tbuckley/cabot-search huggingface dataset:
The Prospective Dutch Colorectal Cancer (PLCRC) Cohort: Towards a unique patient-reported outcome enriched “real-world” data cohort.
Authors: Jeroen W.G. Derksen, Marloes A.G. Elferink, Geraldine R. Vink, Jeanine M.L. Roodhart, Anne Maria May, Miriam Koopman
Journal: Journal of Clinical Oncology (2020)

52 Background: The initiation of high-quality pan-population cohort studies is a major research priority for the improvement of colorectal cancer (CRC) outcomes as advocated by regulators and the research community. In 2013, the PLCRC cohort of the Dutch Colorectal Cancer Group was initiated in which longitudinal clinical data and patient-reported outcomes (PRO) are collected, along with pathology data and biospecimens, to serve as an infrastructure for a broad body of observational and (randomized) interventional research. Here we report on the cohort’s progress and investigate whether it develops in the direction of a nation-wide cohort of “real-world” nature. Methods: Clinical and demographical data of PLCRC participants, as prospectively collected in the Netherlands Cancer Registry by qualified data managers, were compared with the total Dutch CRC population with incidence between 2013-2017 (ref. population) which was also obtained from the Netherlands Cancer Registry. Variable distributions are compared using t-tests and χ 2 -tests, whereas cohort characteristics are descriptive. Results: In June 2019, 5,746 patients were enrolled in 52 / 75 Dutch hospitals, and 81% consented to receive repeated PROs. Compared to patients enrolled between 2013-16 (N = 1,093, 1-17 recruiting hospitals), we found a small shift towards the Dutch ref. population (N = 74,692) for patients enrolled between 2017-19 (N = 4,653, 17-52 hospitals) in terms of age at diagnosis (mean 64.6±10.2 years in 2013-16, 65.2±10.8 in 2017-19, and 69.5±10.9 in the ref. group), sex (65% males in 2013-16, 61% in 2017-19, and 56% in the ref. population), location of primary tumor (56% rectum in 2013-16, 40% in 2017-19, and 31% in the ref. population) and TNM stage (35% stage I-II in 2013-16, 41% in 2017-19, and 48% in the population). Conclusions: Over the past years, the number of PLCRC recruiting centers and participating patients, with high consent rates for PROs, steeply increased. Further improvements in recruitment methodologies and multidisciplinary enrolment of patients will continue to enhance PLCRC’s representation of the “real-world” and its ability to supplement trial-based evidence.
Minimally invasive colorectal resection: Association with elevated levels of plasma TIM-3 post surgery and effect on immune tolerance and the growth of residual metastases.
Authors: Hmc Shantha Kumara, Neil Mitra, Dasuni Niyagama Gamage, Xiaohong Yan, Vesna Cekic, Kathy Baxter, Richard L. Whelan
Journal: Journal of Clinical Oncology (2020)

219 Background: TIM-3 (T cell immunoglobulin and mucin domain-3) is a type I transmembrane glycoprotein expressed on CD4+ T helper 1 (Th1) and CD8+ T cytotoxic 1 (Tc1) T cells and endothelial cells. TIM-3, after binding to its ligand, Galectin-9, inhibits anti-tumor immune function. Co-expression of TIM-3 and PD-1 together is associated with enhanced dysfunctionality of tumor toxic CD8+ T cells. The combination of TIM-3 blockade with anti-PD-1 /PDL1 intervening therapy may enhance response. Tim-3 over expression has been associated with oncogenic activity in colorectal cancer(CRC). Persistently elevated plasma PDL1 levels after CRC resection have been reported. This study’s purpose was to measure plasma TIM3 levels before and during the first month after minimally invasive colorectal resection (MICR) for CRC. Methods: CRC patients (pts) in an IRB approved data/plasma bank who underwent MICR for whom plasma samples were available were studied. Clinical/pathologic data were reviewed. Blood samples were collected preoperatively (PreOp) and at 6 post-operative (Postop) time points (POD 1, 3, 7-13, 14-20, 21-27, 28-41) and processed. TIM3 levels were analyzed in duplicate using ELISA. Wilcoxon paired t-test was used for analysis. Results: A total of 96 CRC pts who had MICR met the study criteria (colon 72%; rectal 28%; mean age 64.8± 13.3). Compared to the mean PreOp plasma TIM3 levels (2619 ± 1410,n = 96;pg/ml ), significantly higher levels (p &lt; 0.001)were noted on (POD)1(2823±1504,n = 95), POD3 (3469±1755,n = 89), POD7-13 (4317±1957,n = 79),POD14-20 (4779±3111,n = 26), POD 21-27(4553± 1846,n = 18) and on POD 28-41 (3621±1859,n = 21). Conclusions: Plasma TIM3 levels were significantly elevated over baseline for 1 month after MICR (% change range, 8-70; peak value weeks 2-4). The acute inflammatory response might account for the early increases but late elevations are more likely associated with wound healing/tissue remodeling. Elevated plasma TIM-3 levels may exhaust tumor infiltrating T-cells which may facilitate the growth of residual tumor. Further investigation is warranted.
Clinical outcomes of patient migration in locally advanced rectal cancer from community cancer centers: An analysis of the National Cancer Database.
Authors: Rohit Kumar, Shruti Bhandari, Phuong Ngo, Sunny R K Singh, Sindhu Janarthanam Malapati, Adam Rojan
Journal: Journal of Clinical Oncology (2020)

