tbuckley/cabot-search huggingface dataset:
Endoscopic sleeve gastroplasty using the novel Endomina device for morbidly obese patients
Authors: Ingo Wallstabe, Nadine Oberaender, Arved Weimann, Ingolf Schiefke
Journal: Endoscopy (2018)

Treatment of obesity is necessary to reduce morbidity and mortality of itself, as well as secondary diseases such as diabetes and hypertension. Endoscopic sleeve gastroplasty (ESG) is a fairly new technique, first described in 2013 [1]. Since then, several methods have been used for the endoscopic creation of a stomach tube to reduce gastric volume [2] [3].
An open-label, randomized cross-over bioavailability and extension study of oral paclitaxel and HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumours.
Authors: Christopher G. C. A. Jackson, Sanjeev Deva, Katherine Francis Bayston, Karen Eden, Blair Richard McLaren, Paula Barlow, Noelyn Anne Hung, Kate Clarke, David Cutler, Gerald Fetterly, Min-Fun Rudolf Kwan, Douglas Kramer, Wing Kai Chan, Tak Hung
Journal: Journal of Clinical Oncology (2018)

2569 Background: Paclitaxel has poor oral bioavailability due to active excretion by p-glycoprotein (Pgp) on intestinal epithelial cells. An oral formulation would reduce IV access, avoid allergic reaction to cremophor, forego steroid premedication, reduce day stay, and improve convenience. With a lower Cmax, oral therapy may have toxicity advantages. Oraxol (Athenex, USA) is a combination of HM30181, a novel, orally active, potent and specific inhibitor of Pgp with low systemic exposure and oral paclitaxel. We report the results of the first scheduled interim analysis of a bio-equivalence study of Oraxol compared to IV paclitaxel, and the results of an extension study with repeat PK sampling after 4 weeks administration. Methods: We conducted a randomized crossover study at 3 sites in New Zealand. HM30181 15mg plus paclitaxel 205mg/m2 was given PO on days 1-3 and compared to a single dose of IV paclitaxel (80 mg/m2) in patients (pts) with advanced solid tumours. PK blood samples were taken d1-9 for PO paclitaxel and d1-5 for IV paclitaxel. Pts who completed were permitted to enroll on an extension study of Oraxol 205mg/m2 d1-3 q1w with repeat PK sampling at week 4. Results: Paclitaxel PK was compared from the first 6 pts in the bioequivalence study, to 10 pts that were enrolled in the extension study. There was one treatment related SAE (tachycardia) which resolved. Treatment related toxicities were mostly GI and haematological, and manageable. One pt remains on study > 1 year without neuropathy. Clinical trial information: ACTRN12615000894594. Conclusions: Oraxol 615mg/m2 PO d1-3 achieved paclitaxel AUC comparable to IV paclitaxel 80mg/m2. This schedule of Oraxol is within predicted range needed to demonstrate bioequivalence. 4-week PK results show PK profile is not altered with repeated dosing. A phase 3 study in patients with metastatic breast cancer is ongoing. Paclitaxel 80mg/m2 IV (n = 6) Mean (SD) Oraxol, Baseline (n = 6) Mean (SD) Oraxol Week 4 (n = 10) Mean (SD) AUC0-∞, (hr*ng/mL) 5652 (1013) 5078 (1723) Cmax (ng/mL) 2269.44 (227.11) 230.99 (133.84) 238.8 (86.11) AUC0-56 2493.4 (731.96) 2615.04 (707.14) GMR (%, 90% CI) 87.09 (74.61-101.66) Intra-subject CV (%) 12.62
Inpatient hematology and oncology rehabilitation.
Authors: Leann Blankenship, Ogunleye Foluso, Thomas B. Lanni, Basil Hakmeh, Adil Jamal Akhtar, Justin Riutta, Susanna S. Gaikazian, Joseph M Anderson, Michael J. Stender, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2017)

