tbuckley/cabot-search huggingface dataset:
P05.07 Three-dimensional multimodal imaging and intraoperative navigation in endonasal endoscopic surgery for non-functioning pituitary adenomas invading the cavernous sinus
Authors: S Geng
Journal: Neuro-Oncology (2018)

To validate the utility of 3-dimensional multimodal imaging (3D-MMI) and intraoperative navigation (ION) in endonasal endoscopic surgery for non-functioning pituitary adenomas invading the cavernous sinus. We performed 13 endonasal endoscopic operations for non-functioning pituitary adenomas invading the cavernous sinus(Knosp gradeI-II 5 cases, Knosp grade III-IV 8 cases) guided by 3D-MMI and ION techniques. The 3D-MMI and ION were used to identify the exact location of the carotid artery, then we operated through the postero-superior and/or anterolateralcorridor of the cavernous carotid artery (CCA) to remove pituitary adenomas invading the cavernous sinus. In all patients, the 3D-MMI and ION techniques enabled adequate visualization of the microsurgical skull base anatomy (bone, tumors, vascular structures) stereoscopically, especially the relationship between tumor and internal carotid artery (ICA). Near total resection (90–95% volume removed) in 2 cases, and gross total resection (>950% volume removed) in 11 cases. Pre-operative cranial neuropathies and visual field defects were improved in all patients. 3D-MMI and ION techniques were found to be helpful for endoscopic skull base surgery. It is convenient for doctors to locate important structures and lesions. allowing the surgeons to increase tumor resection and avoid ICA injury during endonasal endoscopic surgery for non-functioning pituitary adenomas invading the cavernous sinus.
Effect of Ga-68 PSMA-11 PET on management in patients with recurrent prostate cancer.
Authors: Tom Hope, Rahul Raj Aggarwal, Kirsten L Greene, Bryant Chee, Dora Tao, Felix Yi-Chung Feng, Albert Chang, Matthew R. Cooperberg, Charles J. Ryan, Eric Jay Small, Peter Carroll
Journal: Journal of Clinical Oncology (2017)

5057 Background: PET imaging of prostate specific membrane antigen (PSMA) has been shown to have a higher sensitivity and specificity compared to conventional imaging. The objective was to evaluate the impact of PSMA PET on the management of prostate cancer patients with biochemical recurrence following local therapy. Methods: In our initial Ga-68-PSMA-11 PET protocol (NCT02611882), 150 patients with biochemical recurrence were imaged. 63 patients were imaged using PET/CT (GE Discovery VCT) and 63 patients using PET/MRI (GE Signa 3.0T PET/MRI). 110 patients received Lasix injections. Referring clinicians filled out a pretreatment management form and a management form based on the imaging results. Changes in management were graded as major, minor, no change or unknown based upon the responses. Results: We received both pre and post imaging forms in 126 patients, for an 84% response rate. The average PSA in the population was 5.9 ± 5.4 ng/mL with an average doubling time of 9.7 ± 11.0 months, and 60 patients had a PSA of less than 2.0 at the time of imaging. The average time between prior treatment and imaging (RP and/or radiation) was 5.3 ± 5.4 years, with 46 patients imaged within two years of their most recent treatment. 43 patients had a prior prostatectomy, 41 prior radiation, and 33 patients had both. 103 patients (82%) had disease localized on PSMA imaging. Of the 126 patients, 67 (53%) of the imaging studies resulted in a major change in management. The most common major change was converting from active surveillance to radiation therapy (15 patients, 12%), changing from ADT to radiation therapy (16 patients, 13%), and converting from radiation therapy to either active surveillance (6 patients, 5%) or to ADT alone (3 patients, 2%). 10 patients (8%) had a minor change, 42 patients (33%) had no change, and 7 patients (6%) had an unknown change in management. Conclusions: The results of our surveys demonstrate a substantial impact of PSMA PET on the intended patient management. The majority of changes involved converting a targeted therapy to systemic treatment or systemic treatment to a targeted therapy. Prospective studies are warranted to determine whether directed treatment towards PSMA-avid lesions affects long-term disease outcomes. Clinical trial information: NCT02611882.
P05.64 The disease burden of meningioma patients: long-term results on work productivity and healthcare consumption
Authors: A H Zamanipoor Najafabadi, P B van der Meer, F W Boele, J C Reijneveld, M J B Taphoorn, W R van Furth, L Dirven, S M Peerdeman
Journal: Neuro-Oncology (2018)

