tbuckley/cabot-search huggingface dataset:
Some cancers are “missing out” on new drugs
Authors: Jacqui Thornton
Journal: BMJ (2018)

A major analysis of European regulatory data on drugs for cancer has shown that though “incredible” advances in research have led to 97 new medicines in 177 indications being authorised in 16 years, certain cancers were “missing out,” with no new drugs at all.

The new report by the Institute of Cancer Research in London found that no treatments had been authorised by the European Medicines Agency for brain, womb, bladder, and oesophageal cancers between 2000 and 2016 and only one for liver cancer.1

This compared with 64 for blood cancers, 23 for lung cancer, and 15 for breast cancer.

Paul Workman, the institute’s chief executive, said that this was a concern because no treatments existed to “effectively address” these poorly served cancers. He told a briefing in London on 3 December, “More drugs are coming through, but many tumour types are missing out on these great advances.”

Only eight of the 97 new drug authorisations were for children, including two for solid tumours, which account for around 60% of new cases of cancer in childhood each year and are often harder to treat than childhood blood cancers.

Sally George, a consultant paediatrician at the Royal Marsden NHS Foundation Trust and a clinical research fellow at the Institute of Cancer Research, said that there was an urgent need …
<i>In vivo</i> multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy
Authors: Jonathan Noonan, Steven M. Asiala, Gianluca Grassia, Neil MacRitchie, Kirsten Gracie, Jake Carson, Matthew Moores, Mark Girolami, Angela C. Bradshaw, Tomasz J. Guzik, Gavin R. Meehan, Hannah E. Scales, James M. Brewer, Iain B. McInnes, Naveed Sattar, Karen Faulds, Paul Garside, Duncan Graham, Pasquale Maffia
Journal: Theranostics (2018)

Vascular immune-inflammatory responses play a crucial role in the progression and outcome of atherosclerosis.The ability to assess localized inflammation through detection of specific vascular inflammatory biomarkers would significantly improve cardiovascular risk assessment and management; however, no multi-parameter molecular imaging technologies have been established to date.Here, we report the targeted in vivo imaging of multiple vascular biomarkers using antibody-functionalized nanoparticles and surface-enhanced Raman scattering (SERS).Methods: A series of antibody-functionalized gold nanoprobes (BFNP) were designed containing unique Raman signals in order to detect intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin using SERS.Results: SERS and BFNP were utilized to detect, discriminate and quantify ICAM-1, VCAM-1 and P-selectin in vitro on human endothelial cells and ex vivo in human coronary arteries.Ultimately, non-invasive multiplex imaging of adhesion molecules in a humanized mouse model was demonstrated in vivo following intravenous injection of the nanoprobes. Conclusion:This study demonstrates that multiplexed SERS-based molecular imaging can indicate the status of vascular inflammation in vivo and gives promise for SERS as a clinical imaging technique for cardiovascular disease in the future.
Implementation of a rapid access multidisciplinary bone metastases clinic to improve access to care at a large cancer center.
Authors: Lauren Elizabeth Colbert, Meaghan Gomez, Sarah Todd, Chad Tang, Kaitlin Christopherson, David R Grosshans, Lilie L. Lin, Justin E Bird, Bryan Moon, Robert L Satcher, Valerae O. Lewis, Albert Koong, Daniel Richard Gomez
Journal: Journal of Clinical Oncology (2018)