6580 Background: Functional decline in cancer patients impacts quality of life and overall survival. Increasing attention has been focused on cancer rehabilitation in survivors, largely in the outpatient setting. Beaumont Health System has shifted its focus to include the acute setting by developing an inpatient cancer rehabilitation unit (IPCR) to improve the comprehensive care of patients. Methods: We retrospectively reviewed the patients admitted to IPCR from January 1 - December 31, 2016 for the following: demographics, length of stay (LOS), function independence measure (FIM) gain and efficiency, discharge location, and primary tumor type. Results: IPCR had 117 inpatient admissions; 98 (83.7%) were solid malignancies while 19 (16.3%) were benign hematological disorders and hematological malignancies. Of the 98 patients with solid malignancies, 22 (22.4%) patients had breast cancer, 22 (22.4%) had gastrointestinal cancers, 5 (5.1%) had gynecological cancers, 23 (23.5%) had lung cancer, 8 (8.2%) had CNS malignancies, 11 (11.2%) had other cancers, and 7 (7.2%) had prostate cancer with 81.6% of patients having metastatic disease. Among the hematological malignancies, lymphoma was diagnosed in 11 (57.9%) patients while 3 (15.9%) each had multiple myeloma and leukemia. The mean age of the patients was 68 years and 59% were female. The average LOS was 8.6 days. The mean admission total FIM was 66.7 ±12.8 and discharge total FIM was 87.3 ±16.1. The total improvement in FIM was 20.6 ±13.8 with FIM efficiency of 2.9. There were 21 (18%) patients transferred back to acute care units for decompensation, 7 (6%) went to subacute rehabilitation, 1 (0.85%) went to hospice while 87 (74.3%) were discharge to their homes upon completion of IPCR. Conclusions: Our focused rehabilitation was able to decrease the LOS, well above the 90 th percentile Center for Medicare and Medicaid Services (CMS) benchmark and other prior studies, as well as enable patients to safely return home with improved FIM. Creating an IPCR unit proved to be beneficial, allowing for more comprehensive and individualized care, even in the setting of advanced malignancies.
NiCCC (ENGOT-GYN1): A randomized phase II study of nintedanib (BIBF1120) compared to chemotherapy in patients with recurrent clear-cell carcinoma of the ovary or endometrium.
Authors: Rosalind Margaret Glasspool, Iain A. McNeish, James Paul, Claire A Lawless, Diann Taggart, David W. M. Millan, W. Glenn McCluggage, Nafisa Wilkinson, Clare Stephanie Barlow, Geoff Hall, Justin S. Waters, Susana N. Banerjee, Jerome Alexandre, Nathalie LE Fur, A.M. Westermann, Corneel Coens, Christina Jederud, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2016)

TPS5603 Background: Clear-cell carcinoma (CCC) is an uncommon histotype of ovarian and a rare histotype of endometrial cancer. Prognosis for recurrent disease is poor and response rates to standard chemotherapy are < 10%. Ovarian CCC (OCCC) is biologically different from other ovarian cancer histotypes but shares features with renal CCC, including upregulation of angiogenesis pathways; inhibition of angiogenesis may thus be of benefit in OCCC. Nintedanib is a well-tolerated, potent, orally-available, kinase inhibitor targeting VEGFR 1-3, PDGFR α and β, and FGFR 1-3. This is the first randomised trial in relapsed OCCC and the first to include a cohort of endometrial CCC (ECCC). Methods: NiCCC is an international randomized phase II trial of nintedanib versus physician’s choice chemotherapy. Standard arms for OCCC are paclitaxel (80mg/m2) IV d1, 8, 15 q28; pegylated liposomal doxorubicin (40 mg/m2) IV q28 or topotecan 4 mg/m2 IV d1, 8, 15 q28, and carboplatin (AUC 5) and paclitaxel (175 mg/m2) IV q21, or Doxorubicin (60 mg/m2) IV q21 for ECCC. The experimental arm is nintedanib 200mg PO bd continuously until progression. Primary endpoint is progression free survival (PFS). The study is designed to detect an increase in median PFS from 3 to 5 months in OCCC with > 90% power, 20% 1-sided significance. 90 OCCC patients and up to 30 ECCC patients will be included to gain initial data in this rarer group. Eligibility includes prospective central pathology review; ≥ 1 line of platinum-based chemotherapy and, in OCCC, progression within 6 months of last platinum; ECOG PS ≤ 2; adequate hepatic, bone marrow, coagulation and renal function. Archival and fresh tumour, plasma and circulating endothelial cell samples are being collected for translational studies. The study is open in the UK. 6 patients have been recruited. The study will open internationally in 2016 in collaboration with three co-operative groups, NSGO, GINECO and EORTC. The study is sponsored by NHS Greater Glasgow and Clyde and funded by Cancer Research UK (Grant ref: C8361/A15600) and an investigator-led study grant from Boehringer Ingelheim. ISRCTN No: ISRCTN50772895. Clinical trial information: ISRCTN50772895.
P05.45 Hydroxyurea (HU) or VAC (vincristine, adriamycin and cyclophosphamide) in a group of recurrent meningioma patients
Authors: A Silvani, G Simonetti, L Elena Antonia, B Pollo, L Fariselli, P Gaviani
Journal: Neuro-Oncology (2018)