Meningioma patients suffer from short- and long-term neurological sequelae and impaired health-related quality of life (HRQoL). However, it is unknown how these impairments affect patients’ work productivity and healthcare consumption on the long-term. In a multicentre cross-sectional study intracranial meningioma patients of working age (18–67 years) at a median of 10.0 years after anti-tumour therapy were included. Patients completed a validated questionnaire on work productivity (SF-HLQ), and a study-specific questionnaire on healthcare consumption. One-sample t-test was used to compare meningioma patients with normative data of the Dutch population. Generalised linear models were used to compare meningioma patients with a control population, corrected for: age, sex, educational level and comorbidity. Patient recruitment and data collection is still in progress. 106 meningioma patients were included (mean age: 57.7 years, WHO grade I: 93.5%, surgery: 94.2%, radiotherapy: 17.5%). Meningioma patients had a paid job in 48.1% of cases, compared with 71.8% of the Dutch population of working age (p<0.001). More patients reported obstacles at work (49.1%) than controls (n=72, 20.9%, p=0.003). These problems at work included concentration problems (sometimes: 40.0%, often: 28.0%, always: 8.0%), slower work pace (sometimes: 36.0%, often: 36.0%, always: 12.0%), feeling of isolation (sometimes: 12.0%, often: 12.0%, always: 0.0%), delaying work (sometimes: 52.0%, often: 16.0%, always: 4.0%), and the need for someone to take over their work (sometimes: 33.3%, often: 4.2%, always: 4.2%). Furthermore, on the long-term, specialised healthcare consumption (i.e. outpatient clinic visits) was significantly higher in meningioma patients (70.4%) compared with controls (49.5%, p=0.003). Meningioma patients have less often a paid job when compared to the average Dutch population. Moreover, those patients having paid work report more obstacles, particularly concentration problems and a slower work pace. Therefore, employment issues in meningioma should receive more attention, even up to 10 years after intervention.
Diabetes outcomes in patients with breast cancer.
Authors: Martin W. Schoen, Jiajing Chen, Yifan Tu, Kahee A. Mohammed, Miriam B. Rodin, Leslie J. Hinyard
Journal: Journal of Clinical Oncology (2018)

e22078 Background: While diabetes is known to worsen breast cancer outcomes, little is known about the effect of breast cancer on diabetes. Patients with breast cancer are frequently administered cytotoxic chemotherapy, hormonal therapy, and glucocorticoids; each have the potential to alter metabolic pathways and worsen diabetes outcomes, including cardiovascular events and infections. Many patients with breast cancer have early stage disease and are potentially cured with therapy, therefore attention to outcomes of co-morbidities is appropriate for patients treated for breast cancer. Methods: We used a national large administrative claims database provided by Symphony Health and included female patients from 2007 to 2014, aged > 18 years old who had follow-up of at least 5 years available after index date of inclusion into the study. All patients did not have a diagnosis of myocardial infarction (MI), coronary artery disease (CAD), cardiac death or arrhythmia, stroke, heart failure (HF), pneumonia, urinary tract infection (UTI), or sepsis prior to inclusion. Patients with breast cancer had to have diabetes for at least 1 year prior to inclusion and had been treated with either chemotherapy or hormonal therapy. Control patients with diabetes for at least 5 years, but without breast cancer, and were matched by age. Results: The analytic cohort consisted of 1,256,737 patients, of which 7,865 had breast cancer. Patients with breast cancer had a higher rate of heart failure (20.2% vs. 18.0%, p < 0.001), CAD (28.4% vs. 27.2, p < 0.001), and a lower rate of MI (4.1% vs. 4.6%, p = 0.017), with no significant change in stroke (16.4% vs. 16.4%, p = 0.976) or cardiac death or arrhythmia (2.5% vs. 2.2%, p = 0.085). Patients with breast cancer had a higher rate of pneumonia (15.0% vs. 13.1%, p = p < 0.001) and sepsis (8.6% vs. 7.2%, p < 0.001), and no difference in UTI (36.9% vs. 36.1%, p = 0.114). Conclusions: In this population of patients with diabetes, breast cancer diagnosis and treatment was associated with higher rates of heart failure and coronary artery disease as well as pneumonia and sepsis, but with a lower rate of MI. Future studies to understand outcomes in patients at risk of adverse events and control for underlying co-morbidities are warranted.
Efficacy of glutamine in postinfection IBS
Authors: Alexander Charles Ford, Peter R Gibson
Journal: Gut (2018)

