tbuckley/cabot-search huggingface dataset:
Multi-slice computed tomography manifestation of primary pulmonary sarcomatoid carcinoma
Authors: Kai Jiang, Shengde Deng, Zhiqiang Cai, Huanhuan Chen, Yutao Wang, Yu Xu
Journal: BMJ (2015)

Retrospective analysis of multi-slice computed tomography (MSCT) manifestations were conducted for 8 cases of pathologically confirmed primary pulmonary sarcomatoid carcinoma. And the relevant literature was also reviewed. The lesion sites were right upper lobe (n=5), lower lobe (n=2) and left upper lobe (n=1). One case was difficult to distinguish because of its huge mass and the remainder was all peripheral. With pseudocapsule (n=4), coarse calcification (n=1), hilar & mediastinal node metastasis (n=2) and cavity (n=1). The manifestations included extensive lung alveolar septal thickening & ground glass (n=1) and massive deep leaf & glitches (n=2). The scans were non-enhanced alone (n=1) and non-enhanced & enhanced (n=7). Six cases had shaped enhancement while another 5 uneven thickness of annular enhancement. And 4 cases had floating-ice change. Primary pulmonary sarcomatoid carcinoma is common in subpleural lung lobe. And the floating-ice sign is valuable in the diagnosis of sarcomatoid carcinoma.


Key words: 
Lung; Primary sarcomatoid carcinoma
Emerging clinical phenotype of bone metastatic urothelial cancer (mUC): Association of early osseous metastases (EOM) and outcomes.
Authors: Ariel Ann Nelson, Robert Cronk, Aniko Szabo, Emily Lemke, Thomas A. Giever, John D. Burfeind, Deepak Kilari, Matthew John Riese, Kathryn A. Bylow, Leonidas Nikolaos Diamantopoulos, Ali Raza Khaki, Behtash Nezami, Gregory MacLennan, Mary Ann Draves, Gordon Goolamier, Samantha Rosey, Adam Calaway, Petros Grivas, Lee Evan Ponsky, Christopher J. Hoimes
Journal: Journal of Clinical Oncology (2020)

e17007 Background: Outcomes of patients (pts) with mUC with EOM have not thoroughly been described in the age of immuno-oncology. We hypothesized that EOM is associated with worse outcomes when compared to pts with non-osseous metastases (NOM). Methods: We used a multi-institutional database of pts with mUC who received systemic treatment (trt) between March 2005 and August 2019, to assess survival and palliative outcomes of pts with EOM vs NOM at the time of metastatic diagnosis (met dx). Wilcoxon rank-sum and chi-square tests were performed. Survival was estimated by Kaplan-Meier method, Cox regression analysis was performed. Results: We identified 270 pts, 72% men, mean age 67 ± 11 years, 28% never smokers. At met dx, 27% (n = 72) had ≥ 1 EOM; these pts were more likely to have de novo metastases vs. those with recurrent metastases (42% vs 19%, p &lt; 0.001). Pts with EOM were more likely to have a change or stop in 1st line trt due to clinical progression (30.6% vs 15.7%, p = 0.006), and received fewer total lines of systemic trt, median of 1.0 (1.0-5.0) vs. 2.0 (1.0-8.0), p = 0.05. Pts with EOM had shorter median overall survival (OS) vs. those with NOM, (6.1 vs 13.7 months, p &lt; .0001), HR = 2.79 (95% CI:1.95-3.97, p &lt; .0001). Median OS was shorter for pts with EOM who received 1 st line immune checkpoint inhibitor (n = 14) vs platinum-based chemotherapy (n = 43), (1.6 vs 9.1 months, p = 0.003). Pts with EOM received higher opioid analgesic doses at the first and last oncology outpatient visits compared to pts with NOM with mean morphine milligram equivalent (MME) dose of 60 ± 91 vs 28 ± 65 at first visit, p = 0.004, and 171 ± 214 vs. 94 ± 229 at last visit, p &lt; 0.001. Conclusions: The presence of EOM in mUC is associated with worse outcomes vs. pts with NOM. Pts with EOM may benefit from 1 st line platinum-based chemotherapy vs. checkpoint immunotherapy. Furthermore, pts with EOM experience more pain than pts with NOM and may benefit from early engagement with palliative care. Pts with EOM represent a population with a highly unmet need for systemic, targeted and/or radiation interventions. Molecular subtypes may further define these pts and analysis is planned. We encourage ongoing clinical trials to report outcomes in pts with EOM. A consensus on reporting of non-measurable disease is also needed. [Table: see text]
Machine learning-based identification of predictive features of the tumor micro-environment and vasculature in NSCLC patients using the IMpower150 study.
Authors: Amaro Taylor-Weiner, Andrew Beck, James Donovan Cowan, Hunter Elliott, Jane Fridlyand, Benjamin Glass, Ellie Guardino, Priti Hegde, Jennifer K Kerner, Aditya Khosla, Mark Lee, Yi Liu, Mark McCleland, Michael Montalto, Katja Schulze, David S. Shames, Ramprakash Srinivasan, Wei Zou, Ilan Wapinski, Jennifer Margaret Giltnane
Journal: Journal of Clinical Oncology (2020)