A subset of meningiomas recur after surgery and radiation therapy, no proven effective medical therapy for this sub group of meningioma patients exists. Both recurrent or progressive cases, may exhibit tumor growth involving critical neurovascular structures or diffuse growth, resulting in limited efficacy and higher risk of treatments. We retrospectively analysed the efficacy and tolerability of systemic chemotherapy with Hydroxyurea (HU) or more complex VAC (Vincristine, Adriamycin and Cyclophosphamide) in a group of recurrent meningioma patients treated at Fondazione IRCCSS Istituto Neurologico Carlo Besta between 2015 and 2017. Twelve patients with high-grade meningioma (8 atypical and 4 anaplastic) were treated with VAC (7) chemotherapy or HU (5). All, patients were heavily pre-treated (median number of 4 recurrences, range 2–7). Responses were assessed using modified Macdonald criteria. The Kaplan-Meier technique was used to estimate PFS and OS. The 95% confidence intervals (CIs) were calculated for all point estimates. The majority of patients came off treatment because of progressive disease. PFS6 rate was 42%. Median PFS was 5.3 months (95% CI: 2.1–9.3 mo), and median overall survival was 19 months (95% CI: 16.5–38.4 mo). No treatment related death occurred. Main treatment-related toxicities were observe in the patients treated by VAC HU and VAC chemotherapies are feasible but these treatments have limited activity in recurrent meningiomas. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified due to the small number of prospective clinical trials available
Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204.
Authors: Hussein Abdul-Hassan Tawbi, Peter A. J. Forsyth, Alain Patrick Algazi, Omid Hamid, F. Stephen Hodi, Stergios J. Moschos, Nikhil I. Khushalani, Rene Gonzalez, Christopher D. Lao, Michael Andrew Postow, Michael B. Atkins, Marc S. Ernstoff, Igor Puzanov, Ragini Reiney Kudchadkar, Reena Parada Thomas, Ahmad A. Tarhini, Joel Jiang, Alexandre Avila, Sheena Demelo, Kim Allyson Margolin
Journal: Journal of Clinical Oncology (2017)

9507 Background: Brain metastases (BMts) are a major cause of morbidity/death in MEL. We report the first efficacy data in MEL patients (pts) with BMts who received NIVO+IPI in study CheckMate 204. Methods: In this multicenter US trial (NCT02320058), MEL pts with ≥1 measurable BMt 0.5-3.0 cm and no neurologic symptoms or steroid Rx received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until progression or toxicity. Pts with severe adverse events (AEs) during NIVO+IPI could receive NIVO when toxicity resolved; stereotactic radiotherapy (SRT) was allowed for brain oligo-progression if an assessable BMt remained. The primary endpoint was intracranial (IC) clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD] &gt; 6 months). The planned 90-pt accrual is complete; we report efficacy and updated safety for 75 pts with disease assessment before the Nov 2016 database lock. Results: Median age was 59 yrs (range 22–79). Median number of induction doses was 3; 26 pts (35%) received 4 NIVO+IPI doses and 38 pts (51%) began NIVO maintenance. Response data are reported at a median follow-up of 6.3 months (Table). The IC objective response rate (ORR) was 56% (95% CI: 44–68); 19% of pts had a complete response. IC and extracranial responses were largely concordant. Rx-related grade 3/4 AEs occurred in 48% of pts, 8% neurologic, including headache and syncope. Only 3 pts (4%) stopped Rx for Rx-related neurologic AEs. One pt died of immune-related myocarditis. Conclusions: In CheckMate 204, prospectively designed to investigate NIVO+IPI in MEL pts with BMts, NIVO+IPI had high IC antitumor activity with objective responses in 56% of pts, CR in 19%, and no unexpected neurologic safety signals. The favorable safety and high anti-melanoma activity of NIVO+IPI may represent a new Rx paradigm for pts with asymptomatic MEL BMts and could change practice to avoid or delay whole brain RT or SRT. Clinical trial information: NCT02320058. [Table: see text]
Regulating stool for microbiota transplantation
Authors: Pilar N. Ossorio, Yao Zhou
Journal: Gut Microbes (2018)

