefficient (ICC) and Bland-Altman analysis.Overall, 113 of 184 patients (61·4%) completed the provisional questionnaire. The item-reduction process resulted in a 17-item questionnaire, the Cochin 17-item Scleroderma Functional scale (CSF-17). Principal component analysis extracted two dimensions: 10 items related to mobility (CSF-17 section A) and seven items related to general tasks (CSF-17 section B). We observed convergent validity of the CSF-17 total score with global activity limitation, pain, depression and aesthetic burden, and divergent validity with anxiety. Cronbach's α was 0·94 for section A and 0·95 for section B. ICC (n = 25 patients) was 0·92 for the CSF-17 total score. Bland-Altman analysis did not reveal a systematic trend for the test-retest.The CSF-17 is a new PROM assessing activities and participation specifically in people with SSc. Its content and construct validities are very high. What is already known about this topic? In the earliest stages of construction patient-reported outcomes (PROMs) for people with systemic sclerosis (SSc) rarely involve the target population. Instruments able to capture the specific needs of people with SSc in terms of activities and participation are lacking. What does this study add? The Cochin 17-item Scleroderma Functional Scale (CSF-17) is a new PROM assessing global activities and participation specifically in people with SSc. Patients' perspectives were prioritized at all stages of construction. What are the clinical implications of this work? The CSF-17 could be used in clinical practice and research to assess the efficacy of complex multidisciplinary interventions targeting activity limitations and participation restriction in people with SSc. Linked Comment: Clark and Denton. Br J Dermatol 2020; 183:610.
Testing different thresholds for patient global assessment in defining remission for rheumatoid arthritis: are the current ACR/EULAR Boolean criteria optimal?
Authors: Paul Studenic, David Felson, Maarten de Wit, Farideh Alasti, Tanja A Stamm, Josef S Smolen, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2020)

This study aimed to evaluate different patient global assessment (PGA) cut-offs required in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission definition for their utility in rheumatoid arthritis (RA).We used data from six randomised controlled trials in early and established RA. We increased the threshold for the 0-10 score for PGA gradually from 1 to 3 in steps of 0.5 (Boolean1.5 to Boolean3.0) and omitted PGA completely (BooleanX) at 6 and 12 months. Agreement with the index-based (Simplified Disease Activity Index (SDAI)) remission definition was analysed using kappa, recursive partitioning (classification and regression tree (CART)) and receiver operating characteristics. The impact of achieving each definition on functional and radiographic outcomes after 1 year was explored.Data from 1680 patients with early RA and 920 patients with established RA were included. The proportion of patients achieving Boolean remission increased with higher thresholds for PGA from 12.4% to 19.7% in early and 5.9% to 12.3% in established RA at 6 months. Best agreement with SDAI remission occurred at PGA cut-offs of 1.5 and 2.0, while agreement decreased with higher PGA (CART: optimal agreement at PGA≤1.6 cm; sensitivity of PGA≤1.5 95%). Changing PGA thresholds at 6 months did not affect radiographic progression at 12 months (mean ꙙsmTSS for Boolean, 1.5, 2.0, 2.5, 3.0, BooleanX: 0.35±5.4, 0.38±5.14, 0.41±5.1, 0.37±4.9, 0.34±4.9, 0.27±4.7). However, the proportion attaining HAQ≤0.5 was 90.2%, 87.9%, 85.2%, 81.1%, 80.7% and 73.1% for the respective Boolean definitions.Increasing the PGA cut-off to 1.5 cm would provide high consistency between Boolean with the index-based remission; the integer cut-off of 2.0 cm performed similarly.
Exceptional responses to ipilimumab/nivolumab (ipi/nivo) in patients (pts) with refractory pancreatic ductal adenocarcinoma (PDAC) and germline BRCA or RAD51 mutations.
Authors: Gretel Terrero, Terri Pollack, Daniel A. Sussman, Albert Craig Lockhart, Peter Joel Hosein
Journal: Journal of Clinical Oncology (2020)