81 Background: With cancer care changing at a rapid pace, patients are becoming increasingly involved with their management and oftentimes migrating to a different facility to seek better care. Our study evaluated the characteristics of such patients who were initially diagnosed at a community cancer center (CCC) and how this affects clinical outcomes. Methods: The National Cancer Database identified 11,977 patients with stage II/III rectal cancer initially diagnosed at a CCC between 2005 and 2015. Clinical characteristics and outcomes between patients who received all of their treatments at the CCC versus those who received part or all of their treatments elsewhere were compared using rank-sum and X 2 tests where appropriate. Cox model was used for survival analysis. Results: Of the total population, 51% were stage II and 49% were stage III. Gender and ethnic distributions were similar between the groups. Approximately 44 % of patients received all their treatment at the CCC and 56% had part or all of their care elsewhere. Patients who migrated were younger (63 vs 65 years, p&lt;0.001) and had govt insurance (43.5 vs 35.8%, p&lt;0.001). On multivariate analysis, age &lt;65 years (OR 1.12, 95% CI 1.02-1.24), govt insurance (OR 1.17, 95% CI 1.06-1.29), Charlson/Deyo comorbid score &lt;2 (OR 1.29, 95% CI 1.11-1.49), higher income (OR 1.21, 95% CI 1.16-1.27) and Stage III (OR 1.15, 95% CI 1.07-1.24) were associated with higher probability of migration. The treatment characteristics and outcomes are shown in Table. The 5y-OS rate was better in patients who received part or all of their treatment at other institutions (adjusted HR 0.80, 95% CI 0.74-0.86, p&lt;0.001). Conclusions: Further studies are needed to provide direction for future strategies to reduce the apparent survival disparities in patients who migrate from CCC. [Table: see text]
Economic evaluation of trifluridine/tipiracil (TT) versus nivolumab (N) in patients with advanced/metastatic gastric cancer (GC) or gastro-esophageal junction cancer (GEJC) in Canada.
Authors: Kiran Virik, Robert B. Wilson
Journal: Journal of Clinical Oncology (2020)

376 Background: Systemic treatment options in pre-treated patients with advanced/metastatic GC and GEJC have historically been limited especially in the third line or more. Recent potential advances in the therapeutic landscape of this patient population include TT (TAGS study) and immune checkpoint inhibitors (ICI) such as N (ATTRACTION-2 study). There is an anticipated budgetary impact on healthcare systems within the context of these potentially funded options. An economic evaluation can be instrumental in choosing a regimen if survival and quality of life are felt to be comparable. Methods: A cost minimization analysis was performed in Canadian dollars ($) comparing TT and N respectively in advanced de novo and relapsed GC/GEJC cases diagnosed in 2017 and subsequently treated in the third line in Canada. Direct costs including drug acquisition costs, supportive medications, transfusions, laboratory tests, physician visits, pharmacy and nursing time (health resource utilization-HRU) costs were calculated utilizing Ontario data. Direct costs for treatable adverse events G3/4 &gt; 5% were incorporated. The analysis assumed complete drug delivery and the number of target patients was derived from constructed schema. Results: Compared to TT, the use of N was associated with a higher direct cost by a difference of $2.63 million (M) in the third line for GC and GEJC in Canada, principally reflecting a greater drug acquisition cost.The direct costs ranged (IQR) from 3.65M - 10.62M for TT to 3.3M – 15.69 M for N. N also had a greater HRU cost at 2.7 times that of TT and this was 64% of the direct costs for N excluding drug cost versus 42% of the direct non drug costs for TT. Supportive care (GCSF and transfusions) were 34% of the direct cost for TT excluding drug cost. A sensitivity analysis was performed. Conclusions: N generated a higher direct cost both for drug acquisition cost and other direct costs especially in HRU. Despite the increased cost of supportive care for adverse events related to TT, the direct non drug costs were less for this option. The use of biomarkers predictive of response may reduce the potential cost burden of the use of ICIs.
Comparative Effectiveness Studies for Psoriasis—The Methods Matter
Authors: Bruce Strober, Kenneth B. Gordon
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
First-in-human study of the cancer peptide vaccine, TAS0313, in patients with advanced solid tumors: Phase I dose-finding part results.
Authors: Noboru Yamamoto, Jun Sato, Shunsuke Kondo, Takafumi Koyama, Kan Yonemori, Satoru Iwasa, Toshio Shimizu
Journal: Journal of Clinical Oncology (2020)