In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.
Impact of the type of first-cancer therapy in therapy-related myelodysplastic syndromes outcomes.
Authors: Ana Alfonso Pierola, Guillermo Montalban-Bravo, Koichi Takahashi, Elias Jabbour, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes, Courtney Denton Dinardo, Naval Guastad Daver, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos E. Bueso-Ramos, Sherry Pierce, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2017)

e18555 Background: Therapy-related myelodysplastic syndromes (t-MDS) are known to have poor outcomes. The impact of the therapy received for the first cancer remains unknown. Methods: 228 t-MDS diagnosed between July 2001 and December 2015 were retrospectively reviewed. Results: Median age at diagnosis of t-MDS was 66 years (range 13-87). Previous malignancies: 54% hematological cancers and 47% solid tumors. 14% had multiple cancers before the t-MDS. Previous therapy received: 119 (52%) chemotherapy (CT), 17 (8%) radiotherapy (RT), or 92 (40%) both (Table). Median time to develop t-MDS was 73 months (range 5-355). According to IPSS, 13 patients (6%) had low-risk, 65 (29%) intermediate-1 risk, 119 (53%) intermediate-2 risk and 29 (13%) high-risk. 124 patients (58%) had complex karyotype. The most frequent cytogenetic abnormalities detected were: -7/7q (n=99; 46%), -5/5q (n=77; 36%), and +8 (n=13; 6%). TP53was observed in 51% (n=21/41). Median OS was 12 months (CI95% = 10-14). Univariate and multivariate analysis revealed that CT vs RT (p=0.028; HR [CI95%] = 1.988 [1.08-3.67]), and higher IPSS risk (low: p=0.027; intermediate-1: p=0.285 HR [CI95%] = 1.48 [0.72-3.01]; intermediate-2: p=0.055, HR [CI95%] = 1.95 [0.99-3.88]; high: p=0.015 HR [CI95%] = 2.59 [1.21-5.55]), had a poor impact in OS. No statistical differences between OS and type of CT received, molecular or cytogenetic alterations were observed. However, complex karyotype (71% vs 51%, p=0.007) and -7/7 abnormalities (61% vs 36%; p=0.001) were more frequent in patients who had received platinum; -7/7q- abnormalities were also associated to alkylating agents (50% vs 27%, p=0.012), antibiotics (74% vs 42%; p=0.003) and topoisomerase inhibitors (60% vs 37%; p=0.002). Conclusions: t-MDS is associated with poor outcomes. Receiving CT vs RT and higher IPSS risk had a poor impact in OS. The type of CT may be associated with specific cytogenetic alterations. [Table: see text]
Chronic breathlessness: time for Cinderella to go to the ball!
Authors: Miriam J. Johnson, Marie Fallon
Journal: European Respiratory Journal (2018)

<b>If clinicians do not recognise chronic breathlessness as something serious which warrants further intervention and for which interventions are available, much suffering which could be ameliorated will remain hidden</b>http://ow.ly/KP7b30lpzey
Abstract P251: Triggers of Temptations and Urges Do Not Change During a 12-Month Behavioral Intervention for Weight Loss
Authors: Lora E Burke, Saul Shiffman, Daniel Siewiorek, Asim Smailagic, Andrea Kriska, Linda I Ewing, Yaguang Zheng, Juliet Mancino, Stephen L Rathbun
Journal: Circulation (2016)