79 Background: MD Anderson Cancer Center is a large cancer center with 44,000 new patients per year. Radiation therapy (RT) is an effective treatment for bone metastases that can reduce pain medication use and improve quality of life. Our goal was to assess the effect of implementing a rapid access multidisciplinary clinic for bone metastases (RABC). Methods: RABC was instituted to schedule patients for radiation oncology and orthopedic surgery consult within 48 hours of referral. Same day simulation and treatment times were held for these patients for one 8Gy fraction. Thirty sequential patients treated with one fraction to bony sites in the outpatient setting prior to implementation of the clinic were chosen as a comparison group. Time from consult order to consult visit (OTV) and from consult visit to treatment completion (CTT) were recorded, in addition to frequency of multidisciplinary care (MDC; orthopedic surgery and radiation oncology). Overall Time (OT) was calculated from referral to treatment completion. T-test and chi-square test were used for analyses. Results: Between April 2018 and July 2018, 72 patients were referred to RABC. 23 patients were seen in consultation and received RT. Sites treated were pelvis (N = 10), spine (N = 6), lower extremity (N = 4) and upper extremity (N = 3). Patients had one site (N = 20), two sites (N = 2) or three sites treated (N = 1). Histologies included breast (N = 5), thoracic (N = 7), gastrointestinal (N = 6), genitourinary (N = 2) and head/neck (N = 2). OTV was shorter for RABC patients (mean 3.3 [+/-5.7] vs. 9.5 days [12.4]; p = 0.02). CTT was also significantly shorter for RABC patients (mean 5.4 hours [+/-1.8] vs. 6.5 days [+/-6.5]; p &lt; .0001). OT was also shorter (3.5 days [+/-5.6] vs. 16.4 days [+/-14.8]; p &lt; .0001). RABC clinic patients were more likely to receive MDC (100% vs 28%; p &lt; .0001). Conclusions: The rapid access bone metastases clinic significantly decreased overall time from consult to completion of treatment and also decreased time to access radiotherapy. Patients were also more likely to receive multidisciplinary evaluation. The RABC approach is a promising model to improve palliation for patients with painful bony metastases.
Type 2 diabetes: 5000 patients to test feasibility of “remission service”
Authors: Jane Feinmann
Journal: BMJ (2018)

The NHS is to pilot a low calorie diet programme that can put type 2 diabetes into remission as the first treatment option for patients with a new diagnosis of the disease.

The approach will involve GPs prescribing a liquid diet of just over 800 kilocalories a day for three months, then a period of follow-up support, NHS England’s chief executive, Simon Stevens, announced on 30 November. It will first be offered to 5000 patients before being rolled out nationally.

The announcement followed a series of recent studies that have overturned the widely held view that type 2 diabetes is incurable and must be managed with medication. Most recently, the DiRECT trial, funded by Diabetes UK, showed that low calorie diets …
An association between tobacco smoking, daily opioid use, pain response and the risk for aberrant opioid use behaviors.
Authors: Sriram J. Yennu, Tonya Edwards, Zhanni Lu, Janet L. Williams, Joseph Anthony Arthur, Suresh Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2018)

226 Background: Opioid misuse is a growing crisis. Cancer patients at risk of aberrant drug behaviors are frequently underdiagnosed. Primary aim was to determine the association between current tobacco smoking, daily opioid use, pain response, and risk for aberrant opioid use behaviors (AOB) among patients receiving outpatient supportive care consultation at a comprehensive cancer center. Methods: 1,501 consecutive cancer patients referred to a supportive care clinic from March 1, 2016 to June 6, 2018 were reviewed. Patients were eligible if they had diagnosis of cancer, and were on opioids for pain for at least a week. All patients were assessed using Edmonton Symptom Assessment Scale (ESAS), SOAPP-14 (validated questionnaire for assessment of risk for aberrant opioid use behaviors), and CAGE-AID. Patients with AOB (SOAPP+) were defined by SOAPP score ≥7. Results: Median age was 61yrs. Median ESAS pain item score on consultation was 5. Median ECOG was 2. Never smokers, previous smokers, and current smokers were 54%, 40%, and 6.6% respectively. 16.8% were AOB+ and 10.1% were CAGE-AID+. There was no significant difference in ESAS pain response at first follow-up between AOB+ versus AOB negative. Morphine Equivalent Daily Dose (MEDD) in AOB+ never smokers versus previous smokers versus current smokers was 45 mg versus 60 mg versus 75mg respectively (P=0.03). Table 1 shows that male pts and those with current or previous smoking history, anxiety, and prior alcoholism/illicit drug use are at increased risk of AOB. Conclusions: Male patients and those with history of current or previous smoking history, anxiety, and prior alcoholism/illicit drug use are at increased risk of AOB. [Table: see text]
Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2
Authors: Teresa Macarulla, Roberto Pazo-Cid, Carmen Guillén-Ponce, Rafael López, Ruth Vera, Margarita Reboredo, Andrés Muñoz Martin, Fernando Rivera, Roberto Díaz Beveridge, Adelaida La Casta, José Martín Valadés, Joaquina Martínez-Galán, Immaculada Ales, Javier Sastre, Sofia Perea, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2018)