3130 Background: IMpower150 is a phase 3 study measuring the effect of carboplatin and paclitaxel (CP) combined with atezolizumab (A) and/or bevacizumab (B) in patients with advanced nonsquamous NSCLC, testing the hypothesis that anti-PD-L1 therapy may be enhanced by the blockade of VEGF. Here, we apply a machine-learning based approach to quantify the tumor micro-environment (TME) and vasculature and identify associations with clinical outcome in IMpower150. Methods: Digitized H&amp;E images were registered onto the PathAI research platform (n=1027). Over 200K annotations from 90 pathologists were used to train convolutional neural networks (CNNs) that classify human-interpretable features (HIFs) of cells and tissue structures from images. Blood vessel compression (BVC) indices were calculated using the long versus short axes for each predicted blood vessel. HIFs were clustered to reduce redundancy, and selected features were associated with progression free survival (PFS) within each arm (ABCP, ACP, and BCP) using Cox proportional hazard models. Results: We used the trained CNNs to generate 4,534 features summarizing each patient’s histopathology and TME. After association with survival and correction for multiple comparisons we identified clusters that were significantly associated with survival in at least one arm. Among patients receiving treatments that target PD-L1 (ABCP and ACP), high lymphocyte to fibroblast ratio (LFR) was associated with improved PFS (HR=0.64 (0.51, 0.81), p &lt; 0.001) and showed no significant association with PFS among patients treated with BCP alone (HR=1.13 (0.85, 1.51), p=0.4). Among BCP treated patients, a higher average BVC within the tumor tissue was associated with improved PFS (HR=0.67 (0.50,0.90), p=0.01) and worse PFS among patients treated with ACP (HR=1.50 (1.10,2.06), p=0.009). Conclusions: We developed a deep learning-based assay for quantifying pathology features of the TME and vasculature from H&amp;E images. Application of this system to Impower150 identified an association between high LFR and improved PFS among patients receiving PD-L1 targeting therapy, and between low BVC and improved PFS among patients receiving BCP. These findings support the importance of the TME and vasculature in determining response to PD-L1 and VEGF-targeting therapies.
Do assumptions in health economic evaluations hamper drug uptake?
Authors: Fanny Franchini, Koen Degeling, Amanda Pereira-Salgado, Ben Tran, George Au-Yeung, Grant A. McArthur, Belinda Lee, Benjamin J. Solomon, Peter Gibbs, Maarten J. IJzerman
Journal: Journal of Clinical Oncology (2020)

e19289 Background: Health economic studies of anti-cancer systemic treatments typically make strong assumptions regarding the number of drug lines received after initial therapy. This may have a substantial effect on health economic outcomes and impact drug reimbursement and uptake in practice. This study aims to quantify the real-world systemic treatment patterns in 4 metastatic cancers using clinical registries to explore whether health economic assumptions are justifiable. Methods: Data from 4,431 metastatic cancer patients were extracted from Australian clinical registries: colorectal (COL, n = 3087), non-small cell lung (LUN, n = 705), pancreatic (PAN, n = 459), and melanoma (MEL, n = 180). A set of criteria was defined to consistently identify drug lines across the cancer-specific registries. These criteria were based on the type of drug (biological agent or chemotherapy), switches in chemotherapy regimen (whether a chemotherapy agent was added or removed) and the timing of such changes. Consequently, the identified drug lines provide a more detailed view on treatment patterns compared to clinical treatment lines (defined by disease progression), the latter typically including multiple drug lines. Censoring in the number of drug lines received due to ongoing treatment was accounted for in all analyses. Results: Most patients started treatment after diagnosis: 77% (COL), 89% (LUN), 56% (PAN) and 79% (MEL). For COL, LUN, PAN and MEL respectively, the proportion of patients starting a 2nd drug line was 51%, 60%, 19% and 24%, whereas 28%, 35%, 6% and 8% of patients started a 3rd drug line. In all cancers, patients were most likely to receive only a single drug line, i.e. the mode number of drug lines was 1. For all patients, the median number of drug lines were COL: 2, LUN: 2, PAN: 1, MEL: 1. For treated patients only, the median (range) number of drug lines received was COL: 2 (1-9), LUN: 2 (1-8), PAN: 1 (1-5), MEL: 1 (1-5). Conclusions: We show that patients are most likely to receive a single drug line. Considering our findings, most health economic analyses likely overestimate the intensity of drug treatment in metastatic disease, thereby underestimating the impact of initial treatment relative to downstream treatments. This is likely to bias estimates of total treatment cost, cost-effectiveness and budget impact, which will hamper the uptake of novel anti-cancer agents and may lead to suboptimal decisions regarding treatment strategies.
Development and validation of a pediatric disease risk index for allogeneic hematopoietic cell transplantation.
Authors: Muna Qayed, Carrie L Kitko, Kwang Woo Ahn, Mariam H Johnson, Kirk R. Schultz, Angela R. Smith, Gregory A Yanik, Mary Eapen
Journal: Journal of Clinical Oncology (2020)