Introduction: Ecological momentary assessment (EMA) assesses individuals’ behaviors and moods as they occur in their natural environment. We examined self-reported triggers of temptations/urges to eat and compared percent of times each trigger was reported as the top trigger in the 1st 6 mos. vs. the 2nd 6 mos. of a standard behavioral weight loss intervention. Hypothesis: The distribution of self-reported triggers of urges/temptations changes over time. Methods: We provided participants a smartphone app programmed to permit them to self-initiate completing EMA and report temptations/urges in real time. Questions included: What were the triggers for the temptation/urge? What was the top trigger? Only data from subjects reporting ≥ one urge/temptation were included in the analysis. For each trigger, generalized estimating equations were used to fit logistic regression models to test the hypothesis that proportion of urges/temptations including that trigger did not change between the 1st and 2 nd 6 mos. of EMA surveillance. Results: The sample ( N = 139) was 90.6% female, 82.7% White, 50.9±10.10 years of age with a BMI of 34.2±4.6 kg/m2. There were 3175 reported episodes of temptation/urges. During both 6-mo.periods, sight/smell of food was the most frequently reported trigger occurring in 34.8% of temptations/urges in the first 6 mos., increasing to 35.52% in the second 6-mos. This was followed by stress, hunger/thirst, and habit during both 6-mo. periods. There were no significant differences in the frequency or type of triggers over time, except for “out of nowhere”, which occurred less often in the second period (6.98% vs. 5.42%, p = .02). The triggers are plotted in order of most to least frequent for both periods in the figure below. Conclusions: Fewer temptations/urges were reported in the second 6 mos., which likely is attributed to a decrease in compliance by participants to EMA protocols. The sight/smell of food remained the most frequently reported trigger, which is a concern in an environment that is very food centric.
P01.118 Prognostic factors and management of gliomatosi cerebri (GC) from real life experience of two neuroncology centers
Authors: G Lombardi, L Bellu, G Sabatino, M Caccese, F Berti, F Busato, A Della Puppa, D D’Avella, A Olivi, V Zagonel
Journal: Neuro-Oncology (2018)

GC is defined as a rare pattern of growth of gliomas, involving three or more cerebral lobes. Considering its rarity, it’s still difficult to define prognostic factors and standard of treatment. Retrospectively, we analyzed patients (PT) with GC from two neuro-oncology centers to identify main prognostic factors and the optimal management. Medical records of patients ≥ 18years, with histological and/or radiological diagnosis of GC occurred between 2006 and 2017 were reviewed. Median progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. We analyzed 33PT, 22males and 11female; ECOG performance status (PS) was 0–1 in 21PT and ≥ 2 in 12PT. 22PT underwent biopsy: 16 were astrocytomas, 6oligodendrogliomas. MGMT was detected in 14PT: it was metilated in 8cases. IDH1 was analyzed in 16PT: it was mutated in 10PT. 15 of 33PT showed localized enhancing lesions at diagnosis. 9PT(27%) were treated with radiation therapy (RT) plus concurrent temozolomide (TMZ), 22PT(67%) received only TMZ, and 2PT(6%) underwent RT alone. Best response was complete response (CR) in 3PT(3%), partial response (PR) in 9PT(27%) and stable desease (SD) for 15PT(45%); only 8PT(25%) had a progression desease (PD). For all PT, PFS and OS were 19.1 and 30.7 months (ms) respectively. For PS 0–1 and ≥2, PFS was 34.6 vs 3.4ms (p<0.0001) and OS was 42 vs 8.9ms (p<0.0001) respectively. Metilated MGMT was associated with longer PFS (41.6 vs 8.9ms, p=0.05) and OS (52.7 vs 14.6ms, p=0.009); for IDH1 mutated and IDH wt, PFS was 52.7 vs 8.9ms (p=0.006) and OS was 57.7 vs 41ms (p=0.02) respectively. No significantly difference was detected about treatments: PFS was 11.1 vs 19.1ms and OS was 40.4 vs 41.7ms for RT+TMZ and TMZ/RT alone, respectively. No significantly difference was found beetween enhancing and non-enhancing lesions: PFS was 11.1 vs 23.1ms (p=0.2), OS was 14.6 vs 41.7ms (p=0.1). Regarding histological subtype, OS was 42.0 vs 52.7ms and PFS was 41.6 vs 28.6ms for astrocytoma vs oligodendroglioma respectively. PT having PR or CR reported a longer OS versus PT with SD and PD as best response: 4.0ms for PD, 30.7ms for SD and 38.5ms for PR+CR (p<0.0001). 13 of 22PT underwent second-line treatment after relapsing: 1PT did RT+TMZ, 10PT chemotherapy alone (fotemustina, PCV/PC, TMZ), and 2PT RT alone; PTS receiving a second-line treatment had a longer OS: 30.7 vs 6.5ms (p=0.04). PS, MGMT and IDH1 seems to have an important prognostic significance, whereas, type of treatment doesn’t seem to affect survival. Best response could be a good surrogate of OS.