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m 2 [arm A] or 125 mg/m 2 [arm C]) plus gemcitabine 1,000 mg/m 2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m 2 [arm B] or 125 mg/m 2 [arm D]) plus gemcitabine 1,000 mg/m 2 . The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m 2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.
<i>MGMT</i> Promoter Methylation Cutoff with Safety Margin for Selecting Glioblastoma Patients into Trials Omitting Temozolomide: A Pooled Analysis of Four Clinical Trials
Authors: Monika E. Hegi, Els Genbrugge, Thierry Gorlia, Roger Stupp, Mark R. Gilbert, Olivier L. Chinot, L. Burt Nabors, Greg Jones, Wim Van Criekinge, Josef Straub, Michael Weller
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The methylation status of the O6-methylguanine DNA methyltransferase (MGMT) gene promoter is predictive for benefit from temozolomide in glioblastoma (GBM). A clinically optimized cutoff was sought allowing patient selection for therapy without temozolomide, while avoiding to withhold it from patients who may potentially benefit. Experimental Design: Quantitative MGMT methylation-specific PCR data were obtained for newly diagnosed patients with GBM screened or treated with standard radiotherapy and temozolomide in four randomized trials. The pooled dataset was randomly split into a training and test dataset. The unsupervised cutoff was obtained at a 50% probability to be (un)methylated. ROC analysis identified an optimal cutoff supervised by overall survival (OS). Results: For 4,041 patients valid MGMT results were obtained, whereof 1,725 were randomized. The unsupervised cutoff in the training dataset was 1.27 (log2[1,000 × (MGMT+1)/ACTB]), separating unmethylated and methylated patients. The optimal supervised cutoff for unmethylated patients was −0.28 (AUC = 0.61), classifying “truly unmethylated” (≤−0.28) and “gray zone” patients (&amp;gt;−0.28, ≤1.27), the latter comprising approximately 10% of cases. In contrast, for patients with MGMT methylation (&amp;gt;1.27) more methylation was not related to better outcome. Both methylated and gray zone patients performed significantly better for OS than truly unmethylated patients [HR = 0.35, 95% confidence interval (CI), 0.27–0.45, P &amp;lt; 0.0001; HR = 0.58, 95% CI, 0.43–0.78, P &amp;lt; 0.001], validated in the test dataset. The MGMT assay was highly reproducible upon retesting of 218 paired samples (R2 = 0.94). Conclusions: Low MGMT methylation (gray zone) may confer some sensitivity to temozolomide treatment, hence the lower safety margin should be considered for selecting patients with unmethylated GBM into trials omitting temozolomide.
A Radiomics Nomogram for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma
Authors: Li Yang, Dongsheng Gu, Jingwei Wei, Chun Yang, Shengxiang Rao, Wentao Wang, Caizhong Chen, Ying Ding, Jie Tian, Mengsu Zeng
Journal: Liver Cancer (2018)

Radiomics has emerged as a new approach that can help identify imaging information associated with tumor pathophysiology. We developed and validated a radiomics nomogram for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC).Two hundred and eight patients with pathologically confirmed HCC (training cohort: n = 146; validation cohort: n = 62) who underwent preoperative gadoxetic acid-enhanced magnetic resonance (MR) imaging were included. Least absolute shrinkage and selection operator logistic regression was applied to select features and construct signatures derived from MR images. Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and radiomics signatures associated with MVI, which were then incorporated into the predictive nomogram. The performance of the radiomics nomogram was evaluated by its calibration, discrimination, and clinical utility.Higher α-fetoprotein level (p = 0.046), nonsmooth tumor margin (p = 0.003), arterial peritumoral enhancement (p < 0.001), and the radiomics signatures of hepatobiliary phase (HBP) T1-weighted images (p < 0.001) and HBP T1 maps (p < 0.001) were independent risk factors of MVI. The predictive model that incorporated the clinicoradiological factors and the radiomic features derived from HBP images outperformed the combination of clinicoradiological factors in the training cohort (area under the curves [AUCs] 0.943 vs. 0.850; p = 0.002), though the validation did not have a statistical significance (AUCs 0.861 vs. 0.759; p = 0.111). The nomogram based on the model exhibited C-index of 0.936 (95% CI 0.895-0.976) and 0.864 (95% CI 0.761-0.967) in the training and validation cohort, fitting well in calibration curves (p > 0.05). Decision curve analysis further confirmed the clinical usefulness of the nomogram.The nomogram incorporating clinicoradiological risk factors and radiomic features derived from HBP images achieved satisfactory preoperative prediction of the individualized risk of MVI in patients with HCC.
Pharmacological treatment of COPD – New evidence
Authors: N. Pires, P. Pinto, N. Marçal, A.J. Ferreira, C. Rodrigues, C. Bárbara
Journal: Pulmonology (2018)