We read the randomised controlled trial (RCT) by Zhou et al. 1 The authors recruited a highly selected group of patients with increased intestinal permeability and postinfection IBS with diarrhoea (IBS-D), defined by an unconfirmed enteric infection in the 12 months prior to symptom onset, and randomised them to 8 weeks of treatment with either glutamine or placebo. The population screened also had other curious features. For example, only four had rapid orocaecal transit on lactulose hydrogen breath testing, erroneously described as small intestinal bacterial overgrowth. This appears low, compared with other studies examining this issue in patients with IBS.

There are other minor issues with the trial conduct and analysis. First, compliance was checked by telephone calls, not a particularly robust method. Second, the efficacy analysis was per-protocol, rather than intention-to-treat, and minimal information on dropouts …
Phase Ib study of binimetinib (MEK162) in combination with capecitabine in gemcitabine-pretreated advanced biliary tract cancer.
Authors: Jin Won Kim, Kyung-Hun Lee, Ji-Won Kim, Koung Jin Suh, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Journal: Journal of Clinical Oncology (2018)

4079 Background: In biliary tract cancer (BTC), RAS/RAF/MEK/ERK pathway is known to be activated in up to 20-40%. Binimetinib (MEK162) is allosteric MEK1/2 inhibitor, which shows preclinical activity in BTC. Interestingly, MEK inhibitor and 5-FU shows synergistic effects in BTC cells. With that, we conducted phase Ib study of binimetinib and capecitabine in gemcitabine-pretreated BTC patients. Methods: This study consists of dose escalation (DE) part and expansion (EX) part. Binimetinib (B) and capecitabine (C) were dosed twice daily, 2 weeks/1 week on/off. In DE part, 3 dose levels (DL) were tested (DL1: B 15mg, C 1000 mg/m2; DL2: B 30mg, C 1000 mg/m2; DL 3: B 30mg, C 1250 mg/m2) with 3+3 design. The primary end point was maximum tolerated dose in DE part and 3 month-progression free survival (PFS) rate (3m-PFSR) in EX part. Results: In DE part, 9 patients (3 per DL) were recruited and there was no dose limiting toxicity up to DL3. Recommended phase 2 dose (RP2D) was determined as DL3. In EX part, 25 patients were enrolled. Median age was 63 years old (range 48-73). Primary tumor origins were gallbladder (29.4%), intrahepatic (29.4%), extrahepatic (26.5%), and ampulla of vater (14.7%). 25 (73.5%) and 9 patients (26.5%) were 2nd-line and 3rd-line setting, respectively. Of 34 evaluable patients, 6 (17.6%) and 20 patients (58.8%) showed partial response and stable disease (SD). Response rate and disease control rate were 17.6% (95% CI, 4.8 - 30.4) and 76.5% (95% CI, 62.1 - 90.7). Median PFS and overall survival (OS) were 3.9 m (95% CI, 3.0 - 4.8) and 8.0 m (95% CI, 4.9 - 11.1). 3m-PFSR was 61.3%. 60% of patients with SD showed prolonged SD ( > 12 weeks). In biomarker study, RAS/RAF/MEK/ERK pathway activated patients showed longer PFS (5.4 m vs 2.6 m, p = 0.031) and OS (10.8 m vs 5.3 m, p = 0.011) than non-activated patients. Most of adverse events were grade 1/2 and manageable with G3 anemia (11.8%) and G3 fatigue (5.9%). Conclusions: RP2D of binimetinib and capecitabine combination is binimetinib 30mg, capecitabine 1250 mg/m2, twice daily, 2 weeks on/1 week off. This combination shows acceptable tolerability and promising antitumor efficacy, especially in RAS/RAF/MEK/ERK pathway activated BTC patients. Clinical trial information: NCT02773459.
Non-germ cell testicular tumours: Follow-up and outcomes—A literature review and experience from a UK tertiary referral centre over 13 years.
Authors: Louisa Scott, Andrew Protheroe, Robert Watson, Clare Verrill, Lisa Browning, Johnson Joseph, Mark Sullivan, Mark Tuthill
Journal: Journal of Clinical Oncology (2018)