73 Background: TAS0313 is a cancer vaccine cocktail containing three long peptides, with a total of 12 cytotoxic T lymphocyte (CTL) epitope peptides. These peptides were derived from eight cancer-associated antigens that are highly expressed in various cancers. We report the results of a phase I part examining the tolerability, safety, potential efficacy, and immunological responses of 9 and 27 mg TAS0313 in patients (pts) with advanced solid tumors. Methods: The enrolled pts had at least one of the following HLA types: HLA-A*02:01, -A*02:06, -A*02:07, -A*11:01, -A*24:02, -A*31:01, or -A*33:03. TAS0313 was subcutaneously administered on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of Cycle 3 or later in 21-day cycles until disease progression, or unacceptable toxicity. Tolerability was assessed in at least six pts during the first cycle. Tumor response was evaluated using RECIST v1.1. The antigen specific CTL and IgG were analyzed post treatment by blood samples. Optional serial tumor biopsies were performed for tumor infiltrating leukocyte (TIL) analysis. CTL, IgG, and TIL were measured by ELISPOT assay, Luminex assay, and IHC (CD8 positive), respectively. Results: Seventeen pts were enrolled in 9mg (n = 10) and 27mg (n = 7) groups. There was no serious adverse drug reaction (ADR) in any patient. All ADRs were of grade 1 or 2, with the most frequent being dermatological injection site reaction, in 7/10 (70%) and 6/7 (86%) pts and pyrexia, in 1/10 (10%) and 2/7 (29%) for the 9 and 27mg groups, respectively. The best overall response was stable disease, in 2/10 (20%) and 2/7 (28%) pts. One patient with cancer of unknown origin received prolonged administration (over 10 months) of the 9mg dose. Increment of CTL and IgG by treatment were detected in 9 and 27mg groups. TIL counts were increased in 2/3(67%) and 3/4(75%) in 9 and 27mg groups compared with pre-treatment samples, respectively. Conclusions: TAS0313 demonstrated safety, tolerability, and immunological responses in pts with advanced solid tumors in the 9 and 27mg groups. A phase II part, evaluating the efficacy of combination therapy with pembrolizumab in pts with urothelial carcinoma and monotherapy in glioblastoma pts, is currently underway. Clinical trial information: JapicCTI-183824.
Safety and efficacy of chemotherapy in older adults with locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Lorena Ostios-Garcia, Patricia Saade, Joseph Elan Grossman, Leanne Lanniello, Andrea J. Bullock
Journal: Journal of Clinical Oncology (2020)