7503 Background: Characteristics such as disease, disease status and cytogenetic abnormalities impact relapse and survival after transplantation for acute myeloid (AML) and acute lymphoblastic (ALL) leukemia. In adults, these attributes were used to derive the disease risk index for survival. Thus, the current analysis sought to develop and validate a pediatric disease risk index (p-DRI). Methods: Eligible were patients aged &lt;18 years with AML (n=1135) and ALL (n=1228) transplanted between 2008 and 2017 in the United States. Separate analyses were performed for AML and ALL. Patients were randomly assigned (1:1) to a training and validation cohort. Cox proportional hazards model with stepwise selection was used to select significant variables (2-sided p&lt;0.05). The primary outcome was leukemia-free survival (LFS; relapse or death were events). Based on the magnitude of log(HR), a weighted score was assigned to each characteristic that met the level of significance and risk groups were created. Results: Four risk groups were identified for AML and three risk groups for ALL (Table). The 5-year probabilities of LFS for AML were 81% (68-91), 56% (51-61), 44% (39-49) and 21% (15-28) for good, intermediate, high and very high-risk groups, respectively. The 5-year probabilities of LFS for ALL were 68% (63-72), 50% (45-54) and 15% (3-34) for good, intermediate, high risk groups, respectively. Conclusions: This validated p-DRI successfully stratified children with AML and ALL for prognostication undergoing allogeneic transplantation. [Table: see text]
血管紧张素转换酶抑制剂和血管紧张素II受体拮抗剂对糖尿病肾病患者肾保护作用的临床研究
Authors: 何新霞, 薛燕, 韩卫红, 王红燕, 王艳飞
Journal: BMJ (2007)

对120例合并有轻、中度肾损害的2型糖尿病患者,在常规糖尿病治疗的同时分别予血管紧张素转换酶抑制剂(贝那普利)、血管紧张素Ⅱ受体拮抗剂(厄贝沙坦)及两者联合治疗.治疗8周后24 h尿蛋白排泄较治疗前均显著降低,以联合治疗的减少最为明显.提示血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂对2型糖尿病肾病患者有很好的肾脏保护作用。
Oncology team perception and patient experience discordances in triple-negative breast cancer (TNBC) care.
Authors: Sara A. Hurvitz, Rebecca R Crawford, Tamar Sapir, Jeffrey D. Carter
Journal: Journal of Clinical Oncology (2020)

e19176 Background: In TNBC, ensuring patients understand their treatment options and engaging them in shared decision-making (SDM) is vital to patient centered care; however, system-, team-, and individual-level barriers may challenge optimal SDM. As part of a quality improvement, accredited initiative, we identified areas of discordance between oncology healthcare professionals (HCP) perception and actual patient reported experiences. Methods: From 02/2019 – 10/2019, we administered surveys to assess challenges, barriers, attitudes, and experiences of HCP who care for patients with TNBC (N = 77) and their patients with TNBC (N = 65) at 6 community oncology practices. Results: Despite indications of high levels of SDM – 86% of patients indicated that they are always or mostly involved with treatment decisions – survey responses highlight discordances. For example, when asked to identify the most influential factors to patient treatment choice, HCP most commonly indicated side effects (94%), while patients most commonly indicated quality of life (48%). Additionally, when asked to identify the side effect of greatest concern to patients, 61% of patients indicated alopecia, while 45% of HCP indicated gastrointestinal (GI) distress. While both HCP and their patients indicate that the oncology team is the most useful source of patient education, HCP underestimated the extent to which patients rely on their primary care providers (PCPs). Patients and HCP each identified limited time as a barrier to SDM, but patients indicated not knowing what to ask, while HCP indicated that low health literacy was the top barrier to SDM. 31% of patients and their care team identified that improvements in discussions about realistic prognosis were vital to improved care. Conclusions: These survey findings reveal discordances between oncology HCP’s perceptions and patient reported experiences when receiving treatment for TNBC. These findings may highlight areas for improvement in co-productive patient-centered care. [Table: see text]
Covid-19: Papers justifying government’s plans to reopen schools are “inconclusive,” say union bosses
Authors: Adrian O’Dowd
Journal: BMJ (2020)