e16536 Background: Non-germ cell tumours (NGCTs) are a rare form of testicular cancer, making up less than 5% of all testicular cancers. Their behaviour differs significantly from that of the more common testicular germ cell tumours. Consequently, there is a wide heterogeneity in international clinical management of NGCTs and a lack of consensus on follow-up after orchidectomy. Methods: A structured literature review was carried out to identify published studies which included the follow-up and outcomes of patients with NGCTs; the international variation in follow-up of NGCTs was described. We searched the Thames Valley Germ Cell Database (TVGCD), a large UK supra-regional testicular cancer network, which covers a population of approximately 3 million people, for cases of NGCTs treated between 1st January 2004 and 31st December 2017. Diagnosis, tumour histology, follow-up, and outcome were analysed. Results: We identified 16 studies which include 384 NGCT cases. There were 22 deaths from NGCTs. Only three studies described a follow-up protocol. Of the 1526 patients within the TVGCD, 56 patients (aged 18-75 years) had an NGCT diagnosed between 1st January 2004 and 31st December 2017. Of these, 8 were Sertoli, 35 were Leydig, 10 were epidermoid cysts, two were mixed, and one was an unspecified sex cord stromal tumour. Three patients died from NGCTs, including a Sertoli cell tumour, a Leydig cell tumour, and an unspecified sex cord stromal tumour. There were no disease relapses in the 53 patients who survived. Mean length of follow-up was 7.9 months (range 0-62 months, SD 15.0); there was marked variation within our cohort. Conclusions: Our study offers the largest European published series of NGCTs. These tumours are rare and poorly understood; our series adds significantly to the literature currently available. No clear consensus currently exists in the literature for a follow-up protocol indicating a need for a consensus guideline to harmonise national and international clinical practice.
Neoadjuvant carboplatin, nab-paclitaxel and cetuximab prior to standard of care chemoradiotherapy for N2b or unresectable squamous head and neck cancer.
Authors: Jared Weiss, David N. Hayes, Allison Mary Deal, Bhishamjit S. Chera, Mark Christian Weissler, Barbara A. Murphy, Jay Justin Liao, Juneko E. Grilley-Olson, Jill Gilbert
Journal: Journal of Clinical Oncology (2016)