754 Background: Immune checkpoint inhibitors (ICI’s) have not shown meaningful clinical activity in unselected pts with PDAC. BRCA-deficient tumors have increased genomic instability, including increased tumor mutation burden (TMB), more tumor-infiltrating immune cells, and enrichment of a T cell-inflamed signature. We hypothesized that pts with mutations in BRCA or other homologous recombination repair genes may be sensitive to ICI’s. Methods: Utilizing the IRB-approved PDAC database at the University of Miami, we identified pts with relapsed/refractory PDAC with pathogenic germline mutations who were treated with combination ICI’s (ipi 1mg/kg and nivo 3mg/kg every 21 days followed by nivo 240mg every 2 weeks). Results: Five pts were identified (1 BRCA1, 2 BRCA2, 1 RAD51C and 1 RAD51D). Among the 3 evaluable pts, there was one complete response (CR), one partial response (PR) and one had progressive disease (PD). The pt with a CR had BRCA1; he had resection followed by adjuvant gem/cape and had a biopsy-proven recurrence in the lung and retroperitoneum 1y after the end of adjuvant therapy. He received ipi/nivo at recurrence and achieved a CR, ongoing for 17m on nivo maintenance. The patient with a PR had RAD51C; he was diagnosed with mPDAC and received FOLFIRINOX for 6m, followed by olaparib on a trial for 12m. Upon PD, the disease quickly progressed on 5FU/liposomal irinotecan, gemcitabine/nab-paclitaxel/cisplatin and FOLFIRINOX. He then started ipi/nivo with immediate improvement in pain and tumor markers. A radiological PR was seen after 2 doses and is ongoing for 3m with continued clinical and tumor marker improvement. The 3rd evaluable pt had BRCA2 and had PD with an exponential rise in tumor markers accompanied by clinical deterioration. Response data on the final two pts were pending at the time of submission and will be presented at the meeting. Conclusions: In this biomarker selected cohort, 2 out of 3 evaluable pts with PDAC had impressive responses to ipi/nivo. PDAC has generally been refractory to ICI therapy but this series suggests that this subgroup may be responsive to ICI’s. Further evaluation is warranted.
A real-world evidence analysis of periampullary cancers in an academic hospital in Chile.
Authors: Luis Villanueva, Gonzalo Navarrete, Ivan Gallegos, Valentina Castillo, Francisco Dodds, Jaime Gonzalez, Olga Barajas, Rodrigo Vasquez, Barbara Nuñez, Monica Ahumada
Journal: Journal of Clinical Oncology (2020)

663 Background: Periampullary cancers can originate in the pancreas, duodenum, bile duct or structures of the ampullary complex. The treatment of choice in early stages is pancreatoduodenectomy. The management post-surgery can depend on the histology pattern, and the overall survival can vary in different subgroups. Methods: A retrospective cohort study. We examined patients (pts) with invasive periampullary cancer undergoing pancreatoduodenectomy at the Hospital Clinico Universidad de Chile between 2002 to 2018. We analyzed epidemiological, clinical, surgical, and histological data. OS and the hazard ratio (HR) were established by GraphPad Prism 8.0. Results: Thirty-seven cases were registered. Twenty-two (59%) pts were men. The mean age was 62.5 (43-83 years). The histological subtypes were: 15 pts (40.5%) intestinal group (IN), 20 pts (54%) pancreatobiliary group (PB), 1 pt (2.7%) mixed and 1 pt (2.7%) signet ring cell type. A full concordance between histology and immunohistochemistry (CK20, CK7, CDX2, MUC1, and MUC2) patterns was 66% of the PB group, and 0% of the IN group. The stage IB was most frequent in all of the group (36,4%). The most frequent stages were IB (66,6%) in the IN type and IIIA (46%) in the PB type. The level of Ca19-9 was higher the PB group than IN group (629.7 versus 41.5 U/ml, respectively). Seven pts received postoperative adjuvant treatment such as FOLFOX, capecitabine, and gemcitabine. The median OS was 133,5 months (mo) in the intestinal group and 32,6 mo in PB group (P-value = 0.021). The HR was 0.38 (95% CI of ratio 0.1332 to 1.084). The 5-year OS was 75,2% and 45,7% in the IN and PB group, respectively. Conclusions: Periampullary cancer remains very challenging because it is a rare malignancy and present diverse histological pattern. These factors influence the behavior and OS of the disease. Our results showed clinically and statistically relevant differences in the staging, levels of Ca19-9, and OS of the IN and PB subtypes. Our patients received few post-operatory therapies such as chemotherapy; this factor could influence the OS in the high-risk group. According to our data, a personalized treatment by histological type should consider in this disease.