Chronic Obstructive Pulmonary Disease (COPD) is currently the 4th leading cause of death worldwide but is projected to be the 3rd leading cause of death by 2020. In Portugal, the estimated prevalence of COPD in the Lisbon region is 14.2%, and a large proportion of underdiagnosed disease has been detected. In 2016, a Portuguese panel of experts proposed pharmacological treatment approaches to COPD based on the evidence available at the time. However, given that the GOLD 2017 report introduced considerable changes to the 2016 version, and that new evidence has emerged regarding treatment options, these proposals need to be updated. Also, and based on several studies, the concept of Pre-GOLD patients, which has diagnostic, prognostic and therapeutic implications, is introduced, along with a proposed algorithm for the identification and treatment of these patients.
Voriconazole-Induced Periostitis After Allogeneic Stem Cell Transplantation
Authors: Maarten Haemels, Steven Pans, Hélène Schoemans, Karolien Goffin, Olivier Gheysens, Sander Jentjens
Journal: Clinical Nuclear Medicine (2018)

A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A Tc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.
Annals Story Slam - Like Water, Like Wine
Authors: Shaheeda Ahmed
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - Like Water, Like WineFREEShaheeda Ahmed, MDShaheeda Ahmed, MDUniversity of Toronto and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (S.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0040 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Like Water, Like Wine "Like Water, Like Wine," by Shaheeda Ahmed, MD (Duration 4:37)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (S.A.)Current Author Address: Shaheeda Ahmed, MD; e-mail, shaheeda.[email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1KeywordsWine ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Multidisciplinary approach to endobronchial HDR brachytherapy as an alternative to external beam radiation for palliating malignant airway obstruction.
Authors: Hani AL-Halabi, Rabih Bechara, Will Snyder, Kristyn Harpool, Patricia Schantz, Tony Law, Lily Shakibnia, John Swanson, Sean Xavier Cavanaugh
Journal: Journal of Clinical Oncology (2018)

132 Background: Concerns over the safety of high-dose-rate (HDR) endobronchial brachytherapy (EBB) has limited its widespread use in palliating pulmonary airway obstruction. Morbidity following EBB is commonly attributed to fatal hemoptysis and fistula formation. We implemented a procedure to deliver EBB under general anesthesia to minimize procedure risks, while maintaining treatment effectiveness. We hereby report outcomes of consecutive patients treated using this approach to palliate airway obstruction. Methods: We retrospectively reviewed charts of consecutive patients treated with EBB. Treated patients had obstructive lesions &gt;2cm distal to the carina and central structures, who were deemed candidates for EBB by a multidisciplinary team of interventional pulmonologists (IP) and radiation oncologists (RO). All patients were treated under general anesthesia. Bronchoscopy and localization of target lesions was performed by IP. HDR catheters carrying a marker wire were advanced past obstructive lesion. CT simulation was performed to confirm catheter placement, and perform CT-based 3D treatment planning. A dose of 6 -7 Gy/fraction was prescribed at 1 cm from catheter surface. Results: 25 patients (ages 29 -71, mean 52 years) were treated with EPP. 5 had previously received external beam radiation (EBRT) and 3 had concurrent EBRT and EPP. Overall, a total of 76 EBB treatments were performed, with a median of 3 weekly fractions per patient (range 1-6) to total dose of 18Gy. There were no incidences of major bleeding (&gt;50 mL) or fatal hemoptysis in the 30 days following EPP. Moreover, there were no cases of severe (Grade 3 or higher) CTCAE toxicity reported. After a median follow up of 30 months (range 4-42) only 1 out of 17 patients treated with EPP alone required additional EBRT for airway obstruction, 12 months following EPP. Conclusions: Our data suggest the safety and efficacy of an expert multidisciplinary approach to palliating pulmonary airway obstruction using EPP. This approach provides effective palliation of airway obstruction and decreased the need for additional EBRT in majority of treated patients.