6075 Background: Although induction studies of TPF have been negative in locally advanced SCCHN, phase II studies of weekly carboplatin (CbP), paclitaxel and cetuximab (C225) have shown promising results. Nab-paclitaxel-based chemotherapy has demonstrated a higher response rate (RR) than solvent-based paclitaxel in SCC of the lung with favorable toxicity. We evaluated an induction regimen using nab-paclitaxel, CbP and C225 followed by concurrent chemoradiation. Methods: Patients with treatment naïve SCCHN of any site with ≥ N2b disease or that was unresectable by strict criteria were eligible. Subjects were screened for risk of anaphylaxis to C225 with ELISA for IgE antibodies against galactose-α-1,3-galactose (alphagal); negativity was required for subjects residing in the SE of the US. Patients were treated with nab-paclitaxel 100mg/m2, CbP AUC 2 and C225 400mg/m2 week 1 then 250mg/m2for six weeks, followed by standard of care chemoradiotherapy (CRT). Results: 39 subjects were treated and 30 had a response (76.9%); there was no progressive disease. Primary sites were: oropharynx (OPX) (26), larynx (3) oral cavity (OC) (9), hypopharynx (1). Grade 3/4 toxicity included rash (11), decreased neutrophil count (4), decreased white blood cells (2), fatigue (1), palmar-plantar erythrodysesthesia syndrome (1), febrile neutropenia (1), hypocalcemia (1), and hypokalemia (1); there was no anaphylaxis to C225.1 year survival is 89% (95% CI 73-96%) and two-year survival is 80% (62-90%). Median followup for survival for living patients is 1.82 years. 1 year PFS was 81% (64-90%). Median followup for PFS for patients without progression or death is 1.49 years. Amongst p16+ oropharynx patients, 1 year PFS and OS were both 89% (64-97%). Amongst all other patients, 1 year PFS and OS were 74% and 73%, respectively. Conclusions: The combination of nab-paclitaxel, CbP and C225 is tolerable and active against locally advanced SCCHN. Phase III study of this induction regimen followed by standard of care chemoradiotherapy versus standard of care chemoradiotherapy alone is indicated. Clinical trial information: NCT01412229.
A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC
Authors: A. Lisberg, A. Cummings, J.W. Goldman, K. Bornazyan, N. Reese, T. Wang, P. Coluzzi, B. Ledezma, M. Mendenhall, J. Hunt, B. Wolf, B. Jones, J. Madrigal, J. Horton, M. Spiegel, J. Carroll, J. Gukasyan, T. Williams, L. Sauer, C. Wells, A. Hardy, P. Linares, C. Lim, L. Ma, C. Adame, Edward B. Garon
Journal: Journal of Thoracic Oncology (2018)
Inter and intra-observer variability with the assessment of RECIST in ovarian cancer.
Authors: Michelle K. Wilson, Tanya Chawla, Lisa Wang, Michael Friedlander, Amit M. Oza, Stephanie Lheureux
Journal: Journal of Clinical Oncology (2018)