Several documents presented to the UK government from its scientific advisers analysing how and when it may be safe to reopen schools in England on 1 June have now been released after pressure from experts and trade unions. However, the papers have not reassured unions and experts about the wisdom of the timetable and have been described as containing “inconclusive” evidence.

The government’s advisory body, the Scientific Advisory Group for Emergencies (SAGE), has produced several documents1 looking at various scenarios or “options” for relaxing school closures that were implemented in March because of the coronavirus.

One of these documents says, “There is substantial uncertainty, with the relative contribution of school openings being driven also by the relative susceptibility and infectivity of children of different ages compared to adults, as …
Survival benefit of oophorectomy in stage IV gastric cancer patients with Krukenberg tumors.
Authors: Ahmed Abdelhakeem, Brian D. Badgwell, Naruhiko Ikoma, Larissa Meyer, Meina Zhao, Anh Ta, Prajnan Das, Tara L. Sagebiel, Rebecca E Waters, Jeannelyn Estrella, Jaffer A. Ajani, Mariela A. Blum-Murphy
Journal: Journal of Clinical Oncology (2020)

e16566 Background: The management of Krukenberg tumors from primary gastric cancer remains unclear and it is unknown if oophorectomy improves survival. The purpose of this study was to compare the overall survival (OS) of patients with ovarian metastases from gastric cancer treated with standard chemotherapy to chemotherapy and oophorectomy. Methods: Between January 2008 and August 2019, we retrospectively analyzed the clinicopathological features and treatment data of 97 patients with stage IV gastric cancer patients with ovarian metastases. Patients were categorized into two groups: Oophorectomy plus standard chemotherapy treatment vs. standard chemotherapy only (non-oophorectomy). The primary objective was to assess OS. Results: A total of 97 patients were identified. 37 (38.1%) patients had oophorectomy and 60 (61.9%) patients did not have oophorectomy. OS was better in the oophorectomy group relative to the non-oophorectomy group (37 months vs. 20 months; P= 0.0554). Survival from the time of diagnosis of ovarian metastases was significantly better in oophorectomy group relative to the non-oophorectomy group (26 months vs. 12 months; P= 0.0006). Conclusions: Our results showed that Oophorectomy in addition to systemic chemotherapy in this unique population seems to confer survival advantage in this retrospective analysis. Prospective evaluation is warranted.
BRCA testing concordance with national guidelines for patients with breast cancer in community cancer programs.
Authors: Leigh Boehmer, Latha Shivakumar, Christine B. Weldon, Julia Rachel Trosman, Stephanie A. Cohen, Dawn Nixon, Zohra Ali-Khan Catts, Susan Miesfeldt, Stephanie Wiryaman, Lorraine Tafra, Lisa Muto, Natalie Fadrowski, Melissa Hulvat, Tiana Pallister, Charles Hendrix Shelton
Journal: Journal of Clinical Oncology (2020)