654 Background: PDAC is often diagnosed in patients (pts) ≥75yrs. However, older adults comprise a small proportion of subjects in prospective trials, and there is little reported on the safety and efficacy of chemotherapy in this population. Methods: Records were reviewed on all pts ≥75yrs treated with chemotherapy for locally advanced and metastatic PDAC at a single institution from April 2010 - March 2018. Response rate (RR), progression free survival (PFS), overall survival (OS) and toxicities were compared among the different regimens, and among pts &lt; or ≥80yrs. Survival was estimated with the Kaplan-Meier method and compared by log-rank test. Univariate analyses were performed by Fisher’s exact test and multivariate analyses by a Cox-regression model to identify factors associated with PFS and OS in this population. Results: 67 pts were treated, median age 81yrs (range: 75-90), stage III (34, 51%) and IV (33, 49%). Chemotherapy regimens included: gemcitabine alone (39), gemcitabine/nab-paclitaxel (17), gemcitabine/vinorebine (1), FOLFOX (8) and FOLFIRINOX (2). 59 (88%) pts required dose adjustments due to toxicity; no differences by age or regimen. RR, PFS, and OS did not differ by age or regimen (Table), although sample size was small. Age &gt;80yrs was associated with reduced PFS (p 0.03). On univariate analyses liver metastases and performance status (PS)&gt;1 were associated with reduced OS; PS&gt;1 was associated with reduced OS on multivariate analysis. Conclusions: Among pts with locally advanced and metastatic PDAC ≥75yrs, there were no differences in RR, PFS or OS by chemotherapy regimen. PS was the only variable associated with reduced OS. Older adults with PS 0-1 are likely to benefit from chemotherapy for non-resectable PDAC.[Table: see text]
The potential for combined measures of the systemic inflammatory response (SIR) in colon cancer: An analysis of 2,300 patients.
Authors: Allan Matthew Golder, Donald C. McMillan, David Mansouri, James Hugh Park, Campbell SD Roxburgh, Paul G. Horgan
Journal: Journal of Clinical Oncology (2020)

233 Background: The preoperative SIR clearly demonstrates independent prognostic significance following curative resection for colon cancer, independent of TNM stage. SIR can be measured either using acute phase proteins, predominantly the modified Glasgow Prognostic Score (mGPS) or using the differential white cell count, predominantly neutrophil-lymphocyte ratio (NLR) or lymphocyte-monocyte ratio (LMR). The present study investigates the potential to combine these scores to better predict overall/cancer specific survival (OS/CSS). Methods: Patients in the West of Scotland undergoing curative resection for Stage I-III colon cancer from 2011-2015 were identified with survival updated until December 2018. Through uni/multivariate analysis (UVA/MVA) we compared the effect on OS/CSS of the SIR measured using a combination of mGPS and either NLR or LMR with other clinicopathological features. Results: 2312 patients were identified having underwent curative surgery. Median follow up time was 60 months and there were 756 deaths during follow up. On UVA: mGPS (0/1/2), NLR ( &lt; 3/3-5/ &gt; 5) and LMR ( &lt; 2.5/2.5+) were significant for OS and CSS (all p &lt; 0.001). In the multivariate model when a combination of mGPS and NLR were entered, both remained significant for OS (mGPS: HR 1.20, p = 0.002 and NLR: HR 1.23, p = 0.001) and CSS (mGPS: HR 1.25, p = 0.003 and NLR: HR 1.21, p = 0.017) adjusted for age, sex, emergency presentation, site, ASA, TNM stage and margin involvement. With mGPS and LMR in the model similar results were seen for OS (mGPS: HR 1.24, p = 0.005 and LMR: HR 1.49, p = 0.003) and CSS (mGPS: HR 1.20 p = 0.001 and LMR: HR 1.45, p &lt; 0.001). When mGPS and NLR were scored 0/1/2 (mGPS 0/1/2 and NLR &lt; 3/3-5/ &gt; 5) and combined to form a cumulative grade (0/1/2/3/4) this offered better stratification of %OS (86/84/72/61/55) than mGPS (83/75/60) or NLR (86/79/66) alone (all p &lt; 0.001). Similar results were seen for %CSS – mGPS (90/79/71), NLR (91/85/75) and combined grade (92/90/77/71/67). Conclusions: The results of the present study show that the combined use of mGPS and a differential white cell-based score (NLR/LMR) stratify OS/CSS better than a single measure of preoperative SIR alone.
Hepatocellular Carcinoma Demonstrates Heterogeneous Growth Patterns in a Multicenter Cohort of Patients With Cirrhosis
Authors: Nicole E. Rich, Binu V. John, Neehar D. Parikh, Ian Rowe, Neil Mehta, Gaurav Khatri, Smitha M. Thomas, Munazza Anis, Mishal Mendiratta‐Lala, Christopher Hernandez, Mobolaji Odewole, Latha T. Sundaram, Venkata R. Konjeti, Shishir Shetty, Tahir Shah, Hao Zhu, Adam C. Yopp, Yujin Hoshida, Francis Y. Yao, Jorge A. Marrero, Amit G. Singal
Journal: Hepatology (2020)