5555 Background: Measurement of response with RECIST is central to the interpretation of trial outcomes and relies upon accurate and reproducible uni-dimensional tumor measurements. This study assessed intra and inter-observer variability with assessment and selection of target lesions for RECIST in patients with ovarian cancer. Methods: Eight international radiologists measured 30 lesions at 2 discrete time points. Lesion measurements between radiologists were compared to assess inter-observer variability. Percentage difference between lesions was calculated. Measurements of the same lesion at two time points by each radiologist were used to assess intra-observer variability. Radiologists were also asked to select 2 target lesions for RECIST. Reproducibility of lesion selection based on site (peritoneal vs nodal vs visceral) was calculated. Results: 80 lesions were measured with a median size of 2.6cm (range 0.8-9.5cm). Seventy-one lesions (89%) were 1.5cm or larger. Assessments at two time points were performed by 7 radiologists. Inter-observer assessment of a single lesion varied on average by 22% (range 5 to 68%). Measurements differed by ≥20% in 28% of visceral, 79% of nodal and 60% of peritoneal lesions. When measured by the same radiologist only 10% of lesions differed by ≥20%. Intra-observer measurements were less likely to vary by ≥20% (10 vs 54%; p < 0.0001). Radiologists were more likely to measure the same lesion with visceral (7/7 lesions; 100%; p = 0.01) and nodal (9/10; 90%; p = 0.01) lesions versus peritoneal lesions (5/14; 36%). When selecting 2 lesions for RECIST, the largest lesion was most consistently chosen (35/38 target lesions; 92%). When this was repeated, 5 of 7 radiologists (71%) chose the same lesions each time. Conclusions: RECIST underpins trial outcomes yet significant variability in tumor measurements was found in this study. These results suggest RECIST assessments by the same radiologist should improve consistency. Peritoneal lesions are a key site of disease progression in ovarian cancer yet these were the most inconsistent to select and had significant inter-observer variability in measurements. These factors need consideration as we strive to improve response assessment in clinical trials.
TCT-692 Impact of Drug-Eluting Stent Generation in Elderly Patients Undergoing PCI: Five-Year Follow-up From a Patient-Level Analysis of 19 Randomized Trials
Authors: None Paul Guedeney, Roxana Mehran, Bimmer Claessen, Sabato Sorrentino, Mengdan Liu, Serdar Farhan, Martin Leon, Patrick Serruys, Pieter Smits, Clemens von Birgelen, Ori Ben-Yehuda, Mahesh Madhavan, Bjorn Redfors, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
NCD Countdown 2030: worldwide trends in non-communicable disease mortality and progress towards Sustainable Development Goal target 3.4
Authors: James E Bennett, Gretchen A Stevens, Colin D Mathers, Ruth Bonita, Jürgen Rehm, Margaret E Kruk, Leanne M Riley, Katie Dain, Andre P Kengne, Kalipso Chalkidou, Jessica Beagley, Sandeep P Kishore, Wanqing Chen, Shekhar Saxena, Douglas W Bettcher, John T Grove, Robert Beaglehole, Majid Ezzati
Journal: The Lancet (2018)
Triple Positivity for Anti–Citrullinated Protein Autoantibodies, Rheumatoid Factor, and Anti–Carbamylated Protein Antibodies Conferring High Specificity for Rheumatoid Arthritis
Authors: Marije K. Verheul, Stefan Böhringer, Myrthe A. M. van Delft, Jonathan D. Jones, William F. C. Rigby, Ryan W. Gan, V. Michael Holers, Jess D. Edison, Kevin D. Deane, Koen M. J. Janssen, Johanna Westra, Mikael Brink, Solbritt Rantapää‐Dahlqvist, Tom W. J. Huizinga, Annette H. M. van der Helm‐van Mil, Diane van der Woude, Rene E. M. Toes, Leendert A. Trouw
Journal: Arthritis & Rheumatology (2018)

In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly used to aid in the diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPAs and RF alone. In addition, anti-carbamylated protein (anti-CarP) antibodies have diagnostic and prognostic value, since their presence is associated with joint damage in RA patients and also associated with the future development of RA in patients with arthralgia. Therefore, the aim of the present study was to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA.A literature search resulted in identification of 12 relevant studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients, and healthy control subjects, in which data on RF, ACPAs, and anti-CarP antibody status were available. Using these data, random effects meta-analyses were carried out for several antibody combinations.The individual antibodies were highly prevalent in patients with RA (34-80%) compared to the control groups, but were also present in non-RA controls (0-23%). For the classification of most subjects correctly as having RA or as a non-RA control, the combination of ACPAs and/or RF often performed well (specificity 65-100%, sensitivity 59-88%). However, triple positivity for ACPAs, RF, and anti-CarP antibodies resulted in a higher specificity for RA (98-100%), accompanied by a lower sensitivity (11-39%).As the rheumatology field is moving toward very early identification of RA and possible screening for individuals at maximum risk of RA in populations with a low pretest probability, an autoantibody profile of triple positivity for ACPAs, RF, and anti-CarP provides interesting information that might help identify individuals at risk of developing RA.