1526 Background: Current National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment state that testing for highly penetrant breast/ovarian cancer genes is clinically indicated for women with early onset (≤ 45 years) or metastatic HER-2 negative breast cancer. A recent Association of Community Cancer Centers (ACCC) survey (N = 95) showed that &gt; 80% of respondents reported ≤ 50% testing rate of patients with breast cancer who met guidelines. Given this disconnect, ACCC partnered with 15 community cancer programs to assess practice gaps and support interventions to improve access to genetic counseling (GC)/testing. Methods: Pre-intervention data from 9/15 partner programs for women diagnosed with stages 0-III breast cancer between 01/01/2017 and 06/30/2019 was collected. De-identified variables included: family history documentation, GC appointment/test results, and timing of results relative to treatment decisions. Results: There were 2691 women with stages 0-III breast cancer. Forty-eight percent (1284/2691) had a documented high-risk family history, 57% (729/1284) of whom had a GC appointment. This was a significantly higher rate of GC compared to the 23% (181/778) of women with no family history and 6% (35/629) of women with no documentation of family history (p &lt; 0.0001). Patients ≤ 45 years old attended a GC appointment 72% (199/278) of the time and 49% (135/278) had genetic test results, with 84% (113/135) receiving results before surgery. For women with test results available before surgery, 37% (119/322) had breast conserving surgery, compared to 60% (144/240) with test results disclosed post-operatively (p &lt; 0.0001). Conclusions: Genetic testing is underutilized in a community cohort of women with breast cancer. Further analysis is needed to understand the impact genetic test results have on surgical decisions. Opportunities exist to improve current rates of appropriate GC/testing. ACCC will share results of quality improvement projects to illuminate which strategies hold promise in reducing the hereditary breast cancer GC/testing practice gap.
Prognosis of breast cancer patients with initial bone metastasis: A population-based study.
Authors: Deyue LIU, Jiayi Wu, Li Zhu
Journal: Journal of Clinical Oncology (2020)

e13081 Background: Metastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases. Methods: From 2010 to 2015, 6860 breast cancer patients diagnosed with initial bone metastasis were analysed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk group differentiated by nomogram. Results: Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age ( &lt; 60 years old), white race, lower grade, lower T stage ( &lt; = T2), not combining organ metastasistend to have better outcome. About 37% (2249) patients received surgery of primary tumor. Patients of all subtypes can benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery is performed. While patients of bone and brain patients cannot benefit from surgery (p = 0.05). The C-index of nomogram is 0.68. A cutoff value of nomogram point was identified by ROC curve as 93 points, which divided all patients into low-risk group and high-risk group. Patients of both groups showed better overall survival when receiving surgery. Conclusions: Our study has provided population-based nomogram in patients with initial bone metastatic breast cancer. The finding of potential benefit of surgery to overall survival will cast some light on the treatment tactics of this group of patients.
Comparative assessment of different radiological criteria to identify paradoxical hyperprogression (HPD) to IO drugs.
Authors: Ana Luiza Gomes de Morais, Jose M Cardenas, Maria Jose de Miguel Luken, Valentina Boni, Irene Moreno, Gerileto Ao, Run Han Liu, Fernando Bergaz de Hoyos, Antonio Cubillo, Emiliano Calvo
Journal: Journal of Clinical Oncology (2020)

e15229 Background: HPD is a new pattern of response consisting of accelerated tumor growth due to immunotherapy (5%-20% of pts on IO drugs). The tumor growth rate (TGR, Champiat et al.) estimates the differential increase in tumor volume over time, pre- and on IO drugs, to assess for HPD, but it is not easily calculated in practice. A comparison of the different methods to identify HPD is missing. Methods: Retrospective study of 182 consecutive pts treated in Phase 1 studies of IO drugs at START Madrid-CIOCC in 2017-8, comparing 3 HPD measurement criteria (Champiat, Matos -which does not use pre-baseline CT scans-, and Saâda-Bouzid). Cohen’s Kappa index was calculated as a measure of the agreement between the 3 methods, being those values closer to 1 the more concordant ones. Overall survival (OS) rates were calculated by Kaplan-Meier (p &lt; 0.05 to be significant). Results: 99 (54%) of 182 pts had progressive disease at cycle 1 of treatment and in 62 (34%) pre-baseline CT scans were available to calculate TGR. The Champiat method identified 18 (9.9%) pts with HPD. Of 61 cases validated to comparison, the Matos criteria labeled 27 pts (14.8% of 182) with HPD, of whom only 10 pts coincided with those identified by Champiat with a low agreement (Kappa: 0.140, p:0.251). No significant differences in OS between pts with non-HPD vs HPD by Matos criteria were seen (p = 0.16). With Saâda-Bouzid method, of 59 cases validated to comparison, 17 pts (9.3% of 182) were labeled with HPD and 13 of them coincided with those identified by Champiat method with a high agreement (Kappa:0.706, p:0.000). Differences in OS between non-HPD vs HPD pts were statistically significant (p = 0.038). Conclusions: HPD might have a detrimental effect to 10% of pts on IO drugs, also in our series. Every effort should be done to obtain pre-baseline CT scans to identify HPD response to IO drugs, based on differential TGR. The use of Saâda-Bouzid method is preferred due to its practical application and its correlation with survival. [Table: see text]