Background and Aims There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study’s aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. Approach and Results We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast‐enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT &gt; 365 days) and rapid (TDT &lt; 90 days) tumor growth. In the primary cohort (n = 242 patients from four centers), median TDT was 229 days (interquartile range [IQR], 89‐627) and median SGR was 0.3% per day (IQR, 0.1%‐0.8%). Over one‐third (38%) of HCCs had indolent growth, 36.8% intermediate growth, and 25.2% rapid growth. In multivariable analysis, indolent growth was associated with larger tumor diameter (odds ratio [OR], 1.15, 95% confidence interval [CI], 1.03–1.30) and alpha‐fetoprotein &lt; 20 ng/mL (OR, 1.90; 95% CI, 1.12‐3.21). Indolent growth was more common in nonviral than viral cirrhosis (50.9% versus 32.1%), particularly in patients with T1 HCC (OR, 3.41; 95% CI, 1.08‐10.80). Median TDT (169 days; IQR 74‐408 days) and SGR (0.4% per day) were similar in an independent cohort (n = 176 patients from two centers). Conclusions In a large Western cohort of patients with HCC, we found heterogeneous tumor growth patterns, with one‐fourth exhibiting rapid growth and over one‐third having indolent growth. Better understanding different tumor growth patterns may facilitate a precision approach to prognostication and treatment.
No flow through the vitreous humor: How strong is the evidence?
Authors: David W. Smith, Chang-Joon Lee, Bruce S. Gardiner
Journal: Progress in Retinal and Eye Research (2020)

When analyzing vitreal drug delivery, or the pharmacological effects of drugs on intraocular pressure, or when interpreting outflow facility measurements, it is generally accepted that the fluid in the vitreous humor is stagnant. It is accepted that for all practical purposes, the aqueous fluid exits the eye via anterior pathways only, and so there is negligible if any posteriorly directed flow of aqueous through the vitreous humor. This assumption is largely based on the interpretation of experimental data from key sources including Maurice (1957), Moseley (1984), Gaul and Brubaker (1986), Maurice (1987) and Araie et al. (1991). However, there is strong independent evidence suggesting there is a substantial fluid flow across the retinal pigment epithelium from key sources including Cantrill and Pederson (1984), Chihara and Nao-i, Tsuboi (1985), Dahrouj et al. (2014), Smith and Gardiner (2017) and Smith et al. (2019). The conflicting evidence creates a conundrum-how can both interpretations be true? This leads us to re-evaluate the evidence. We demonstrate that the data believed to be supporting no aqueous flow through the vitreous are in fact compatible with a significant normal aqueous flow. We identify strong and independent lines of evidence supporting fluid flow across the RPE, including our new outflow model for the eye. On balance it appears the current evidence favors the view that there is normally a significant aqueous flow across the RPE in vivo. This finding suggests that past and future analyses of outflow facility, interpretations of some drug distributions and the interpretation of some drug effects on eye tissues, may need to be revised.
The prolactin receptor long isoform regulates nociceptor sensitization and opioid-induced hyperalgesia selectively in females
Authors: Yanxia Chen, Aubin Moutal, Edita Navratilova, Caroline Kopruszinski, Xu Yue, Megumi Ikegami, Michele Chow, Iori Kanazawa, Shreya Sai Bellampalli, Jennifer Xie, Amol Patwardhan, Kenner Rice, Howard Fields, Armen Akopian, Volker Neugebauer, David Dodick, Rajesh Khanna, Frank Porreca
Journal: Science Translational Medicine (2020)

Pain is more prevalent in women for reasons that remain unclear. We have identified a mechanism of injury-free nociceptor sensitization and opioid-induced hyperalgesia (OIH) promoted by prolactin (PRL) in females. PRL signals through mutually inhibitory long (PRLR-L) and short (PRLR-S) receptor isoforms, and PRLR-S activation induces neuronal excitability. PRL and PRLR expression were higher in females. CRISPR-mediated editing of PRLR-L promoted nociceptor sensitization and allodynia in naïve, uninjured female mice that depended on circulating PRL. Opioids, but not trauma-induced nerve injury, decreased PRLR-L promoting OIH through activation of PRLR-S in female mice. Deletion of both PRLR-L and PRLR-S (total PRLR) prevented, whereas PRLR-L overexpression rescued established OIH selectively in females. Inhibition of circulating PRL with cabergoline, a dopamine D2 agonist, up-regulated PRLR-L and prevented OIH only in females. The PRLR-L isoform therefore confers protection against PRL-promoted pain in females. Limiting PRL/PRLR-S signaling pharmacologically or with gene therapies targeting the PRLR may be effective for reducing pain in a female-selective manner.